Tyrosine kinases of the Src family participate in signaling to MAP kinase from both Gq and Gi-coupled receptors.

Src-related kinases have been recently implicated in signaling from Gi-coupled receptors to MAP kinase. Whether Src-like kinases participate in MAP kinase activation by the large family of receptors coupled to G proteins of the Gq family is still unclear. Here, we show that a specific inhibitor for Src-like kinases, 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1), and dominant negative mutants of Src suppress MAP kinase activation in COS-7 cells when elicited by either m1 and m2 muscarinic receptors, which are typical Gq and Gi-coupled receptors, respectively. Furthermore, activation of MAP kinase by overexpression 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-MAP kinase activation. We concluded that Src like kinase(s), acting downstream from beta gamma dimers, play an important role relaying signals from both Gq and Gi-coupled receptors to MAP kinase.