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

Biochem Pharmacol. 1998 Aug 1;56(3):269-77. doi: 10.1016/s0006-2952(98)00059-8.


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 (p44mapk and p42mapk, 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 Galpha and Gbetagamma subunits involving a common signaling pathway with receptor-tyrosine-kinases. Gbetagamma-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 Gbetagamma proteins in a pathway involving Rho family proteins including RhoA, Rac1, and Cdc42.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Enzyme Activation
  • GTP-Binding Proteins / physiology*
  • Humans
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinases / metabolism
  • Signal Transduction*


  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • GTP-Binding Proteins