Igishi T, Gutkind J S
Oral and Pharyngeal Cancer Branch, National Institute of Dental Research, Bethesda, Maryland 20892-4330, USA.
Biochem Biophys Res Commun. 1998 Mar 6;244(1):5-10. doi: 10.1006/bbrc.1998.8208.
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.
Src相关激酶最近被认为参与了从Gi偶联受体到丝裂原活化蛋白激酶（MAP激酶）的信号传导。Src样激酶是否参与由与Gq家族G蛋白偶联的大量受体介导的MAP激酶激活仍不清楚。在此，我们表明，一种Src样激酶的特异性抑制剂，4-氨基-5-（4-甲基苯基）-7-（叔丁基）吡唑并[3,4-d]嘧啶（PP1），以及Src的显性负性突变体，在COS-7细胞中，当由m1和m2毒蕈碱受体引发时，可抑制MAP激酶的激活，m1和m2毒蕈碱受体分别是典型的Gq和Gi偶联受体。此外，显性负性Src也抑制了通过βγ亚基过表达激活的MAP激酶，但不抑制佛波酯刺激激活的MAP激酶。相反，显性负性Pyk2对m1和m2介导的MAP激酶激活只有轻微影响。我们得出结论，位于βγ二聚体下游的Src样激酶在将来自Gq和Gi偶联受体的信号传递给MAP激酶方面发挥重要作用。
