HPK1 is activated by lymphocyte antigen receptors and negatively regulatesAP-1

Citation
J. Liou et al., HPK1 is activated by lymphocyte antigen receptors and negatively regulatesAP-1, IMMUNITY, 12(4), 2000, pp. 399-408
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
IMMUNITY
ISSN journal
1074-7613 → ACNP
Volume
12
Issue
4
Year of publication
2000
Pages
399 - 408
Database
ISI
SICI code
1074-7613(200004)12:4<399:HIABLA>2.0.ZU;2-7
Abstract
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 pathw ays. Here, we demonstrate the involvement of HPK1 in antigen receptor signa ling. Engagement of the TCR or the BCR resulted in a marked induction of HP K1 catalytic activity. Subsequent analysis revealed that Src and Syk/ZAP-70 tyrosine kinases and the adaptor proteins LAT, SLP-76, BLNK, Grb2, and Gra p are involved in HPK1 activation. Overexpression of HPK1 inhibited TCR act ivation of AP-1. and ERK2, whereas the kinase-inactive mutant of HPK1 poten tiated these responses. Neither form of HPK1 affected PMA or v-Ras activati on of AP-1 and ERK2. Thus, HPK1 is a negative regulator of the TCR-induced AP-1 response pathway.