Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling
Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling
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DOI：
10.1126/science.272.5265.1173
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发表时间：
1996-05-24
期刊：
影响因子：
56.9
通讯作者：
Thomas, ML
中科院分区：
文献类型：
--
作者：
Plas, DR;Johnson, R;Thomas, ML
抗原触发淋巴细胞激活的阈值由调节酪氨酸磷酸化的酶设定。当T细胞被激活时，蛋白酪氨酸磷酸酶SHP-1被发现与蛋白酪氨酸激酶ZAP-70结合。这种相互作用导致SHP-1磷酸酶活性增加，而ZAP-70激酶活性降低。在T细胞中表达SHP-1的显性负性突变体可提高抗原受体的敏感性。因此，SHP-1作为T细胞抗原受体的负调节因子，并在设定激活阈值方面发挥作用。
The threshold at which antigen triggers lymphocyte activation is set by the enzymes that regulate tyrosine phosphorylation. Upon T cell activation, the protein tyrosine phosphatase SHP-1 was found to bind to the protein tyrosine kinase ZAP-70. This interaction resulted in an increase in SHP-1 phosphatase activity and a decrease in ZAP-70 kinase activity. Expression of a dominant negative mutant of SHP-1 in T cells increased the sensitivity of the antigen receptor. Thus, SHP-1 functions as a negative regulator of the T cell antigen receptor and in setting the threshold of activation.