Activation of ZAP-70 through specific dephosphorylation at the inhibitory Tyr-292 by the low molecular weight phosphotyrosine phosphatase (LMPTP)
Activation of ZAP-70 through specific dephosphorylation at the inhibitory Tyr-292 by the low molecular weight phosphotyrosine phosphatase (LMPTP)
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DOI：
10.1074/jbc.m202885200
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发表时间：
2002-07-05
影响因子：
4.8
通讯作者：
Mustelin, T
中科院分区：
文献类型：
--
作者：
Bottini, N;Stefanini, L;Mustelin, T
ZAP-70蛋白酪氨酸激酶在来自T细胞抗原受体的信号传导中起核心作用。ZAP-70的募集和激活是短暂的，并通过负调节酪氨酸残基的磷酸化和正作用位点的去磷酸化而终止。我们报告，低分子量蛋白酪氨酸磷酸酶（LMPTP）特异性去磷酸化的负调控Tyr-292的ZAP-70，从而抵消ZAP-70的失活。低水平LMPTP的表达导致ZAP-70磷酸化增加，可能是在激活Tyr-493和其他位点，激酶活性增加，并增强了促分裂原活化蛋白激酶途径的下游信号传导。ZAP-70 Y292 F突变体不受LMPTP的影响。我们的研究结果表明，LMPTP，像CD 45，去磷酸化的蛋白质酪氨酸激酶的负调控酪氨酸位点，从而加强T细胞受体信号。
The ZAP-70 protein-tyrosine kinase plays a central role in signaling from the T cell antigen receptor. Recruitment and activation of ZAP-70 are transient and are terminated by phosphorylation of negative regulatory tyrosine residues and dephosphorylation of positively acting sites. We report that the low molecular weight protein-tyrosine phosphatase (LMPTP) specifically dephosphorylates the negative regulatory Tyr-292 of ZAP-70, thereby counteracting inactivation of ZAP-70. Expression of low levels of LMPTP resulted in increased ZAP-70 phosphorylation, presumably at the activating Tyr-493 and other sites, increased kinase activity, and augmented downstream signaling to the mitogen-activated protein kinase pathway. The ZAP-70 Y292F mutant was not affected by LMPTP. Our results indicate that LMPTP, like CD45, dephosphorylates a negative regulatory tyrosine site in a protein-tyrosine kinase and thereby strengthens T cell receptor signaling.