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Updated: Aug 9, 2026

A High-content Imaging Workflow to Study Grb2 Signaling Complexes by Expression Cloning
Published on: October 30, 2012
Extracellular signal-regulated kinases control expression of G protein-coupled receptor kinase 2 (GRK2)
Juliane Theilade1, Jakob Lerche Hansen, Stig Haunsø
1Laboratory for Molecular Cardiology and Department of Medicine B, Rigshospitalet 9312, University of Copenhagen, Juliane Mariesvej 20, DK-2100, Copenhagen, Denmark.
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.
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