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Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the beta1-adrenergic receptor.

dc.contributor.author DeCamilli, P
dc.contributor.author Hall, RA
dc.contributor.author Hu, LA
dc.contributor.author Lefkowitz, Robert J
dc.contributor.author Miller, WE
dc.contributor.author Pitcher, JA
dc.contributor.author Ringstad, N
dc.contributor.author Tang, Y
dc.coverage.spatial United States
dc.date.accessioned 2013-09-05T18:13:44Z
dc.date.issued 1999-10-26
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/10535961
dc.identifier.issn 0027-8424
dc.identifier.uri https://hdl.handle.net/10161/7817
dc.description.abstract Several G-protein coupled receptors, such as the beta1-adrenergic receptor (beta1-AR), contain polyproline motifs within their intracellular domains. Such motifs in other proteins are known to mediate protein-protein interactions such as with Src homology (SH)3 domains. Accordingly, we used the proline-rich third intracellular loop of the beta1-AR either as a glutathione S-transferase fusion protein in biochemical "pull-down" assays or as bait in the yeast two-hybrid system to search for interacting proteins. Both approaches identified SH3p4/p8/p13 (also referred to as endophilin 1/2/3), a SH3 domain-containing protein family, as binding partners for the beta1-AR. In vitro and in human embryonic kidney (HEK) 293 cells, SH3p4 specifically binds to the third intracellular loop of the beta1-AR but not to that of the beta2-AR. Moreover, this interaction is mediated by the C-terminal SH3 domain of SH3p4. Functionally, overexpression of SH3p4 promotes agonist-induced internalization and modestly decreases the Gs coupling efficacy of beta1-ARs in HEK293 cells while having no effect on beta2-ARs. Thus, our studies demonstrate a role of the SH3p4/p8/p13 protein family in beta1-AR signaling and suggest that interaction between proline-rich motifs and SH3-containing proteins may represent a previously underappreciated aspect of G-protein coupled receptor signaling.
dc.language eng
dc.relation.ispartof Proc Natl Acad Sci U S A
dc.subject Adaptor Proteins, Signal Transducing
dc.subject Adrenergic beta-1 Receptor Agonists
dc.subject Animals
dc.subject Carrier Proteins
dc.subject Cattle
dc.subject Cell Line
dc.subject GTP-Binding Protein alpha Subunits, Gs
dc.subject Humans
dc.subject Proline
dc.subject Protein Binding
dc.subject Receptors, Adrenergic, beta-1
dc.subject src Homology Domains
dc.title Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the beta1-adrenergic receptor.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/10535961
pubs.begin-page 12559
pubs.end-page 12564
pubs.issue 22
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biochemistry
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 Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group Trinity College of Arts & Sciences
pubs.publication-status Published
pubs.volume 96


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