TY - JOUR
T1 - HPK1 is activated by lymphocyte antigen receptors and negatively regulates AP-1
AU - Liou, Jen
AU - Kiefer, Friedemann
AU - Dang, Alphons
AU - Hashimoto, Ari
AU - Cobb, Melanie H.
AU - Kurosaki, Tomohiro
AU - Weiss, Arthur
N1 - Funding Information:
We thank D. Qian for providing the Myc-tagged human HPK1 construct. We thank J. Baker, M. Tomlinson, and J. Lin for critically reading this manuscript and the members of the Weiss laboratory for helpful discussions. This work was supported by a grant from National Cancer Institute (RO1 CA72531).
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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U2 - 10.1016/S1074-7613(00)80192-2
DO - 10.1016/S1074-7613(00)80192-2
M3 - Article
C2 - 10795738
AN - SCOPUS:0033711185
SN - 1074-7613
VL - 12
SP - 399
EP - 408
JO - Immunity
JF - Immunity
IS - 4
ER -