Regulation of T-Cell Antigen Receptor Signalling by Syk Tyrosine Protein Kinase

Latour, Sylvain; Fournel, Marielle; Veillette, André

doi:10.1128/mcb.17.8.4434

Cited by 70 publications

(82 citation statements)

References 43 publications

(59 reference statements)

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“…Syk is associated with the T-cell receptor prior to the stimulation, and CD3 engagement induces activation of Syk, independent of Lck or CD45 (32,33). In addition, Syk augments tyrosine phosphorylation of CD3 to stimulate the kinase activity of Syk by itself (34). We have demonstrated that 3BP2 is preferentially tyrosine-phosphorylated by Syk in COS-7 cells.…”

Section: Phosphorylation Of Tyr 446 But Not the Sh2 Domain Of 3bp2 Comentioning

confidence: 76%

Adaptor Protein 3BP2 Is a Potential Ligand of Src Homology 2 and 3 Domains of Lyn Protein-tyrosine Kinase

Maeno

Sada

Kyo

et al. 2003

Journal of Biological Chemistry

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Adaptor protein 3BP2 was originally isolated as a proteintyrosine kinase c-Abl-Src homology 3 (SH3) 1 domain-binding protein of unknown function (1). 3BP2 was also identified as a Syk kinase-interacting protein by the yeast two-hybrid screening (2). Transient overexpression of 3BP2 resulted in a transcriptional activation of nuclear factor of activated T cell and activator protein 1, which is induced by T-cell receptor aggregation. Ser 225 and Ser 277 of 3BP2 were identified as essential sites for interacting with 14-3-3 to negatively regulate the function of 3BP2 in lymphocytes (3). Moreover, infection of 3BP2 wild type into NK cells by vaccinia virus enhanced cell cytotoxicity. An in vitro binding study suggested that phosphorylation of Tyr 183 of 3BP2 could be associated with Vav and phospholipase C-␥ (4). In mast cells, overexpression of the 3BP2-SH2 domain suppressed high affinity IgE receptor (Fc⑀RI)-mediated tyrosine phosphorylation of phospholipase C-␥, Ca 2ϩ mobilization, and degranulation (5). These findings have demonstrated that 3BP2 plays a critical role in hematopoietic cells.To propagate the immunoreceptor signal, adaptor proteins contribute to protein-protein and protein-lipid interactions through multiple domains and/or specific phosphotyrosine-containing sequences. Tyrosine phosphorylation of 3BP2 was observed in NK cells and mast cells by cross-linking Fc␥R and Fc⑀RI, respectively (4, 5). To elucidate the function of 3BP2, it is necessary to determine the protein-tyrosine kinase (PTK) that phosphorylates 3BP2 and its binding partner to assemble a signaling complex through specific phosphotyrosine-containing motifs in 3BP2.The Src family PTK Lyn is associated with Fc⑀RI␤. Upon aggregation of Fc⑀RI, Lyn is critical for phosphorylating Fc⑀RI␤ and -␥ subunits on Tyr residues within the immunoreceptor tyrosine-based activating motif (ITAM) (6 -8). By analogy with studies on Hck, Lyn is thought to be activated by the disassembly of the closed intramolecular interaction by (i) CD45-mediated dephosphorylation of C-terminal regulatory Tyr residue, (ii) binding to SH3 and SH2 ligands, and (iii) autophosphorylation of Tyr in the activation loop (9). What is the binding ligand of the SH3 and SH2 domains of Lyn in Fc⑀RI signaling pathway? Pull-down experiments using glutathione S-transferase (GST)-Lyn-SH2 fusion protein indicated that there were multiple phosphoproteins interacting with the Lyn-SH2 after the antigen stimulation of RBL-2H3 cells (10). In addition, although the displacement of intramolecular SH3 interaction is not well understood, it seems likely that some aggregation-induced change in an associated molecule provides a higher affinity SH3 ligand that binds to the Lyn-SH3 domain (11). The SH3 domain is directed toward the proline-rich region, but such a ligand has not been identified yet in the Fc⑀RI signaling.We isolated nonreceptor type PTK Syk from porcine spleen (12). Syk is expressed in hematopoietic, epithelial, and endothelial cells (13)(14)(15)(16). When the ITAM of Fc⑀RI␥ subunits is...

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Section: Phosphorylation Of Tyr 446 But Not the Sh2 Domain Of 3bp2 Comentioning

confidence: 76%

Adaptor Protein 3BP2 Is a Potential Ligand of Src Homology 2 and 3 Domains of Lyn Protein-tyrosine Kinase

Maeno

Sada

Kyo

et al. 2003

Journal of Biological Chemistry

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“…In the standard model of TCR signaling, phosphorylation of ITAM on the CD3 subunits by Src family kinases is a prerequisite for Syk family kinases to bind and become activated. While this appears to be true for Zap70, Syk can be activated by TCR signaling even in the absence of Src family kinase activation, probably because, unlike Zap70, it can phosphorylate the ITAM directly [35][36][37]. Despite this, Zap70 has been reported to be much better than Syk at promoting phosphorylation of the TCRf chain by recruiting Lck to the signaling complex [38].…”

Section: Discussionmentioning

confidence: 99%

Redundant role for Zap70 in B cell development and activation

Fallah-Arani

Schweighoffer²,

Vanes³

et al. 2008

Eur J Immunol

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Expression of the Syk family tyrosine kinase Zap70 is strongly correlated with poor clinical outcome in chronic lymphocytic leukemia, the most common human leukemia characterized by B cell accumulation. The expression of Zap70 may reflect the specific cell of origin of the tumor or may contribute to pathology. Thus, the normal role of Zap70 in B cell physiology is of great interest. While initial studies reported that Zap70 expression in the mouse was limited to T and NK cells, more recent work has shown expression in early B cell progenitors and in splenic B cells, suggesting that the kinase may play a role in the development or activation of B cells. In this study, we show that Zap70 is expressed in all developing subsets of B cells as well as in recirculating B cells, marginal zone B cells and peritoneal B1 cells. Analysis of Zap70-deficient mice shows no unique role for Zap70 in either the development of B cells or in their in vitro and in vivo activation. However, we show that Zap70 can rescue the defective positive selection of immature B cells into the recirculating pool in Syk-deficient mice, demonstrating functional redundancy between these two kinases.

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“…Full protection of these riboprobes by cellular luciferase transcripts resulted in a 282-nucleotide fragment. Size markers were prepared by end-labeling MspI-digested pBR322 fragments with Klenow DNA polymerase and [␣- Transfections-BI-141 cells were stably transfected by electroporation (260 V, 960 microfarads) and selected in the presence of G418 (0.75 mg/ml), according to a protocol described elsewhere (36). Monoclonal cell lines expressing the transfected cDNAs were identified by a combination of RNase protection assays and immunoprecipitations (data not shown).…”

Section: Methodsmentioning

confidence: 99%

Regulation of SOCS-1 Expression by Translational Repression

Gregorieff¹,

Pyronnet²,

Sonenberg³

et al. 2000

Journal of Biological Chemistry

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Accumulating evidence demonstrates that cytokine receptor signaling is negatively regulated by a family of Src homology 2 domain-containing adaptor molecules termed SOCS (suppressor of cytokine signaling). Previous studies have indicated that the expression of SOCSrelated molecules is tightly controlled at the level of transcription. Furthermore, it has been reported that SOCS polypeptides are relatively unstable in cells, unless they are associated with elongins B and C. Herein, we document the existence of a third mechanism of regulation of SOCS function. Our data showed that expression of SOCS-1, a member of the SOCS family, is strongly repressed at the level of translation initiation. Structure-function analyses indicated that this effect is mediated by the 5 untranslated region of socs-1 and that it relates to the presence of two upstream AUGs in this region. Further studies revealed that socs-1 translation is cap-dependent and that it is modulated by eIF4E-binding proteins. In combination, these results uncover a novel level of regulation of SOCS-related molecules. Moreover, coupled with previous findings, they suggest that SOCS expression is tightly regulated through multiple mechanisms, in order to avoid inappropriate interference with cytokine-mediated effects. Cytokines such as interleukins (ILs)1 and interferons (IFNs) play pivotal roles in a wide spectrum of processes (1-3). For example, they are required for normal hemopoietic cell development and immunity. Moreover, they participate in the pathophysiology of various autoimmune disorders like rheumatoid arthritis and systemic lupus erythematosus. Cytokines mediate their biological effects by binding to specific transmembrane receptors on target cells. As is the case for many other receptors, engagement of these receptors triggers the tyrosine phosphorylation of cellular proteins, including the cytokine receptors themselves, members of the Jak family of proteintyrosine kinases, and the STAT transcription factors. Since cytokine receptors are devoid of intrinsic protein-tyrosine kinase activity, these phosphorylation events necessitate the participation of cytoplasmic protein-tyrosine kinases. Accumulating data show that receptor-associated Jak kinases are activated upon ligand stimulation, thus allowing tyrosine phosphorylation of the receptor and subsequent recruitment and activation of Src homology 2 domain-containing effectors such as the STATs.Given the deleterious consequences of excessive cytokine stimulation, there has been significant interest in identifying mechanisms restricting their effects. The protein-tyrosine phosphatase SHP-1 and possibly its relative SHP-2 have been shown to play important roles in this process, by dephosphorylating the cytokine receptors and the Jak kinases (4 -6). Additionally, a new group of molecules termed PIAS (protein inhibitor of activated STAT) was found to inhibit STAT function by interfering with their ability to bind DNA (7, 8). Finally, members of the SOCS (suppressor of cytokine signaling) family of ada...

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Regulation of T-Cell Antigen Receptor Signalling by Syk Tyrosine Protein Kinase

Cited by 70 publications

References 43 publications

Adaptor Protein 3BP2 Is a Potential Ligand of Src Homology 2 and 3 Domains of Lyn Protein-tyrosine Kinase

Adaptor Protein 3BP2 Is a Potential Ligand of Src Homology 2 and 3 Domains of Lyn Protein-tyrosine Kinase

Redundant role for Zap70 in B cell development and activation

Regulation of SOCS-1 Expression by Translational Repression

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