Immunological ReviewsThis 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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Organization of immunoreceptor signaling by adaptersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Immunological Reviews)
Source: Immunological Reviews - October 25, 2009 Category: Allergy & Immunology Authors: André Veillette Tags: Introduction Source Type: journals

Adapter and enzymatic functions of proteases in T-cell activationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Proteases control many vital aspects of humoral and cellular immune responses, including the maturation of cytokines and the killing of target cells. Recently, it has become evident that triggering of the T-cell receptor controls T-cell proliferation through proteases such as mucosa-associated lymphoid tissue 1 (MALT1) and Caspase-8 that act both as adapters and enzymes. Here, we discuss the role of these and other proteases that are relevant to the control of the T-cell response and represent interesting targets of therapeutic immunomodulation. (Source: Immunological Reviews)
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Stephan Hailfinger, Fabien Rebeaud, Margot Thome Tags: Review Articles Source Type: journals

SWAP-70-like adapter of T cells: a novel Lck-regulated guanine nucleotide exchange factor coordinating actin cytoskeleton reorganization and Ca2+ signaling in T cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: SWAP-70-like adapter of T cells (SLAT) is a recently identified guanine nucleotide exchange factor (GEF) for Cdc42 and Rac1, which is highly expressed in both thymocytes and peripheral T cells. Here, we present and discuss findings resulting from biochemical and genetic analyses aimed at unveiling the role of SLAT in CD4+ T-cell development, activation, and T-helper (Th) cell differentiation. Slat[minus]/[minus] mice display a developmental defect at one of the earliest stages of thymocyte differentiation, the double negative 1 (DN1) stage, leading to decreased peripheral T-cell numbers. Slat[minus]/[minus] periph...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Stéphane Bécart, Amnon Altman Tags: Review Articles Source Type: journals

Comprehending the complex connection between PKCβ, TAK1, and IKK in BCR signalingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: The transcription factor nuclear factor-[kappa]B (NF-[kappa]B) contributes to many events in the immune system. Characterization of NF-[kappa]B has facilitated our understanding of immune cell differentiation, survival, proliferation, and effector functions. Intense research continues to elucidate the role of NF-[kappa]B, which is shared in several receptor signaling pathways, such as Toll-like receptors, the tumor necrosis factor receptor, and antigen receptors. The specificity of cellular responses emanating from stimulation of these receptors is determined by post-translational modification, or 'fine tuning', w...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Hisaaki Shinohara, Tomohiro Kurosaki Tags: Review Articles Source Type: journals

Autoinhibition and adapter function of SykEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Development, survival, and activation of B lymphocytes are controlled by signals emanating from the B-cell antigen receptor (BCR). The BCR has an autonomous signaling function also known as tonic signaling that allows for long-term survival of B cells in the immune system. Upon binding of antigen to the BCR, the tonic signal is amplified and diversified, leading to alteration in gene expression and B-cell activation. The spleen tyrosine kinase (Syk) intimately cooperates with the signaling subunits of the BCR and plays a central role in the amplification and diversification of BCR signals. In this review, we discu...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Yogesh Kulathu, Gesina Grothe, Michael Reth Tags: Review Articles Source Type: journals

The roles of Dok family adapters in immunoreceptor signalingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: The mammalian Dok protein family has seven members (Dok-1[ndash]Dok-7). The Dok proteins share structural similarities characterized by the NH2-terminal pleckstrin homology and phosphotyrosine-binding domains followed by SH2 target motifs in the COOH-terminal moiety, indicating an adapter function. Indeed, Dok-1 was originally identified as a 62 kDa protein that binds with p120 rasGAP, a potent inhibitor of Ras, upon tyrosine phosphorylation by a variety of protein tyrosine kinases. Among the Dok family, only Dok-1, Dok-2, and Dok-3 are preferentially expressed in hematopoietic/immune cells. Dok-1 and its closest ...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Ryuichi Mashima, Yukihiro Hishida, Tohru Tezuka, Yuji Yamanashi Tags: Review Articles Source Type: journals

Phosphoinositide 3-kinase-regulated adapters in lymphocyte activationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Signaling via phosphoinositide 3-kinases (PI3Ks) has emerged as a central component of lymphocyte activation via immunoreceptors, costimulatory receptors, cytokine receptors, and chemokine receptors. The discovery of phosphoinositide-binding pleckstrin homology (PH) domains has substantially increased understanding of how PI3Ks activate cellular responses. Accumulating evidence indicates that PH-domain containing adapter molecules provide important links between PI3K and lymphocyte function. Here, we review data on PI3K-regulated adapter proteins of the Grb-associated binder (GAB), Src kinase-associated phosphopro...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Ting-ting Zhang, Hongzhao Li, Samuel M. Cheung, Jennifer L. Costantini, Sen Hou, Monther Al-Alwan, Aaron J. Marshall Tags: Review Articles Source Type: journals

The T-cell-specific adapter protein family: TSAd, ALX, and SH2D4A/SH2D4BEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Adapter proteins play key roles in intracellular signal transduction through complex formation with catalytically active signaling molecules. In T lymphocytes, the role of several different types of adapter proteins in T-cell antigen receptor signal transduction is well established. An exception to this is the family of T-cell-specific adapter (TSAd) proteins comprising of TSAd, adapter protein of unknown function (ALX), SH2D4A, and SH2D4B. Only recently has the function of these adapters in T-cell signal transduction been explored. Here, we discuss advances in our understanding of the role of this family of adapt...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Philip E. Lapinski, Jennifer A. Oliver, Jennifer N. Bodie, Francesc Marti, Philip D. King Tags: Review Articles Source Type: journals

Importance and mechanism of 'switch' function of SAP family adaptersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: The signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) family of adapters includes SAP, Ewing's sarcoma-associated transcript-2 (EAT-2), and EAT-2-related transducer (ERT). These Src homology-2 (SH2) domain-only molecules play critical roles in immune regulation. The prototype of the SAP family, SAP, is mutated in X-linked lymphoproliferative disease in humans. Moreover, genetically engineered mice lacking one or more SAP family members have defects in multiple immune cell types including T cells, natural killer (NK) cells, NKT cells, and B cells. Accumulating data show that SAP family adapt...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: André Veillette, Zhongjun Dong, Luis-Alberto Pérez-Quintero, Ming-Chao Zhong, Mario-Ernesto Cruz-Munoz Tags: Review Articles Source Type: journals

SLAP, a regulator of immunoreceptor ubiquitination, signaling, and traffickingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Src-like adapter proteins (SLAP and SLAP-2) constitute a family of proteins that are expressed in a variety of cell types but are studied most extensively in lymphocytes. They have been shown to associate with proximal components of the T-cell receptor (TCR) and B-cell receptor (BCR) signaling complexes. An interaction of SLAP with c-Cbl leads to the ubiquitination and degradation of phosphorylated components of the TCR- and BCR-signaling complexes. The absence of this process in immature SLAP-deficient T and B cells leads to increased immunoreceptor levels due to decreased intracellular retention and degradation....
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Leonard L. Dragone, Laura A. Shaw, Margaret D. Myers, Arthur Weiss Tags: Review Articles Source Type: journals

Adapters in the organization of mast cell signalingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Mast cells are pivotal in innate immunity and play an important role in amplifying adaptive immunity. Nonetheless, they have long been known to be central to the initiation of allergic disorders. This results from the dysregulation of the immune response whereby normally innocuous substances are recognized as non-self, resulting in the production of IgE antibodies to these 'allergens'. Preformed and newly synthesized inflammatory (allergic) mediators are released from the mast cell following allergen-mediated aggregation of allergen-specific IgE bound to the high-affinity receptors for IgE (Fc[epsilon]RI). Thus, t...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Damiana Alvarez-Errico, Eva Lessmann, Juan Rivera Tags: Review Articles Source Type: journals

Contributions of Wiskott–Aldrich syndrome family cytoskeletal regulatory adapters to immune regulationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Cytoskeletal structure and dynamic rearrangement are integrally involved in coupling external stimuli to the orchestrated network of molecular interactions and cellular responses required for T-cell effector function. Members of the Wiskott[ndash][ndash]Aldrich syndrome protein (WASp) family are now widely recognized as cytoskeletal scaffolding adapters that coordinate the transmission of stimulatory signals to downstream induction of actin remodeling and cytoskeletal-dependent T-cell responses. In this review, we discuss the structural and functional properties of the WASp family members, with an emphasis on the ...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Jinyi Zhang , Baoxia Dong, Katherine A. Siminovitch Tags: Review Articles Source Type: journals

Regulation of T-lymphocyte physiology by the Chat-H/CasL adapter complexEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: The Cas family of proteins consists of at least four members implicated in the regulation of diverse cellular processes such as cell proliferation, adhesion, motility, and cancer cell metastasis. Cas family members have conserved C-termini that mediate constitutive heterotypic interactions with members of a different group of proteins, the NSP family. Both the Cas and NSP proteins have conserved domains that mediate protein[ndash]protein interactions with other cytoplasmic intermediates. Signaling modules assembled by these proteins in turn regulate signal transduction downstream of a variety of receptors includin...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Konstantina Alexandropoulos, Adam G. Regelmann Tags: Review Articles Source Type: journals

Grb2, a simple adapter with complex roles in lymphocyte development, function, and signalingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Lymphocyte development, activation, and tolerance depend on antigen receptor signaling transduced via multiple intracellular signalosomes. These signalosomes are assembled by different adapters. Given that signaling molecules can be either positive or negative regulators for a biochemical target, the complex of a target with different regulator may dictate the final signaling outcome. Grb2 is a simple adapter known to be involved in a variety of growth factor receptor signaling. However, its role in antigen receptor signaling as well as lymphocyte development and function has emerged only recently. Despite its sim...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Ihn Kyung Jang, Jinping Zhang, Hua Gu Tags: Review Articles Source Type: journals

The B-lymphoid Grb2 interaction codeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: The growth factor receptor-bound protein 2 (Grb2) is a ubiquitously expressed and evolutionary conserved adapter protein possessing a plethora of described interaction partners for the regulation of signal transduction. In B lymphocytes, the Grb2-mediated scaffolding function controls the assembly and subcellular targeting of activating as well as inhibitory signalosomes in response to ligation of the antigen receptor. Also, integration of simultaneous signals from B-cell coreceptors that amplify or attenuate antigen receptor signal output relies on Grb2. Hence, Grb2 is an essential signal integrator. The key ques...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Konstantin Neumann, Thomas Oellerich, Henning Urlaub, Jürgen Wienands Tags: Review Articles Source Type: journals

Positive and negative regulation of antigen receptor signaling by the Shc family of protein adaptersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: The Shc adapter family includes four members that are expressed as multiple isoforms and participate in signaling by a variety of cell-surface receptors. The biological relevance of Shc proteins as well as their variegated function, which relies on their highly conserved modular structure, is underscored by the distinct and dramatic phenotypic alterations resulting from deletion of individual Shc isoforms both in the mouse and in two model organisms, Drosophila melanogaster and Caenorhabditis elegans. The p52 isoform of ShcA couples antigen and cytokine receptors to Ras activation in both lymphoid and myeloid cell...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Francesca Finetti, Maria Teresa Savino, Cosima T. Baldari Tags: Review Articles Source Type: journals

Cooperation of adapter molecules in proximal signaling cascades during allergic inflammationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Activation of mast cells through their high-affinity immunoglobulin E receptor (Fc[epsilon]RI) plays an important role in allergic disorders. Other mast cell-activating stimuli, such as Toll-like receptor (TLR) ligands, synergize with Fc[epsilon]RI to enhance allergic inflammation. Thus, there is much interest in understanding how signaling occurs downstream of these receptors. One key event for Fc[epsilon]RI-mediated mast cell activation is the inducible formation of multimolecular proximal signaling complexes. These complexes are nucleated by adapter proteins, scaffolds that localize various signaling molecules ...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Taku Kambayashi, David F. LaRosa, Michael A. Silverman, Gary A. Koretzky Tags: Review Articles Source Type: journals

Endocytic events in TCR signaling: focus on adapters in microclustersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Although the critical role of T-cell receptor (TCR) microclusters in T-cell activation is now widely accepted, the mechanisms of regulation of these TCR-rich structures, which also contain enzymes, adapters, and effectors, remain poorly defined. Soon after microcluster formation, several signaling proteins rapidly dissociate from the TCR. Recent studies from our laboratory demonstrated that the movement of the adapters linker for activation of T cells (LAT) and Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) away from initial microcluster formation sites represents endocytic events. Ubiquityl...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Lakshmi Balagopalan, Valarie A. Barr, Lawrence E. Samelson Tags: Review Articles Source Type: journals

Regulation of lymphocyte development and activation by the LAT family of adapter proteinsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Transmembrane adapter proteins (TRAPs) are critical components of signaling pathways in lymphocytes, linking antigen receptor engagement to downstream cellular processes. While these proteins lack intrinsic enzymatic activity, their phosphorylation following receptor ligation allows them to function as scaffolds for the assembly of multi-molecular signaling complexes. Many TRAPs have recently been discovered, and numerous studies demonstrate their roles in the positive and negative regulation of lymphocyte maturation, activation, and differentiation. One such example is the linker for activation of T cells (LAT) f...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Deirdre M. Fuller, Weiguo Zhang Tags: Review Articles Source Type: journals

Inhibitory ITAMs as novel regulators of immunityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Immune homeostasis is regulated by a finely tuned network of positive[ndash]negative regulatory mechanisms that guarantees proper surveillance avoiding hyperactivity that would lead to autoimmunity and inflammatory diseases. Immune responses involve the activation of immunoreceptors that contain tyrosine-based activation motifs (ITAMs). One arm of control involves immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing receptors, which upon co-aggregation initiate an inhibitory signal through recruitment of signal-aborting phosphatases. Recently, a new immunoregulatory function has been ascribed to ITAMs, wh...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Ulrich Blank, Pierre Launay, Marc Benhamou, Renato C. Monteiro Tags: Review Articles Source Type: journals

The expanding roles of ITAM adapters FcRγ and DAP12 in myeloid cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: The adapter proteins DAP12 and FcR[gamma] associate with a wide spectrum of receptors in a variety of innate immune cells to mediate intracellular signaling pathways when their cognate receptor is engaged. These adapter proteins are coupled to their receptors through charged residues within the transmembrane regions of the adapter and receptor. DAP12 and FcR[gamma] contain specific protein domains (referred to as immunoreceptor tyrosine-based activation motifs) that serve as the substrates and docking sites for kinases, allowing amplification of intracellular signaling reactions. Recent research has broadened the ...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Jessica A. Hamerman, Minjian Ni, Justin R. Killebrew, Ching-Liang Chu, Clifford A. Lowell Tags: Review Articles Source Type: journals

The molecular assembly and organization of signaling active B-cell receptor oligomersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: In B cells, antigen drives the formation of B-cell receptor (BCR) clusters that initiate the formation of signaling complexes associated with the cytoplasmic domains of the BCRs. These signaling active complexes contain a number of protein and lipid kinases and phosphatases and adapter and scaffolding proteins that together function to trigger downstream signaling cascades leading to the activation of a variety of genes associated with B-cell activation. Although we are learning a considerable amount about the molecular details of the assembly of immune receptor signaling complexes, as reviewed in this volume, a f...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Pavel Tolar, Hae Won Sohn, Wanli Liu, Susan K. Pierce Tags: Review Articles Source Type: journals

Hierarchical role of CD3 chains in thymocyte developmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Assembly, expression, and signal transduction by the pre-T-cell receptor (pre-TCR) and TCR complexes are critical for normal thymocyte development. How environmental cues sensed by these two receptor complexes are translated into biological responses that result in the generation of functionally mature T cells is increasingly better understood. Invariant CD3[gamma], [delta], [epsilon], and [zeta] polypeptides are central to the function of these two receptor complexes. CD3 chains ensure correct intracellular assembly, surface expression, and signal transduction via the receptors in ligand-independent and -dependen...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Vibhuti P. Dave Tags: Review Articles Source Type: journals

Organization of proximal signal initiation at the TCR:CD3 complexEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: The series of events leading to T-cell activation following antigen recognition has been extensively investigated. Although the exact mechanisms of ligand binding and transmission of this extracellular interaction into a productive intracellular signaling sequence remains incomplete, it has been known for many years that the immunoreceptor tyrosine activation motifs (ITAMs) of the T-cell receptor (TCR):CD3 complex are required for initiation of this signaling cascade because of the recruitment and activation of multiple protein tyrosine kinases, signaling intermediates, and adapter molecules. It however remains un...
Source: Immunological Reviews - October 23, 2009 Category: Allergy & Immunology Authors: Clifford S. Guy, Dario A. A. Vignali Tags: Review Articles Source Type: journals

Dendritic cell altered states: what role for calcium?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Ca2+-driven responses in dendritic cells (DCs) are less well characterized than in lymphocytes. When DCs undergo a sequence of activation/maturation events, typically beginning with exposure to pathogens in the periphery, Ca2+ entry into the cytosol from stores in the endoplasmic reticulum or from outside the cell can occur at various steps and participate in intracellular signaling. However, not all cellular processes identified in these cells are Ca2+ dependent. While immigration of precursor DCs into the peripheral tissues as well as emigration to secondary lymphoid sites following microbial challenge depend on...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Russell D. Salter, Simon C. Watkins Tags: Review articles Source Type: journals

B-lymphocyte calcium inFluxEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Dynamic changes in cytoplasmic calcium concentration dictate the immunological fate and functions of lymphocytes. During the past few years, important details have been revealed about the mechanism of store-operated calcium entry in lymphocytes, including the molecular identity of calcium release-activated calcium (CRAC) channels and the endoplasmic reticulum (ER) calcium sensor (STIM1) responsible for CRAC channel activation following calcium depletion of stores. However, details of the potential fine regulation of CRAC channel activation that may be imposed on lymphocytes following physiologic stimulation within...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Leslie B. King, Bruce D. Freedman Tags: Review articles Source Type: journals

Roles of Cav channels and AHNAK1 in T cells: the beauty and the beastEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: T lymphocytes require Ca2+ entry though the plasma membrane for their activation and function. Recently, several routes for Ca2+ entry through the T-cell plasma membrane after activation have been described. These include calcium release-activated channels (CRAC), transient receptor potential (TRP) channels, and inositol-1,4,5-trisphosphate receptors (IP3Rs). Herein we review the emergence of a fourth new route for Ca2+ entry, composed of Cav channels (also known as L-type voltage-gated calcium channels) and the scaffold protein AHNAK1 (AHNAK/desmoyokin). Both helper (CD4+) and killer (CD8+) T cells express high l...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Didi Matza, Richard A. Flavell Tags: Review articles Source Type: journals

Ca2+-NFATc1 signaling is an essential axis of osteoclast differentiationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Osteoclasts are unique, multinucleated giant cells that decalcify and degrade the bone matrix. They originate from hematopoietic cells and their differentiation is dependent on a tumor necrosis factor (TNF) family cytokine, receptor activator of nuclear factor-[kappa]B (NF-[kappa]B) ligand (RANKL), as well as macrophage-colony stimulating factor (M-CSF). Recent studies have unveiled the precise molecular mechanism underlying osteoclastogenesis. In particular, the discovery of nuclear factor of activated T cells c1 (NFATc1), the master regulator of osteoclastogenesis, has proven to be a breakthrough in this field. ...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Takako Negishi-Koga, Hiroshi Takayanagi Tags: Review articles Source Type: journals

Regulation of T-cell tolerance by calcium/NFAT signalingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Cells that escape negative selection in the thymus must be inactivated or eliminated in the periphery through a series of mechanisms that include the induction of anergy, dominant suppression by regulatory T cells, and peripheral deletion of self-reactive T cells. Calcium signaling plays a central role in the induction of anergy in T cells, which become functionally inactivated and incapable of proliferating and expressing cytokines following antigen re-encounter. Suboptimal stimulation of T cells results in the activation of a calcium/calcineurin/nuclear factor of activated T cells-dependent cell-intrinsic progra...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Ian Baine, Brian T. Abe, Fernando Macian Tags: Review articles Source Type: journals

Calcium signaling in the development and function of T-lineage cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Ca2+ signals are essential for diverse cellular functions including differentiation, effector function, and gene transcription in the immune system. In lymphocytes, sustained Ca2+ entry is necessary for complete and long-lasting activation of calcineurin/nuclear factor of activated T cells (NFAT) pathways. Engagement of immunoreceptors, such as the T-cell antigen receptor, induces store-operated Ca2+ entry (SOCE) through plasma membrane Ca2+ channels. In lymphocytes, mast cells, and other immune cell types, SOCE through highly Ca2+-selective Ca2+ release-activated Ca2+ (CRAC) channels constitute the major pathway ...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Masatsugu Oh-hora Tags: Review articles Source Type: journals

ORAI1 and STIM1 deficiency in human and mice: roles of store-operated Ca2+ entry in the immune system and beyondEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Store-operated Ca2+ entry (SOCE) is a mechanism used by many cells types including lymphocytes and other immune cells to increase intracellular Ca2+ concentrations to initiate signal transduction. Activation of immunoreceptors such as the T-cell receptor, B-cell receptor, or Fc receptors results in the release of Ca2+ ions from endoplasmic reticulum (ER) Ca2+ stores and subsequent activation of plasma membrane Ca2+ channels such as the well-characterized Ca2+ release-activated Ca2+ (CRAC) channel. Two genes have been identified that are essential for SOCE: ORAI1 as the pore-forming subunit of the CRAC channel in t...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Stefan Feske Tags: Review articles Source Type: journals

Physiological function and molecular basis of STIM1-mediated calcium entry in immune cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Calcium signals in immune cells regulate a variety of physiological responses such as cell activation, differentiation, gene transcription, and effector functions. Surface receptor stimulation induces an increase in the concentration of cytosolic calcium ions (Ca2+), which are derived mainly from two sources, intracellular endoplasmic reticulum (ER) Ca2+ stores and the extracellular space. The major cascade for Ca2+ entry in immune cells is through store-operated Ca2+ entry (SOCE) and Ca2+ release-activated Ca2+ (CRAC) channels. Activation of SOCE is triggered by depletion of intracellular ER Ca2+ stores, but the ...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Yoshihiro Baba, Tomohiro Kurosaki Tags: Review articles Source Type: journals

Calcium influx and signaling in cytotoxic T-lymphocyte lytic granule exocytosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Cytotoxic T lymphocytes (CTLs) kill targets by releasing cytotoxic agents from lytic granules. Killing is a multi-step process. The CTL adheres to a target, allowing its T-cell receptors to recognize antigen. This triggers a signal transduction cascade that leads to the polarization of the microtubule cytoskeleton and granules towards the target, followed by exocytosis that occurs specifically at the site of contact. As with cytokine production by helper T cells (Th cells), target cell killing is absolutely dependent on Ca2+ influx, which is involved in regulating both reorientation and release. Current evidence s...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Arun T. Pores-Fernando, Adam Zweifach Tags: Review articles Source Type: journals

Formation of STIM and Orai complexes: puncta and distal capsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: In the last few years, great progress has been made in understanding how stromal interacting molecule 1 (STIM1), a protein containing a calcium sensor that is located in the endoplasmic reticulum, and Orai1, a protein that forms a calcium channel in the plasma membrane, interact and give rise to store-operated calcium entry. Pharmacological depletion of calcium stores leads to the formation of clusters containing STIM and Orai that appear to be sites for calcium influx. Similar puncta are also produced in response to physiological stimuli in immune cells. In T cells engaged with antigen-presenting cells, clusters ...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Valarie A. Barr, Kelsie M. Bernot, Meredith H. Shaffer, Janis K. Burkhardt, Lawrence E. Samelson Tags: Review articles Source Type: journals

The immunological synapse controls local and global calcium signals in T lymphocytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Cell polarization is a key feature of T-cell function. The immunological synapse (IS) between T cells and antigen-presenting cells is a beautiful example of how polarization of cells is used to guide cell function. Receptors, signal transducers, the cytoskeleton, and organelles are enriched at or depleted from the IS after its formation, and in many cases these re-localizations have already been linked with certain T-cell functions. One key step for T-cell activation is a rise in the cytoplasmic calcium concentration. Whereas it is undisputed that the IS initiates and controls calcium signals in T cells, very litt...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Carsten Kummerow, Christian Junker, Karsten Kruse, Heiko Rieger, Ariel Quintana, Markus Hoth Tags: Review articles Source Type: journals

Structurally delineating stromal interaction molecules as the endoplasmic reticulum calcium sensors and regulators of calcium release-activated calcium entryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: The endoplasmic reticulum (ER) lumen stores a crucial source of calcium (Ca2+) maintained orders of magnitude higher than the cytosol for the activation of a plethora of cellular responses transmitted in health and disease by a mutually efficient and communicative exchange of Ca2+ between compartments. A coordination of the Ca2+ signal is evident in the development of Ca2+ release-activated Ca2+ (CRAC) entry, vital to lymphocyte activation and replenishing of the ER Ca2+ stores, where modest decreases in ER luminal Ca2+ induce sustained increases in cytosolic Ca2+ sourced from steadfast extracellular Ca2+ supplies...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Peter B. Stathopulos, Mitsuhiko Ikura Tags: Review articles Source Type: journals

Mechanistic view on domains mediating STIM1–Orai couplingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Calcium (Ca2+) entry into non-excitable cells is mainly carried by store-operated channels, which serve essential functions ranging from regulation of transcription to cell growth. The best-characterized store-operated current, initially discovered in T lymphocytes and mast cells, is the Ca2+ release-activated Ca2+ (CRAC) current. The search for the molecular components of the CRAC channel has recently identified stromal interaction molecule 1 (STIM1) as the Ca2+ sensor in the endoplasmic reticulum (ER) and Orai1 as the CRAC channel pore. ER store depletion results in formation of STIM1 puncta that trigger Ca2+ in...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Marc Fahrner, Martin Muik, Isabella Derler, Rainer Schindl, Reinhard Fritsch, Irene Frischauf, Christoph Romanin Tags: Review articles Source Type: journals

The molecular physiology of CRAC channelsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: The Ca2+release-activated Ca2+ (CRAC) channel is a highly Ca2+-selective store-operated channel expressed in T cells, mast cells, and various other tissues. CRAC channels regulate critical cellular processes such as gene expression, motility, and the secretion of inflammatory mediators. The identification of Orai1, a key subunit of the CRAC channel pore, and STIM1, the endoplasmic reticulum (ER) Ca2+ sensor, have provided the tools to illuminate the mechanisms of regulation and the pore properties of CRAC channels. Recent evidence indicates that the activation of CRAC channels by store depletion involves a coordin...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Murali Prakriya Tags: Review articles Source Type: journals

The functional network of ion channels in T lymphocytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: For more than 25 years, it has been widely appreciated that Ca2+ influx is essential to trigger T-lymphocyte activation. Patch clamp analysis, molecular identification, and functional studies using blockers and genetic manipulation have shown that a unique contingent of ion channels orchestrates the initiation, intensity, and duration of the Ca2+ signal. Five distinct types of ion channels [ndash] Kv1.3, KCa3.1, Orai1+ stromal interacting molecule 1 (STIM1) [Ca2+-release activating Ca2+ (CRAC) channel], TRPM7, and Clswell[ndash] comprise a network that performs functions vital for ongoing cellular homeostasis and ...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Michael D. Cahalan, K. George Chandy Tags: Review articles Source Type: journals

CRAC channels and Ca2+ signaling in mast cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Mast cells are integral members of the immune system. Upon activation by a rise in cytoplasmic Ca2+, they release a battery of paracrine signals, chemokines, and cytokines, which help sculpt the subsequent immune response. Ca2+ entry through store-operated Ca2+ release-activated Ca2+ (CRAC) channels in the plasma membrane is central for driving most of these responses. The molecular basis of the CRAC channel has been identified, with Orai1 forming the channel pore. Recent work has revealed that a range of mast cell responses are activated by spatially restricted Ca2+ signals just below the plasma membrane. These C...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Joseph Di Capite, Anant B. Parekh Tags: Review articles Source Type: journals

IP3 receptors: some lessons from DT40 cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Inositol-1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca2+ channels that are regulated by IP3 and Ca2+ and are modulated by many additional signals. These properties allow them to initiate and, via Ca2+-induced Ca2+ release, regeneratively propagate Ca2+ signals evoked by receptors that stimulate formation of IP3. The ubiquitous expression of IP3R highlights their importance, but it also presents problems when attempting to resolve the behavior of defined IP3R. DT40 cells are a pre-B-lymphocyte cell line in which high rates of homologous recombination afford unrivalled opportunities to disrupt endogenou...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: Colin W. Taylor, Taufiq Rahman, Stephen C. Tovey, Skarlatos G. Dedos, Emily J. A. Taylor, Saroj Velamakanni Tags: Review articles Source Type: journals

Capacitative calcium entry: from concept to moleculesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Rapid to moderately rapid changes in intracellular Ca2+ concentration, or Ca2+ signals, control a variety of critical cellular functions in the immune system. These signals are comprised of Ca2+ release from intracellular stores coordinated with Ca2+ influx across the plasma membrane. The most common mechanisms by which these two modes of signaling occur is through inositol 1,4,5-trisphosphate (IP3)-induced release of Ca2+ from the endoplasmic reticulum (ER) and store-operated Ca2+ entry across the plasma membrane. The latter process was postulated over 20 years ago, and in just the past few years, the key molecul...
Source: Immunological Reviews - September 9, 2009 Category: Allergy & Immunology Authors: James W. Putney Tags: Review articles Source Type: journals

Calcium signaling in cells of the immune and hematopoietic systemsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Immunological Reviews)
Source: Immunological Reviews - August 31, 2009 Category: Allergy & Immunology Authors: Anjana Rao, Patrick G Hogan Tags: Introduction Source Type: journals

Glycoimmunology: ignore at your peril!Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Immunological Reviews)
Source: Immunological Reviews - June 30, 2009 Category: Allergy & Immunology Authors: Linda G. Baum, Paul R. Crocker Tags: Introduction Source Type: journals

Modulation of host immune responses by helminth glycansEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Parasitic infections regulate/alter host immune responses. Among parasitic infections, helminth infection often leads to systemic immune suppression or anergy. Helminth infection or helminth extracts drive CD4+ T-helper (Th) cell responses towards Th2 type and activate antigen-presenting cells (APCs) such that these cells express an anti-inflammatory phenotype. Among the myriad molecules present on or secreted by helminth parasites, glycans have been shown to be key in inducing Th2-type and anti-inflammatory immune responses. The majority of studies on immune modulatory helminth glycans have focused on Lacto-N-fuc...
Source: Immunological Reviews - June 28, 2009 Category: Allergy & Immunology Authors: Donald A. Harn, Jasmine McDonald, Olga Atochina, Akram A. Da'dara Tags: Review articles Source Type: journals

T-cell growth, cell surface organization, and the galectin–glycoprotein latticeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Basal, activation, and arrest signaling in T cells determines survival, coordinates responses to pathogens, and, when dysregulated, leads to loss of self-tolerance and autoimmunity. At the T-cell surface, transmembrane glycoproteins interact with galectins via their N-glycans, forming a molecular lattice that regulates membrane localization, clustering, and endocytosis of surface receptors. Galectin[ndash]T-cell receptor (TCR) binding prevents ligand-independent TCR signaling via Lck by blocking spontaneous clustering and CD4-Lck recruitment to TCR, and in turn F-actin transfer of TCR/CD4-Lck complexes to membrane...
Source: Immunological Reviews - June 28, 2009 Category: Allergy & Immunology Authors: Ani Grigorian, Sevan Torossian, Michael Demetriou Tags: Review articles Source Type: journals

Immunological functions of hyaluronan and its receptors in the lymphaticsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: The lymphatic system is best known for draining interstitial fluid from the tissues and returning it to the blood circulation. However, the lymphatic system also provides the means for immune surveillance in the immune system, acting as conduits that convey soluble antigens and antigen-presenting cells from the tissues to the lymph nodes, where primary lymphocyte responses are generated. One macromolecule that potentially unites these two functions is the large extracellular matrix glycosaminoglycan hyaluronan (HA), a chemically simple copolymer of GlcNAc and GlcUA that fulfills a diversity of functions from dange...
Source: Immunological Reviews - June 28, 2009 Category: Allergy & Immunology Authors: David G. Jackson Tags: Review articles Source Type: journals

Regulation of Notch signaling during T- and B-cell development by O-fucose glycansEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Notch signaling is required for the development of all T cells and marginal zone (MZ) B cells. Specific roles in T- and B-cell differentiation have been identified for different Notch receptors, the canonical Delta-like (Dll) and Jagged (Jag) Notch ligands, and downstream effectors of Notch signaling. Notch receptors and ligands are post-translationally modified by the addition of glycans to extracellular domain epidermal growth factor-like (EGF) repeats. The O-fucose glycans of Notch cell-autonomously modulate Notch[ndash]ligand interactions and the strength of Notch signaling. These glycans are initiated by prot...
Source: Immunological Reviews - June 28, 2009 Category: Allergy & Immunology Authors: Pamela Stanley, Cynthia J. Guidos Tags: Review articles Source Type: journals

Carbohydrate specificity of the recognition of diverse glycolipids by natural killer T cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: Most T lymphocytes recognize peptide antigens bound to or presented by molecules encoded in the major histocompatibility complex (MHC). The CD1 family of antigen-presenting molecules is related to the MHC-encoded molecules, but CD1 proteins present lipid antigens, mostly glycolipids. Here we review T-lymphocyte recognition of glycolipids, with particular emphasis on the subpopulation known as natural killer T (NKT) cells. NKT cells influence many immune responses, they have a T-cell antigen receptor (TCR) that is restricted in diversity, and they share properties with cells of the innate immune system. NKT cells r...
Source: Immunological Reviews - June 28, 2009 Category: Allergy & Immunology Authors: Dirk M. Zajonc, Mitchell Kronenberg Tags: Review articles Source Type: journals

Galectins in innate immunity: dual functions of host soluble β-galactoside-binding lectins as damage-associated molecular patterns (DAMPs) and as receptors for pathogen-associated molecular patterns (PAMPs)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Summary: The glycocalyx is a glycan layer found on the surfaces of host cells as well as microorganisms and enveloped virus. Its thickness may easily exceed 50 nm. The glycocalyx does not only serve as a physical protective barrier but also contains various structurally different glycans, which provide cell- or microorganism-specific 'glycoinformation'. This information is decoded by host glycan-binding proteins, lectins. The roles of lectins in innate immunity are well established, as exemplified by collectins, dectin-1, and dendritic cell (DC)-specific intracellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). Th...
Source: Immunological Reviews - June 28, 2009 Category: Allergy & Immunology Authors: Sachiko Sato, Christian St-Pierre, Pampa Bhaumik, Julie Nieminen Tags: Review articles Source Type: journals