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

Jen Liou, Friedemann Kiefer, Alphons Dang, Ari Hashimoto, Melanie H. Cobb, Tomohiro Kurosaki, Arthur Weiss

Research output: Contribution to journalArticle

85 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)399-408
Number of pages10
JournalImmunity
Volume12
Issue number4
DOIs
StatePublished - Jan 1 2000

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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