title: Pathophysiological roles of G-protein-coupled receptor kinases.
abstract: G-protein-coupled receptor kinases (GRKs) interact with the agonist-activated form of G-protein-coupled receptors (GPCRs) to effect receptor phosphorylation and to initiate profound impairment of receptor signalling, or desensitization. GPCRs form the largest family of cell surface receptors known and defects in GRK function have the potential consequence to affect GPCR-stimulated biological responses in many pathological situations. This review focuses on the physiological role of GRKs revealed by genetically modified animals but also develops the involvement of GRKs in human diseases as, Oguchi disease, heart failure, hypertension or rhumatoid arthritis. Furthermore, the regulation of GRK levels in opiate addiction, cancers, psychiatric diseases, cystic fibrosis and cardiac diseases is discussed. Both transgenic mice and human pathologies have demonstrated the importance of GRKs in the signalling pathways of rhodopsin, beta-adrenergic and dopamine-1 receptors. The modulation of GRK activity in animal models of cardiac diseases can be effective to restore cardiac function in heart failure and opens a novel therapeutic strategy in diseases with GPCR dysregulation.
authors.affiliation: Department of Nuclear Medicine and Biophysics, Groupe de Recherche en Endocrinologie Expérimentale et Clinique, CHU de Poitiers, France. t.metaye@chu-poiters.edu
authors.forename: Thierry
authors.initials: T
authors.lastname: Métayé
authors.forename: Hélène
authors.initials: H
authors.lastname: Gibelin
authors.forename: Rémy
authors.initials: R
authors.lastname: Perdrisot
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Kraimps
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D006331:Heart Diseases / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases