HPK1 is activated by lymphocyte antigen receptors and negatively regulates AP-1

被引:113
作者
Liou, J
Kiefer, F
Dang, A
Hashimoto, A
Cobb, MH
Kurosaki, T
Weiss, A [1 ]
机构
[1] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Med, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
[2] Max Planck Inst Physiol & Clin Res, WG Kerckhoff Inst, D-61231 Bad Nauheim, Germany
[3] Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA
[4] Kansai Med Univ, Dept Mol Genet, Inst Liver Res, Moriguchi, Osaka 5708506, Japan
关键词
D O I
10.1016/S1074-7613(00)80192-2
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:399 / 408
页数:10
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