Show simple item record Noma, T Lemaire, A Naga Prasad, SV Barki-Harrington, L Tilley, DG Chen, J Le Corvoisier, P Violin, JD Wei, H Lefkowitz, RJ Rockman, HA
dc.coverage.spatial United States 2012-10-24T18:01:01Z 2007-09
dc.identifier.citation J Clin Invest, 2007, 117 (9), pp. 2445 - 2458
dc.identifier.issn 0021-9738
dc.description.abstract Deleterious effects on the heart from chronic stimulation of beta-adrenergic receptors (betaARs), members of the 7 transmembrane receptor family, have classically been shown to result from Gs-dependent adenylyl cyclase activation. Here, we identify a new signaling mechanism using both in vitro and in vivo systems whereby beta-arrestins mediate beta1AR signaling to the EGFR. This beta-arrestin-dependent transactivation of the EGFR, which is independent of G protein activation, requires the G protein-coupled receptor kinases 5 and 6. In mice undergoing chronic sympathetic stimulation, this novel signaling pathway is shown to promote activation of cardioprotective pathways that counteract the effects of catecholamine toxicity. These findings suggest that drugs that act as classical antagonists for G protein signaling, but also stimulate signaling via beta-arrestin-mediated cytoprotective pathways, would represent a novel class of agents that could be developed for multiple members of the 7 transmembrane receptor family.
dc.format.extent 2445 - 2458
dc.language eng
dc.relation.ispartof J Clin Invest
dc.relation.isversionof 10.1172/JCI31901
dc.subject Animals
dc.subject Arrestins
dc.subject Cell Line
dc.subject Heart
dc.subject Humans
dc.subject Mice
dc.subject Mice, Transgenic
dc.subject Mutation
dc.subject Myocardium
dc.subject Phosphorylation
dc.subject Protein Binding
dc.subject Protein-Serine-Threonine Kinases
dc.subject Receptor, Epidermal Growth Factor
dc.subject Receptors, Adrenergic, beta-1
dc.subject Signal Transduction
dc.subject Transcriptional Activation
dc.subject beta-Arrestins
dc.title Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection.
dc.type Journal Article
duke.description.endpage 2458 en_US
duke.description.issue 9 en_US
duke.description.startpage 2445 en_US
duke.description.volume 117 en_US
dc.relation.journal Journal of Clinical Investigation en_US
pubs.issue 9
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Biochemistry
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Cell Biology
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Molecular Genetics and Microbiology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Cardiology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.organisational-group /Duke/Trinity College of Arts & Sciences
pubs.organisational-group /Duke/Trinity College of Arts & Sciences/Chemistry
pubs.publication-status Published
pubs.volume 117

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