G protein-coupled receptor kinases

Annu Rev Biochem. 1998;67:653-92. doi: 10.1146/annurev.biochem.67.1.653.

Abstract

G protein-coupled receptor kinases (GRKs) constitute a family of six mammalian serine/threonine protein kinases that phosphorylate agonist-bound, or activated, G protein-coupled receptors (GPCRs) as their primary substrates. GRK-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling, or desensitization. This review focuses on the regulation of GRK activity by a variety of allosteric and other factors: agonist-stimulated GPCRs, beta gamma subunits of heterotrimeric GTP-binding proteins, phospholipid cofactors, the calcium-binding proteins calmodulin and recoverin, posttranslational isoprenylation and palmitoylation, autophosphorylation, and protein kinase C-mediated GRK phosphorylation. Studies employing recombinant, purified proteins, cell culture, and transgenic animal models attest to the general importance of GRKs in regulating a vast array of GPCRs both in vitro and in vivo.

Publication types

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

MeSH terms

  • Allosteric Regulation
  • Animals
  • Disease / etiology
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Mammals
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Receptors, Cell Surface / agonists
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction
  • Substrate Specificity

Substances

  • Receptors, Cell Surface
  • Protein-Serine-Threonine Kinases
  • GTP-Binding Proteins