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Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase-5 in transgenic mice.

dc.contributor.author Rockman, HA
dc.contributor.author Choi, DJ
dc.contributor.author Rahman, NU
dc.contributor.author Akhter, SA
dc.contributor.author Lefkowitz, RJ
dc.contributor.author Koch, WJ
dc.coverage.spatial United States
dc.date.accessioned 2013-09-10T14:58:58Z
dc.date.issued 1996-09-03
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/8790438
dc.identifier.issn 0027-8424
dc.identifier.uri https://hdl.handle.net/10161/7834
dc.description.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.
dc.language eng
dc.publisher Proceedings of the National Academy of Sciences
dc.relation.ispartof Proc Natl Acad Sci U S A
dc.subject Animals
dc.subject Cyclic AMP-Dependent Protein Kinases
dc.subject G-Protein-Coupled Receptor Kinase 5
dc.subject GTP-Binding Proteins
dc.subject Mice
dc.subject Mice, Transgenic
dc.subject Myocardial Contraction
dc.subject Myocardium
dc.subject Phenotype
dc.subject Protein-Serine-Threonine Kinases
dc.subject RNA, Messenger
dc.subject Receptor Protein-Tyrosine Kinases
dc.subject Receptors, Adrenergic, beta
dc.subject Receptors, Angiotensin
dc.subject beta-Adrenergic Receptor Kinases
dc.title Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase-5 in transgenic mice.
dc.type Journal article
duke.contributor.id Rockman, HA|0223027
duke.contributor.id Lefkowitz, RJ|0096962
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/8790438
pubs.begin-page 9954
pubs.end-page 9959
pubs.issue 18
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biochemistry
pubs.organisational-group Cell Biology
pubs.organisational-group Chemistry
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group Trinity College of Arts & Sciences
pubs.publication-status Published
pubs.volume 93


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