Extracellular signal-regulated kinases control expression of G protein-coupled receptor kinase 2 (GRK2)

FEBS Lett. 2002 May 8;518(1-3):195-9. doi: 10.1016/s0014-5793(02)02701-1.

Abstract

G protein-coupled receptor kinase 2 (GRK2) phosphorylates G protein-coupled receptors resulting in uncoupling from G proteins. Receptors modulate GRK2 expression, however the mechanistic basis for this effect is largely unknown. Here we report a novel mechanism by which receptors use the extracellular signal-regulated kinase (ERK) cascade to regulate GRK2 cellular levels. ERK activation by receptor stimulation elevated endogenous GRK2 while antagonist treatment decreased cellular GRK2. Activating ERK by overexpressing constitutive active MEK-1 or Ras elevated GRK2 protein levels while blocking ERK using PD98059 or dominant negative Ras abolished this effect. These data suggest ERK is a critical regulator of GRK2 levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • COS Cells
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / biosynthesis*
  • Down-Regulation
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • G-Protein-Coupled Receptor Kinase 2
  • MAP Kinase Signaling System / drug effects
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / physiology*
  • Mutation
  • Myocardium / enzymology*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Rats
  • Rats, Wistar
  • Receptor, Angiotensin, Type 1
  • Receptors, Angiotensin / metabolism
  • Up-Regulation
  • beta-Adrenergic Receptor Kinases

Substances

  • Enzyme Inhibitors
  • Flavonoids
  • Receptor, Angiotensin, Type 1
  • Receptors, Angiotensin
  • Cyclic AMP-Dependent Protein Kinases
  • Grk2 protein, rat
  • beta-Adrenergic Receptor Kinases
  • G-Protein-Coupled Receptor Kinase 2
  • Mitogen-Activated Protein Kinases
  • Proto-Oncogene Proteins p21(ras)
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one