A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation

I. Dikic, G. Tokiwa, S. Lev, Sara Courtneidge, J. Schlessinger

Research output: Contribution to journalArticle

854 Scopus citations

Abstract

THE mechanisms by which mitogenic G-protein-coupled receptors activate the MAP kinase signalling pathway are poorly understood. Candidate protein tyrosine kinases that link G-protein-coupled receptors with MAP kinase include Src family kinases, the epidermal growth factor receptor, Lyn and Syk. Here we show that lysophosphatidic acid (LPA) and bradykinin induce tyrosine phosphorylation of Pyk2 and complex formation between Pyk2 and activated Src. Moreover, tyrosine phosphorylation of Pyk2 leads to binding of the SH2 domain of Src to tyrosine 402 of Pyk2 and activation of Src. Transient overexpression of a dominant interfering mutant of Pyk2 or the protein tyrosine kinase Csk reduces LPA- or bradykinin-induced activation of MAP kinase. LPA-or bradykinin-induced MAP kinase activation was also inhibited by overexpression of dominant interfering mutants of Grb2 and Sos. We propose that Pyk2 acts with Src to link G(i)- and G(q)-coupled receptors with Grb2 and Sos to activate the MAP kinase signalling pathway in PCI2 cells.

Original languageEnglish (US)
Pages (from-to)547-550
Number of pages4
JournalNature
Volume383
Issue number6600
DOIs
Publication statusPublished - 1996
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this