title: Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase-5 in transgenic mice.
abstract: Transgenic mice were generated with cardiac-specific overexpression of the G protein-coupled receptor kinase-5 (GRK5), a serine/threonine kinase most abundantly expressed in the heart compared with other tissues. Animals overexpressing GRK5 showed marked beta-adrenergic receptor desensitization in both the anesthetized and conscious state compared with nontransgenic control mice, while the contractile response to angiotensin II receptor stimulation was unchanged. In contrast, the angiotensin II-induced rise in contractility was significantly attenuated in transgenic mice overexpressing the beta-adrenergic receptor kinase-1, another member of the GRK family. These data suggest that myocardial overexpression of GRK5 results in selective uncoupling of G protein-coupled receptors and demonstrate that receptor specificity of the GRKs may be important in determining the physiological phenotype.
authors.affiliation: Department of Medicine, University of California San Diego School of Medicine, La Jolla 92093, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Rockman
authors.forename: D J
authors.initials: DJ
authors.lastname: Choi
authors.forename: N U
authors.initials: NU
authors.lastname: Rahman
authors.forename: S A
authors.initials: SA
authors.lastname: Akhter
authors.forename: R J
authors.initials: RJ
authors.lastname: Lefkowitz
authors.forename: W J
authors.initials: WJ
authors.lastname: Koch
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D054774:G-Protein-Coupled Receptor Kinase 5; D019204:GTP-Binding Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D051552:beta-Adrenergic Receptor Kinases
chemical_list: D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D011945:Receptors, Angiotensin; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D054774:G-Protein-Coupled Receptor Kinase 5; C517895:Grk5 protein, mouse; D019204:GTP-Binding Proteins