Cellular SignallingThis is an RSS file. You can use it to subscribe to this data in your favourite RSS reader, such as GoogleReader, or to display this data on your own website or blog. Subscribe to this data using MyMedWorm.Subscribe to this data using GoogleReader.Subscribe to this data using Bloglines.Subscribe to this data using MyYahoo.

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406 records returned

A role for the phosphatidylinositol 3-kinase - protein kinase C zeta - Sp1 pathway in the 1,25-dihydroxyvitamin D3 induction of the 25-hydroxyvitamin D3 24-hydroxylase gene in human kidney cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The molecular mechanisms that underlie non-genomic induction of the 25-hydroxyvitamin D3 24-hydroxylase (CYP24) gene promoter by the steroid hormone, 1,25-Dihydroxyvitamin D3 (1,25D), are poorly understood. Although we have previously identified a functional inverted GC-box in the early promoter at -113/-105 bp, it is not known whether this site is important for 1,25D induction of the promoter. Using transfected human embryonic kidney (HEK) 293T cells, we now report the functional characterisation of the GC box and that 1,25D induction of the promoter requires PI3-kinase, PKCzeta and Sp1 but not Sp3. The data show that...
Source: Cellular Signalling - November 13, 2009 Category: Cytology Authors: Dwivedi PP, Gao XH, Tan JC, Evdokiou A, Ferrante A, Morris HA, May BK, Hii CS Tags: Cell Signal Source Type: journals

Effects of angiopoietins-1 and -2 on the receptor tyrosine kinase tie2 are differentially regulated at the endothelial cell surface.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study we have investigated binding of Ang1 and Ang2 to Tie2 in endothelial cells. In contrast to Ang1, binding of Ang2 to Tie2 was found to be not affected by Tie1. Neither PMA-induced Tie1 ectodomain cleavage nor suppression of Tie1 expression by siRNA affected the ability of Ang2 to bind Tie2. Analysis of the level of Tie1 co-immunoprecipitating with angiopoietin-bound Tie2 demonstrated that Ang2 can bind Tie2 in Tie2:Tie1 complexes whereas Ang1 preferentially binds non-complexed Tie2. Stimulation of Tie1 ectodomain cleavage did not increase the agonist activity of Ang2 for Tie2. Similarly, the Tie2-agonist activ...
Source: Cellular Signalling - November 13, 2009 Category: Cytology Authors: Hansen TM, Singh H, Tahir TA, Brindle NP Tags: Cell Signal Source Type: journals

Serotonin 4 receptor (5-HT4R) internalization is isoform-specific: Effects of 5-HT and RS67333 on isoforms A and B.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Serotonin 4 receptors (5-HT4Rs) are particularly abundant within the limbic system, where they constitute potential targets for the development of novel, rapid acting antidepressants. However, the population of limbic 5-HT4Rs is not homogenous, comprising various isoforms of which 5-HT4(a) and 5-HT4(b) are among the most abundant variants. Sequence divergence at their C-termini is predictive of specificity in isoform signalling and regulation, but the differences, if any, remain ill-defined. The present study compared isoforms 5-HT4(a) and 5-HT4(b) in their ability to undergo endocytic regulation following exposure to ...
Source: Cellular Signalling - November 13, 2009 Category: Cytology Authors: Mnie-Filali O, Amraei MG, Benmbarek S, Archer-Lahlou E, Peñas-Cazorla R, Vilaró MT, Boye SM, Piñeyro G Tags: Cell Signal Source Type: journals

PPARgamma regulates LIF-induced growth and self-renewal of mouse ES cells through Tyk2-Stat3 pathway.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study we demonstrate that the PPARgamma antagonist Bisphenol A diglycidyl ether (BADGE) and 2-Chloro-5-nitro-N-(4-pyridyl)benzamide (T0070907) reverse the inhibition of ES cell proliferation by PPARgamma agonists. Stable transfection of ES cells with a dominant negative PPARgamma1 mutant also reduced the inhibition of proliferation by PPARgamma agonists. While 15d-PGJ2 and ciglitazone induced growth-arrest in ES cells by blocking LIF signaling, PPARgamma antagonists and dominant negative PPARgamma1 mutant reversed proliferation by restoring LIF-induced Tyk2-Stat3 signaling. These results suggest that PPARgamma regu...
Source: Cellular Signalling - November 13, 2009 Category: Cytology Authors: Mo C, Chearwae W, Bright JJ Tags: Cell Signal Source Type: journals

Impaired TNF-alpha Control of IP(3)R-mediated Ca(2+) Release in Alzheimer's Disease Mouse Neurons TNF-alpha signaling in 3xTg-AD neurons.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The misguided control of inflammatory signaling has been previously implicated in the pathogenesis of several neurological disorders, including Alzheimer's disease (AD). Induction of tumor necrosis factor-alpha (TNF-alpha), a central mediator of neuroinflammation, occurs commensurate with the onset of early disease in 3xTg-AD mice, which develop both amyloid plaque and neurofibrillary tangle pathologies in an age- and region-dependent pattern. Herein, we describe regulation inherent to 3xTg-AD neurons, which results in the loss of TNF-5 mediated enhancement of inositol 1,4,5 trisphosphate (IP(3)R)-mediated Ca(2+) relea...
Source: Cellular Signalling - November 13, 2009 Category: Cytology Authors: Park KM, Yule DI, Bowers WJ Tags: Cell Signal Source Type: journals

Lysophosphatidic acid induces upregulation of Mcl-1 and protects apoptosis in a PTX-dependent manner in H19-7 cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lysophosphatidic acid (LPA) is a lipid growth factor known to regulate diverse cell functions, including cell proliferation, survival, and apoptosis. Tight regulation of cell survival in neuronal precursor is essential during neurogenesis in both developing and adult brain. Increasing data show that diverse external factors including LPA play roles in controlling cell survival and apoptosis in early developing neurons. However, underlying control mechanism remains unclear. To explore how LPA regulates cell survival or apoptosis in developing neuron, mechanism for cell survival and signaling cascades by LPA were investi...
Source: Cellular Signalling - November 10, 2009 Category: Cytology Authors: Sun Y, Nam JS, Han DH, Kim NH, Choi HK, Lee JK, Rhee HJ, Huh SO Tags: Cell Signal Source Type: journals

Enhanced Ca(2+) storage in sphingosine-1-phosphate lyase-deficient fibroblasts.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sphingosine-1-phosphate (S1P) regulates cell growth and survival, migration and adhesion in many cell types. S1P is generated by sphingosine kinases (SphKs), and dephosphorylated by phosphatases or cleaved by S1P lyase. Extracellular S1P activates specific G protein-coupled receptors while intracellular S1P can mobilize Ca(2+) from thapsigargin-sensitive stores. Here, we have studied Ca(2+) signalling in mouse embryonic fibroblasts (MEFs) deficient in S1P lyase. In these cells, S1P and sphingosine concentrations were elevated about 6-fold and 2-fold, respectively, as measured by liquid chromatography/tandem mass spectr...
Source: Cellular Signalling - November 10, 2009 Category: Cytology Authors: Claas RF, Ter Braak M, Hegen B, Hardel V, Angioni C, Schmidt H, Jakobs KH, Van Veldhoven PP, Heringdorf DM Tags: Cell Signal Source Type: journals

Caspase-8-mediated cleavage of Bid and Protein Phosphatase 2A-mediated activation of Bax are necessary for Verotoxin-1-induced apoptosis in Burkitt's lymphoma cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this report, we provide new insights into this signal transduction pathway. First, we demonstrate that VT-1-induced apoptosis requires degradation of the caspase-8 inhibitory molecule c-FLIP(L) and that this degradation occurs through the ubiquitin-proteasome pathway. Furthermore, we show that mitochondrial activation is mainly due to i) cleavage and activation of the pro-apoptotic Bcl-2 family member Bid by caspase-8 and ii) Bax relocalization to mitochondrial membranes which lead to cytochrome c release. However, tBid is not involved in Bax relocalization, and relocalization is most likely controlled by the extent of ...
Source: Cellular Signalling - November 3, 2009 Category: Cytology Authors: Garibal J, Hollville E, Renouf B, Tétaud C, Wiels J Tags: Cell Signal Source Type: journals

Fps/Fes protein-tyrosine kinase regulates mast cell adhesion and migration downstream of Kit and beta1 integrin receptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we show that SCF induces transient tyrosine phosphorylation of wild-type Fes as well as kinase-dead Fes in bone marrow-derived mast cells (BMMCs). The latter finding implicates an upstream kinase acting on Fes, which we identified as Fyn PTK. SCF treatment of BMMCs promoted recruitment of Fes to Kit, potentially via direct interaction of the Fes SH2 domain with phosphorylated Kit. While Fes was not required for SCF-induced signaling to Akt and Erk kinases, Fes-deficient (fes-/-) BMMCs displayed a defect in sustained p38 kinase activation, compared to control cells. SCF treated Fes-deficient BMMCs also displa...
Source: Cellular Signalling - November 2, 2009 Category: Cytology Authors: Smith JA, Samayawardhena LA, Craig AW Tags: Cell Signal Source Type: journals

A non-catalytic function of the Src family tyrosine kinases controls prolactin-induced Jak2 signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The cytokine prolactin (PRL) plays important roles in the proliferation and differentiation of the mammary gland and it has been implicated in tumorigenesis. The prolactin receptor (PRLR) is devoid of catalytic activity and its mitogenic response is controlled by cytoplasmic tyrosine kinases of the Src (SFK) and Jak families. How PRLR uses these kinases for signaling is not well understood. Previous studies indicated that PRLR-induced Jak2 activation does not required SFK catalytic activity in favor of separate signaling operating on this cellular response. Here we show that, nevertheless, PRLR requires Src-SH2 and -SH...
Source: Cellular Signalling - November 2, 2009 Category: Cytology Authors: García-Martínez JM, Calcabrini A, González L, Martín-Forero E, Agulló-Ortuño MT, Simon V, Watkin H, Anderson SM, Roche S, Martín-Pérez J Tags: Cell Signal Source Type: journals

Distinct roles for Mitogen Activated Protein Kinase Phosphatase-1 (MKP-1) and ERK-MAPK in PTH1R signaling during osteoblast proliferation and differentiation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study we investigate the role of MAPK phosphatase-1 (MKP-1) in PTHrP regulation of ERK1/2 activity in relation to osteoblast proliferation, differentiation and bone formation. Here we show that PTHrP increases MKP-1 expression in differentiated osteoblastic MC3T3-E1 cells, primary cultures of differentiated bone marrow stromal cells (BMSCs) and calvarial osteoblasts. PTHrP had no effect on MKP-1 expression in proliferating osteoblastic cells. Overexpression of MKP-1 in MC-4 cells inhibited osteoblastic cell proliferation. Cell extracts from differentiated MC-4 cells treated with PTHrP inactivate/dephosphorylate pER...
Source: Cellular Signalling - November 2, 2009 Category: Cytology Authors: Datta NS, Kolailat R, Fite A, Pettway G, Abou-Samra AB Tags: Cell Signal Source Type: journals

GPCR signalling to the translation machinery.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of this review paper is to address the following questions: i/ is there as "GPCR signature" impacting on the translational machinery, and ultimately on the type of mRNA translated? ii/ are the regulatory networks involved similar as those utilized by tyrosine kinase receptors? In particular, we will discuss the specific features of translational control mediated by GPCRs and highlights the intrinsic properties of GPCRs these mechanisms could rely on. PMID: 19887105 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - October 31, 2009 Category: Cytology Authors: Musnier A, Blanchot B, Reiter E, Crépieux P Tags: Cell Signal Source Type: journals

Light-dependent translocation of arrestin in rod photoreceptors is signaled through a phospholipase C cascade and requires ATP.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we demonstrate that components of the G-protein-linked phospholipase C (PLC) pathway play a role in initiating arrestin translocation. Our results show that arrestin translocation can be stimulated by activators of PLC and protein kinase C (PKC), and by cholera toxin in the absence of light. Arrestin translocation to the outer segments is significantly reduced by inhibitors of PLC and PKC. Importantly, we find that treatment with potassium cyanide inhibits arrestin translocation in response to light. Collectively, our results suggest that arrestin translocation is initiated by a G-protein- coupled cascade th...
Source: Cellular Signalling - October 31, 2009 Category: Cytology Authors: Orisme W, Li J, Goldmann T, Bolch S, Wolfrum U, Smith WC Tags: Cell Signal Source Type: journals

EGF-induced tyrosine phosphorylation of Endofin is dependent on PI3K activity and proper localization to endosomes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In our previous study, Endofin was validated to be a novel tyrosine phosphorylation target downstream of EGFR. Here, we attempted to map the signaling events associated with Endofin following activation of EGFR with EGF. Tyrosine phosphorylation of endogenous Endofin peaked around 15minutes and was modulated within 30minutes of EGF treatment. Phosphatidylinositol 3-kinase (PI3K) activity and FYVE domain-mediated localization of Endofin to EEA1-marked endosomes were shown to be necessary for the tyrosine phosphorylation of Endofin. Tyrosine 515 was mapped to be a major phosphorylation site on Endofin but disruption of p...
Source: Cellular Signalling - October 31, 2009 Category: Cytology Authors: Toy W, Lim SK, Shia ML, Lim YP Tags: Cell Signal Source Type: journals

Dual Function of Cysteine Rich Domain (CRD) 1 of TNF Receptor Type 1: Conformational Stabilization of CRD2 and Control of Receptor Responsiveness.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The proinflammatory cytokine Tumor Necrosis Factor (TNF) exists as a homotrimer, capable of binding three receptor molecules. However, signal competent ligand/receptor complexes form large clusters, likely to be stabilized by additional molecular interactions. Both TNF receptors, TNFR1 and TNFR2, contain four cysteine rich domains (CRD) in their extracellular parts. Previous work showed that the membrane distal CRD1 carries a homophilic interaction domain. Here, we investigated the functional role of CRD1 and its two submodules, A1(CRD1) and B2(CRD1), in a TNFR1-Fas chimera model system. Removal of CRD1 abolishes TNF b...
Source: Cellular Signalling - October 28, 2009 Category: Cytology Authors: Branschädel M, Aird A, Zappe A, Tietz C, Krippner-Heidenreich A, Scheurich P Tags: Cell Signal Source Type: journals

Non-T cell activation linker regulates ERK activation in Helicobacter pylori-infected epithelial cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It is supposed that human pathogens, e.g. Helicobacter pylori abuse lipid raft domains on the host cell plasma membrane to infect the cell. Investigating DRM-associated molecules we identified the transmembrane adapter proteins (TRAPs), non-T cell activation linker (NTAL) and lymphocyte-specific protein tyrosine kinase (Lck)-interacting membrane protein (LIME) to be regulated by H. pylori in the human epithelial cell line HCA-7. Up to now, raft-associated TRAPs were exclusively described to mediate signal propagation downstream of antigen receptors. Our results posed the question whether these proteins adopt a role in ...
Source: Cellular Signalling - October 28, 2009 Category: Cytology Authors: Rieke C, Kähne T, Schweitzer K, Schraven B, Wienands J, Engelke M, Naumann M Tags: Cell Signal Source Type: journals

RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase signalling pathways.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report here that RGS14 is an integrator of G protein and MAPKinase signalling pathways. RGS14 contains a GPR/GoLoco (GL) domain that forms a stable complex with inactive Gialpha1/3-GDP, and a tandem (R1, R2) Ras binding domain (RBD). We find that RGS14 binds and regulates the subcellular localization and activities of H-Ras and Raf kinases in cells. Activated H-Ras binds RGS14 at the R1 RBD to form a stable complex at cell membranes. RGS14 also co-localizes with and forms a complex with Raf kinases in cells. The regulatory region of Raf-1 binds the RBD region of RGS14, and H-Ras and Raf each facilitate one another's bin...
Source: Cellular Signalling - October 27, 2009 Category: Cytology Authors: Shu FJ, Ramineni S, Hepler JR Tags: Cell Signal Source Type: journals

Transdominant regulation of integrin function: Mechanisms of crosstalk.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe how the interaction of talin and the cytoplasmic tail of beta integrin is controlled and how competitive inhibitors of this binding play a role in integrin crosstalk. We conclude with a discussion of how integrin crosstalk impacts the interpretation of integrin inhibitor and knockdown studies in both the laboratory and clinical setting. PMID: 19874888 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - October 26, 2009 Category: Cytology Authors: Gonzalez AM, Bhattacharya R, Dehart GW, Jones JC Tags: Cell Signal Source Type: journals

USP11 Negatively Regulates TNFalpha-Induced NF-kappaB Activation by Targeting on IkappaBalpha.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
IkappaBalpha serves as a central anchoring molecule in the sequestration of NF-kappaB transcription factor in the cytoplasm. Ubiquitination-mediated IkappaBalpha degradation immediately precedes and is required for NF-kappaB nuclear translocation and activation. However, the precise mechanism for the deubiquitination of IkappaBalpha is still not fully understood. Using a proteomic approach, we have identified Ubiquitin Specific Peptidase 11 (USP11) as an IkappaBalpha associated deubiquitinase. Overexpression of USP11 inhibits IkappaBalpha ubiquitination. Recombinant USP11 catalyzes deubiquitination of IkappaBalpha in v...
Source: Cellular Signalling - October 26, 2009 Category: Cytology Authors: Sun W, Tan X, Shi Y, Xu G, Mao R, Gu X, Fan Y, Yu Y, Burlingame S, Zhang H, Rednam SP, Lu X, Zhang T, Fu S, Cao G, Qin J, Yang J Tags: Cell Signal Source Type: journals

Insulin/IGF-1 paradox of aging: Regulation via AKT/IKK/NF-kappaB signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
GH/insulin/IGF-1 signaling is a vital pathway e.g. in the regulation of protein synthesis and glucose metabolism. However, mouse dwarf strains which exhibit reduced GH secretion and subsequently a decline in IGF-1 signaling can live longer than their wild type counterparts. There is striking evidence indicating that the IGF-1/PI-3K/AKT signaling enhances growth of animals during development but later in life can potentiate the aging process. This conserved pleiotropy has been called the insulin/IGF-1 paradox. In Caenorhabditiselegans, the decline in this pathway activates the DAF-16 gene, an ortholog of mammalian FoxO ...
Source: Cellular Signalling - October 26, 2009 Category: Cytology Authors: Salminen A, Kaarniranta K Tags: Cell Signal Source Type: journals

Oxygen-sensing under the influence of nitric oxide.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The transcription factor complex Hypoxia inducible factor 1 (HIF-1) controls the expression of most genes involved in adaptation to hypoxic conditions. Oxygen-dependency is maintained by prolyl- and asparagyl-4-hydroxylases (PHDs/FIH-1) belonging to the superfamily of iron(II) and 2-oxoglutarate dependent dioxygenases. Hydroxylation of the HIF-1alpha subunit by PHDs and FIH-1 leads to its degradation and inactivation. By hydroxylating HIF-1alpha in an oxygen-dependent manner PHDs and FIH-1 function as oxygen-sensing enzymes of HIF signalling. Besides molecular oxygen nitric oxide (NO), a mediator of the inflammatory re...
Source: Cellular Signalling - October 24, 2009 Category: Cytology Authors: Berchner-Pfannschmidt U, Tug S, Kirsch M, Fandrey J Tags: Cell Signal Source Type: journals

Modulation of Immune Cell Signalling by the Leukocyte Common Tyrosine Phosphatase, CD45.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CD45 is a leukocyte specific transmembrane glycoprotein and a receptor like protein tyrosine phosphatase (PTP). CD45 can be expressed as several alternatively spliced isoforms that differ in the extracellular domain. The isoforms are regulated in a cell type and activation state-dependent manner, yet their function has remained elusive. The Src family kinase members Lck and Lyn are key substrates for CD45 in T and B lymphocytes, respectively. CD45 lowers the threshold of antigen receptor signalling, which impacts T and B cell activation and development. CD45 also regulates antigen triggered FcR signalling in mast cells...
Source: Cellular Signalling - October 24, 2009 Category: Cytology Authors: Saunders AE, Johnson P Tags: Cell Signal Source Type: journals

c-Cbl acts as a mediator of Src-induced activation of the PI3K-Akt signal transduction pathway during TRAIL treatment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we report that Src, c-Cbl, and PI3K are involved in the phosphorylation of Akt during TRAIL treatment. Data from immunoprecipitation and immunblotting assay reveal that Src interacts with c-Cbl and PI3K. Data from immune complex kinase assay demonstrate that Src can directly phosphorylate c-Cbl and PI3K p85 subunit protein. Data from gene knockdown experiments with an RNA interference (RNAi) technique show that c-Cbl is involved in the interaction between Src and PI3K p85 during TRAIL treatment, playing an important role in TRAIL-induced Akt phosphorylation. Taken together, c-Cbl may act as a mediator to reg...
Source: Cellular Signalling - October 24, 2009 Category: Cytology Authors: Song JJ, Kim JH, Sun BK, Alcala MA, Bartlett DL, Lee YJ Tags: Cell Signal Source Type: journals

Differential regulation of map kinase activation by a novel splice variant of human map kinase phosphatase -2.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
MAP kinase phosphatase-2 (MKP-2) is a member of the family of dual specificity phosphatases that functions to inactivate the ERK and JNK MAP kinase signalling pathways. Here, we identify a novel human MKP-2 variant (MKP-2-S) lacking the MAP kinase binding site but retaining the phosphatase catalytic domain. Endogenous MKP-2-S transcripts and proteins were found in PC3 prostate and MDA-MB-231 breast cancer cells and also human prostate biopsies. Cellular transfection of MKP-2-S gave rise to a nuclear protein of 33kDa which displayed phosphatase activity comparable to the formerly described long form of MKP-2 (MKP-2-L). ...
Source: Cellular Signalling - October 16, 2009 Category: Cytology Authors: Cadalbert LC, Sloss CM, Cunningham MR, Al-Mutairi M, McIntire A, Shipley J, Plevin R Tags: Cell Signal Source Type: journals

Rif take to the RhoD: Rho GTPases in the crossroad of actin dynamics and membrane trafficking.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Rif and RhoD proteins belong to the Rho subfamily of small GTPases. Rif and RhoD have for long remained in the shadows of the better known Rho GTPases Cdc42, Rac1 and RhoA. With this review article, our aim is provide the currently available information regarding Rif and RhoD. Taken together, the data available to date indicate that Rif and RhoD have unique roles in the regulation of actin dynamics, and that RhoD can link actin reorganisation to endosomal vesicle transport. PMID: 19818399 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - October 6, 2009 Category: Cytology Authors: Gad AK, Aspenström P Tags: Cell Signal Source Type: journals

Tyrosine 170 is dispensable for c-Jun turnover.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The turnover rate of many transcription factors such as c-Jun, a member of the AP-1 family of transcription factors, is regulated by phosphorylation events. Phosphorylation on serine residues 63 and 73 (S63/73) by the c-Jun-N-terminal kinases (JNKs) regulates c-Jun's turnover, and is critical for its ability to regulate cell death and proliferation. Recently, biochemical evidence indicated that the c-Abl and Csk kinases were able to phosphorylate the tyrosine 170 (Y170) residue of c-Jun - which lies within the recognition motif of the Itch ubiquitin ligase - and also regulate its stability independent of the JNK phosph...
Source: Cellular Signalling - October 5, 2009 Category: Cytology Authors: Xie M, Sabapathy K Tags: Cell Signal Source Type: journals

Endothelin-1 induces p66Shc activation through EGF receptor transactivation: Role of beta(1)Pix/Galpha(i3) interaction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we demonstrate that ET-1-induced serine phosphorylation of p66Shc is mediated through Galpha(i3). Pertussis toxin treatment of cells induced a significant decrease in the interaction between beta(1)Pix and ET(A)-R, and an increase in the binding of Galpha(i3) and G(beta1) to beta(1)Pix. Activation of heterotrimeric G proteins by AlF(4)(-) resulted in an increase of Galpha(i3) binding to beta(1)Pix, which was significantly disrupted in cells expressing beta(1)Pix dimerization deficient mutant, beta(1)PixDelta (602-611). In cells expressing beta(1)PixDelta (602-611), ET-1-induced p66Shc activation was also sig...
Source: Cellular Signalling - October 1, 2009 Category: Cytology Authors: Chahdi A, Sorokin A Tags: Cell Signal Source Type: journals

Structural determinants underlying constitutive dimerization of unoccupied human follitropin receptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The human follitropin receptor (hFSHR) is a G protein-coupled receptor (GPCR) central to reproductive physiology that is composed of an extracellular domain (ECD) fused to a serpentine region. Using bioluminescence resonance energy transfer (BRET) in living cells, we show that hFSHR dimers form constitutively during their biosynthesis. Mutations in TM1 and TM4 had no effect on hFSHR dimerization, alone or when combined with mutation of Tyr(110) in the ECD, a residue predicted to mediate dimerization of the soluble hormone-binding portion of the ECD complexed with FSH (Q. Fan and W. Hendrickson, Nature 433:269-277, 2005...
Source: Cellular Signalling - September 29, 2009 Category: Cytology Authors: Guan R, Wu X, Feng X, Zhang M, Hébert TE, Segaloff DL Tags: Cell Signal Source Type: journals

Enterovirus 71 induces COX-2 expression via MAPKs, NF-kappaB, and AP-1 in SK-N-SH cells: Role of PGE(2) in viral replication.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The enterovirus 71 (EV71) causes severe neurological diseases that were mediated through cyclooxygenase-2 (COX-2) expression in brain. However, the mechanisms underlying EV71-initiated intracellular signaling pathways leading to COX-2 expression remain unknown in neurons. Here we report that exposure of SK-N-SH cells to EV71 increased COX-2 expression and PGE(2) generation in a time- and concentration-dependent manner, revealed by Western blot, real-time PCR, and PGE(2) analyses. These EV71-induced responses were mediated through activation of MEK1/2, p38, JNK, NF-kappaB, and AP-1, revealed by using selective pharmacol...
Source: Cellular Signalling - September 29, 2009 Category: Cytology Authors: Tung WH, Hsieh HL, Yang CM Tags: Cell Signal Source Type: journals

Induction of indoleamine 2, 3-dioxygenase by death receptor activation contributes to apoptosis of melanoma cells via mitochondrial damage-dependent ROS accumulation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although the induction of indoleamine 2, 3-dioxygenase (IDO) by several agents is well established, the mechanisms of its transcriptional regulation and those regulating its function as apoptotic mediator seem to be complex, agent-dependent, and cell type-specific. Besides their pro-apoptotic activity in melanoma cells, both anti-Fas agonist antibody (CH11) and the tumour necrosis factor (TNF)-alpha were found to induce IDO gene expression, the activation of apoptosis signal-regulating kinase (ASK1), and the activation of both c-Jun N-terminal kinase (JNK) and NF-kappaB pathways. In addition, the treatment of melanoma ...
Source: Cellular Signalling - September 28, 2009 Category: Cytology Authors: Cetindere T, Nambiar S, Santourlidis S, Essmann F, Hassan M Tags: Cell Signal Source Type: journals

Cellular signaling of Dock family proteins in neural function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dock180-related proteins are genetically conserved from Drosophila and C. elegans to mammals and are atypical types of guanine-nucleotide exchange factors (GEFs) for Rac and/or Cdc42 of small GTPases of the Rho family. Eleven members of the family occur in mammalian cells, each playing key roles in many aspects of essential cellular functions such as regulation of cytoskeletal organization, phagocytosis, cell migration, polarity formation, and differentiation. This review will summarize the newly accumulated findings concerning the Dock180-related proteins' molecular and cellular functions, emphasizing the roles of the...
Source: Cellular Signalling - September 27, 2009 Category: Cytology Authors: Miyamoto Y, Yamauchi J Tags: Cell Signal Source Type: journals

Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The ectodomain of TOLL-like receptors (TLR) is highly glycosylated with several N-linked gylcosylation sites located in the inner concave surface. The precise role of these sugar N-glycans in TLR receptor activation is unknown. Recently, we have shown that Neu1 sialidase and not Neu2,-3 and-4 forms a complex with TLR-2,-3 and-4 receptors on the cell surface membrane of naïve and activated macrophage cells (Glycoconj J DOI 10.1007/s10719-009-9239-8). Activation of Neu1 is induced by TLR ligands binding to their respective receptors. Here, we show that endotoxin lipopolysaccharide (LPS)-induced MyD88/TLR4 complex fo...
Source: Cellular Signalling - September 27, 2009 Category: Cytology Authors: Amith SR, Jayanth P, Franchuk S, Finlay T, Seyrantepe V, Beyaert R, Pshezhetsky AV, Szewczuk MR Tags: Cell Signal Source Type: journals

Inhibition of tumor necrosis factor- induced phenotypes by short intracellular versions of latent membrane protein-1.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tumor Necrosis Factor (TNF) is a potent multi-functional cytokine with an homeostatic role in host defence. In case of deregulation, TNF is implicated in numerous pathologies. The latent membrane protein-1 (LMP1) is expressed by Epstein-Barr virus during viral latency and displaying properties of a constitutively activated member of the TNF receptor family. Both TNFR1 and LMP1 share a similar set of proximal adapters and signalling pathways although they display different biological responses. We previously demonstrated that the intracellular part of LMP1, LMP1-CT, a dominant negative form of LMP1, inhibits LMP1 signal...
Source: Cellular Signalling - September 27, 2009 Category: Cytology Authors: Ndour PA, Ouk TS, Brocqueville G, Mougel A, Vanhecke E, Feuillard J, Coll J, Adriaenssens E Tags: Cell Signal Source Type: journals

Differential modulation of BRCA1 and BARD1 nuclear localisation and foci assembly by DNA damage.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we evaluated the localisation patterns of BRCA1 and BARD1 in response to different types of DNA damaging agents and chemotherapeutic drugs. In MCF-7 cells, endogenous BRCA1 increased transiently in the nucleus at 2h after ionising radiation (IR), whereas BARD1 was unaffected. IR treatment did not induce nuclear export of either protein, in contrast to previous reports. DNA damage by UV radiation, etoposide or camptothecin caused a preferential down-regulation of nuclear BARD1 at 6h post-treatment. The UV-dependent loss of nuclear BARD1 was blocked by the proteasome inhibitor MG132, but not by leptomycin B, i...
Source: Cellular Signalling - September 27, 2009 Category: Cytology Authors: Brodie KM, Henderson BR Tags: Cell Signal Source Type: journals

Non-apoptotic Fas signaling regulates invasiveness of glioma cells and modulates MMP-2 activity via NFkappaB-TIMP-2 pathway.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fas (CD95/APO-1) is a cell surface "death receptor" that mediates apoptosis upon engagement by its ligand, FasL. Paradoxically, Fas/FasL can also promote cell invasion among non-apoptotic cells; here, we show that Fas/FasL signaling can promote tumor invasion when apoptosis is compromised. We have developed a recombinant FasL Interfering Protein (FIP) to interfere with Fas signaling in C6 glioma cells expressing both Fas receptor and its ligand. FIP administration did not affect cell viability but impaired cell motility and invasiveness of glioma cells. Blockade of Fas signaling reduced MMP-2 activity in glioma cells, ...
Source: Cellular Signalling - September 25, 2009 Category: Cytology Authors: Wisniewski P, Ellert-Miklaszewska A, Kwiatkowska A, Kaminska B Tags: Cell Signal Source Type: journals

Downregulation of stathmin expression is mediated directly by Egr1 and associated with p53 activity in lung cancer cell line A549.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Stathmim is overexpressed in a variety of assessed human malignancies and is correlated with tumor progression and poor prognosis. Downregulation of its expression will contribute to optimize therapeutic outcomes in the treatment of various malignancies. However, the mechanisms of stathmin gene overexpression are not completely elucidated at present. Early growth response 1 (Egr1) is a transcription factor that triggers transcription of downstream genes that mediate cell growth and angiogenesis upon various stimulations. Following the previous computational identification of a site that was thought to be an Egr1 consen...
Source: Cellular Signalling - September 24, 2009 Category: Cytology Authors: Lin F, Long M, Yan L, Gao P, Wang R, Zhang Y, Wang X, He T, Liu L, Dong K, Ren J, Zhang H Tags: Cell Signal Source Type: journals

Prenylation-deficient G protein gamma subunits disrupt GPCR signaling in the zebrafish.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Prenylation of G protein gamma (gamma) subunits is necessary for the membrane localization of heterotrimeric G proteins and for functional heterotrimeric G protein coupled receptor (GPCR) signaling. To evaluate GPCR signaling pathways during development, we injected zebrafish embryos with mRNAs encoding Ggamma subunits mutated so that they can no longer be prenylated. Low-level expression of these prenylation-deficient Ggamma subunits driven either ubiquitously or specifically in the primordial germ cells (PGCs) disrupts GPCR signaling and manifests as a PGC migration defect. This disruption results in a reduction of c...
Source: Cellular Signalling - September 24, 2009 Category: Cytology Authors: Mulligan T, Blaser H, Raz E, Farber SA Tags: Cell Signal Source Type: journals

ARAP3 binding to phosphatidylinositol-(3,4,5)-trisphosphate depends on N-terminal tandem PH domains and adjacent sequences.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pleckstrin homology (PH) domains are modules characterised by a conserved three-dimensional protein fold. Several PH domains bind phosphoinositides with high affinity and specificity whilst most others do not. ARAP3 is a dual GTPase activating protein for Arf6 and RhoA which was identified in a screen for phosphatidylinositol-(3,4,5)-trisphophate (PtdIns(3,4,5)P(3)) binding proteins. It is a regulator of cell shape and adhesion, and is itself regulated by PtdIns(3,4,5)P(3,) which acts to recruit ARAP3 to the plasma membrane and to catalytically activate it. We show here that ARAP3 binds to PtdIns(3,4,5)P(3) in an unusu...
Source: Cellular Signalling - September 24, 2009 Category: Cytology Authors: Craig HE, Coadwell J, Guillou H, Vermeren S Tags: Cell Signal Source Type: journals

Role of the extracellular amino terminus and first membrane-spanning helix of dopamine d1 and d5 receptors in shaping ligand selectivity and efficacy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transmembrane (TM) helices of human D1-like dopaminergic receptors (hD1R and hD5R) harbor the same residues implicated in ligand binding and activation of catecholamine G protein-coupled receptors (GPCRs). Yet, hD1R and hD5R naturally display the distinct functional properties shared by wild type and constitutively active mutant GPCRs, respectively. Interestingly, we show in the present study that a class of synthetic phenylbenzazepine agonists containing a methyl on the azepine ring exhibited lower affinity for the more constitutively activated hD5R. These results cannot be explained by the "allosteric ternary complex...
Source: Cellular Signalling - September 24, 2009 Category: Cytology Authors: D'Aoust JP, Tiberi M Tags: Cell Signal Source Type: journals

IKKalpha negatively regulates IRF5 function in a MyD88-TRAF6 pathway.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transcription factors of IRF family, IRF-3, IRF-5 and IRF-7 play a critical role in the innate antiviral response. In infected cells, IRF-3 and IRF-7 are activated by TBK-1 and IKKepsilon mediated phosphorylation, while the kinase, phosphorylating IRF-5 in the MyD88 signalling pathway has not yet been identified. We now show that IKKalpha phosphorylates IRF5 and induces formation of IRF-5 dimers, which have been indicative of IRF-5 activation. However, IKKalpha induced IRF5 phosphorylation exerts inhibitory effect on the transcriptional activation of type 1 interferon and promoters of the inflammatory cytokines. Addres...
Source: Cellular Signalling - September 24, 2009 Category: Cytology Authors: Balkhi MY, Fitzgerald KA, Pitha PM Tags: Cell Signal Source Type: journals

TNFalpha activation of PKCdelta, mediated by NFkappaB and ER stress, cross-talks with the insulin signaling cascade.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
TNFalpha plays key roles in the regulation of inflammation, cell death, and proliferation and it's signaling cascade cross-talks with the insulin signaling cascade. PKCdelta, a novel PKC isoform, is known to participate in proximal TNFalpha signaling events. However, it has remained unclear whether PKCdelta plays a role in distal TNFalpha signaling events. Here we demonstrate that PKCdelta is activated by TNFalpha in a delayed fashion that is temporally associated with JNK activation. To investigate the signaling pathways activating PKCdelta and JNK, we used pharmacological and genetic inhibitors of NFkappaB. We found ...
Source: Cellular Signalling - September 23, 2009 Category: Cytology Authors: Greene MW, Ruhoff MS, Burrington CM, Garofalo RS, Oreña SJ Tags: Cell Signal Source Type: journals

EP2 receptor mediated cAMP release is augmented by PGF(2alpha) activation of the FP receptor via the calcium-calmodulin pathway.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, this study demonstrates that co-activation of the FP and EP2 receptors results in enhanced release of cAMP via FP receptor-Galpha(q)-Ca(2+)-calmodulin pathway by activating calcium sensitive AC3 isoform. PMID: 19782748 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - September 23, 2009 Category: Cytology Authors: Abera AB, Sales KJ, Catalano RD, Katz AA, Jabbour HN Tags: Cell Signal Source Type: journals

THE dopamine D4 receptor activates intracellular platelet-derived growth factor receptor beta to stimulate ERK 1/2.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dopamine receptors are GPCRs(1) that play important roles in locomotion, reward, and cognitive processes. Previously, we demonstrated that this receptor transactivates PDGFRbeta to modulate ERK1/2 and NMDA receptor activity. Downregulation of maturely glycosylated PDGFRbeta by prolonged exposure to PDGF-BB eliminated PDGF-BB-mediated ERK1/2 activation. The DRD4-mediated ERK1/2 response was only partially blunted by PDGF-BB-mediated downregulation, but remained sensitive to the PDGFRbeta kinase inhibitor tyrphostin A9. Tunicamycin prevented the N-linked glycosylation and maturation of PDGFRbeta as well as its activation...
Source: Cellular Signalling - September 22, 2009 Category: Cytology Authors: Gill RS, Hsiung MS, Sum CS, Lavine N, Clark SD, Van Tol HH Tags: Cell Signal Source Type: journals

Serine threonine receptor associated protein (strap) plays a role in the maintenance of mesenchymal morphology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The stromal tissue, made of extracellular matrix and mesenchymal cells, is vital for the functional design of all complex tissues. Fibroblasts are key components of stromal tissue and play a crucial role during organ development, wound repair, angiogenesis and fibrosis. We have previously reported the identification of a novel WD-domain protein, STRAP(1) that inhibits transforming growth factor-beta (TGF-beta) signaling and enhances tumorigenicity via TGF-beta-dependent and TGF-beta-independent mechanisms. Here, we report, for the first time, that deletion of STRAP from Mouse Embryonic Fibroblasts (MEFs) results in a l...
Source: Cellular Signalling - September 21, 2009 Category: Cytology Authors: Kashikar ND, Reiner J, Datta A, Datta PK Tags: Cell Signal Source Type: journals

The cardioprotective effects of zileuton, a 5-lipoxygenase inhibitor, are mediated by COX-2 via activation of PKCdelta.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Zileuton has been demonstrated to act as an anti-inflammatory agent by virtue of its well-known ability to inhibit 5-lipoxygenase (5-LO). However, the effects of zileuton on cardiovascular disease and cardiomyocyte apoptosis are unclear. Here, we investigated the effects of zileuton on apoptosis of cardiac myogenic H9c2 cells and neonatal rat cardiomyocytes (NRCMs), and examined the possible role of PKCdelta-mediated induction of COX-2 in these effects. Treatment of H9c2 cells with zileuton efficiently induced COX-2 expression and PGE(2) biosynthesis in a time- and dose-dependent manner. Zileuton also exerted a profoun...
Source: Cellular Signalling - September 21, 2009 Category: Cytology Authors: Kwak HJ, Park KM, Choi HE, Lim HJ, Park JH, Park HY Tags: Cell Signal Source Type: journals

UNC119 Inhibits dynamin and dynamin-dependent endocytic processes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Unc119 is an adapter signaling molecule, which regulates activation of tyrosine kinases in T cells, eosinophils and fibroblasts. It plays important role in the photoreceptor synapses of the retina. Recently, we have shown that it inhibits bacterial uptake through macropinocytosis. In this paper we demonstrate a role for Unc119 in clathrin- and caveolae-based endocytosis as well as macropinocytosis. Depletion of Unc119 in fibroblasts increases, whereas overexpression inhibits uptake of transferrin, FM4-64, albumin, viruses, and ligand-coated beads. Physiological stimuli that upregulate the expression of Unc119 also inhi...
Source: Cellular Signalling - September 21, 2009 Category: Cytology Authors: Karim MZ, Vepachedu R, Gorska M, Alam R Tags: Cell Signal Source Type: journals

Proteinase-activated receptor-2 mediated inhibition of TNFalpha -stimulated JNK activation - a novel paradigm for Gq/11 linked GPCRs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study we examined the potential for PAR(2) and TNFalpha to synergise at the level of MAP kinase signalling in PAR(2) expressing NCTC2544 cells. However, to our surprise we found that activation of PAR(2) by trypsin or the specific activating peptide SLIGKV-OH strongly inhibited both the phosphorylation and activity of JNK. In contrast neither p38 MAP kinase nor ERK activation was affected although TNFalpha stimulated IkappaBalpha loss was partially reversed. The inhibitory effect was not observed in parental cells nor in cells expressing PAR(4), however inhibition was reversed by pre-incubation with the novel PAR(2...
Source: Cellular Signalling - September 21, 2009 Category: Cytology Authors: McIntosh K, Cunningham MR, Cadalbert L, Lockhart J, Boyd G, Ferrell WR, Plevin R Tags: Cell Signal Source Type: journals

Mathematical modelling of interferon-gamma signalling in pancreatic stellate cells reflects and predicts dynamics of STAT1 pathway activity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Signal transducer and activator of transcription (STAT) 1 is essentially involved in the mediation of antifibrotic interferon-gamma (IFNgamma) effects in pancreatic stellate cells (PSC). Here, we have further analysed activation of the STAT1 pathway in a PSC line by combining quantitative data generation with mathematical modelling. At saturating concentrations of IFNgamma, a triphasic pattern of STAT1 activation was observed. An initial, rapid induction of phospho-STAT1 was followed by a plateau phase and another, long-lasting phase of further increase. The late increase occurred despite enhanced expression of the fee...
Source: Cellular Signalling - September 21, 2009 Category: Cytology Authors: Rateitschak K, Karger A, Fitzner B, Lange F, Wolkenhauer O, Jaster R Tags: Cell Signal Source Type: journals

Suppression of DNA-PKcs enhances FGF-2 dependent human endothelial cell proliferation via negative regulation of Akt.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Angiogenesis initiation is crucially dependent on endothelial proliferation and can be stimulated by the fibroblast growth factor 2 (FGF-2). The DNA dependent protein kinase (DNA-PK), long known for its importance in repairing DNA double strand breaks, belongs to the phosphatidylinositol-3 kinase (PI3-K) super family and has recently been identified as one of the enzymes phosphorylating and activating Akt. Due to its similarity with PI3-K, we hypothesized that DNA-PK may have similar effects on endothelial angiogenic processes and signalling. We used primary endothelial cells (HUVEC, PAEC) and human microvascular endot...
Source: Cellular Signalling - September 21, 2009 Category: Cytology Authors: Mannell H, Hammitzsch A, Mettler R, Pohl U, Krötz F Tags: Cell Signal Source Type: journals

Odorant-stimulated phosphoinositide signaling in mammalian olfactory receptor neurons.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent evidence has revived interest in the idea that phosphoinositides (PIs) may play a role in signal transduction in mammalian olfactory receptor neurons (ORNs). To provide direct evidence that odorants indeed activate PI signaling in ORNs, we used adenoviral vectors carrying two different fluorescently tagged probes, the pleckstrin homology (PH) domains of phospholipase Cdelta1 (PLCdelta1) and the general receptor of phosphoinositides (GRP1), to monitor PI activity in the dendritic knobs of ORNs in vivo. Odorants mobilized PI(4,5)P(2)/IP(3) and PI(3,4,5)P(3), the substrates and products of PLC and PI3K. We then mea...
Source: Cellular Signalling - September 21, 2009 Category: Cytology Authors: Klasen K, Corey EA, Kuck F, Wetzel CH, Hatt H, Ache BW Tags: Cell Signal Source Type: journals