期刊
EMBO JOURNAL
卷 20, 期 13, 页码 3414-3426出版社
OXFORD UNIV PRESS
DOI: 10.1093/emboj/20.13.3414
关键词
inhibition; lymphocyte; phosphatase; PTP-PEST; Shc
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 She, paxillin, Csk and Gas. The interaction between She 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 She, Pyk2, Fak and Gas, 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.
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