Journal
FEBS LETTERS
Volume 518, Issue 1-3, Pages 195-199Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(02)02701-1
Keywords
G protein-coupled receptor; receptor desensitisation; angiotensin II; mitogen activated kinase; signal transduction
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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 ERR 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. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
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