Negative regulation of T-cell receptor signalling by tyrosine protein kinase p50csk

Chow, Lionel M.L.; Fournel, Marielle; Davidson, Dominique; Veillette, André

doi:10.1038/365156a0

Cited by 264 publications

(233 citation statements)

References 23 publications

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“…Fyn has been shown to play an essential role in the platelet-derived growth factor receptor (51), Ig (52), and T-cell receptor (53) signaling. In addition, we have shown that Fyn is activated during PRL stimulation of Nb2 cells (11,50).…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of the Intermediate Isoform of the Human Prolactin Receptor

Kline

Roehrs

Clevenger

1999

Journal of Biological Chemistry

124

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Section: Discussionmentioning

confidence: 99%

Functional Characterization of the Intermediate Isoform of the Human Prolactin Receptor

Kline

Roehrs

Clevenger

1999

Journal of Biological Chemistry

124

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“…Thus, in order to elucidate whether the weak responses to anti-oxidant treatment were related to ongoing apoptotic cell death, we measured the ratio of apoptotic 14 A. Cayota et al cells by flow cytometry [19,20]. Results depicted in Fig.…”

Section: Anti-oxidant Treatment Restored Cd45-associated Phosphatase mentioning

confidence: 99%

CD4+ lymphocytes from HIV-infected patients display impaired CD45-associated tyrosine phosphatase activity which is enhanced by anti-oxidants

Cayota

Vuillier

González

et al. 1996

Clinical and Experimental Immunology

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SUMMARYIt has been proposed that signal transduction defects may, at least partially, account for the functional impairment of CD4 lymphocytes during HIV-1 infection. Recently, we have demonstrated that unresponsive CD4 lymphocytes from these patients had reduced protein tyrosine phosphorylation after CD3 engagement, and that this defect was associated with constitutively altered levels of p56 lck and p59 fyn kinases. Since CD45 is essential for T cell receptor (TCR) and CD2-mediated activation of protein tyrosine kinases, we study here CD45-associated tyrosine phosphatase activity in resting and activated CD4 T cells from HIV-infected patients. We found a significant decrease in the basal and postactivation phosphatase activity of CD45 which correlated well with impairment of proliferative responses. In addition, decreased levels of cellular thiols observed in resting CD4 lymphocytes from these patients suggested a disturbed redox status. Although expression levels of CD45 were decreased in most patients, a significant recovery of phosphatase activity and proliferative responses was observed in most patients by preincubating cells with N-acetyl-L-cysteine and 2 -mercaptoethanol. In some patients, anti-oxidant treatment failed to significantly enhance phosphatase activity and proliferative responses. The low responses of purified CD4 lymphocytes from these patients were associated with a high ratio of apoptotic cell death which did not appear to be influenced by anti-oxidant treatment.

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“…Rabbit antisera directed against Lck, Fyn, Csk, Chk, Zap-70, Syk, Cbl, Vav, and Shc were described previously (36,(42)(43)(44)(45)(46)(47)(48). Monoclonal antibodies (MAbs) reacting with CD45 (M1.89.18.7), TCR (F23.1 and H57), CD3 (145-2C11 for immunoprecipitation; HMT-3 for immunoblotting), (H146), Thy-1 (G7), CD4 (GK1.5), CD8 (2.43), Tac (7G7), and Myc (9E10) were reported elsewhere.…”

Section: Methodsmentioning

confidence: 99%

Interactions of CD45-associated Protein with the Antigen Receptor Signaling Machinery in T-lymphocytes

Veillette¹,

Soussou²,

Latour³

et al. 1999

Journal of Biological Chemistry

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CD45 is a transmembrane protein tyrosine phosphatase playing an essential role during T-cell activation. This function relates to the ability of CD45 to regulate p56 lck , a cytoplasmic protein tyrosine kinase necessary for T-cell antigen receptor (TCR) signaling. Previous studies have demonstrated that CD45 is constitutively associated in T-lymphocytes with a transmembrane molecule termed CD45-AP (or lymphocyte phosphatase-associated phosphoprotein). Even though the exact role of this polypeptide is unclear, recent analyses of mice lacking CD45-AP have indicated that its expression is also required for optimal T-cell activation. Herein, we wished to understand better the function of CD45-AP. The results of our studies showed that in T-cells, CD45-AP is part of a multimolecular complex that includes not only CD45, but also TCR, the CD4 and CD8 coreceptors, and p56 lck . The association of CD45-AP with TCR, CD4, and CD8 seemed to occur via the shared ability of these molecules to bind CD45. However, binding of CD45-AP to p56 lck could take place in the absence of other lymphoid-specific components, suggesting that it can be direct. Structure-function analyses demonstrated that such an interaction was mediated by an acidic segment in the cytoplasmic region of CD45-AP and by the kinase domain of p56 lck . Interestingly, the ability of CD45-AP to interact with Lck in the absence of other lymphoid-specific molecules was proportional to the degree of catalytic activation of p56 lck . Together, these findings suggest that CD45-AP is an adaptor molecule involved in orchestrating interactions among components of the antigen receptor signaling machinery. Moreover, they raise the possibility that one of the functions of CD45-AP is to recognize activated Lck molecules and bring them into the vicinity of CD45.Activation of T-lymphocytes by antigen is initiated by protein tyrosine phosphorylation (1-4). Although the T-cell antigen receptor (TCR) 1 and the associated CD3 and subunits are devoid of intrinsic protein tyrosine kinase activity, they can recruit two classes of cytoplasmic protein tyrosine kinases to mediate this response, the Src family and the Syk/Zap-70 family. The Src-related enzymes Lck and FynT initiate TCR-mediated signals by phosphorylating a signaling motif in the cytoplasmic domain of CD3 and termed ITAM (for immunoreceptor tyrosine-based activation motif). Following this phosphorylation, the Syk/Zap-70 family kinases are activated through binding of their tandem Src homology 2 (SH2) domains to doubly phosphorylated ITAMs. Together with Src family kinases, Zap-70 and Syk are responsible for subsequent tyrosine phosphorylation of several signal transduction molecules including phospholipase C-␥1, Cbl, Vav, Slp-76, and Lat.CD45 is a 180 -220-kDa transmembrane protein tyrosine phosphatase expressed on all nucleated hemopoietic cells (5, 6). In T-cells it constitutes ϳ10% of all cell surface glycoproteins. Previous studies have shown that CD45 is necessary for T-cell activation because of its ability to promot...

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Negative regulation of T-cell receptor signalling by tyrosine protein kinase p50csk

Cited by 264 publications

References 23 publications

Functional Characterization of the Intermediate Isoform of the Human Prolactin Receptor

Functional Characterization of the Intermediate Isoform of the Human Prolactin Receptor

CD4+ lymphocytes from HIV-infected patients display impaired CD45-associated tyrosine phosphatase activity which is enhanced by anti-oxidants

Interactions of CD45-associated Protein with the Antigen Receptor Signaling Machinery in T-lymphocytes

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