PTP-PEST, a scaffold protein tyrosine phosphatase, negatively regulates lymphocyte activation by targeting a unique set of substrates
PTP-PEST, a scaffold protein tyrosine phosphatase, negatively regulates lymphocyte activation by targeting a unique set of substrates
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DOI：
10.1093/emboj/20.13.3414
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发表时间：
2001-07-02
期刊：
影响因子：
11.4
通讯作者：
Veillette, A
中科院分区：
文献类型：
--
作者：
Davidson, D;Veillette, A
阐明淋巴细胞活化的负调节机制越来越受到人们的关注。在此，我们表明，胞浆蛋白酪氨酸磷酸酶PTP-PEST在各种各样的造血细胞类型，包括B细胞和T细胞中大量表达。在模型B细胞系中，发现PTP-PEST与几种信号分子组成性相关，包括She、桩蛋白、Csk和Gas。抗原受体刺激进一步增强She与PTP-PEST之间的相互作用。过量表达研究、反义实验和结构功能分析证明PTP-PEST是一种有效的淋巴细胞活化负调节因子。该功能与PTP-PEST诱导She、Pyk 2、Fak和Gas去磷酸化以及阻断Ras途径的能力相关。两者合计，这些数据表明，PTP-PEST是一个新的和独特的组成部分，在淋巴细胞中的抑制性信号传导机制。
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.