G protein-coupled receptor kinases in cardiovascular disease: why "where" matters.
Cardiac function is mainly controlled by β-adrenergic receptors (β-ARs), members of the G protein-coupled receptor (GPCR) family. GPCR signaling and expression are tightly controlled by G protein-coupled receptor kinases (GRKs), which induce GPCR internalization and signal termination through phosphorylation. Reduced β-AR density and activity associated with elevated cardiac GRK expression and activity have been described in various cardiovascular diseases. Moreover, alterations in extracardiac GRKs have been observed in blood vessels, adrenal glands, kidneys, and fat cells. The broad tissue distribution of GPCRs and GRKs suggests that a keen appreciation of integrative physiology may drive future therapeutic development. In this review, we provide a brief summary of GRK isoforms, subcellular localization, and interacting partners that impinge directly or indirectly on the cardiovascular system. We also discuss GRK/GPCR interactions and their implications in cardiovascular pathophysiology.
The Heart Institute, Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Fadia A
FA
Kamal
Joshua G
JG
Travers
Burns C
BC
Blaxall
D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000503:physiopathology; D054768:G-Protein-Coupled Receptor Kinases / Q000145:classification / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance; D007674:Kidney Diseases / Q000201:enzymology / Q000503:physiopathology; D015394:Molecular Structure; D010766:Phosphorylation; D011941:Receptors, Adrenergic / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D011941:Receptors, Adrenergic; D043562:Receptors, G-Protein-Coupled; D054768:G-Protein-Coupled Receptor Kinases