Signaling from G-protein-coupled receptors to mitogen-activated protein (MAP)-kinase cascades

Heterotrimeric GTP binding protein (G-protein)-coupled receptors are able to induce a variety of responses including cell proliferation, differentiation, and activation of several intracellular kinase cascades. Prominent among these kinases are the activation of mitogen-activated protein (MAP) kinase, including the extracellular signal regulated kinases (ERKs), ERK1 and ERK2 (p44(mapk) and p42(mapk), respectively); stress-activated protein kinases (SAPKs/JNKs); and p38 kinase. These receptors signal through G-proteins. Recent data have shown that the activation of mitogen activated protein/ERK kinase induced by G-protein-coupled receptors is mediated by both G alpha and G beta gamma subunits involving a common signaling pathway with receptor-tyrosine-kinases. G beta gamma-mediated mitogen-activated protein kinase activation is mediated by activation of phosphoinositide 3-kinase, followed by a tyrosine phosphorylation event, and proceeds in a sequence of events that involve functional association among the adaptor proteins Shc, Grb2, and Sos. SAPKs/JNKs and p38 are able to be activated by G beta gamma proteins in a pathway involving Rho family proteins including RhoA, Rac1 and Cdc42. BIOCHEM PHARMACOL 56;3:269-277, 1998. (C) 1998 Elsevier Science Inc.