Transient hypoxia differentially decreases GRK2 protein levels in CHO cells stably expressing the m1 mAChR.
G protein-coupled kinase 2 (GRK2) has a key role in regulating signaling activities of a variety of G protein-coupled receptors (GPCRs). Several recent studies have directly implicated GRK2 phosphorylation in desensitization of GPCRs. In addition, binding by G(betagamma) or phosphorylation by PKC or c-Src [corrected] has been shown to activate or enhance GRK2 activity, respectively. Conversely, the calcium binding protein calmodulin or the serine/threonine kinase ERK has been implicated in inhibiting GRK2 activity. However, with the exception of a recent report indicating that activation of beta2-adrenergic receptor results in the ubiquitination and rapid degradation of GRK2, very little is known about cellular mechanisms that alter the protein levels of GRK2 [corrected]. Here, we report a novel serendipitous observation regarding alteration of GRK2 [corrected] protein levels. Exposure of CHO cells stably expressing the m1 muscarinic acetylcholine receptor (mAChR) to transient hypoxia caused near ablation of the GRK2 protein. In contrast, GRK2 protein levels remained unchanged in the parental CHO cells or in CHO cells stably expressing the m2 mAChR when exposed to transient hypoxia. The present study reports a novel observation that is unveiled by transient hypoxia in which GRK2 protein levels are altered by cellular mechanisms involving the m1 mAChR.
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Department of Anatomy and Neurobiology, Neuroscience Institute, Morehouse School of Medicine, MRC Building Room 206, Atlanta, Georgia 30310-1495, USA.
Jackson
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D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D000860:Hypoxia; D015151:Immunoblotting; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000378:metabolism*; D015398:Signal Transduction; D051552:beta-Adrenergic Receptor Kinases
D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D016392:Proto-Oncogene Proteins pp60(c-src); D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D051552:beta-Adrenergic Receptor Kinases; D010100:Oxygen