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PTP‐PEST, a scaffold protein tyrosine phosphatase, negatively regulates lymphocyte activation by targeting a unique set of substrates
Author(s) -
Davidson Dominique,
Veillette André
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.13.3414
Subject(s) - biology , protein tyrosine phosphatase , microbiology and biotechnology , phosphatase , scaffold , lymphocyte activation , scaffold protein , tyrosine , protein phosphatase 2 , biochemistry , phosphorylation , immunology , signal transduction , immune system , t cell , medicine , biomedical engineering
There is increasing interest in elucidating the mechanisms involved in the negative regulation of lymphocyte activation. Herein, we show that the cytosolic protein tyrosine phosphatase PTP‐PEST is expressed abundantly in a wide variety of haemopoietic cell types, including B cells and T cells. In a model B‐cell line, PTP‐PEST was found to be constitutively associated with several signalling molecules, including Shc, paxillin, Csk and Cas. The interaction between Shc and PTP‐PEST was augmented further by antigen receptor stimulation. Overexpression studies, antisense experiments and structure–function analyses provided evidence that PTP‐PEST is an efficient negative regulator of lymphocyte activation. This function correlated with the ability of PTP‐PEST to induce dephosphorylation of Shc, Pyk2, Fak and Cas, and inactivate the Ras pathway. Taken together, these data suggest that PTP‐PEST is a novel and unique component of the inhibitory signalling machinery in lymphocytes.