MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Cellular Signalling' source. Tue, 07 Feb 2012 08:48:56 +0100 http://www.medworm.com/index.php?rid=5659126&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22286105%26dopt%3DAbstract Authors: Smrcka AV, Brown JH, Holz GG Abstract Receptor-initiated phospholipase C activation and generation of IP(3) and DAG are important common triggers for a diversity of signal transduction processes in many cell types. Contributing to this diversity is the existence and differential cellular and subcellular distribution of distinct phospholipase C isoforms with distinct regulatory properties. The recently identified PLCε enzyme is an isoform that is uniquely regulated by multiple upstream signals including ras-family GTP binding proteins as well as heterotrimeric G-proteins. In this review we will consider the well documented biochemical regulation of this isoform in the context of cell and whole animal physiology and in the context of other G protein-regulated PLC isoforms. ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5659126 Fri, 20 Jan 2012 05:00:00 +0100 5659126 http://www.medworm.com/index.php?rid=5659125&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22286106%26dopt%3DAbstract Authors: Ray PD, Huang BW, Tsuji Y Abstract Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism as well as in cellular response to xenobiotics, cytokines, and bacterial invasion. Oxidative stress refers to the imbalance due to excess ROS or oxidants over the capability of the cell to mount an effective antioxidant response. Oxidative stress results in macromolecular damage and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging. Paradoxically, accumulating evidence indicates that ROS also serve as critical signaling molecules in cell proliferation and survival. While there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5659125 Fri, 20 Jan 2012 05:00:00 +0100 5659125 http://www.medworm.com/index.php?rid=5659124&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22286107%26dopt%3DAbstract Authors: Guo Y, Rosati B, Scarlata S Abstract α-Synuclein is a conserved protein that is a key component in neurodegenerative plaques [1,2]. α-Synuclein binds strongly to phospholipase Cβ (PLCβ) and promotes Ca(2+) release in cells. Here, we show that expression of α-synuclein increases the cellular level of PLCβ1 in two neuronal cell lines: PC12 and SK-N-S-SH. The increase in PLCβ1 is not accompanied by changes in the level of RNA or in ubiquitination. Instead, we find that α-synuclein protects PLCβ1 from trypsin digestion and from degradation by the Ca(+2) activated protease calpain. Calpain removes the C-terminal region of the enzyme which mediates activation by Gα(q). We find that in SK-N-SH cells, α-synuclein reduced degradation of PLCβ1 by calpain during Ca(2+) si... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5659124 Fri, 20 Jan 2012 05:00:00 +0100 5659124 http://www.medworm.com/index.php?rid=5659129&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22274732%26dopt%3DAbstract Authors: Zhou A, Zhang S Abstract In order to successfully survive in host and persistent infection, porcine reproductive and respiratory syndrome virus (PRRSV) utilized sophisticated mechanisms to suppress or escape from the host' innate and adaptive immune systems, and then changed host gene expression. Signaling pathways play a pivotal role in the regulation of diverse biological processes. Once signaling pathways are activated by a variety of different stimuli, immune responses will be triggered by the activation of chemokines, transcription factors, and inflammatory cytokines to adjust the aggressive replication and dissemination of viruses. PRRSV infection is able to get many signaling pathways activation that facilitates distinct cell functions to modulate immune responses. ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5659129 Tue, 17 Jan 2012 05:00:00 +0100 5659129 http://www.medworm.com/index.php?rid=5659128&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22285803%26dopt%3DAbstract Authors: Hesabi B, Danziger RS, Kotlo KU Abstract Two classes of guanylyl cyclases (GC) form intracellular cGMP. One is a receptor for atrial natriuretic peptide (ANP) and the other for nitric oxide (NO). The ANP receptor guanylyl cyclase (GC-A) is a membrane-bound, single subunit protein. Nitric oxide activated or soluble guanylyl cyclases (NOGC) are heme-containing heterodimers. These have been shown to be important in cGMP mediated regulation of arterial vascular resistance and renal sodium transport. Recent studies have shown that cGMP produced by both GCs is compartmentalized in the heart and vascular smooth muscle cells. To date, however, how intracellular cGMP generated by ANP and NO is compartmentalized and how it triggers specific downstream targets in kidney cells has not... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5659128 Tue, 17 Jan 2012 05:00:00 +0100 5659128 http://www.medworm.com/index.php?rid=5659127&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22285804%26dopt%3DAbstract Authors: Rebeyrol C, Saint-Criq V, Guillot L, Riffault L, Corvol H, Chadelat K, Ray DW, Clement A, Tabary O, Le Rouzic P Abstract Reduction of lung inflammation is one of the goals of cystic fibrosis (CF) therapy. Among anti-inflammatory molecules, glucocorticoids (GC) are one of the most prescribed. However, CF patients seem to be resistant to glucocorticoid treatment. Several molecular mechanisms that contribute to decrease anti-inflammatory effects of glucocorticoids have been identified in pulmonary diseases, but the molecular actions of glucocorticoids have never been studied in CF. In the cytoplasm, glucocorticoids bind to glucocorticoid receptor (GR) and then, control NF-κB and MAPK pathways through direct interaction with AP-1 and NF-κB in the nucleus. Conversely, MAPK ca... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5659127 Tue, 17 Jan 2012 05:00:00 +0100 5659127 http://www.medworm.com/index.php?rid=5659130&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266116%26dopt%3DAbstract Authors: Jiang Y, Zhang Q, Soderland C, Steinle JJ Abstract Rates of diabetes are reaching epidemic levels. The key problem in both type 1 and type 2 diabetes is dysfunctional insulin signaling, either due to lack of production or due to impaired insulin sensitivity. A key feature of diabetic retinopathy in animal models is degenerate capillary formation. The goal of this present study was to investigate a potential mechanism for retinal endothelial cell apoptosis in response to hyperglycemia. The hypothesis was that hyperglycemia-induced TNFα leads to retinal endothelial cell apoptosis through inhibition of insulin signaling. To test the hypothesis, primary human retinal endothelial cells were grown in normal glucose (5mM) or high glucose (25mM) and treated with exogenous TNFα, ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5659130 Thu, 12 Jan 2012 05:00:00 +0100 5659130 http://www.medworm.com/index.php?rid=5623177&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261253%26dopt%3DAbstract We report here the characterization of a nuclear variant of the kinase-defective ErbB3 receptor, ErbB3(80kDa), spanning the intracytoplasmic domain of the receptor. We assessed the putative transcriptional functions of ErbB3(80KDa) in cancer cells, through the regulation of the proliferative Cyclin D1 gene, an already known target of the ErbB3 cytoplasmic signaling. We demonstrate here that the binding of ErbB3(80KDa) on the promoter activates the Cyclin D1 transcription and subsequent protein expression, leading to an increased cell proliferation. This mechanism can be balanced in response to the ectopic expression of the tumor suppressor p14(ARF) that physically interacts with ErbB3(100kDa) and sequesters it into nucleoli. Our data also show that ErbB3(80kDa) increases the transcription ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5623177 Wed, 11 Jan 2012 05:00:00 +0100 5623177 http://www.medworm.com/index.php?rid=5623176&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261254%26dopt%3DAbstract Authors: Martin VA, Wang WH, Lipchik AM, Parker LL, He Y, Zhang S, Zhang ZY, Geahlen RL Abstract The engagement of antigen receptors on lymphocytes leads to the activation of phospholipase C-γ, the mobilization of intracellular calcium and the activation of the NFAT transcription factor. The coupling of antigen receptors to the activation of NFAT is modulated by numerous cellular effectors including phosphoinositide 3-kinase (PI3K), which is activated following receptor cross-linking. The activation of PI3K has both positive and negative effects on the receptor-mediated activation of NFAT. An increase in the level and activity of Akt2, a target of activated PI3K, potently inhibits the subsequent activation of NFAT. In contrast, an elevation in Akt1 has no effect on signaling. Sign... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5623176 Wed, 11 Jan 2012 05:00:00 +0100 5623176 http://www.medworm.com/index.php?rid=5602322&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245141%26dopt%3DAbstract In this study, we have examined whether or not BCL11B directly affects the p53 signaling pathway including HDM2, a ubiquitin ligase for p53 degradation. The p53 pathway regulates cell proliferation and the response to DNA damages to maintain genome integrity. Here we show that BCL11B binds to human HDM2-P2 promoter by ChIP (chromatin immuno-precipitation) assay and inhibits HDM2 expression in a p53-dependent manner. Deletion of the distal p53 responsive element in HDM2 promoter region or the lack of p53 in HCT116 cells greatly reduced the repressive effect of BCL11B on HDM2-P2 promoter activity. The repressive activity was alleviated in γ-ray induced DNA damage conditions that activate p53, suggesting interaction between BCL11B and p53 for HDM2 expression. These date suggest that BCL11B a... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5602322 Thu, 05 Jan 2012 05:00:00 +0100 5602322 http://www.medworm.com/index.php?rid=5602321&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245142%26dopt%3DAbstract This report is designed to explore the roles of the upstream mediators of the intrinsic pathway, such as Bak/Bax, Bim, Puma and Noxa, during RV-induced apoptosis in human lung adenocarcinoma (ASTC-a-1 and A549) cell lines. RV treatment remarkably induced the activation of Bak but not Bax, and silencing Bak but not Bax by shRNA almost completely prevented RV-induced cell death, mitochondrial dysfunction and also largely prevented RV-induced AIF release, demonstrating the preferential engagement of Bak but not Bax during RV-induced apoptosis. In addition, although RV treatment induced a significant degradation of Mcl-1, knockdown of Mcl-1 by shRNA only modestly increased RV-induced Bak activation. Interestingly, silencing Bim but not Puma and Noxa remarkably attenuated RV-induced cell death,... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5602321 Thu, 05 Jan 2012 05:00:00 +0100 5602321 http://www.medworm.com/index.php?rid=5602320&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245495%26dopt%3DAbstract Authors: Ghosh AK, Nagpal V, Covington JW, Michaels MA, Vaughan DE Abstract Fibroblasts are responsible for producing the majority of collagen and other extracellular matrix (ECM) proteins in tissues. In the injured tissue, transforming growth factor-β (TGF-β)-activated fibroblasts or differentiated myofibroblasts synthesize excessive ECM proteins and play a pivotal role in the pathogenesis of fibrosis in heart, kidney and other organs. Recent studies suggest that fibroblast-like cells, derived from endothelial cells by endothelial-to-mesenchymal transition (EndMT), contribute to the pathogenesis of cardiac fibrosis. The molecular basis of EndMT, however, is poorly understood. Here, we investigated the molecular basis of EndMT in mouse cardiac endothelial cells (MCECs) in respons... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5602320 Thu, 05 Jan 2012 05:00:00 +0100 5602320 http://www.medworm.com/index.php?rid=5602319&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245496%26dopt%3DAbstract Authors: Matthys A, Van Craenenbroeck K, Lintermans B, Haegeman G, Vanhoenacker P Abstract The 5-hydroxytryptamine (5-HT)7 receptor is the most recently identified serotonin receptor and is involved in a wide variety of central nervous system (CNS) functions, namely circadian rhythm, REM sleep, depression, thermoregulation, obsessive-compulsive disorder (OCD), anxiety, schizophrenia, epilepsy, nociception, migraine, sensation-seeking behavior, impulsivity, learning and memory. These numerous (patho)physiological processes of the CNS, in which the 5-HT7 receptor is involved, most likely reflect a diverse set of signaling pathways arising from this receptor. In order to reveal new interaction partners and possibly new signaling and/or trafficking pathways, we performed a yeast two-hy... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5602319 Thu, 05 Jan 2012 05:00:00 +0100 5602319 http://www.medworm.com/index.php?rid=5602325&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22237159%26dopt%3DAbstract Authors: Hill CR, Sanchez NS, Love JD, Arrieta JA, Hong CC, Brown CB, Austin AF, Barnett JV Abstract Coronary vessel development depends on a subpopulation of epicardial cells that undergo epithelial to mesenchymal transformation (EMT) and invade the subepicardial space and myocardium. These cells form the smooth muscle of the vessels and fibroblasts, but the mechanisms that regulate these processes are poorly understood. Mice lacking the Type III Transforming Growth Factor β Receptor (TGFβR3) die by E14.5 due to failed coronary vessel development accompanied by reduced epicardial cell invasion. BMP2 signals via TGFβR3 emphasizing the importance of determining the relative contributions of the canonical BMP signaling pathway and TGFβR3-dependent signaling to BMP2 responsiveness... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5602325 Tue, 03 Jan 2012 05:00:00 +0100 5602325 http://www.medworm.com/index.php?rid=5602324&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245064%26dopt%3DAbstract Authors: Finch AR, Caunt CJ, Perrett RM, Tsaneva-Atanasova K, McArdle CA Abstract We have explored the possible role of dual specificity phosphatases (DUSPs) on acute EGF-mediated ERK signalling using high content imaging and a delayed MEK inhibition protocol to distinguish direct and indirect effects of the phosphatases on ERK activity. Using siRNAs, we were unable to find evidence that any of the MAPK phosphatases (MKPs) expressed in HeLa cells acts directly to dephosphorylate ppERK1/2 (dual phosphorylated ERKs 1 and/or 2) in the acute time-frame tested (0-14min). Nevertheless, siRNAs against two p38/JNK MKPs (DUSPs 10 and 16) inhibited acute EGF-stimulated ERK activation. No such effect was seen for acute effects of the protein kinase C activator PDBu (phorbol 12,13 dibutyrate) ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5602324 Tue, 03 Jan 2012 05:00:00 +0100 5602324 http://www.medworm.com/index.php?rid=5602323&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245140%26dopt%3DAbstract Authors: Sevcik J, Falk M, Kleiblova P, Lhota F, Stefancikova L, Janatova M, Weiterova L, Lukasova E, Kozubek S, Pohlreich P, Kleibl Z Abstract The BRCA1 gene codes for a protein involved in the DNA double strand break (DDSB) repair. Alongside the dominant full-length splicing form of BRCA1, numerous endogenously expressed alternative splicing variants of unknown significance have been described in various tissues. Some of them retain the original BRCA1 reading frame but lack several critical BRCA1 structural domains, suggesting an altered function of the resulting protein in the BRCA1-regulated processes. To characterize the effect of the BRCA1Δ14-15 splicing variant (with an in-frame deletion affecting the regulatory serine-containing domain) on the DDSB repair, we constructed t... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5602323 Tue, 03 Jan 2012 05:00:00 +0100 5602323 http://www.medworm.com/index.php?rid=5602326&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22234345%26dopt%3DAbstract Authors: Yan H, Zhu S, Song C, Liu N, Kang J Abstract Aberrant expression of mitotic checkpoint genes compromises mitotic checkpoint, leads to chromosome instability and tumorigenesis. However, the cell signals that control mitotic checkpoint gene expression have not been reported so far. In the present study we show that, in human breast cancer cells, chemical inhibition of Bone morphogenetic proteins (BMPs), but not Transforming Growth Factor-β (TGF-β), abrogates the mitotic arrest induced by nocodazole. Protein expression analysis reveals that inhibition of BMP signaling dramatically down regulates protein levels of mitotic checkpoint components BUB3, Hec1, TTK and MAD2, but inhibition of TGF-β has relatively minor effect on the expression of these proteins. Activation of BMP... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5602326 Fri, 30 Dec 2011 05:00:00 +0100 5602326 http://www.medworm.com/index.php?rid=5578523&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22230687%26dopt%3DAbstract In this study, patulin was found to induce G1/S accumulation and cell growth arrest accompanied by caspase-3 activation, PARP cleavage and ATF3 expression in human colon cancer cell line HCT116. Ser/Thr phosphorylation of a transcription factor, EGR-1, was increased while its expression did not change upon patulin treatment to the cells. Knockdown of ATF3 and EGR-1 using their respective siRNAs showed EGR-1 dependent ATF3 expression. Moreover, treatment of the cells with antioxidants N-acetylcysteine (NAC) and glutathione (GSH) revealed that patulin induced ATF3 expression and apoptosis were dependent on ROS generation. ATF3 expression was also increased by patulin in other colorectal cancer cell types, Caco2 and SW620. Collectively, our data present a new anti-cancer molecular mechanism o... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5578523 Fri, 30 Dec 2011 05:00:00 +0100 5578523 http://www.medworm.com/index.php?rid=5578522&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22230688%26dopt%3DAbstract Authors: Trincavelli ML, Daniele S, Orlandini E, Navarro G, Casadó V, Giacomelli C, Nencetti S, Nuti E, Macchia M, Huebner H, Gmeiner P, Rossello A, Lluís C, Martini C Abstract The structural and functional interaction between D(2) dopamine receptor (DR) and A(2A) adenosine receptor (AR) has suggested these two receptors as a pharmacological target in pathologies associated with dopamine dysfunction, such as Parkinson's disease. In transfected cell lines it has been demonstrated the activation of D(2)DR induces a significant negative regulation of A(2A)AR-mediated responses, whereas few data are at now available about the regulation of A(2A)AR by D(2)DR agonists at receptor recognition site. In this work we confirmed that in A(2A)AR/D(2)DR co-transfected cells, these receptors ex... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5578522 Fri, 30 Dec 2011 05:00:00 +0100 5578522 http://www.medworm.com/index.php?rid=5578521&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22230689%26dopt%3DAbstract Authors: Barth BM, Gustafson SJ, Hankins JL, Kaiser JM, Haakenson JK, Kester M, Kuhn TB Abstract A persistent inflammatory reaction is a hallmark of chronic and acute pathologies in the central nervous system (CNS) and greatly exacerbates neuronal degeneration. The proinflammatory cytokine tumor necrosis factor alpha (TNFα) plays a pivotal role in the initiation and progression of inflammatory processes provoking oxidative stress, eicosanoid biosynthesis, and the production of bioactive lipids. We established in neuronal cells that TNFα exposure dramatically increased Mg(2+)-dependent neutral sphingomyelinase (nSMase) activity thus generating the bioactive lipid mediator ceramide essential for subsequent NADPH oxidase (NOX) activation and oxidative stress. Since many of the pleio... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5578521 Fri, 30 Dec 2011 05:00:00 +0100 5578521 http://www.medworm.com/index.php?rid=5578526&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227247%26dopt%3DAbstract This study reveals a novel mechanism that interconnects ERα and TGF-β signaling pathways by SnoN. Accordingly, the results indicate that high SnoN level promotes ERα signaling and possibly breast cancer progression. PMID: 22227247 [PubMed - as supplied by publisher] (Source: Cellular Signalling) Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5578526 Thu, 29 Dec 2011 05:00:00 +0100 5578526 http://www.medworm.com/index.php?rid=5578525&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227248%26dopt%3DAbstract Authors: Waldron RT, Innamorati G, Torres-Marquez ME, Sinnett-Smith J, Rozengurt E Abstract Protein kinase D (PKD) is activated within cells by stimulation of multiple G protein coupled receptors (GPCR). Earlier studies demonstrated a role for PKC to mediate rapid activation loop phosphorylation-dependent PKD activation. Subsequently, a novel PKC-independent pathway in response to Gαq-coupled GPCR stimulation was identified. Here, we examined further the specificity and PKC-dependence of PKD activation using COS-7 cells cotransfected with different Gq-family Gα and stimulated with aluminum fluoride (AlF4(-)). PKD activation was measured by kinase assays, and Western blot analysis of activation loop sites Ser(744), a prominent and rapid PKC transphosphorylation site, and Ser(748),... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5578525 Thu, 29 Dec 2011 05:00:00 +0100 5578525 http://www.medworm.com/index.php?rid=5578524&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227249%26dopt%3DAbstract Authors: Ray R, Li C, Bhattacharya S, Naren AP, Johnson LR Abstract Intracellular polyamine levels are highly regulated by the activity of ornithine decarboxylase (ODC), which catalyzes the first rate-limiting reaction in polyamine biosynthesis, producing putrescine, which is subsequently converted to spermidine and spermine. We have shown that polyamines regulate proliferation, migration, and apoptosis in intestinal epithelial cells. Polyamines regulate key signaling events at the level of the EGFR and Src. However, the precise mechanism of action of polyamines is unknown. In the present study, we demonstrate that ODC localizes in lamellipodia and in adhesion plaques during cell spreading. Spermine regulates EGF-induced migration by modulating the interaction of the EGFR with Src.... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5578524 Thu, 29 Dec 2011 05:00:00 +0100 5578524 http://www.medworm.com/index.php?rid=5550425&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22200678%26dopt%3DAbstract Authors: Li Y, Chen J, Bai B, Du H, Liu Y, Liu H Abstract Apelin receptor (APJ) and kappa opioid receptor (KOR) are members of the family A of G protein-coupled receptors (GPCRs). These two receptors are involved in the central nervous system regulation of the cardiovascular system. Here, we explore the possibility of heterodimerization between APJ and KOR and investigate their novel signal transduction characteristics. Co-immunoprecipitation (Co-IP), co-localization and bioluminescence resonance energy transfer (BRET) assays confirmed the heterodimerization of APJ and KOR. In APJ and KOR stably transfected HEK293 cells, treatment with APJ ligand apelin-13 or KOR ligand dynorphinA (1-13) resulted in higher phosphorylation levels of extracellular-regulated kinases 1/2 (ERK1/2) compa... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5550425 Tue, 20 Dec 2011 05:00:00 +0100 5550425 http://www.medworm.com/index.php?rid=5550424&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22200679%26dopt%3DAbstract Authors: Manetsch M, Che W, Seidel P, Chen Y, Ammit AJ Abstract Airway smooth muscle (ASM) plays an important immunomodulatory role in airway inflammation in asthma. In our previous in vitro studies in ASM cells delineating the pro-inflammatory mitogen-activated protein kinase (MAPK) signaling pathways activated by tumor necrosis factor α (TNFα), we observed that TNFα concomitantly induces the rapid, but transient, upregulation of the anti-inflammatory protein-mitogen-activated protein kinase phosphate 1 (MKP-1). As this was suggestive of a negative feedback loop, the aim of this study was to investigate the molecular mechanisms of MKP-1 upregulation by TNFα and to determine whether MKP-1 is a negative feedback effector that represses MAPK-mediated pro-inflammatory signaling pa... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5550424 Mon, 19 Dec 2011 05:00:00 +0100 5550424 http://www.medworm.com/index.php?rid=5550423&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22201561%26dopt%3DAbstract In this study, we investigated the effects of TRPC channels and their STIM1-induced SOC activity on neurite outgrowth of PC12 cells. We report that PC12 cell differentiation down-regulates TRPC5 expression, whereas TRPC1 expression is retained. TRPC1 and TRPC5 interact with STIM1 through the STIM1 ERM domain. Transfection of TRPC1 and TRPC5 increased the receptor-activated Ca(2+) influx that was markedly augmented by the co-expression of STIM1. Topical expression of TRPC1 in PC12 cells markedly increased neurite outgrowth while that of TRPC5 suppressed neurite outgrowth. Suppression of neurite outgrowth by TRPC5 requires the channel function of TRPC5. However, strikingly, multiple lines of evidence show that the TRPC1-induced neurite outgrowth was independent of TRPC1-mediated Ca(2+) influ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5550423 Mon, 19 Dec 2011 05:00:00 +0100 5550423 http://www.medworm.com/index.php?rid=5535208&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178220%26dopt%3DAbstract Authors: Zhang L, Yi Y, Guo Q, Sun Y, Ma S, Xiao S, Geng J, Zheng Z, Song S Abstract Heat shock protein 90 (Hsp90) serves to stabilise and correctly fold multiple significant client proteins associated with cell proliferation and cell survival. However, little is known about the Hsp90 client proteins that regulate cell metabolism. Here, we describe a unique ability of Hsp90 to regulate the stability and activity of AMP-activated kinase (AMPK), a key sensor of cellular energy status. Hsp90 is found to interact with AMPK and to maintain its AMP-activated kinase activity, which in turn is required for the phosphorylation of its substrate, acetyl-CoA carboxylase (ACC), the key enzyme in fatty acid metabolism. Our binding analysis reveals that both the γ subunit and the α subunit of A... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5535208 Tue, 13 Dec 2011 05:00:00 +0100 5535208 http://www.medworm.com/index.php?rid=5535204&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22182508%26dopt%3DAbstract Authors: Curran SP, Hickey FB, Watson A, Godson C, Brazil DP Abstract Gremlin1 (Grem1) is an antagonist of bone morphogenetic proteins (BMPs) that plays a critical role in embryonic and postnatal development. Grem1 has been implicated as both a promoter and an inhibitor of cell proliferation driven by BMP-4 and other mitogens in a diverse range of cell types. Recent data showing that Grem1 can trigger angiogenesis via vascular endothelial growth factor receptor (VEGFR2) binding, highlighting that the precise modalities of Grem1 signalling require further elucidation. In an attempt to enhance our understanding of the role of Grem1 in cell proliferation, mouse embryonic fibroblasts lacking grem1 (grem1-/-) were generated. Grem1-/- cells showed elevated levels of proliferation in vitr... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5535204 Tue, 13 Dec 2011 05:00:00 +0100 5535204 http://www.medworm.com/index.php?rid=5535202&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22182510%26dopt%3DAbstract Authors: King TD, Zhang W, Suto MJ, Li Y Abstract Wnt proteins are secreted glycoproteins that bind to the N-terminal extra-cellular cysteine-rich domain of the Frizzled (Fzd) receptor family. The Fzd receptors can respond to Wnt proteins in the presence of Wnt co-receptors to activate the canonical and non-canonical Wnt pathways. Recent studies indicated that, among the Fzd family, Fzd7 is the Wnt receptor most commonly upregulated in a variety of cancers including colorectal cancer, hepatocellular carcinoma and triple negative breast cancer. Fzd7 plays an important role in stem cell biology and cancer development and progression. In addition, it has been demonstrated that siRNA knockdown of Fzd7, the anti-Fzd7 antibody or the extracellular peptide of Fzd7 (soluble Fzd7 peptide) d... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5535202 Tue, 13 Dec 2011 05:00:00 +0100 5535202 http://www.medworm.com/index.php?rid=5535201&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22182511%26dopt%3DAbstract In conclusion, data obtained by solely using the MEK inhibitor U0126 have to be carefully corroborated by using more selective inhibitors, such as PD0325901 or PD184352. SF-induced expression of the transcription factor KLF2 and its regulation by the MEK/Erk and PI3K pathways could impact on physiological as well as pathophysiological MC functions. PMID: 22182511 [PubMed - as supplied by publisher] (Source: Cellular Signalling) Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5535201 Tue, 13 Dec 2011 05:00:00 +0100 5535201 http://www.medworm.com/index.php?rid=5535200&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22182512%26dopt%3DAbstract Authors: Nizamutdinova IT, Kim YM, Lee JH, Chang KC, Kim HJ Abstract Cell adhesion molecules (CAMs) are involved in a variety of pathologies including cancer, inflammation, pathogenic infections and autoimmune disease. In particular, VCAM-1, rather than ICAM-1, plays a major role in the initiation of atherosclerosis and tumor progression. Therefore, we attempted to elucidate differential mechanisms that regulate VCAM-1 and ICAM-1 expressions. Down-regulation of JNK by a specific inhibitor (SP600125) or dominant negative (DN) JNK1 plasmid enhanced TNF-α-induced VCAM-1 but not ICAM-1 expression. Moreover, transfection with a JNK1-overexpressing vector resulted in the inhibition of VCAM-1 expression stimulated by TNF-α in HUVECs, suggesting that JNK negatively regulates TNF-α-induc... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5535200 Tue, 13 Dec 2011 05:00:00 +0100 5535200 http://www.medworm.com/index.php?rid=5535196&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22182514%26dopt%3DAbstract Authors: Tarr JM, Ding N, Kaul K, Antonell A, Pérez-Jurado LA, Chibber R Abstract Increasing evidence suggests that chronic, sub-clinical inflammation plays an important role in the pathogenesis of diabetic retinopathy. We have established the potential role of the inflammatory enzyme, core 2 β-1, 6-N-acetylglucosaminyltransferase (C2GNT) in diabetic retinopathy. The present study was designed to explore the NADPH oxidase signaling pathway in the tumor necrosis factor-alpha (TNF-α)-induced activity of C2GNT in leukocytes. Human leukocytes (U937 cells) and an Epstein-Barr-transformed lymphoblastoid cell line deficient in p47phox (F10007 cells) were used for the study. Cells were exposed to TNF-α for 24h in the presence and absence of 1) NADPH oxidase inhibitors (apocynin and scr... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5535196 Tue, 13 Dec 2011 05:00:00 +0100 5535196 http://www.medworm.com/index.php?rid=5535205&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22182507%26dopt%3DAbstract Authors: Salminen A, Kauppinen A, Kaarniranta K Abstract The major hallmark of cellular senescence is an irreversible cell cycle arrest and thus it is a potent tumor suppressor mechanism. Genotoxic insults, e.g. oxidative stress, are important inducers of the senescent phenotype which is characterized by an accumulation of senescence-associated heterochromatic foci (SAHF) and DNA segments with chromatin alte rations reinforcing senescence (DNA-SCARS). Interestingly, senescent cells secrete pro-inflammatory factors and thus the condition has been called the senescence-associated secretory phenotype (SASP). Emerging data has revealed that NF-κB signaling is the major signaling pathway which stimulates the appearance of SASP. It is known that DNA damage provokes NF-κB signaling via ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5535205 Sun, 11 Dec 2011 05:00:00 +0100 5535205 http://www.medworm.com/index.php?rid=5535203&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22182509%26dopt%3DAbstract Authors: White CD, Erdemir HH, Sacks DB Abstract IQGAP proteins have been identified in a wide spectrum of organisms, ranging from yeast to humans. The most extensively studied family member is the ubiquitously expressed scaffold protein IQGAP1, which participates in multiple essential aspects of mammalian biology. IQGAP1 mediates these effects by binding to and regulating the function of numerous interacting proteins. Over ninety proteins have been reported to associate with IQGAP1, either directly or as part of a larger complex. In this review, we summarise those IQGAP1 binding partners that have been identified in the last five years. The molecular mechanisms by which these interactions contribute to the functions of receptors and their signalling cascades, small GTPase function... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5535203 Sun, 11 Dec 2011 05:00:00 +0100 5535203 http://www.medworm.com/index.php?rid=5535199&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22182513%26dopt%3DAbstract Authors: Järvinen PM, Laiho M Abstract Epithelial to mesenchymal transition (EMT) is a process during which junctions of the cell-cell contacts are dissolved, actin cytoskeleton is deformed, apical-basolateral cell polarity is lost and cell motility is increased. EMT is needed during normal embryonal development and wound healing, but may also lead to pathogenic transformation and formation of myofibroblasts. Transforming growth factor β (TGFβ) is a multifunctional cytokine promoting EMT and myofibroblast differentiation, and its dysregulation is involved in pathological disorders like cancer and fibrosis. Lin11, Isl-1 and Mec-3 (LIM) domain proteins are associated with actin cytoskeleton and linked to regulation of cell growth, damage signaling, cell fate determination and sign... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5535199 Sun, 11 Dec 2011 05:00:00 +0100 5535199 http://www.medworm.com/index.php?rid=5513770&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155737%26dopt%3DAbstract In conclusion, Twist1 expression, owing to the abnormal NPM-ALK/STAT3 signaling, contributes to its invasiveness and decreased sensitivity to PF-2341066 in ALK+ALCL. PMID: 22155737 [PubMed - as supplied by publisher] (Source: Cellular Signalling) Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5513770 Thu, 08 Dec 2011 05:00:00 +0100 5513770 http://www.medworm.com/index.php?rid=5281324&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21802511%26dopt%3DAbstract Authors: Filigheddu N, Sampietro S, Chianale F, Porporato PE, Gaggianesi M, Gregnanin I, Rainero E, Ferrara M, Perego B, Riboni F, Baldanzi G, Graziani A, Surico N Abstract Increased levels of endogenous and/or exogenous estrogens are one of the well known risk factors of endometrial cancer. Diacylglycerol kinases (DGKs) are a family of enzymes which phosphorylate diacylglycerol (DAG) to produce phosphatidic acid (PA), thus turning off and on DAG-mediated and PA-mediated signaling pathways, respectively. DGK α activity is stimulated by growth factors and oncogenes and is required for chemotactic, proliferative, and angiogenic signaling in vitro. Herein, using either specific siRNAs or the pharmacological inhibitor R59949, we demonstrate that DGK α activity is required for 17-β-e... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5281324 Tue, 04 Oct 2011 07:27:29 +0100 5281324 http://www.medworm.com/index.php?rid=5281323&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864675%26dopt%3DAbstract Authors: Quintá HR, Galigniana NM, Erlejman AG, Lagadari M, Piwien-Pilipuk G, Galigniana MD Abstract Cytoskeletal structure is continually remodeled to accommodate normal cell growth and to respond to pathophysiological cues. As a consequence, several cytoskeleton-interacting proteins become involved in a variety of cellular processes such as cell growth and division, cell movement, vesicle transportation, cellular organelle location and function, localization and distribution of membrane receptors, and cell-cell communication. Molecular chaperones and immunophilins are counted among the most important proteins that interact closely with the cytoskeleton network, in particular with microtubules and microtubule-associated factors. In several situations, heat-shock proteins and immu... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5281323 Tue, 04 Oct 2011 07:25:31 +0100 5281323 http://www.medworm.com/index.php?rid=5281322&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864676%26dopt%3DAbstract In this study we explored the role of the ezrin, radixin, and moesin (ERM) family of actin-binding linker protein in modulating S1P-induced human pulmonary EC barrier enhancement. S1P induces ERM translocation to the EC periphery and promotes ERM phosphorylation on a critical threonine residue (Ezrin-567, Radixin-564, Moesin-558). This phosphorylation is dependent on activation of PKC isoforms and Rac1. The majority of ERM phosphorylation on these critical threonine residues after S1P occurs in moesin and ezrin. Baseline radixin phosphorylation is higher than in the other two ERM proteins but does not increase after S1P. S1P-induced moesin and ezrin threonine phosphorylation is not mediated by the barrier enhancing receptor S1PR1 because siRNA downregulation of S1PR1 fails to inhibit these... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5281322 Tue, 04 Oct 2011 07:25:21 +0100 5281322 http://www.medworm.com/index.php?rid=5281328&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21946431%26dopt%3DAbstract In this study, we tested the signaling mechanism mediating 5-HT1A receptor-regulated GSK3 in the hippocampus. Using mutant GSK3 knock-in mice, we also tested the role of GSK3 in the behavioral effects of 5-HT1A receptors and the serotonin reuptake inhibitor fluoxetine. The results showed that activation of 5-HT1A receptors by 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) increased phosphorylation of the N-terminal serine of both GSK3α and GSK3β in several areas of the hippocampus. The effect of 8-OH-DPAT was accompanied by an increase in the active phosphorylation of Akt, and was blocked by LY294002, an inhibitor of phosphoinositide 3-kinases (PI3K). Phosphorylation of GSK3β, but not GSK3α, was necessary for 5-HT1A receptors to suppress the hippocampus-associated contextual fear l... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5281328 Sat, 17 Sep 2011 04:00:00 +0100 5281328 http://www.medworm.com/index.php?rid=5281327&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21946432%26dopt%3DAbstract Authors: Veeravalli KK, Ponnala S, Chetty C, Tsung AJ, Gujrati M, Rao JS Abstract The α9β1 integrin accelerates cell migration through binding of the α9 cytoplasmic domain to SSAT, which catalyzes the catabolism of higher order polyamines, spermidine and spermine, to the lower order polyamine, putrescine. SSAT levels were downregulated at both the mRNA and protein levels by shRNA-mediated simultaneous knockdown of MMP-9 and uPAR/cathepsin B. In addition, we noted a prominent reduction in the expression of SSAT with MMP-9 and uPAR/cathepsin B knockdown in the tumor regions of 5310 injected nude mice brains. Further, SSAT knockdown in glioma xenograft cells significantly reduced their migration potential. Interestingly, MMP-9, uPAR and cathepsin B overexpression in these xenograft... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5281327 Sat, 17 Sep 2011 04:00:00 +0100 5281327 http://www.medworm.com/index.php?rid=5281326&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21951603%26dopt%3DAbstract Authors: Xu D, Kishi H, Kawamichi H, Kajiya K, Takada Y, Kobayashi S Abstract Sphingosylphosphorylcholine (SPC), a bioactive sphingolipid, has recently been reported to modulate actin cytoskeleton rearrangement. We have previously demonstrated Fyn tyrosine kinase is involved in SPC-induced actin stress fiber formation in fibroblasts. However, Fyn-dependent signaling pathway remains to be elucidated. The present study demonstrates that RhoA-ROCK signaling downstream of Fyn controls stress fiber formation in SPC-treated fibroblasts. Here, we found that SPC-induced stress fiber formation was inhibited by C3 transferase, dominant negative RhoA or ROCK. SPC activated RhoA, which was blocked by pharmacological inhibition of Fyn activity or dominant negative Fyn. Constitutively active Fyn... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5281326 Sat, 17 Sep 2011 04:00:00 +0100 5281326 http://www.medworm.com/index.php?rid=5281325&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21951604%26dopt%3DAbstract Authors: Grøvdal LM, Kim J, Holst MR, Knudsen SL, Grandal MV, van Deurs B Abstract The potential benefits of drugs directly targeting the ErbB receptors for cancer therapy have led to an extensive development within this field. However, the clinical effects of ErbB receptor-targeting drugs in cancer treatment are limited due to a high frequency of resistance. It has been reported that, when inhibiting the epidermal growth factor receptor (EGFR) with the tyrosine kinase inhibitor gefitinib, increased activation of ErbB3 via MET, or by re-localization of ErbB3 mediates cell survival. Here we show further evidence that members of the ErbB receptor family facilitate resistance to EGFR inhibitor treatment in ErbB2 overexpressing breast cancer cells. We found that gefitinib treatment in... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5281325 Sat, 17 Sep 2011 04:00:00 +0100 5281325 http://www.medworm.com/index.php?rid=5281330&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945409%26dopt%3DAbstract In this study we characterize basal BMP signaling in the healthy tubular nephron, and show that BMP2 is expressed in proximal nephron epithelial cells. Comparative gene profiling of proximal tubule cell responses to BMP2 and BMP7 does not reveal any qualitative difference, suggesting that identical BMP gene targets may be activated in healthy and injured organs. Interestingly, our gene profiling analysis shows that BMP signaling activates a number of Notch regulated transcription factors, including HEY1. As in other biological systems, HEY1 functions as a negative feedback regulator of BMP2 expression in the proximal tubule. In summary, this work reveals endogenous BMP signaling patterns in the healthy human and mouse kidneys, and identifies novel gene targets, some of which are involved i... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5281330 Fri, 16 Sep 2011 04:00:00 +0100 5281330 http://www.medworm.com/index.php?rid=5281329&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21946088%26dopt%3DAbstract Authors: Ponyeam W, Hagen T Abstract Cul1 and Cul7 are cullin E3 ubiquitin ligase scaffold proteins. Cul1 is known to form a complex with the RING domain protein Rbx1 and one of approximately 70 different F-box proteins. F-box proteins function as substrate receptor subunits and recruit numerous substrates for poly-ubiquitination. Similarly to Cul1, Cul7 interacts with Rbx1, however, only one F-box protein, Fbxw8, has been shown to bind to Cul7. To date only few Cul7 E3 ubiquitin ligase substrates, including cyclin D1, IRS-1 and GRASP65, have been reported, and using Fbxw8 affinity purification, we were unable to identify additional substrate proteins. Here we provide evidence for a model in which Cul7-Rbx1 can promote the ubiquitination of Cul1 substrates by forming high order com... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5281329 Fri, 16 Sep 2011 04:00:00 +0100 5281329 http://www.medworm.com/index.php?rid=5281332&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945155%26dopt%3DAbstract Authors: Mergler S, Skrzypski M, Sassek M, Pietrzak P, Pucci C, Wiedenmann B, Strowski MZ Abstract Transient receptor potential channels (TRPs) regulate tumor growth via calcium-dependent mechanisms. The (thermosensitive) capsaicin receptor TRPV1 is overexpressed in numerous highly aggressive cancers. TRPV1 has potent antiproliferative activity and is therefore potentially applicable in targeted therapy of malignancies. Recently, we characterized TRPM8 functions in pancreatic neuroendocrine tumors (NETs), however, the role of TRPV1 is unknown. Here, we studied the expression and the role of TRPV1 in regulating intracellular Ca(2+) and chromogranin A (CgA) secretion in pancreatic NET BON-1 cell line and in primary NET cells (prNET). TRPV1 expression was detected by RT-PCR, Western b... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5281332 Wed, 14 Sep 2011 04:00:00 +0100 5281332 http://www.medworm.com/index.php?rid=5281331&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945156%26dopt%3DAbstract Authors: Townsend TA, Robinson JY, How T, Delaughter DM, Blobe GC, Barnett JV Abstract An early event in heart valve formation is the epithelial-mesenchymal transformation (EMT) of a subpopulation of endothelial cells in specific regions of the heart tube, the endocardial cushions. The Type III TGFβ receptor (TGFβR3) is required for TGFβ2- or BMP-2-stimulated EMT in atrioventricular endocardial cushion (AVC) explants in vitro but the mediators downstream of TGFβR3 are not well described. Using AVC and ventricular explants as an in vitro assay, we found an absolute requirement for specific TGFβR3 cytoplasmic residues, GAIP-interacting protein, C terminus (GIPC), and specific Activin Receptor-Like Kinases (ALK)s for TGFβR3-mediated EMT when stimulated by TGFβ2 or BMP-2. The in... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5281331 Wed, 14 Sep 2011 04:00:00 +0100 5281331 http://www.medworm.com/index.php?rid=5247263&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21930201%26dopt%3DAbstract Authors: Heckman CA, Varghese M, Cayer ML, Boudreau NS Abstract Although growth factor-initiated cascades in cells are networked with mechanisms such as "inside-out signaling", it is not known how these pathways are integrated. Earlier studies reported that ruffling was enhanced and filopodia reduced in transformed cells. Since dissecting relationships among features was impossible if subjective recognition was relied upon, features in two epithelial cell lines were recognized by latent factor analysis. Factor-based classification revealed four protrusion classes, but none of them corresponded to ruffles. Loss of filopodia, defined by factor 4 (F4) values, accounted for the greatest change in features of oncogenically transformed cells. Factor 5 (F5, lamella) was unchanged during t... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5247263 Sat, 10 Sep 2011 04:00:00 +0100 5247263 http://www.medworm.com/index.php?rid=5231575&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21914472%26dopt%3DAbstract Authors: Potter LR Abstract Nitric oxide, bicarbonate, natriuretic peptides (ANP, BNP and CNP), guanylins, uroguanylins and guanylyl cyclase activating proteins (GCAPs) activate a family of enzymes variously called guanyl, guanylyl or guanylate cyclases that catalyze the conversion of guanosine triphosphate to cyclic guanosine monophosphate (cGMP) and pyrophosphate. Intracellular cyclic GMP is a second messenger that modulates: platelet aggregation, neurotransmission, sexual arousal, gut peristalsis, blood pressure, long bone growth, intestinal fluid secretion, lipolysis, phototransduction, cardiac hypertrophy and oocyte maturation. This review briefly discusses the discovery of cGMP and guanylyl cyclases, then nitric oxide, nitric oxide synthase and soluble guanylyl cyclase are de... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5231575 Sat, 10 Sep 2011 04:00:00 +0100 5231575 http://www.medworm.com/index.php?rid=5231574&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920434%26dopt%3DAbstract Authors: Tsang SH, Woodruff ML, Lin CS, Jacobson BD, Naumann MC, Hsu CW, Davis RJ, Cilluffo MC, Chen J, Fain GL Abstract The light-dependent decrease in cyclic guanosine monophosphate (cGMP) in the rod outer segment is produced by a phosphodiesterase (PDE6), consisting of catalytic α and β subunits and two inhibitory γ subunits. The molecular mechanism of PDE6γ regulation of the catalytic subunits is uncertain. To study this mechanism in vivo, we introduced a modified Pde6g gene for PDE6γ into a line of Pde6g(tm1)/Pde6g(tm1) mice that do not express PDE6γ. The resulting ILE86TER mice have a PDE6γ that lacks the two final carboxyl-terminal Ile(86) and Ile(87) residues, a mutation previously shown in vitro to reduce inhibition by PDE6γ. ILE86TER rods showed a decreased sensit... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5231574 Thu, 08 Sep 2011 04:00:00 +0100 5231574 http://www.medworm.com/index.php?rid=5219212&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21911055%26dopt%3DAbstract In this study, we sought to investigate the mechanism by which HER2 musters signaling and transformation potency. We show that HER2 overexpression per se induces a significant increase in basal mitogenic and cell survival signaling, which was augmented by EGF stimulation. Inhibition of the normally expressed EGFR significantly suppressed the ability of overexpressed HER2 to induce enhanced signaling and cell transformation, suggesting that HER2 requires the EGFR and potentially other members to maximize its signaling and transformation potency. The novel observation revealed by prolonged EGF stimulation studies was the biphasic signaling pattern in the presence of HER2 overexpression that suggested the induction of a short-circuited mechanism, permitting sustained signaling. Our results fu... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5219212 Sat, 03 Sep 2011 04:00:00 +0100 5219212 http://www.medworm.com/index.php?rid=5219214&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907280%26dopt%3DAbstract Authors: Hewavitharana T, Wedegaertner PB Abstract Heterotrimeric G proteins typically transduce signals from G protein-coupled receptors (GPCRs) to effector proteins. In the conventional G protein signaling paradigm, the G protein is located at the cytoplasmic surface of the plasma membrane, where, after activation by an agonist-bound GPCR, the GTP-bound Gα and free Gβγ bind to and regulate a number of well-studied effectors, including adenylyl cyclase, phospholipase Cβ, RhoGEFs and ion channels. However, research over the past decade or more has established that G proteins serve non-canonical roles in the cell, whereby they regulate novel effectors, undergo activation independently of a GPCR, and/or function at subcellular locations other than the plasma membrane. This review... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5219214 Thu, 01 Sep 2011 04:00:00 +0100 5219214 http://www.medworm.com/index.php?rid=5219213&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907792%26dopt%3DAbstract Authors: Gupta N, Grebhardt S, Mayer D Abstract Estrogen receptor α (ERα) functions as a transcription factor to regulate a wide range of cellular activities in response to 17β-estradiol (E2). The regulation of ERα transcriptional activity is highly complex and not yet fully understood. In this respect, recent studies have highlighted the importance of certain cellular protein kinases. To identify novel protein kinases regulating ERα activity, we performed a high-throughput siRNA screening in combination with a luciferase reporter assay in an ERα positive breast cancer cell line. Among the vast majority of potential positive regulators, we found Janus kinase 2 (JAK2), a member of the Janus kinase family of non-receptor tyrosine kinases, to have a negative regulatory effect on... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5219213 Thu, 01 Sep 2011 04:00:00 +0100 5219213 http://www.medworm.com/index.php?rid=5219215&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21906675%26dopt%3DAbstract Authors: Wang H, Zhang Q, Wen Q, Zheng Y, Philip L, Jiang H, Lin J, Zheng W Abstract Alterations (modifications) in signaling of The Proline-rich Akt substrate of 40-kDa (PRAS40) pathway is implicated in type 2 diabetes and melanoma. PRAS40 is known for its ability to regulate the mammalian target of rapamycin complex 1 (mTORC1) kinase activity, possessing a key regulatory role at the cross point of signal transduction pathways activated by growth factor receptors. Recently it has been found that PRAS40 is regulated by its upstream phosphatidylinositol 3-kinase/Akt (PI3K/Akt) which is activated by many tyrosine kinase receptors growth factors including insulin-like growth factor 1. Also, PRAS40 functions downstream of mTORC1 and upstream from its effectors ribosomal protein S6 kina... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5219215 Wed, 31 Aug 2011 04:00:00 +0100 5219215 http://www.medworm.com/index.php?rid=5219219&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21893191%26dopt%3DAbstract Authors: Wertheimer E, Gutierrez-Uzquiza A, Rosemblit C, Lopez-Haber C, Soledad Sosa M, Kazanietz MG Abstract Rac GTPases, small G-proteins widely implicated in tumorigenesis and metastasis, transduce signals from tyrosine-kinase, G-protein-coupled receptors (GPCRs), and integrins, and control a number of essential cellular functions including motility, adhesion, and proliferation. Deregulation of Rac signaling in cancer is generally a consequence of enhanced upstream inputs from tyrosine-kinase receptors, PI3K or Guanine nucleotide Exchange Factors (GEFs), or reduced Rac inactivation by GTPase Activating Proteins (GAPs). In breast cancer cells Rac1 is a downstream effector of ErbB receptors and mediates migratory responses by ErbB1/EGFR ligands such as EGF or TGFα and ErbB3 ligan... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5219219 Sat, 27 Aug 2011 04:00:00 +0100 5219219 http://www.medworm.com/index.php?rid=5219216&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21893194%26dopt%3DAbstract Authors: Wang K, Holterman AX Abstract Hepatocyte nuclear factor 6 (HNF6) is one of liver-enriched transcription factors. HNF6 utilizes the bipartite onecut-homeodomain sequence to localize the HNF6 protein to the nuclear compartment and binds to specific DNA sequences of numerous target gene promoters. HNF6 regulates an intricate network and mediates complex biological processes that are best known in the liver and pancreas. The function of HNF6 is correlated to cell proliferation, cell cycle regulation, cell differentiation and organogenesis, cell migration and cell-matrix adhesion, glucose metabolism, bile homeostasis, inflammation and so on. HNF6 controls the transcription of its target genes in different ways. The details of the regulatory pathways and their mechanisms are sti... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5219216 Sat, 27 Aug 2011 04:00:00 +0100 5219216 http://www.medworm.com/index.php?rid=5219220&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889978%26dopt%3DAbstract This study aimed to investigate the impact of rate and irregularity on nerve growth factor (NGF) expression in cardiomyocytes, since NGF is known to be the main contributor to cardiac sympathetic innervation density. Cell cultures of neonatal rat ventricular myocytes were electrically stimulated for 48h with increasing rates (0, 5 and 50Hz) and irregularity (standard deviation (SD)=5%, 25% and 50% of mean cycle length). Furthermore, we analyzed the calcineurin-NFAT and the endothelin-1 signalling pathways as possible contributors to NGF regulation during arrhythmic stimulation. We found that the increase of NGF expression reached its maximum at the irregularity of 25% SD by 5Hz (NGF: 5Hz 0% SD=1 vs. 5Hz 25% SD=1.57, P<0.05). Specific blockade of the ET-A receptor by BQ123 could abolish ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5219220 Fri, 26 Aug 2011 04:00:00 +0100 5219220 http://www.medworm.com/index.php?rid=5219218&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21893192%26dopt%3DAbstract Authors: Plouffe B, Yang X, Tiberi M Abstract We previously showed that phorbol-12-myristate-13-acetate (PMA) mediates a robust PKC-dependent sensitization and desensitization of the highly homologous human Gs protein and adenylyl cyclase (AC)-linked D1 (hD1R) and D5 (hD5R) dopaminergic receptors, respectively. Here, we demonstrate using forskolin-mediated AC stimulation that PMA-mediated hD1R sensitization and hD5R desensitization is not associated with changes in AC activity. We next employed a series of chimeric hD1R and hD5R to delineate the underlying structural determinants dictating the subtype-specific regulation of human D1-like receptors by PMA. We first used chimeric receptors in which the whole terminal region (TR) spanning from the extracellular face of transmembrane d... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5219218 Fri, 26 Aug 2011 04:00:00 +0100 5219218 http://www.medworm.com/index.php?rid=5219217&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21893193%26dopt%3DAbstract In this study, we have attempted to investigate the effects of PDCD6 on the inhibition of angiogenesis-mediated cell growth as a novel anti-angiogenic protein. Purified recombinant human PDCD6 inhibited cell migration in a concentration-time-dependent manner. We also found that overexpressed PDCD6 suppressed vascular endothelial growth factor (VEGF)-induced proliferation, invasion, and capillary-like structure tube formation in vitro. PDCD6 suppressed phosphorylation of signaling regulators downstream from PI3K, including Akt, mammalian target of rapamycin (mTOR), glycogen synthase kinase-3β(GSK-3β), ribosomal protein S6 kinase (p70S6K), and also decreased cyclin D1 expression. We found binding PDCD6 to VEGFR-2, a key player in the PI3K/mTOR/P70S6K signaling pathway. Taken together, thes... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5219217 Fri, 26 Aug 2011 04:00:00 +0100 5219217 http://www.medworm.com/index.php?rid=5157449&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21855629%26dopt%3DAbstract Authors: Kapuria V, Levitzki A, Bornmann WG, Maxwell D, Priebe W, Sorenson RJ, Showalter HD, Talpaz M, Donato NJ Abstract AG490 is a tyrosine kinase inhibitor with activity against Jak2 and apoptotic activity in specific leukemias. Due to its weak kinase inhibitory activity and poor pharmacology, we conducted a cell-based screen for derivatives with improved Jak2 inhibition and activity in animals. Two hits emerged from an initial small chemical library screen, and more detailed structure-activity relationship studies led to the development of WP1130 with 50-fold greater activity in suppressing Jak2-dependent cytokine signaling than AG490. However, WP1130 did not directly suppress Jak2 kinase activity, but mediated Jak2 ubiquitination resulting in its trafficking through HDAC6 to p... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5157449 Mon, 08 Aug 2011 23:00:00 +0100 5157449 http://www.medworm.com/index.php?rid=5157448&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21855630%26dopt%3DAbstract Authors: Ponnala S, Chetty C, Veeravalli KK, Dinh DH, Klopfenstein JD, Rao JS Abstract In more than 90% of cancers including glioma, telomere elongation reverse transcriptase (hTERT) is overexpressed. In the present study, we sought to explore whether matrix metalloproteinase-9 (MMP-9) shRNA could alter hTERT-mediated proliferation in glioma cells. MMP-9 shRNA induced senescence and apoptosis in glioma cells by inhibiting hTERT expression and telomere activity. MMP-9 silencing decreased oncogenic c-Myc expression (hTERT activator), whereas the expression of the c-Myc antagonist MAD increased drastically (hTERT repressor); both c-Myc and MAD are transcription factors for hTERT. In addition, MMP-9 suppression turns the switch from c-Myc/MAX to MAD/MAX heterodimer binding to the hTERT... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5157448 Mon, 08 Aug 2011 23:00:00 +0100 5157448 http://www.medworm.com/index.php?rid=5141583&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840391%26dopt%3DAbstract Authors: Wang J, Beauchemin M, Bertrand R Abstract Functional analysis of a Bcl-xL phosphorylation mutant series has revealed that cells expressing Bcl-xL(Ser49Ala) mutant are less stable at G2 checkpoint after DNA damage and enter cytokinesis more slowly after microtubule poisoning, than cells expressing wild-type Bcl-xL. These effects of Bcl-xL(Ser49Ala) mutant seem to be separable from Bcl-xL function in apoptosis. Bcl-xL(Ser49) phosphorylation is cell cycle-dependent. In synchronized cells, phospho-Bcl-xL(Ser49) appears during the S phase and G2, whereas it disappears rapidly in early mitosis during prometaphase, metaphase and early anaphase, and re-appears during telophase and cytokinesis. During DNA damage-induced G2 arrest, an important pool of phospho-Bcl-xL(Ser49) accumula... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5141583 Thu, 04 Aug 2011 23:00:00 +0100 5141583 http://www.medworm.com/index.php?rid=5141580&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840394%26dopt%3DAbstract Authors: Elmageed ZY, Naura AS, Errami Y, Zerfaoui M Abstract Post-transcriptional modification of proteins is crucial for balancing protein structure and function in many biological processes. The addition of polymers of adenosine diphosphate (ADP)-ribose (PAR), which are synthesized by PAR polymerases (PARPs) from nicotinamide adenine dinucleotide (NAD), is one such distinctive post-translational modification. PARP-1, the best characterized of the 17-member PARP family, is considered a key isoform responsible for poly(ADP-ribosyl)ation of several nuclear proteins. ADP-ribose polymers add a highly negative charge to their target proteins, resulting in a modification of their activities and functions. PARPs not only participate in regulating cell survival and cell death programs, b... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5141580 Thu, 04 Aug 2011 23:00:00 +0100 5141580 http://www.medworm.com/index.php?rid=5141582&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840392%26dopt%3DAbstract Authors: Pannekoek WJ, van Dijk JJ, Chan OY, Huveneers S, Linnemann JR, Spanjaard E, Brouwer PM, van der Meer AJ, Zwartkruis FJ, Rehmann H, de Rooij J, Bos JL Abstract Epac1 and its effector Rap1 are important mediators of cAMP induced tightening of endothelial junctions and consequential increased barrier function. We have investigated the involvement of Rap1 signalling in basal, unstimulated, barrier function of a confluent monolayer of HUVEC using real time Electric Cell-substrate Impedance Sensing. Depletion of Rap1, but not Epac1, results in a strong decrease in barrier function. This decrease is also observed when cells are depleted of the cAMP independent Rap exchange factors PDZ-GEF1 and 2, showing that PDZ-GEFs are responsible for Rap1 activity in control of basal barrier ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5141582 Wed, 03 Aug 2011 23:00:00 +0100 5141582 http://www.medworm.com/index.php?rid=5141581&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840393%26dopt%3DAbstract Authors: Block ER, Tolino MA, Klarlund JK Abstract Wounding usually causes considerable cell damage, and released ATP promotes migration of nearby epithelium. ATP binds to purinergic receptors on the cell surface and induces transactivation of the EGF receptor through signaling by the Src family kinases (SFKs). Here we tested whether ATP activates these kinases through Pyk2, a member of the focal adhesion kinase family. Pyk2 was rapidly and potently activated by treating corneal epithelial cells with ATP, and physical interaction of Pyk2 with the SFKs was enhanced. Disruption of Pyk2 signaling either by siRNA or by expression of a dominant-negative mutant led to inhibition of ATP-induced activation of the SFKs and the EGF receptor. Inhibiting Pyk2 activity also blocked ATP stimulat... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5141581 Wed, 03 Aug 2011 23:00:00 +0100 5141581 http://www.medworm.com/index.php?rid=5141579&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843636%26dopt%3DAbstract Authors: Borland MG, Khozoie C, Albrecht PP, Zhu B, Lee C, Lahoti TS, Gonzalez FJ, Peters JM Abstract Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) function and receptor cross-talk with other nuclear receptors, including PPARγ and retinoic acid receptors (RARs), was examined using stable human HaCaT keratinocyte cell lines over-expressing PPARβ/δ or PPARγ. Enhanced ligand-induced expression of two known PPAR target genes, adipocyte differentiation-related protein (ADRP) and angiopoietin-like protein 4 (ANGPTL4), was found in HaCaT keratinocytes over-expressing PPARβ/δ or PPARγ. Over-expression of PPARβ/δ did not modulate the effect of a PPARγ agonist on up-regulation of ADRP or ANGPTL4 mRNA in HaCaT keratinocytes. All-trans retinoic acid (atRA) increased ex... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5141579 Wed, 03 Aug 2011 23:00:00 +0100 5141579 http://www.medworm.com/index.php?rid=5141586&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820049%26dopt%3DAbstract Authors: Leem YE, Han JW, Lee HJ, Ha HL, Kwon YL, Ho SM, Kim BG, Tran P, Bae GU, Kang JS Abstract Skeletal myogenesis is a multistep process that involves cell cycle exit, expression of muscle-specific genes and formation of multinucleated myotubes. Growth arrest specific gene 1 (Gas1) is a GPI-linked membrane protein and originally identified as a growth arrest-linked gene in fibroblasts. Promyogenic cell surface protein, Cdo functions as a component of multiprotein complexes that include other cell adhesion molecules, like Cadherins to mediate cell contact signaling. Here we report that Gas1 and Cdo are coexpressed in muscle cells and form a complex in differentiating myoblasts. Interestingly, Cdo(-/-) myoblasts display defects in Gas1 induction during differentiation. Overexpres... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5141586 Sat, 23 Jul 2011 23:00:00 +0100 5141586 http://www.medworm.com/index.php?rid=5141585&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21821120%26dopt%3DAbstract Authors: Goodman CA, Mayhew DL, Hornberger TA Abstract The maintenance of muscle mass is critical for health and issues associated with the quality of life. Over the last decade, extensive progress has been made with regard to our understanding of the molecules that regulate skeletal muscle mass. Not surprisingly, many of these molecules are intimately involved in the regulation of protein synthesis and protein degradation [e.g. the mammalian target of rapamycin (mTOR), eukaryotic initiation factor 2B (eIF2B), eukaryotic initiation factor 3f (eIF3f) and the forkhead box O (FoxO) transcription factors]. It is also becoming apparent that molecules which sense, or control, the energetic status of the cell play a key role in the regulation of muscle mass [e.g. AMP-activated protein kin... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5141585 Fri, 22 Jul 2011 23:00:00 +0100 5141585 http://www.medworm.com/index.php?rid=5141584&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21821121%26dopt%3DAbstract Authors: Hsu YC, Ip MM Abstract Conjugated linoleic acid (CLA) has shown chemopreventive activity in several tumorigenesis models, in part through induction of apoptosis. We previously demonstrated that the t10,c12 isomer of CLA induced apoptosis of TM4t mouse mammary tumor cells through both mitochondrial and endoplasmic reticulum (ER) stress pathways, and that the AMP-activated protein kinase (AMPK) played a critical role in the apoptotic effect. In the current study, we focused on the upstream pathways by which AMPK was activated, and additionally evaluated the contributing role of oxidative stress to apoptosis. CLA-induced activation of AMPK and/or induction of apoptosis were inhibited by infection of TM4t cells with an adenovirus expressing a peptide which blocks the interacti... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5141584 Fri, 22 Jul 2011 23:00:00 +0100 5141584 http://www.medworm.com/index.php?rid=5103927&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21798346%26dopt%3DAbstract Authors: Bhoopathi P, Gondi CS, Gujrati M, Dinh DH, Lakka SS The matricellular glycoprotein Secreted Protein Acidic and Rich in Cysteine (SPARC) plays an important role in the regulation of cell adhesion and proliferation as well as in tumorigenesis and metastasis. Earlier, we reported that, in addition to its potent anti-angiogenic functions, SPARC also induces apoptosis in medulloblastoma cells, mediated by autophagy. We therefore sought to investigate the underlying molecular mechanism through which SPARC inhibits migration and invasion of Daoy medulloblastoma cells, both in vitro and in vivo. For this study, we used SPARC-overexpressing stable Daoy medulloblastoma cells. SPARC overexpression in Daoy medulloblastoma cells inhibited migration and invasion in vitro. Additionally, SPAR... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5103927 Fri, 22 Jul 2011 23:00:00 +0100 5103927 http://www.medworm.com/index.php?rid=5103924&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803152%26dopt%3DAbstract This study aimed to investigate the effects of these proteins on the differentiation and functions of mouse bone marrow-derived mast cells (BMMCs). To identify the target proteins related to the differentiation of BMMCs, we examined the protein expression pattern of BMMCs using 2-dimensional electrophoresis (2-DE) and MALDI-TOF analysis. Expressions of FcεRIα, surface molecules (c-kit, CD40, CD40L, VCAM-1), tryptase, and cytokines were examined in BMMCs using FACS analysis, Western blot, and RT-PCR respectively. Enolase 1 and calreticulin were transfected into BMMCs, and [Ca(2+)]i levels were determined by confocal microscope, while amounts of TNF-α and LTs were measured by ELISA. Eight proteins were identified by proteomic analysis. Enolase and calreticulin siRNA transfection inhibited... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5103924 Fri, 22 Jul 2011 23:00:00 +0100 5103924 http://www.medworm.com/index.php?rid=5103923&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21807092%26dopt%3DAbstract Authors: Green MF, Anderson KA, Means AR The AMP-activated protein kinase (AMPK) is a critical regulator of energy homeostasis, and is a potential target for treatment of metabolic diseases as well as cancer. AMPK can be phosphorylated and activated by the tumor suppressor LKB1 or the Ca(2+)/CaM-dependent protein kinase kinase β (CaMKKβ). We previously identified a physical complex between CaMKKβ and AMPK (Anderson, K. A., Ribar, T. J., Lin, F., Noeldner, P. K., Green, M. F., Muehlbauer, M. J., Witters, L. A., Kemp, B. E., and Means, A. R. (2008) Cell Metabolism 7, 377-388). Here we expand our analysis of the CaMKKβ-AMPK signaling complex and show that whereas CaMKKβ can form a complex with and activate AMPK, CaMKKα cannot. In addition, we show that CaMKKβ and AMPK associate thr... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5103923 Fri, 22 Jul 2011 23:00:00 +0100 5103923 http://www.medworm.com/index.php?rid=5103926&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21802511%26dopt%3DAbstract Authors: Filigheddu N, Sampietro S, Chianale F, Porporato PE, Gaggianesi M, Gregnanin I, Rainero E, Ferrara M, Perego B, Riboni F, Baldanzi G, Graziani A, Surico N Increased levels of endogenous and/or exogenous estrogens are one of the well known risk factors of endometrial cancer. Diacylglycerol kinases (Dgks) are a family of enzymes which phosphorylate diacylglycerol (DAG) to produce phosphatidic acid (PA), thus turning off and on DAG-mediated and PA-mediated signaling pathways, respectively. Dgk α activity is stimulated by growth factors and oncogenes and is required for chemotactic, proliferative, and angiogenic signaling in vitro. Herein, using either specific siRNAs or the pharmacological inhibitor R59949, we demonstrate that Dgk α activity is required for 17-β-estradiol (E2)... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5103926 Thu, 21 Jul 2011 23:00:00 +0100 5103926 http://www.medworm.com/index.php?rid=5103925&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803151%26dopt%3DAbstract Authors: Tanfin Z, Serrano-Sanchez M, Leiber D Sphingosine 1-phosphate (S1P), a bioactive lipid generated by sphingosine kinases (SphK1/2), initiates different signalling pathways involved in physiological and pathological processes. We previously demonstrated that in rat myometrium at late (day 19) gestation, SphK1 increases the expression of COX2 via S1P generation and release. In rat uterine leiomyoma cells (ELT3), SphK1/S1P axis controls survival and proliferation. In the present study we demonstrate that PDBu activates SphK1 but not SphK2. SphK1 activation requires PKC and MAPK ERK1/2. S1P produced by PDBu is released in the medium. PDBu-induced S1P export is abolished by Ro-318220 and BIM (PKC inhibitors), by U0126 and PD98059 (MEK inhibitors), SKI-II (SphKI/2 inhibitor) and SphK... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5103925 Thu, 21 Jul 2011 23:00:00 +0100 5103925 http://www.medworm.com/index.php?rid=5103928&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787862%26dopt%3DAbstract Authors: Hall EH, Gurel V, Dahlberg AE, McMichael J, Brautigan DL Streptolysin O (SLO) is a protein cytotoxin derived from Group A beta-hemolytic streptococci that associates with membranes and permeabilizes cells. Oxidation inactivates SLO, eliminating the characteristic hemolytic and cytotoxic activities. However, oxidized SLO produces beneficial therapeutic effects in vivo on scleroderma, scar formation and wound healing. Here we report that oxidized SLO also significantly inhibited invasion by human metastatic breast cancer MDA-MB-231 cells through Matrigel in an in vitro model of metastatic disease. This dose-dependent response corresponded to selective SLO activation of epidermal growth factor receptor (EGFR) ErbB1. SLO and EGF were equally selective in activation of EGFR, but EG... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5103928 Tue, 19 Jul 2011 23:00:00 +0100 5103928 http://www.medworm.com/index.php?rid=5058014&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767636%26dopt%3DAbstract Authors: Su CH, Wang CY, Lan KH, Li CP, Chao Y, Lin HC, Lee SD, Lee WP Phosphorylation at Thr308 and Ser473 is known to activate Akt, a major kinase in mammalian cells. Once activated to turn on downstream signaling pathways, Akt returns to an inactive pool via PP2A-mediated dephosphorylation. We show here that Thr308 and Ser473 phosphorylations prompt Akt to enter the CHIP-mediated ubiquitin-proteasome pathway. Mutation at either Thr308 or Ser473 dampened its ability to bind to the U-box E3 ligase CHIP (C-terminal Hsp70 -interacting protein), and the Akt mutants revealed decreased rate of ubiquitination by CHIP. Our study unveils that the well-known phosphorylations responsible for Akt activation turn out to transduce recognition signals for Akt-CHIP binding and ensuing degradation. ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058014 Thu, 14 Jul 2011 23:00:00 +0100 5058014 http://www.medworm.com/index.php?rid=5058008&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777673%26dopt%3DAbstract Authors: Leem YE, Choi HK, Jung SY, Kim BJ, Lee KY, Yoon K, Qin J, Kang JS, Kim ST Esco2 is an acetyltransferase that is required for the establishment of sister chromatid cohesion. Roberts-SC phocomelia (RBS) syndrome caused by the mutations of Esco2 gene, is an autosomal recessive development disorder characterized by growth retardation, limb reduction and craniofacial abnormalities including cleft lip and palate. Here, we show that Esco2 protein co-immunoprecipitates with Notch but not with CBF1. Esco2 represses the transactivational activity of Notch protein in an acetyltransferase-independent manner. Chromatin immunoprecipitation experiments suggest that Esco2 might regulate the activity of NICD-CBF1 via attenuating NICD binding to CBF1 on the promoter of Hes1, the downstream targ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058008 Wed, 13 Jul 2011 23:00:00 +0100 5058008 http://www.medworm.com/index.php?rid=5058013&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767637%26dopt%3DAbstract Authors: Sun C, Li F, Meng Q Both p38 MAPK and JNK belonged to stress activated protein kinases (SAPKs). It has been shown that JNK was involved in the progress of endoplasmic reticulum stress (ER stress). As another kind of SAPK, however, whether p38 MAPK participates in ER stress still remains unclear. Our results presented here show that anisomycin- (ANS) or TNFα-mediated SAPK activation attenuates ER stress induced by tunicamycin (Tun) or dithiothreitol (DTT) in MEF cells. These effects caused by ANS or TNFα were completely reversed by p38 MAPK inhibitor SB203580, while no changes were observed by JNK inhibitor (JNKi). Moreover, ANS or TNFα treatment fails to alleviate ER stress in p38 MAPK low-expressing cells, suggesting the attenuating effects of ANS or TNFα on ER stress are... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058013 Mon, 11 Jul 2011 23:00:00 +0100 5058013 http://www.medworm.com/index.php?rid=5058012&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21771656%26dopt%3DAbstract This study addresses the signal transduction pathways for protein phosphorylation and gene induction following IL-1β stimulation in human fetal lung fibroblasts. Our results utilizing both inhibitors and kinase-deficient cells demonstrate that cPLA(2)α is phosphorylated within 10min of IL-1β treatment, an event requiring p38 MAPK as well as the upstream kinase, MKK3/MKK6. Inhibition of p38 MAPK also blocks the phosphorylation of a downstream, nuclear kinase, MSK-1. Our results further demonstrate that the activities of both cPLA(2)α and a downstream lipoxygenase (15-LOX2) are required for IL-1β-dependent induction of cPLA(2)α mRNA expression. Overall, these data support an MKK3/MKK6→p38 MAPK→MSK-1→cPLA(2)α→15-LOX2-dependent, positive feedback loop where a protein's enzymatic... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058012 Mon, 11 Jul 2011 23:00:00 +0100 5058012 http://www.medworm.com/index.php?rid=5058011&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777670%26dopt%3DAbstract Authors: Grabinski N, Bartkowiak K, Grupp K, Brandt B, Pantel K, Jücker M Single disseminated tumor cells (DTC) can be detected in the bone marrow (BM) from 20% to 60% of patients with various tumors including non-small cell lung cancer (NSCLC). Detection of DTC in the BM of NSCLC patients is associated with poor prognosis and may be responsible for metastatic relapse. However, the functional properties of DTC are widely unknown. Here, we performed the first functional analysis of DTC focusing on the activation of the PI3K/Akt signalling pathway and the functional roles of Akt isoforms. In vitro kinase assays revealed a high activity of Akt3 in NSCLC-derived DTC. Proliferation and survival of DTC was reduced by depletion of Akt3 and to a lesser extend by Akt1, but not after depletion ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058011 Mon, 11 Jul 2011 23:00:00 +0100 5058011 http://www.medworm.com/index.php?rid=5058010&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777671%26dopt%3DAbstract Authors: Pavone LM, Cattaneo F, Rea S, De Pasquale V, Spina A, Sauchelli E, Mastellone V, Ammendola R Hepatocyte Growth Factor (HGF)/c-MET signaling has an emerging role in promoting cell proliferation, survival, migration, wound repair and branching in a variety of cell types. HGF plays a crucial role as a mediator of stromal-epithelial interactions in the normal prostate but the precise biological function of HGF/c-Met interaction in the normal prostate and in prostate cancer is not clear. HGF has two naturally occurring splice variants and NK1, the smallest of these HGF variants, consists of the HGF amino terminus through the first kringle domain. We evaluated the intracellular signaling cascades and the morphological changes triggered by NK1 in human prostate epithelial cell line P... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058010 Mon, 11 Jul 2011 23:00:00 +0100 5058010 http://www.medworm.com/index.php?rid=5058009&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777672%26dopt%3DAbstract In this study we examined the role of PKC in the regulation of RTVP-1 expression and found that PMA and overexpression of PKCα and PKCε increased the expression of RTVP-1, whereas PKCδ exerted an opposite effect. Using the MatInspector software, we identified a SRF binding site on the RTVP-1 promoter. Chromatin immunoprecipitation (ChIP) assay revealed that SRF binds to the RTVP-1 promoter in U87 cells, and that this binding was significantly increased in response to serum addition. Moreover, silencing of SRF blocked the induction of RTVP-1 expression in response to serum. We found that overexpression of PKCα and PKCε increased the activity of the RTVP-1 promoter and the binding of SRF to the promoter. In contrast, overexpression of PKCδ blocked the increase in RTVP-1 expression in r... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058009 Mon, 11 Jul 2011 23:00:00 +0100 5058009 http://www.medworm.com/index.php?rid=5058015&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763421%26dopt%3DAbstract In this study, we show that the pharmacological elevation of [cAMP](i) in mouse embryonic fibroblasts (MEFs) and human embryonic kidney 293 (HEK293) cells inhibits mTORC1 activation via a PKA-dependent mechanism. Although the inhibitory effect of cAMP on mTOR could be mediated by impinging on signalling cascades (i.e. PKB, MAPK and AMPK) that inhibit TSC1/2, an upstream negative regulator of mTORC1, we show that cAMP inhibits mTORC1 in TSC2 knockout (TSC2(-/-)) MEFs. We also show that cAMP inhibits insulin and amino acid-stimulated mTORC1 activation independently of Rheb, Rag GTPases, TSC2, PKB, MAPK and AMPK, indicating that cAMP may act independently of known regulatory inputs into mTOR. Moreover, we show that the prolonged elevation in [cAMP](i) can also inhibit mTORC2. We provide evide... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058015 Tue, 05 Jul 2011 23:00:00 +0100 5058015 http://www.medworm.com/index.php?rid=5058019&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21749919%26dopt%3DAbstract Authors: Kuramasu A, Sukegawa J, Sato T, Sakurai E, Watanabe T, Yanagisawa T, Yanai K Functional roles of putative helix 8 in the carboxy-terminal tail of the human histamine H(3) receptor were investigated using deleted and alanine-substituted mutant receptors. While the deletion of the carboxy-terminal tail did not decrease the total expression level, surface expression, or ligand binding affinity, the agonist-stimulated cAMP response, [((35))S] GTPγS binding, and MAPK activation were totally abolished. The receptor lacking the carboxy-terminal tail also failed to respond to an inverse agonist, thioperamide, suggesting that the carboxy-terminal tail is involved in the regulation of receptor activity by changing G-protein coupling with the receptor. Site-directed mutagenesis revealed... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058019 Sat, 02 Jul 2011 23:00:00 +0100 5058019 http://www.medworm.com/index.php?rid=5058018&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21756999%26dopt%3DAbstract Authors: Sinha S, Koul N, Dixit D, Sharma V, Sen E The insulin-like growth factor (IGF-1) induces hypoxia inducible factor (HIF-1α) regulated genes in glioblastoma multiforme (GBM). As HIF-1α links inflammatory and oncogenic pathways in GBM, we investigated whether IGF-1 affects HIF-1α to regulate inflammatory response in glioma cells under normoxia. IGF-1 induced Ras and Calmodulin-dependent kinase II (CaMKII) regulated HIF-1α transcriptional activity in glioma cells. Increase in HIF-1α was concurrent with decreased Toll-like receptor (TLR9) and CXCR4 expression and elevated suppressor of cytokine signaling (SOCS3) levels. Interestingly, while synthetic CpG containing oligodeoxynucleotide TLR9 agonist (CpG DNA) decreased IGF-1 mediated increase in HIF-1α activity, siRNA media... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058018 Sat, 02 Jul 2011 23:00:00 +0100 5058018 http://www.medworm.com/index.php?rid=5058017&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21757000%26dopt%3DAbstract CONCLUSIONS: Our results indicate that the CIRB site of TRPC6 plays an important functional role in platelets both modulating Ca(2+) entry and aggregation through its interaction with CaM and IP(3)Rs. PMID: 21757000 [PubMed - as supplied by publisher] (Source: Cellular Signalling) Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058017 Sat, 02 Jul 2011 23:00:00 +0100 5058017 http://www.medworm.com/index.php?rid=5058016&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21757001%26dopt%3DAbstract Authors: Deneubourg L, Ralea S, Gromova P, Parsons R, Vanderwinden JM, Erneux C Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Approximately 85% of GISTs harbor activating mutations of the KIT or PDGFRA receptor tyrosine kinases. PTEN and SHIP2 are major phosphatases that dephosphorylate PI(3,4,5)P(3), one of the intracellular signal pathways downstream of KIT. PTEN is an important tumor suppressor, whereas the involvement of SHIP2 in cancer has been proposed based essentially on cell line studies. We have used a mouse model of GIST, i.e. Kit(K641E) knock-in mice, resulting in the substitution of a Lys by Glu at position 641 of Kit. In homozygous Kit(K641E) mice, PTEN-immunoreactivity (ir) in antrum was found in the hyperpl... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058016 Sat, 02 Jul 2011 23:00:00 +0100 5058016 http://www.medworm.com/index.php?rid=5058022&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741477%26dopt%3DAbstract In this study, via the genetic and molecular approach, we further demonstrated that Ca(2+)-permeable stretch-activated nonselective cation channel-MidA, calcium/calmodulin-dependent protein phosphatase catalatic subunit-CnaA and external calcium, but not voltage-gated calcium channel homolog-CchA, were required for the osmotic stabilizer-coupled suppression. The up-regulation of calcium/calcineurin signaling pathway induced by osmotic stress might be the reason for bypassing the requirements of NDR kinase complex, which is otherwise necessary for polar morphogenesis. Our results suggest that calcium-calcineurin signaling pathway coordinates with MobB/CotA kinase complex in regulating polarity growth via maintaining cellular calcium homeostasis. However, CchA may act differently as other co... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058022 Wed, 29 Jun 2011 23:00:00 +0100 5058022 http://www.medworm.com/index.php?rid=5058021&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741478%26dopt%3DAbstract Twice switched at birth: Cell cycle-independent roles of the "neuron-specific" cyclin-dependent kinase 5 (Cdk5) in non-neuronal cells. Cell Signal. 2011 Jun 30; Authors: Liebl J, Fürst R, Vollmar AM, Zahler S Cdk5 (cyclin-dependent kinase 5 or initially NCLK for neuronal CDC2-like kinase) was switched twice at its birth nearly twenty years ago: first it was thought to be cyclin-dependent, second it was assumed to be primarily of importance in neuronal cells-both turned out not to be the case. In this review we want to discuss issues of pharmacological inhibition, to highlight the versatile roles, and to summarize the growing evidence for the functional importance of Cdk5 in non-neuronal tissues, such as blood cells, tumor cells, epithelial cells, the vascular endothelium, test... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058021 Wed, 29 Jun 2011 23:00:00 +0100 5058021 http://www.medworm.com/index.php?rid=5058020&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21745565%26dopt%3DAbstract Authors: Jin Y, Zhen Y, Haugsten EM, Wiedlocha A The KG-1a cell line is developed from a human stem cell myeloproliferative neoplasm as the result of intragenic disruption and a chromosomal translocation of the FGFR1 gene and the FGFR1OP2 gene encoding a protein of unknown function called FOP2 (FGFR1 Oncogene Partner 2). The resulting fusion protein FOP2-FGFR1 is soluble and has constitutive tyrosine kinase activity. Since the heat shock protein HSP90 and its co-chaperone CDC37 have been shown to stabilize many oncogenic proteins, we investigated the requirement for HSP90 or HSP90-CDC37 assistance to maintain the stability or activity of FOP2-FGFR1 expressed in KG-1a cells. We found that HSP90-CDC37 forms a permanent complex with FOP2-FGFR1. This results in protection against degradati... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058020 Wed, 29 Jun 2011 23:00:00 +0100 5058020 http://www.medworm.com/index.php?rid=5058025&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21740965%26dopt%3DAbstract In this study the activity of PLCη2 was examined via [(3)H]inositol phosphate release in COS7 cells expressing the enzyme. PLCη2 activity increased approximately 5-fold in response to monensin, a Na(+)/H(+) antiporter. This was significantly inhibited by CGP-37157 which implies that the effect of monensin was due, at least in part, to mitochondrial Na(+)/Ca(2+)-exchange. Direct activation of PLCη2 by <1μM Ca(2+) was confirmed in permeabilised transfected cells. The roles of the PH and C2 domains in controlling PLCη2 activity via membrane association were also investigated. A PH domain-lacking mutant exhibited no detectable activity in response to monensin or Ca(2+) due to an inability to associate with the cell membrane. Within the C2 domain, mutation of D920 to alanine at the pred... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058025 Tue, 28 Jun 2011 23:00:00 +0100 5058025 http://www.medworm.com/index.php?rid=5058024&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21740966%26dopt%3DAbstract In this study, we examine the specificities and potencies of the most frequently used small molecule inhibitors of the TGFß pathway (SB-431542, SB-505124, LY-364947 and A-83-01) and the BMP pathway (Dorsomorphin and LDN-193189) against a panel of up to 123 protein kinases covering a broad spectrum of the human kinome. We demonstrate that the inhibitors of the TGFß pathway are relatively more selective than the inhibitors of the BMP pathway. Based on our specificity and potency profile and published data, we recommend SB-505124 as the most suitable molecule for use as an inhibitor of ALKs 4, 5 and 7 and the TGFß pathway. We do not recommend Dorsomorphin, also called Compound C, for use as an inhibitor of the BMP pathway. Although LDN-193189, a Dorsomorphin derivative, is a very potent in... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058024 Tue, 28 Jun 2011 23:00:00 +0100 5058024 http://www.medworm.com/index.php?rid=5058023&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21740967%26dopt%3DAbstract Authors: Gomez-Cambronero J PLD catalyzes the conversion of the membrane phospholipid phosphatidylcholine to choline and phosphatidic acid (PA). PLD's mission in the cell is two-fold: phospholipid turnover with maintenance of the structural integrity of cellular/intracellular membranes and cell signaling through PA and its metabolites. Precisely, through its product of the reaction, PA, PLD has been implicated in a variety of physiological cellular functions, such as intracellular protein trafficking, cytoskeletal dynamics, chemotaxis of leukocytes and cell proliferation. The catalytic (HKD) and regulatory (PH and PX) domains were studied in detail in the PLD1 isoform, but PLD2 was traditionally studied in lesser detail and much less was known about its regulation. Our laboratory has b... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5058023 Tue, 28 Jun 2011 23:00:00 +0100 5058023 http://www.medworm.com/index.php?rid=5009095&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21726628%26dopt%3DAbstract Authors: Lin YC, Wang FF Polo-like kinase 1 (Plk1) plays key roles in many aspects of mitosis. We have previously shown that induction of p21(Waf1) by p53 is responsible for protection of cells against adriamycin-induced polyploidy formation and mitotic catastrophe. Here we show that adriamycin treatment suppressed Plk1 expression in a p53- and p21(Waf1)-dependent manner. Ablation of p21(Waf1) inhibited the adriamycin-induced p53 activation, and this inhibition was alleviated by knockdown of Plk1, suggesting that p21(Waf1)-dependent suppression of Plk1 expression is responsible for maintaining p53 activation during stress response. Plk1 associated with p53 and disrupted its interaction with target gene promoters in cells treated with adriamycin. Overexpression of Plk1 inhibited the p53... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5009095 Tue, 28 Jun 2011 23:00:00 +0100 5009095 http://www.medworm.com/index.php?rid=5009094&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21726629%26dopt%3DAbstract Authors: Sayyah J, Gnanasambandan K, Kamarajugudda S, Tsuda S, Caldwell-Busby J, Sayeski PP Jak2 tyrosine kinase plays an important role in cytokine mediated signal transduction. There are 49 tyrosine residues in Jak2 and phosphorylation of some of these are known to play important roles in the regulation of Jak2 kinase activity. Here, using mass spectrometry, we identified tyrosine residues Y372 and Y373 as novel sites of Jak2 phosphorylation. Mutation of Y372 to F (Y372F) significantly inhibited Jak2 phosphorylation, including that of Y1007, whereas the Jak2-Y373F mutant displayed only modest reduction in phosphorylation. Relative to Jak2-WT, the ability of Jak2-Y372F to bind to and phosphorylate STAT1 was decreased, resulting in reduced Jak2-mediated downstream gene transcription. W... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5009094 Tue, 28 Jun 2011 23:00:00 +0100 5009094 http://www.medworm.com/index.php?rid=5009099&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21712088%26dopt%3DAbstract Authors: Sandoval YH, Li Y, Anand-Srivastava MB We earlier showed that the increased expression of Gi proteins exhibited by vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) was attributed to the enhanced levels of endogenous endothelin. Since the levels of angiotensin II (Ang II) are also enhanced in VSMC from SHR, the present study was undertaken to examine the role of enhanced levels of endogenous Ang II in the overexpression of Giα proteins in VSMC from SHR and to further explore the underlying mechanisms responsible for this increase. The enhanced expression of Giα-2 and Giα-3 proteins in VSMC from SHR compared to WKY was attenuated by the captopril, losartan and AG1478, inhibitors of angiotensin converting enzyme, AT(1) receptor and epidermal growt... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5009099 Fri, 24 Jun 2011 23:00:00 +0100 5009099 http://www.medworm.com/index.php?rid=5009096&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21726627%26dopt%3DAbstract In this study, we applied a sequential inhibitory analysis of various signaling intermediates to examine the hierarchy of protein interactions within the PRL signaling network and to evaluate the relative contributions of multiple signaling branches downstream of PRL-R to the activation of the extracellular signal-regulated kinases ERK1 and ERK2 in T47D and MCF-7 human breast cancer cells. Quantitative measurements of the phosphorylation/activation patterns of proteins showed that PRL simultaneously activated Src family kinases (SFKs) and the JAK/STAT, phosphoinositide-3 (PI3)-kinase/Akt and MAPK signaling pathways. The specific blockade or siRNA-mediated suppression of SFK/FAK, JAK2/STAT5, PI3-kinase/PDK1/Akt, Rac/PAK or Ras regulatory circuits revealed that (1) the PI3-kinase/Akt pathway... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5009096 Fri, 24 Jun 2011 23:00:00 +0100 5009096 http://www.medworm.com/index.php?rid=5009093&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21726630%26dopt%3DAbstract This study identifies a novel paradigm of innate immune regulation rendered by NFAT which is a well known family of adaptive immune regulatory proteins. PMID: 21726630 [PubMed - as supplied by publisher] (Source: Cellular Signalling) Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5009093 Fri, 24 Jun 2011 23:00:00 +0100 5009093 http://www.medworm.com/index.php?rid=5009098&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723942%26dopt%3DAbstract In this study, NTN activation of GFRα2a and GFRα2c but not GFRα2b induced biphasic ERK1/2 activation and phosphorylation of the major cAMP target CREB. Interestingly, inhibition of cAMP signalling significantly impaired GFRα2a and GFRα2c-mediated neurite outgrowth while cAMP agonists cooperated with GFRα2b to induce neurite outgrowth. Importantly, the specific cAMP effector PKA but not Epac was essential for NTN-induced neurite outgrowth, through transcription and translation-dependent activation of late phase ERK1/2. Taken together, these results not only demonstrated the essential role of cAMP-PKA signalling in NTN-induced biphasic ERK1/2 activation and neurite outgrowth, but also suggested cAMP-PKA signalling as a hitherto unrecognized underlying mechanism contributing to the diff... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5009098 Thu, 23 Jun 2011 23:00:00 +0100 5009098 http://www.medworm.com/index.php?rid=5009097&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723943%26dopt%3DAbstract Authors: Charette N, Holland P, Frazer J, Allen H, Dupré DJ Much is known about G protein coupled receptor trafficking and internalization following agonist stimulation. However, much less is known about outward trafficking of receptors from synthesis in the endoplasmic reticulum to the plasma membrane, or the role that trafficking might play in the assembly of receptor signaling complexes, important for targeting, specificity, and rapidity of subsequent signaling events. Up to now, very little is understood about receptor hetero-oligomers other than the fact that their assembly is done rapidly after biosynthesis. In our study we use bimolecular fluorescence complementation to selectively follow receptor dimers when expressed in Jurkat cells in order to clarify the trafficking itinera... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=5009097 Thu, 23 Jun 2011 23:00:00 +0100 5009097 http://www.medworm.com/index.php?rid=4961645&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21689743%26dopt%3DAbstract In conclusion, IL1β upregulates the LKB1-AMPK-INOS pathway, while Alloxan acts through CaMKII-AMPK-INOS, both ultimately leading to beta cell death. In this context, CNTF protects beta cells against apoptosis, induced by either IL1β or Alloxan, through downregulation of the CaMKII-AMPK-INOS pathway. PMID: 21689743 [PubMed - as supplied by publisher] (Source: Cellular Signalling) Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961645 Thu, 16 Jun 2011 23:00:00 +0100 4961645 http://www.medworm.com/index.php?rid=4961644&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21689744%26dopt%3DAbstract Authors: Sun L, Cao X, Liu B, Huang H, Wang X, Sui L, Yin W, Ma K Prohibitin 2 (PHB2) is an evolutionarily conserved and ubiquitously expressed multifunctional protein which is present in various cellular compartments including the nucleus. However, mechanisms underlying various functions of PHB2 are not fully explored yet. Previously we showed that PHB2 interacts with Akt and inhibits muscle differentiation by repressing the transcriptional activity of both MyoD and MEF2. Here we show that Calcium/Calmodulin-dependent kinase IV (CaMK IV) specifically binds to the C terminus of PHB2 and phosphorylates PHB2 at serine 91. Ectopic expression of CaMK IV and PHB2 in C2C12 cells results effectively in decreased PHB2-mediated repression of MEF2-dependent gene expression. Conversely, PHB2 muta... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961644 Thu, 16 Jun 2011 23:00:00 +0100 4961644 http://www.medworm.com/index.php?rid=4961648&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21683138%26dopt%3DAbstract Authors: Chatel G, Fahrenkrog B The nuclear envelope (NE) separates the cytoplasm and the cell nucleus of interphase eukaryotic cells and nuclear pore complexes (NPCs) mediate the macromolecular exchange between these two compartments. The NE and the NPCs of vertebrate cells disassemble during prophase and the nuclear pore proteins (nucleoporins) are distributed within the mitotic cytoplasm. For an increasing number of them active mitotic functions have been assigned over the past few years. Nucleoporins are participating in spindle assembly, kinetochore organisation, and the spindle assembly checkpoint, all processes that control chromosome segregation and are important for maintenance of genome integrity. But nucleoporins are also engaged in early and late mitotic events, such as cen... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961648 Mon, 13 Jun 2011 23:00:00 +0100 4961648 http://www.medworm.com/index.php?rid=4961647&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21683139%26dopt%3DAbstract Authors: Chiu TT, Jensen TE, Sylow L, Richter EA, Klip A Small Rho family GTPases are important regulators of cellular traffic. Emerging evidence now implicates Rac1 and Rac-dependent actin reorganisation in insulin-induced recruitment of glucose transporter-4 (GLUT4) to the cell surface of muscle cells and mature skeletal muscle. This review summarises the current thinking on the regulation of Rac1 by insulin, the role of Rac-dependent cortical actin remodelling in GLUT4 traffic, and the impact of Rac1 towards insulin resistance in skeletal muscle. PMID: 21683139 [PubMed - as supplied by publisher] (Source: Cellular Signalling) Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961647 Mon, 13 Jun 2011 23:00:00 +0100 4961647 http://www.medworm.com/index.php?rid=4961646&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21683788%26dopt%3DAbstract Authors: Palmer CS, Osellame LD, Stojanovski D, Ryan MT Mitochondria typically form a reticular network radiating from the nucleus, creating an interconnected system that supplies the cell with essential energy and metabolites. These mitochondrial networks are regulated through the complex coordination of fission, fusion and distribution events. While a number of key mitochondrial morphology proteins have been identified, the precise mechanisms which govern their activity remain elusive. Moreover, post translational modifications including ubiquitination, phosphorylation and sumoylation of the core machinery are thought to regulate both fusion and division of the network. These proteins can undergo several different modifications depending on cellular signals, environment and energetic... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961646 Sun, 12 Jun 2011 23:00:00 +0100 4961646 http://www.medworm.com/index.php?rid=4961643&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21689745%26dopt%3DAbstract In this study, we hypothesized that activation of the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress could be one of the underlying mechanisms involved in GC-induced beta cell dysfunction. We report here that PRED did not affect basal insulin release but time-dependently inhibited glucose-stimulated insulin secretion in INS-1E cells. PRED treatment also decreased both PDX1 and insulin expression, leading to a marked reduction in cellular insulin content. These PRED-induced detrimental effects were found to be prevented by prior treatment with the glucocorticoid receptor (GR) antagonist RU486 and associated with activation of two of the three branches of the UPR. Indeed, PRED induced a GR-mediated activation of both ATF6 and IRE1/XBP1 pathways but was found to r... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961643 Sun, 12 Jun 2011 23:00:00 +0100 4961643 http://www.medworm.com/index.php?rid=4961642&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21689746%26dopt%3DAbstract Authors: Lin VT, Lin FT Thyroid hormone receptor interacting protein 6 (TRIP6), also known as zyxin-related protein-1 (ZRP-1), is an adaptor protein that belongs to the zyxin family of LIM proteins. TRIP6 is primarily localized in the cytosol or focal adhesion plaques, and may associate with the actin cytoskeleton. Additionally, it is capable of shuttling to the nucleus to serve as a transcriptional coregulator. Structural and functional analyses have revealed that through multidomain-mediated protein-protein interactions, TRIP6 serves as a platform for the recruitment of a wide variety of signaling molecules involved in diverse cellular responses, such as actin cytoskeletal reorganization, cell adhesion and migration, antiapoptotic signaling, osteoclast sealing zone formation and tran... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961642 Sun, 12 Jun 2011 23:00:00 +0100 4961642 http://www.medworm.com/index.php?rid=4961641&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21693187%26dopt%3DAbstract This study is to clarify the function of iNOS/NO and its mechanisms during the apoptotic process. The apoptosis was brought about by GCDC in rat primary hepatocytes. iNOS/NO signaling was then investigated. iNOS inhibitor 1400W enhanced the GCDC-induced apoptosis as reflected by caspase-3 activity and TUNEL assay. Exogenous NO regulated the apoptosis subsequent to NO donor S-nitroso-N-acetyl-penicillamine (SNAP) or sodium nitroprusside (SNP). The GCDC-induced apoptosis was decreased with 0.1mM SNAP or 0.15mM SNP, while it was increased with 0.8mM SNAP or 1.2mM SNP. The endogenous iNOS inhibited apoptosis, but the exogenous NO played a dual role during the GCDC-induced apoptosis. There was a potential iNOS/Akt/survivin axis that inhibited the hepatocyte apoptosis in low doses of NO donors. ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961641 Sun, 12 Jun 2011 23:00:00 +0100 4961641 http://www.medworm.com/index.php?rid=4961649&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21672629%26dopt%3DAbstract Authors: Mahon MJ The parathyroid hormone 1 receptor (PTH1R), a primary regulator of mineral ion homeostasis, is expressed on both the apical and basolateral membranes of kidney proximal tubules and in the LLC-PK1 kidney cell line. In LLC-PK1 cells, apical PTH1R subpopulations are far more effective at signaling via phospholipase (PLC) than basolateral counterparts, revealing the presence of compartmental signaling. Apical PTH1R localization is dependent upon direct interactions with ezrin, an actin-membrane cross-linking scaffold protein. Ezrin undergoes an activation process that is dependent upon phosphorylation and binding to phosphatidylinositol-4,5-bisphosphate (PIP2), a lipid that is selectively concentrated to apical surfaces of polarized epithelia. Consistently, the intracellu... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961649 Mon, 06 Jun 2011 23:00:00 +0100 4961649 http://www.medworm.com/index.php?rid=4961652&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21664272%26dopt%3DAbstract Authors: Ger M, Zitkus Z, Valius M Adaptor protein Nck1 binds a number of intracellular proteins and influences various signaling pathways. Here we show that Nck1 directly binds and activates the GTPase-activating protein of Ras (RasGAP), which is responsible for the down-regulation of Ras. The first and the third SH3 domains of Nck1 and the NH(2)-terminal proline-rich sequence of RasGAP contribute most to the complex formation causing direct molecular interaction between the two proteins. Cell adhesion to the substrate is obligatory for the Nck1 and RasGAP association, as cell detachment makes RasGAP incapable of associating with Nck1. This leads to the complex dissipation, decrease of RasGAP activity and the increase of H-Ras-GTP level in the detached cells. Our findings reveal unexp... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961652 Wed, 01 Jun 2011 23:00:00 +0100 4961652 http://www.medworm.com/index.php?rid=4961650&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21664967%26dopt%3DAbstract Authors: Lin LC, Hsu SL, Wu CL, Liu WC, Hsueh CM The primary goal of the study was to investigate how peroxisome proliferator-activated receptor γ (PPARγ) played a critical role in the protection of H460 cell, one of the non-small cell lung cancer (NSCLC) cells with multidrug resistance, from transforming growth factor β (TGFβ)-mediated mitoinhibition. In the study, TGFβ resistance of H460 cell was first confirmed by analyses of PPARγ expression, its interaction with TGFβ-induced Smad3 and phospho-Smad3 (p-Smad3) and survival of H460. Results showed that enable to escape from G2/M phase arrest, H460 cell had higher resistance to TGFβ-mediated mitoinhibition than CH27 (a drug sensitive control). TGFβ significantly increased PPARγ expression of H460 but not of CH27 cell whereas... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961650 Wed, 01 Jun 2011 23:00:00 +0100 4961650 http://www.medworm.com/index.php?rid=4961653&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21658446%26dopt%3DAbstract In this study, mouse mesangial cells were transiently transfected with Nrf2-plasmid or the Nrf2-specific siRNA. The high glucose-induced intracellular ROS, malondialdehyde, cell proliferation, and TGF-β1 secretion were measured. The levels of Nrf2, heme oxygenase-1 (HO-1), γ-glutamylcysteine synthethase (γ-GCS) expression, and nuclear expression of Nrf2 in mouse mesangial cells were determined. We found that high glucose induced ROS and malondialdehyde generation in mouse mesangial cells. Induction of Nrf2 over-expression reduced the high glucose-induced ROS and malondialdehyde production, inhibited cell proliferation and TGF-β1 secretion, accompanied by up-regulating the expressions of HO-1 and γ-GCS in mouse mesangial cells. However, knockdown of Nrf2 expression displayed reverse ef... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961653 Tue, 31 May 2011 23:00:00 +0100 4961653 http://www.medworm.com/index.php?rid=4961651&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21664461%26dopt%3DAbstract We report here that the redox-sensitive Src homology region 2 domain-containing phosphatase 1 (SHP1) is a critical regulator of M-CSF-mediated signaling in bone marrow monocyte/macrophage lineage cells (BMMs). Application of diphenylene iodonium (DPI) inhibited the responses of BMMs to M-CSF, including ROS production, cell proliferation, and phosphorylation of c-Fms as well as Akt kinase, but not of MAP kinases such as ERK, p38, and JNK. Dysregulation of SHP1 by overexpression or RNA interference in BMMs showed that SHP1 specifically regulates PI3 kinase (PI3K)/Akt signaling, but not MAP kinases in a redox-dependent manner, thereby regulating proliferation of BMMs through cyclins D1 and D2. These findings demonstrate that M-CSF-mediated ROS generation leads to SHP1 oxidation, which promote... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4961651 Tue, 31 May 2011 23:00:00 +0100 4961651 http://www.medworm.com/index.php?rid=4912704&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21620966%26dopt%3DAbstract In conclusion, these data demonstrate that, despite difficulties in measuring endogenous RGS protein expression, RGS17 is differentially expressed in HCC and plays a central role in regulating transformed hepatocyte tumorgenicity. PMID: 21620966 [PubMed - as supplied by publisher] (Source: Cellular Signalling) Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4912704 Tue, 17 May 2011 23:00:00 +0100 4912704 http://www.medworm.com/index.php?rid=4912746&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21620965%26dopt%3DAbstract Authors: Corbin JD, Francis SH Phosphodiesterase-5 (PDE5) is a dimer containing a cGMP-specific catalytic domain and an allosteric cGMP-binding subdomain (GAF A) on each subunit. PDE5 exhibits three conformational forms that can be separated by Native PAGE and are denoted as Bands 1, 2, and 3 in decreasing order of mobility. A preparation comprised mainly of Band 2 PDE5 was partially converted to Band 3 PDE5 by 1h incubation with cGMP or the PDE5-specific inhibitors sildenafil, vardenafil, or tadalafil, but not with cAMP, milrinone (PDE3-specific), or rolipram (PDE4-specific). Band 2 PDE5 was converted almost entirely to Band 3 PDE5 by overnight incubation with sildenafil at 30°C. This time-dependent conversion was accompanied by a 7-fold increase in allosteric cGMP-binding activity, ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4912746 Mon, 16 May 2011 23:00:00 +0100 4912746 http://www.medworm.com/index.php?rid=4865945&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21609762%26dopt%3DAbstract Authors: Huang Z, Chen X, Chen D Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, is a critical autocrine/paracrine inhibitor of skeletal muscle growth. Since the first observed double-muscling phenotype was reported in myostatin-null animals, a functional role of myostatin has been demonstrated in the control of skeletal muscle development. However, beyond the confines of its traditional role in muscle growth inhibition, myostatin has recently been shown to play an important role in metabolism. During the past several years, it has been well established that Smads are canonical mediators of signals for myostatin from the receptors to the nucleus. However, growing evidence supports the notion that Non-Smad signal pathways also participate in myostatin sign... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4865945 Sat, 14 May 2011 23:00:00 +0100 4865945 http://www.medworm.com/index.php?rid=4865946&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21596133%26dopt%3DAbstract Authors: Lu N, Wang W, Liu J, Wong CW Members of the protein kinase C (PKC) family have been implicated in controlling cell proliferation, differentiation, and motility. Many of these processes are energy demanding. How PKCs affect mitochondrial function to regulate energy production is not well defined. Using an inhibitor Gö6983 with broad specificity, we found that inhibiting PKCs reduced mitochondrial mass and altered mitochondrial function characterized by elevations in mitochondrial membrane potential (Δψm) and reactive oxygen species (ROS) levels. These alterations indicated that Gö6983 suppressed the activities of mitochondrial regulators such as estrogen-related receptor α (ERRα). Indeed, Gö6983 dose-dependently suppressed the expression levels of ERRα-target genes pero... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4865946 Sun, 08 May 2011 23:00:00 +0100 4865946 http://www.medworm.com/index.php?rid=4865948&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21596131%26dopt%3DAbstract Authors: Boran AD, Chen Y, Iyengar R The role of Gβγ in adenylyl cyclase (AC) signaling is complicated due to its role as a conditional activator (AC2, AC4 and AC7) and an inhibitor (AC1, AC3 and AC8). AC2 is stimulated by Gα(s) and if Gβγ is present the stimulation is synergistic. The precise mechanism of this synergistic activation is still not known. In order to further elucidate the role of Gβγ in AC2 activation by Gα(s), peptides derived from the C1 domains of AC2 were synthesized and the ability of the various peptides to regulate AC2 function was tested. Our results identify two new Gβγ-binding sites in the AC2 C1 domain, AC2 C1a 339-360 and AC2 C1b 578-602 that are involved with stimulation of AC2 by Gβγ. These two regions are different from the previously described... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4865948 Sat, 07 May 2011 23:00:00 +0100 4865948 http://www.medworm.com/index.php?rid=4865947&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21596132%26dopt%3DAbstract Authors: Moon EY, Lee JH, Lee YS, Lee JW, Song JH B-cell activating factor (BAFF) plays a role for the maturation and the maintenance of B cells. Lipopolysaccharide (LPS) activates toll-like receptor 4 (TLR4)-dependent signal transduction, which resulted in BAFF expression through nuclear factor kappa B (NF-κB) activation. Here, we investigated whether BAFF expression could be regulated by p65 phosphorylation through the production of reactive oxygen species (ROS) or cyclic AMP (cAMP) in Raw264.7 murine macrophages. mBAFF expression was reduced by ROS scavengers and it was increased by dibutyl-cAMP, a cAMP analogue. mBAFF expression and mBAFF promoter activity were increased by co-transfection of p65 but they were reduced by p65-small interference (si) RNA. Serine (Ser) 276 phosphoryl... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4865947 Sat, 07 May 2011 23:00:00 +0100 4865947 http://www.medworm.com/index.php?rid=4813743&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21554950%26dopt%3DAbstract Authors: Chhipa RR, Wu Y, Ip C The present study was designed to investigate (i) the role of AMPK activation in inducing autophagy in androgen-dependent prostate cancer cells subjected to androgen deprivation and hypoxia, and (ii) whether autophagy offers a survival advantage under these harsh conditions. Low androgen and low oxygen are two co-existing conditions frequently found in prostate cancer tissue following surgical or medical castration. In LNCaP cells, androgen deprivation and hypoxia together boosted AMPK activation to a higher level than that seen with either condition alone. The augmented AMPK response was associated with improved viability and the induction of autophagy. These observations suggest that a threshold of AMPK activity has to be attained in order to trigger au... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4813743 Wed, 27 Apr 2011 23:00:00 +0100 4813743 http://www.medworm.com/index.php?rid=4813745&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21536126%26dopt%3DAbstract Authors: Huang H, Deng X, He X, Yang W, Li G, Shi Y, Shi L, Gao J, Zhou N Neuropeptides of the adipokinetic hormone (AKH) family play important roles in insect hemolymph sugar homeostasis, larval lipolysis and storage-fat mobilization. Our previous studies have shown that the adipokinetic hormone receptor (AKHR), a Gs-coupled receptor, induces intracellular cAMP accumulation, calcium mobilization and ERK1/2 phosphorylation upon agonist stimulation. However, the underlying molecular mechanisms that regulate the internalization and desensitization of AKHR remain largely unknown. In the current study we made a construct to express AKHR fused with enhanced green fluorescent protein (EGFP) at its C-terminal end to further characterize AKHR internalization. In stable AKHR-EGFP-expressing HEK... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4813745 Wed, 20 Apr 2011 23:00:00 +0100 4813745 http://www.medworm.com/index.php?rid=4813744&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21539912%26dopt%3DAbstract Authors: Hergovich A The family of Mps One binder (MOB) co-activator proteins is highly conserved from yeast to man. At least two different MOB proteins have been identified in every eukaryote analysed to date. Initially, yeast genetics revealed essential roles for Mob1p and Mob2p in the regulation of mitotic exit and cell morphogenesis. Studies in flies then showed that dMOB1/MATS is a core component of Hippo signalling. Loss of dMOB1 resulted in increased cell proliferation and decreased cell death, suggesting that MOB1 acts as tumour suppressor protein. Recent work focused primarily on mammalian cells has shown how hMOB1 can regulate NDR/LATS kinases, a function that can to be counteracted by hMOB2. Here we summarise and discuss our current knowledge of this emerging protein family,... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4813744 Wed, 20 Apr 2011 23:00:00 +0100 4813744 http://www.medworm.com/index.php?rid=4759409&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21515363%26dopt%3DAbstract Authors: Stengel K, Zheng Y The Rho family of GTPases represents a class of Ras-related signaling molecules often deregulated in cancer. Rho GTPases switch from a GDP-bound, inactive state to a GTP-bound, active state in response to extracellular stimuli such as mitogens and extracellular matrix. In addition, Rho GTPase signaling can be altered in response to cell intrinsic factors such as changes in oncogenic or tumor suppressor signaling. In their active form, these proteins bind to a number of effector molecules, activating signaling cascades which regulate a variety of cellular processes including cytoskeletal reorganization, cell cycle progression, cell polarity and transcription. Here, we focus on one Rho family member, Cdc42, which is overexpressed in a number of human cancers. ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4759409 Fri, 15 Apr 2011 23:00:00 +0100 4759409 http://www.medworm.com/index.php?rid=4759412&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21514376%26dopt%3DAbstract Authors: Kong X, Shen Y, Jiang N, Fei X, Mi J The DNA-dependent protein kinase (DNA-PK) is a DNA-activated serine/threonine protein kinase, and abundantly expressed in almost all mammalian cells. The roles of DNA-PK in DNA-damage repair pathways, including non-homologous end-joining (NHEJ) repair and homologous recombinant (HR) repair, have been studied intensively. However, the high levels of DNA-PK in human cells are somewhat paradoxical in that it does not impart any increased ability to repair DNA damage. If DNA-PK essentially exceeds the demand for DNA damage repair, why do human cells universally express such high levels of this huge complex? DNA-PK has been recently reported to be involved in metabolic gene regulation in response to feeding/insulin stimulation; our studies have ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4759412 Thu, 14 Apr 2011 23:00:00 +0100 4759412 http://www.medworm.com/index.php?rid=4759411&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21514377%26dopt%3DAbstract Authors: Valbuena A, Sanz-García M, López-Sánchez I, Vega FM, Lazo PA Cell division, in addition to an accurate transmission of genetic information to daughter cells, also requires the temporal and spatial coordination of several biological processes without which cell division would not be feasible. These processes include the temporal coordination of DNA replication and chromosome segregation, regulation of nuclear envelope disassembly and assembly, chromatin condensation and Golgi fragmentation for its redistribution into daughter cells, among others. However, little is known regarding regulatory proteins and signalling pathways that might participate in the coordination of all these different biological functions. Such regulatory players should directly have a role in the proces... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4759411 Wed, 13 Apr 2011 23:00:00 +0100 4759411 http://www.medworm.com/index.php?rid=4759410&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21515362%26dopt%3DAbstract Authors: Ehrlich M, Horbelt D, Marom B, Knaus P, Henis YI Transforming growth factor-β (TGF-β) ligands and bone morphogenetic proteins (BMPs) play myriad roles in many biological processes and diseases. Their pluripotent activities are subject to multiple levels of regulation, including receptor oligomerization, endocytosis, association with co-receptors, cellular scaffolds or membrane domains, as well as transcriptional control. In this review, we focus on TGF-β and BMP receptor homomeric and heteromeric complex formation and their modulation by ligand binding, which regulate signaling on a near-immediate timescale. We discuss the current structural, biochemical and biophysical evidence for the oligomerization of these receptors, and the potential roles of distinct oligomeric inter... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4759410 Wed, 13 Apr 2011 23:00:00 +0100 4759410 http://www.medworm.com/index.php?rid=4759413&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21511030%26dopt%3DAbstract Authors: Chen Z, Ma X, Zhang H, Sun X, Shen S, Li Y, Gu Y, Wang Y, Yan S, Yu Q Signal transducer and activator of transcription 1 (STAT1) is an important mediator for cytokine signal transduction, particularly IFN-γ. Following IFN-γ stimulation, STAT1 is activated through tyrosine phosphorylation. Little is known about the function and regulation of STAT1 dephosphorylation after activation. We studied the regulation and function of STAT1 dephosphorylation in different types of cells and found that the phosphorylated STAT1 was quickly dephosphorylated in most of epithelial cells. Further studies revealed that the dephosphorylation of STAT1 was regulated by cell shape/adhesion. Actin cytoskeleton and extracellular matrix (ECM) proteins mediated the STAT1 dephosphorylation through the T... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4759413 Tue, 12 Apr 2011 23:00:00 +0100 4759413 http://www.medworm.com/index.php?rid=4759414&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21504789%26dopt%3DAbstract Authors: Ho PC, Chuang YS, Hung CH, Wei LN Receptor-interacting protein 140 (RIP140) is abundantly expressed in mature adipocyte and modulates gene expression involved in lipid and glucose metabolism. Protein kinase C epsilon and protein arginine methyltransferase 1 can sequentially stimulate RIP140 phosphorylation and then methylation, thereby promoting its export to the cytoplasm. Here we report a lipid signal triggering cytoplasmic accumulation of RIP140, and a new functional role for cytoplasmic RIP140 in adipocyte to regulate lipolysis. Increased lipid content, particularly an elevation in diacylglycerol levels, promotes RIP140 cytoplasmic accumulation and increased association with lipid droplets (LDs) by its direct interaction with perilipin. By interacting with RIP140, perilipi... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4759414 Fri, 08 Apr 2011 23:00:00 +0100 4759414 http://www.medworm.com/index.php?rid=4759416&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21447383%26dopt%3DAbstract In conclusion this study points to RGS2 as being an important regulatory factor in controlling body weight and adipose function. PMID: 21447383 [PubMed - as supplied by publisher] (Source: Cellular Signalling) Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4759416 Mon, 04 Apr 2011 23:00:00 +0100 4759416 http://www.medworm.com/index.php?rid=4759415&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21447384%26dopt%3DAbstract Authors: Bergström Lind S, Artemenko KA, Elfineh L, Mayrhofer C, Zubarev RA, Bergquist J, Pettersson U Tyrosine phosphorylation (pTyr) regulates important cell functions and plays a key role in carcinogenesis. The purpose of this study was to perform a comprehensive study of the phosphotyrosine proteome. Immunoaffinity enriched pTyr proteins and peptides from K562 leukemia cells were analyzed with high-resolving liquid chromatography mass spectrometry. Two different antibodies selective for the pTyr modification were used in repeated enrichments to identify as many pTyr peptides as possible. Stringent verification of putative pTyr sites was performed to assure high reliability in the subsequent biological interpretation of the data. Identified pTyr proteins were subjected to pathway a... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4759415 Mon, 04 Apr 2011 23:00:00 +0100 4759415 http://www.medworm.com/index.php?rid=4759417&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443947%26dopt%3DAbstract We report here that the AtoSC signal transduction is inhibited by established histidine kinase inhibitors. Closantel, RWJ-49815 and TNP-ATP belonging to different chemical classes of inhibitors, abrogated the in vitro AtoS kinase autophosphorylation. However, when AtoS was embedded in the membrane fractions, higher inhibitor concentrations were required for total inhibition. When AtoS interacted with AtoC forming complex, the intrinsic histidine kinase was protected by the response regulator, requiring increased inhibitors concentrations for partially AtoS autophosphorylation reduction. The inhibitors exerted an additional function on AtoSC, blocking the phosphotransfer from AtoS to AtoC, without however, affecting AtoC~P dephosphorylation. Their in vivo consequences through the AtoSC inhi... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4759417 Sat, 02 Apr 2011 23:00:00 +0100 4759417 http://www.medworm.com/index.php?rid=4649709&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21419846%26dopt%3DAbstract Authors: Mahankali M, Peng HJ, Cox D, Gomez-Cambronero J Membrane protrusion or ruffling is the formation of actin rich membrane protrusions, essential for cell motility. The exact mechanism of ruffling is not fully known. Using YFP and CFP fluorescent chimeras, we show for the first time a co-localization of Phospholipase D2 (PLD2) and Growth factor Receptor Bound protein-2 (Grb2) with actin-rich membrane protrusions of macrophages. Grb2 cooperates with PLD2 in enhancing membrane ruffling, whether in resting cells or in cells stimulated with the growth factor M-CSF, although in the latter an increase in dorsal ruffles was observed, consistent with receptor-ligand internalization. Cells transfected with PLD2 mutated in the PH domain (Y169F) or with Grb2 mutated in the SH2 site (R86K) n... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649709 Thu, 24 Mar 2011 00:00:00 +0100 4649709 http://www.medworm.com/index.php?rid=4649704&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21440619%26dopt%3DAbstract Authors: Liu S, Yuan Q, Zhao S, Wang J, Guo Y, Wang F, Zhang Y, Liu Q, Zhang S, Ling EA, Hao A Diabetic-induced neural tube defects in embryos are caused by apoptosis of neural progenitor cells (NPCs); however, the underlying mechanisms are poorly understood. The present study is aimed to investigate the specific cellular proteins that may be involved in apoptosis of NPCs. We show here that hyperglycemia-induced apoptosis of NPCs was through a PKCδ-dependent mechanism. Tyrosine phosphorylation of PKCδ was required for PKCδ binding to c-Abl in the cytoplasm, and inhibition of c-Abl by STI571 or knock-down of c-Abl by RNAi decreased the phosphorylation of PKCδ. Moreover, translocation of PKCδ and c-Abl complex from the cytoplasm to the nucleus, was blocked by down-regulation of PKCÎ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649704 Thu, 24 Mar 2011 00:00:00 +0100 4649704 http://www.medworm.com/index.php?rid=4649703&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21440620%26dopt%3DAbstract Authors: Jastrzebski K, Hannan KM, House CM, Hung SS, Pearson RB, Hannan RD S6K1, a critical downstream substrate of mTORC1, has been implicated in regulating protein synthesis and a variety of processes that impinge upon cell growth and proliferation. While the role of the cytoplasmic p70(S6K1) isoform in the regulation of translation has been intensively studied, the targets and function of the nuclear p85(S6K1) isoform remain unclear. Therefore, we carried out a phospho-proteomic screen to identify novel p85(S6K1) substrates. Four novel putative p85(S6K1) substrates, GRP75, CCTβ, PGK1 and RACK1, and two mTORC1 substrates, ANXA4 and PSMA6 were identified, with diverse roles in chaperone function, ribosome maturation, metabolism, vesicle trafficking and the proteasome, respectively. ... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649703 Thu, 24 Mar 2011 00:00:00 +0100 4649703 http://www.medworm.com/index.php?rid=4649702&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21440621%26dopt%3DAbstract Authors: Grinstein E, Mahotka C, Borkhardt A Retinoblastoma protein (Rb) controls cell proliferation, differentiation, survival and gene expression and it has a central role in the signaling network that provides a cell cycle checkpoint in the G1 phase of the cell cycle. Studies in mice have shown that Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment and it acts as a critical regulator of hematopoietic stem and progenitor cells under stress. In human hematopoiesis, the CD34 protein is expressed on a subset of progenitor cells capable of self-renewal, multilineage differentiation, and hematopoietic reconstitution, and CD34 has a role in differentiation of hematopoietic cells. Here we find that, in CD34-positive hematopoietic cells, Rb con... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649702 Thu, 24 Mar 2011 00:00:00 +0100 4649702 http://www.medworm.com/index.php?rid=4649701&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21440622%26dopt%3DAbstract In this study we examined the effects of proteasome inhibitors on cell apoptosis in TRAIL-resistant glioma cells and glioma stem cells (GSCs). Treatment with proteasome inhibitors and TRAIL induced apoptosis in all the resistant glioma cells and GSCs, but not in astrocytes and neural progenitor cells. Since PKCε has been implicated in the resistance of glioma cells to TRAIL, we examined its role in TRAIL and proteasome inhibitor-induced apoptosis. We found that TRAIL did not induce significant changes in the expression of PKCε, whereas a partial decrease in PKCε expression was obtained by proteasome inhibitors. A combined treatment of TRAIL and proteasome inhibitors induced accumulation of the catalytic fragment of PKCε and significantly and selectively decreased its protein and mRNA l... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649701 Thu, 24 Mar 2011 00:00:00 +0100 4649701 http://www.medworm.com/index.php?rid=4649705&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21440060%26dopt%3DAbstract Authors: Jeon H, Kwak D, Noh J, Lee MN, Lee CS, Suh PG, Ryu SH Phospholipase D (PLD) is involved in diverse cellular processes including cell movement, adhesion, and vesicle trafficking through cytoskeletal rearrangements. However, the mechanism by which PLD induces cytoskeletal reorganization is still not fully understood. Here, we describe a new link to cytoskeletal changes that is mediated by PLD2 through direct nucleotide exchange on RhoA. We found that PLD2 induces RhoA activation independent of its lipase activity. PLD2 directly interacted with RhoA, and the PX domain of PLD2 specifically recognized nucleotide-free RhoA. Finally, we found that the PX domain of PLD2 has guanine nucleotide-exchange factor (GEF) activity for RhoA in vitro. In addition, we verified that overexpressio... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649705 Wed, 23 Mar 2011 00:00:00 +0100 4649705 http://www.medworm.com/index.php?rid=4649710&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406225%26dopt%3DAbstract Authors: Haeusgen W, Herdegen T, Waetzig V c-Jun N-terminal kinases (JNKs) are the exclusive downstream substrates of mitogen-activated protein kinase kinase 7 (MKK7). Recently, we have shown that a single MKK7 splice variant, MKK7γ1, substantially changes the functions of JNKs in naïve PC12 cells. Here we provide evidence that MKK7γ1 blocks NGF-mediated differentiation and sustains proliferation by interfering with the NGF-triggered differentiation programme at several levels: (i) down-regulation of the NGF receptors TrkA and p75; (ii) attenuation of the differentiation-promoting pathways ERK1/2 and AKT; (iii) increase of JNK1 and JNK2, especially the JNK2 54kDa splice variants; (iv) repression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1), which normally supports NGF-med... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649710 Tue, 22 Mar 2011 00:00:00 +0100 4649710 http://www.medworm.com/index.php?rid=4649714&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402149%26dopt%3DAbstract Authors: Breckler M, Berthouze M, Laurent AC, Crozatier B, Morel E, Lezoualc'h F Epac proteins respond to the second messenger cyclic AMP (cAMP) and are activated by Gs coupled receptors. They act as specific guanine nucleotide exchange factors (GEFs) for the small G proteins, Rap1 and Rap2 of the Ras family. A plethora of studies using 8-pCPT-2'-O-Me-cAMP, an Epac agonist, has revealed the importance of these multi-domain proteins in the control of key cellular functions such as cell division, migration, growth and secretion. Epac and protein kinase A (PKA) may act independently but are often associated with the same biological process, in which they fulfill either synergistic or opposite effects. In addition, compelling evidence is now accumulating about the formation of molecular co... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649714 Mon, 21 Mar 2011 00:00:00 +0100 4649714 http://www.medworm.com/index.php?rid=4649706&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21435393%26dopt%3DAbstract Authors: Müller G, Schneider M, Biemer-Daub G, Wied S Small microvesicles, such as microparticles and exosomes, have been demonstrated to transfer proteins and nucleic acids from a variety of donor to acceptor cells with corresponding (patho)physiological consequences. Recently the in vitro transfer of glycosylphosphatidylinositol (GPI)-anchored proteins from microvesicles released from large rat adipocytes to intracellular lipid droplets (LD) of small adipocytes has been shown to be upregulated by physiological (palmitate, H(2)O(2)) and pharmacological (anti-diabetic sulfonylurea drug glimepiride) stimuli and to increase the esterification into as well as to reduce the release of fatty acids from triacylglycerol. Here microvesicles derived from (preferentially large) rat adipocytes o... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649706 Mon, 21 Mar 2011 00:00:00 +0100 4649706 http://www.medworm.com/index.php?rid=4649713&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402150%26dopt%3DAbstract Authors: Suarez A, Huber R, Myre M, O'Day DH CyrA is a novel cysteine-rich protein with four EGFL repeats that was isolated using the calmodulin (CaM) binding overlay technique (CaMBOT), suggesting it is a CaM-binding protein (CaMBP). The full-length 63kDa cyrA is cleaved into two major C-terminal fragments, cyrA-C45 and cyrA-C40. A putative CaM-binding domain was detected and both CaM-agarose binding and CaM immunoprecipitation verified that cyrA-C45 and cyrA-C40 each bind to CaM in both a Ca(2+)-dependent and -independent manner. cyrA-C45 was present continuously throughout growth and development but was secreted at high levels during the multicellular slug stage of Dictyostelium development. At this time, cyrA localizes to the extracellular matrix (ECM). ECM purification verified th... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649713 Sat, 19 Mar 2011 00:00:00 +0100 4649713 http://www.medworm.com/index.php?rid=4649711&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402152%26dopt%3DAbstract Authors: Reiterer V, Grossniklaus L, Tschon T, Kasper CA, Sorg I, Arrieumerlou C Shigella flexneri type III secreted effector OspF harbors a phosphothreonine lyase activity that irreversibly dephosphorylates MAP kinases (MAPKs) p38 and ERK in infected epithelial cells and thereby, dampens innate immunity. Whereas this activity has been well characterized, the impact of OspF on other host signaling pathways that control inflammation was unknown. Here we report that OspF potentiates the activation of the MAPK JNK and the transcription factor NF-κB during S. flexneri infection. This unexpected effect of OspF was dependent on the phosphothreonine lyase activity of OspF on p38, and resulted from the disruption of a negative feedback loop regulation between p38 and TGF-beta activated kinase... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649711 Sat, 19 Mar 2011 00:00:00 +0100 4649711 http://www.medworm.com/index.php?rid=4649708&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21426932%26dopt%3DAbstract Authors: Das F, Dey N, Venkatesan B, Kasinath BS, Ghosh-Choudhury N, Choudhury GG The Akt kinase signaling pathway is frequently deregulated in many human diseases including cancer, autoimmune disease and diabetes. In nephropathy, associated with diabetes, increased Akt signal transduction results in glomerular especially mesangial cell hypertrophy. The mechanism of Akt activation by elevated glucose is poorly understood. The oncogene DJ-1 prevents oxidative damage and apoptosis of dopaminergic neurons in animal models of Parkinson's disease and in culture. We identified DJ-1 to increase in response to high glucose in renal glomerular mesangial cells concomitant with an increase in phosphorylation of Akt in a time-dependent manner. Plasmid-derived overexpression as well as downregulati... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649708 Sat, 19 Mar 2011 00:00:00 +0100 4649708 http://www.medworm.com/index.php?rid=4649707&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21426933%26dopt%3DAbstract Authors: Nalla AK, Gogineni VR, Gupta R, Dinh DH, Rao JS Chemokines play a vital role in recruiting various cell types in the process of tissue repair. Radiation, a major therapeutic modality in cancer treatment, has been described to induce inflammatory response that might lead to the expression of several chemokines. In the present study, we investigated the mechanism of monocyte chemoattractant protein-1 (MCP-1) induction by radiation in meningioma cell lines and the paracrine effect on human microvascular endothelial cells (HMEC). After radiation, meningioma cell lines (IOMM Lee and SF-3061) showed an increased expression of MCP-1. In addition, irradiated meningioma cancer cell conditioned medium (CM) showed increased ability to attract HMEC and stimulate MCP-1-induced protein (MCP... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649707 Sat, 19 Mar 2011 00:00:00 +0100 4649707 http://www.medworm.com/index.php?rid=4649712&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402151%26dopt%3DAbstract Authors: Yuasa K, Matsuda T, Tsuji A The cGMP/cGMP-dependent protein kinase (cGK) signaling pathway is implicated in the functional regulation of intracellular calcium levels. In the present study, we investigated the regulation of transient receptor potential canonical 7 (TRPC7) by the cGMP/cGK-I pathway. TRPC7 contains three putative cGK phosphorylation sites (Arg-Arg/Lys-Xaa-Ser/Thr). However, the role of cGK-I in the regulation of TRPC7 activity remains unclear. In vitro and in vivo kinase assays have revealed that cGK-Iα phosphorylates mouse TRPC7 but not mouse TRPC3. Site-directed mutagenesis analysis revealed that TRPC7 was phosphorylated by cGK-Iα at threonine 15. Phosphorylation of TRPC7 significantly suppressed carbachol-induced calcium influx and CREB phosphorylation. Furt... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4649712 Thu, 17 Mar 2011 00:00:00 +0100 4649712 http://www.medworm.com/index.php?rid=4530475&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21345368%26dopt%3DAbstract Authors: Ren J, Singh BN, Huang Q, Li Z, Gao Y, Mishra P, Hwa YL, Li J, Dowdy SC, Jiang SW Epigenetics refers to partially reversible, somatically inheritable, but DNA sequence-independent traits that modulate gene expression, chromatin structure, and cell functions such as cell cycle and apoptosis. DNA methylation is an example of a crucial epigenetic event; aberrant DNA methylation patterns are frequently found in human malignancies. DNA hypermethylation and the associated expression silencing of tumor suppressor genes represents a hallmark of neoplastic cells. The cancer methylome is highly disrupted, making DNA methylation an excellent target for anticancer therapies. Several small synthetic and natural molecules, are able to reverse the DNA hypermethylation through inhibition of D... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4530475 Sun, 20 Feb 2011 00:00:00 +0100 4530475 http://www.medworm.com/index.php?rid=4530474&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21345369%26dopt%3DAbstract Authors: Banerjee R, Henson BS, Russo N, Tsodikov A, D'Silva NJ Previously we showed that galanin, a neuropeptide, is secreted by human squamous cell carcinoma of the head and neck (SCCHN) in which it exhibits an autocrine mitogenic effect. We also showed that rap1, a ras-like signaling protein, is a critical mediator of SCCHN progression. Given the emerging importance of the galanin cascade in regulating proliferation and survival, we investigated the effect of GAL on SCCHN progression via induction of galanin receptor 2 (GALR2)-mediated rap1 activation. Studies were performed in multiple SCCHN cell lines by inducing endogenous GALR2, by stably overexpressing GALR2 and by downregulating endogenous GALR2 with siGALR2. Cell proliferation and survival, mediated by the ERK and AKT signali... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4530474 Sun, 20 Feb 2011 00:00:00 +0100 4530474 http://www.medworm.com/index.php?rid=4530476&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21342664%26dopt%3DAbstract Authors: Dovas A, Cox D Podosomes are ventral adhesion structures prominent in cells of the myeloid lineage. A common aspect of these cells is that they are highly motile and are required to traverse multiple tissue barriers in order to perform their functions. Recently podosomes have gathered attention from researchers as important cellular structures that can influence cell adhesion, motility and matrix remodeling. Adhesive and soluble ligands act via transmembrane receptors and propagate signals to the leukocyte cytoskeleton via small G proteins of the Rho family, tyrosine kinases and scaffold proteins and are able to induce podosome formation and rearrangements. Manipulation of the signals that regulate podosome formation and dynamics can therefore be a strategy to interfere with l... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4530476 Sat, 19 Feb 2011 00:00:00 +0100 4530476 http://www.medworm.com/index.php?rid=4530477&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21329754%26dopt%3DAbstract Authors: Zhang Y, Zhang L, Wang F, Zhang Y, Wang J, Qin Z, Jiang X, Tao J Cobrotoxin (CbT), a short-chain postsynaptic α-neurotoxin, has been reported to play a role in analgesia. However, to date, the detailed mechanisms still remain unknown. In the present study, we identify a novel functional role of CbT in modulating T-type Ca(2+) channel currents (T-currents) in small dorsal root ganglia (DRG) neurons as well as pain behaviors in mice. We found that CbT inhibited T-currents in a dose-dependent manner. CbT at 1μM reversibly inhibited T-currents by ~26.3%. This inhibitory effect was abolished by the non-selective muscarinic acetylcholine receptor (mAChR) antagonist atropine, or the selective M3 mAChR antagonist 4-DAMP, while naloxone, an opioid receptor antagonist had no effect. I... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4530477 Tue, 15 Feb 2011 00:00:00 +0100 4530477 http://www.medworm.com/index.php?rid=4475646&cid=s_35396_171_f&fid=35396&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21300149%26dopt%3DAbstract Authors: Zheng W, Lennartsson J, Hendriks W, Heldin CH, Hellberg C The receptor tyrosine phosphatase (RPTP) LAR negatively regulates the activity of several receptor tyrosine kinases. To investigate if LAR affects the platelet-derived growth factor (PDGF) receptor signaling, mouse embryonic fibroblasts (MEFs) from mice where the LAR phosphatase domains were deleted (LARΔP), and wt littermates, were stimulated with 20ng/ml PDGF-BB. In LAR phosphatase deficient MEFs, the phosphorylation of the PDGF β-receptor was surprisingly reduced, an event that was rescued by re-expression of wt LAR. The decreased phosphorylation of the PDGF β-receptor was observed independent of ligand concentration and occurred on all tyrosine residues, as determined by immunoblotting analysis using site-selecti... Cellular Signalling journals http://www.medworm.com/rss/comments.php?id=4475646 Fri, 04 Feb 2011 00:00:00 +0100 4475646