Theilade Juliane, Lerche Hansen Jakob, Haunsø Stig, Sheikh Søren P
Laboratory for Molecular Cardiology and Department of Medicine B, Rigshospitalet 9312, University of Copenhagen, Juliane Mariesvej 20, DK-2100, Copenhagen, Denmark.
FEBS Lett. 2002 May 8;518(1-3):195-9. doi: 10.1016/s0014-5793(02)02701-1.
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.
G蛋白偶联受体激酶2（GRK2）使G蛋白偶联受体磷酸化，导致其与G蛋白解偶联。受体可调节GRK2的表达，然而这种效应的机制基础在很大程度上尚不清楚。在此我们报告一种新机制，即受体利用细胞外信号调节激酶（ERK）级联反应来调节GRK2的细胞水平。受体刺激激活ERK可提高内源性GRK2水平，而拮抗剂处理则降低细胞内GRK2水平。通过过表达组成型活性MEK-1或Ras激活ERK可提高GRK2蛋白水平，而使用PD98059阻断ERK或使用显性负性Ras则消除了这种效应。这些数据表明ERK是GRK2水平的关键调节因子。
