HPK1 is activated by lymphocyte antigen receptors and negatively regulates AP-1
HPK1 is activated by lymphocyte antigen receptors and negatively regulates AP-1
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DOI：
10.1016/s1074-7613(00)80192-2
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发表时间：
2000-04-01
期刊：
影响因子：
32.4
通讯作者：
Weiss, A
中科院分区：
文献类型：
--
作者：
Liou, J;Kiefer, F;Weiss, A
丝氨酸/苏氨酸激酶HPK 1是与MAP激酶途径的调节有关的生发中心激酶（GCK）家族的成员。在这里，我们证明了HPK 1参与抗原受体信号传导。TCR或BCR的参与导致HPK 1催化活性的显著诱导。随后的分析显示，Src和Syk/ZAP-70酪氨酸激酶以及衔接蛋白LAT、SLP-76、BLNK、Grb 2和Grap参与HPK 1的激活。HPK 1的过表达抑制AP-1的TCR活化。和ERK 2，而HPK 1的激酶失活突变体增强了这些反应。两种形式的HPK 1都不影响PMA或v-Ras对AP-1和ERK 2的激活。因此，HPK 1是TCR诱导的AP-1反应途径的负调节因子。
The serine/threonine kinase HPK1 is a member of the germinal center kinase (GCK) family that has been implicated in the regulation of MAP kinase pathways. Here, we demonstrate the involvement of HPK1 in antigen receptor signaling. Engagement of the TCR or the BCR resulted in a marked induction of HPK1 catalytic activity. Subsequent analysis revealed that Src and Syk/ZAP-70 tyrosine kinases and the adaptor proteins LAT, SLP-76, BLNK, Grb2, and Grap are involved in HPK1 activation. Overexpression of HPK1 inhibited TCR activation of AP-1. and ERK2, whereas the kinase-inactive mutant of HPK1 potentiated these responses. Neither form of HPK1 affected PMA or v-Ras activation of AP-1 and ERK2. Thus, HPK1 is a negative regulator of the TCR-induced AP-1 response pathway.