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

FEBS Letters

Lerche Hansen, Jakob¹  Theilade, Juliane¹  Haunsø, Stig¹  Sheikh, Søren P¹ 

[1] Laboratory for Molecular Cardiology and Department of Medicine B, Rigshospitalet 9312, University of Copenhagen, Juliane Mariesvej 20, DK-2100 Copenhagen, Denmark

关键词: G protein-coupled receptor;    Receptor desensitisation;    Angiotensin II;    Mitogen activated kinase;    Signal transduction;   

DOI  :  10.1016/S0014-5793(02)02701-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown