G-protein-coupled receptors and their regulation: activation of the MAP kinase signaling pathway by G-protein-coupled receptors

Adv Second Messenger Phosphoprotein Res. 1997;31:263-77.

Abstract

G-protein-coupled receptors that mediate cellular responses to a variety of humoral, endothelial-, or platelet-derived substances are able to stimulate MAP kinase activity. In transfected model systems, G-protein-coupled receptors that couple to pertussis toxin-insensitive G proteins of the Gq/11 family mediate this activation predominantly via a PKC-dependent mechanism. In contrast, activation of MAP kinase by receptors that couple to pertussis toxin-sensitive Gi proteins is PKC-independent and requires downstream activation of the low-molecular-weight G protein, Ras. This pathway can be inhibited by coexpression of peptides that sequester Gbetagamma subunits, and is mimicked by overexpression of Gbetagamma subunits. This Ras-dependent MAP kinase activation requires tyrosine phosphorylation of "docking proteins," including the shc adapter protein, and depends upon recruitment of Grb2/Sos1 complexes to the plasma membrane, thus resembling the pathway of MAP kinase activation employed by the receptor tyrosine kinases. Other molecules, including PI-3-kinases and phosphotyrosine phosphatases, probably also contribute to Gbetagamma-subunit-mediated assembly of a mitogenic signaling complex. Identification of the G-protein-coupled, receptor-regulated tyrosine kinase(s), and the means by which the mitogenic signaling complex is assembled at the plasma membrane, remain subjects of further study.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Blood Proteins / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Enzyme Activation
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Phosphoproteins*
  • Phosphorylation
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction
  • Tyrosine / metabolism
  • ras Proteins / metabolism

Substances

  • Blood Proteins
  • Phosphoproteins
  • Receptors, Cell Surface
  • platelet protein P47
  • Tyrosine
  • Calcium-Calmodulin-Dependent Protein Kinases
  • GTP-Binding Proteins
  • ras Proteins