Transient hypoxia differentially decreases GRK2 protein levels in CHO cells stably expressing the m1 mAChR

G protein-coupled kinase 2 (GR-K2) has a key role in regulating signaling a ctivities of a variety of G protein-coupled receptors (GPCRs). Several rece nt studies have directly implicated GRK2 phosphorylation in desensitization of GPCRs. In addition, binding by Gp, or phosphorylation by PKC or c-SRC h as been shown to activate or enhance GRK2 activity, respectively. Conversel y, the calcium binding protein calmodulin or the serine/threonine kinase ER K has been implicated in inhibiting GRK2 activity. However, with the except ion of a recent report indicating that activation of beta2-adrenergic recep tor results in the ubiquitination and rapid degradation of GRK2, very littl e is known about cellular mechanisms that alter the protein levels GRK2. He re, we report a novel serendipitous observation regarding alteration GRK2 p rotein levels. Exposure of CHO cells stably expressing the ml muscarinic ac etylcholine receptor (mAChR) to transient hypoxia caused near ablation of t he GRK2 protein. In contrast, GRK2 protein levels remained unchanged in the parental CHO cells or in CHO cells stably expressing the m2 mAChR when exp osed to transient hypoxia. The present study reports a novel observation th at is unveiled by transient hypoxia in which GRK2 protein levels are altere d by cellular mechanisms involving the mi mAChR. (C) 2001 Academic Press.