GRK mythology: G-protein receptor kinases in cardiovascular disease.
G-protein receptor kinases (GRKs) are indispensable for terminating signaling of G-protein coupled receptors (GPCR) through receptor desensitization and downregulation. Increased neurohormone levels in heart failure and the adverse consequences of constant neurohormonal stimulation suggest an important protective role for mechanisms that desensitize neurohormone receptor responses. For that reason, GRK2, the first GRK identified in the heart, has been extensively studied in heart failure, cardiac hypertrophy, and myocardial infarction. However, our understanding of the roles of GRKs in general, and the differential effects of cardiac receptor phosphorylation by individual cardiac-expressed GRKs, have evolved considerably in the last few years. Here, recent developments are reviewed, with an emphasis on novel GRK functions and signaling pathways.
Dorn
Gerald W
GW
Center for Pharmacogenomics, Washington University, 660 S. Euclid Ave., Campus Box 8086, St. Louis, MO 63110, USA. gdorn@dom.wustl.edu
D000818:Animals; D019390:Arrestins / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D054768:G-Protein-Coupled Receptor Kinases / Q000378:metabolism*; D006801:Humans; D008955:Models, Cardiovascular; D010766:Phosphorylation; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D000071557:beta-Arrestins
D019390:Arrestins; D011943:Receptors, Adrenergic, beta; D000071557:beta-Arrestins; D054768:G-Protein-Coupled Receptor Kinases