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Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection.

dc.contributor.author Barki-Harrington, L
dc.contributor.author Chen, J
dc.contributor.author Le Corvoisier, P
dc.contributor.author Lefkowitz, Robert J
dc.contributor.author Lemaire, A
dc.contributor.author Naga Prasad, SV
dc.contributor.author Noma, T
dc.contributor.author Rockman, Howard A
dc.contributor.author Tilley, DG
dc.contributor.author Violin, JD
dc.contributor.author Wei, H
dc.coverage.spatial United States
dc.date.accessioned 2012-10-24T18:01:01Z
dc.date.issued 2007-09
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/17786238
dc.identifier.issn 0021-9738
dc.identifier.uri https://hdl.handle.net/10161/5925
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.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.issue 9
duke.description.volume 117
dc.relation.journal Journal of Clinical Investigation
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/17786238
pubs.begin-page 2445
pubs.end-page 2458
pubs.issue 9
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 117


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