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Beta-agonist- and prostaglandin E1-induced translocation of the beta-adrenergic receptor kinase: evidence that the kinase may act on multiple adenylate cyclase-coupled receptors.

dc.contributor.author Benovic, JL
dc.contributor.author Caron, MG
dc.contributor.author Lefkowitz, Robert J
dc.contributor.author Strasser, RH
dc.coverage.spatial United States
dc.date.accessioned 2013-09-24T18:15:16Z
dc.date.issued 1986-09
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/3018728
dc.identifier.issn 0027-8424
dc.identifier.uri http://hdl.handle.net/10161/7878
dc.description.abstract beta-Adrenergic receptor kinase (beta-AR kinase) is a cytosolic enzyme that phosphorylates the beta-adrenergic receptor only when it is occupied by an agonist [Benovic, J. Strasser, R. H., Caron, M. G. & Lefkowitz, R. J. (1986) Proc. Natl. Acad. Sci. USA 83, 2797-2801.] It may be crucially involved in the processes that lead to homologous or agonist-specific desensitization of the receptor. Stimulation of DDT1MF-2 hamster smooth muscle cells or S49 mouse lymphoma cells with a beta-agonist leads to translocation of 80-90% of the beta-AR kinase activity from the cytosol to the plasma membrane. The translocation process is quite rapid, is concurrent with receptor phosphorylation, and precedes receptor desensitization and sequestration. It is also transient, since much of the activity returns to the cytosol as the receptors become sequestered. Stimulation of beta-AR kinase translocation is a receptor-mediated event, since the beta-antagonist propranolol blocks the effect of agonist. In the kin- mutant of the S49 cells (lacks cAMP-dependent protein kinase), prostaglandin E1, which provokes homologous desensitization of its own receptor, is at least as effective as isoproterenol in promoting beta-AR kinase translocation to the plasma membrane. However, in the DDT1MF-2 cells, which contain alpha 1-adrenergic receptors coupled to phosphatidylinositol turnover, the alpha 1-agonist phenylephrine is ineffective. These results suggest that the first step in homologous desensitization of the beta-adrenergic receptor may be an agonist-promoted translocation of beta-AR kinase from cytosol to plasma membrane and that beta-AR kinase may represent a more general adenylate cyclase-coupled receptor kinase that participates in regulating the function of many such receptors.
dc.language eng
dc.relation.ispartof Proc Natl Acad Sci U S A
dc.subject Alprostadil
dc.subject Animals
dc.subject Cell Compartmentation
dc.subject Cell Line
dc.subject Cell Membrane
dc.subject Cytosol
dc.subject Isoproterenol
dc.subject Mice
dc.subject Phosphorylation
dc.subject Protein Kinases
dc.subject Receptors, Adrenergic, beta
dc.title Beta-agonist- and prostaglandin E1-induced translocation of the beta-adrenergic receptor kinase: evidence that the kinase may act on multiple adenylate cyclase-coupled receptors.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/3018728
pubs.begin-page 6362
pubs.end-page 6366
pubs.issue 17
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 Duke Institute for Brain Sciences
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Neurobiology
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group Trinity College of Arts & Sciences
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 83


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