TYROSINE KINASES OF THE SRC FAMILY PARTICIPATE IN SIGNALING TO MAP KINASE FROM BOTH G(Q), AND G(I)-COUPLED RECEPTORS

Src-related kinases have been recently implicated in signaling from G( i)-coupled receptors to MAP kinase. Whether Src-like kinases participa te in MAP kinase activation by the large family of receptors coupled t o G proteins of the G(q) family is still unclear. Here, we show that a specific inhibitor for Src-like kinases, methylphenyl)-7-(t-butyl)pyr azolo[3,4-d]pyrimidine (PP1), and dominant negative mutants of Src sup press MAP kinase activation in COS-7 cells when elicited by either m1 and m2 muscarinic receptors, which are typical G(q) and G(i)-coupled r eceptors, respectively. Furthermore, activation of MAP kinase by overe xpression of beta gamma subunits, but not by stimulation with phorbol esters was also inhibited by the dominant-negative Src. In contrast, a dominant negative Pyk2 had only mild effects on m1 and m2 mediated-MA P kinase activation. We concluded that Src like kinase(s), acting down stream from beta gamma dimers, play an important role relaying signals from both G(q), and G(i)-coupled receptors to MAP kinase. (C) 1998 Ac ademic Press.