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Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference.

dc.contributor.author Ahn, S
dc.contributor.author Garrison, TR
dc.contributor.author Lefkowitz, Robert J
dc.contributor.author Miller, WE
dc.contributor.author Nelson, CD
dc.coverage.spatial United States
dc.date.accessioned 2013-09-05T15:29:13Z
dc.date.issued 2003-02-18
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/12582207
dc.identifier 262789099
dc.identifier.issn 0027-8424
dc.identifier.uri http://hdl.handle.net/10161/7800
dc.description.abstract Beta-arrestins bind to activated G protein-coupled receptor kinase-phosphorylated receptors, which leads to their desensitization with respect to G proteins, internalization via clathrin-coated pits, and signaling via a growing list of "scaffolded" pathways. To facilitate the discovery of novel adaptor and signaling roles of beta-arrestins, we have developed and validated a generally applicable interfering RNA approach for selectively suppressing beta-arrestins 1 or 2 expression by up to 95%. Beta-arrestin depletion in HEK293 cells leads to enhanced cAMP generation in response to beta(2)-adrenergic receptor stimulation, markedly reduced beta(2)-adrenergic receptor and angiotensin II receptor internalization and impaired activation of the MAP kinases ERK 1 and 2 by angiotensin II. This approach should allow discovery of novel signaling and regulatory roles for the beta-arrestins in many seven-membrane-spanning receptor systems.
dc.language eng
dc.relation.ispartof Proc Natl Acad Sci U S A
dc.relation.isversionof 10.1073/pnas.262789099
dc.subject Arrestins
dc.subject Base Sequence
dc.subject Blotting, Western
dc.subject Cell Line
dc.subject DNA Primers
dc.subject Endocytosis
dc.subject Enzyme Activation
dc.subject Humans
dc.subject Mitogen-Activated Protein Kinase 1
dc.subject Mitogen-Activated Protein Kinase 3
dc.subject Mitogen-Activated Protein Kinases
dc.subject Molecular Sequence Data
dc.subject Phosphorylation
dc.subject RNA, Small Interfering
dc.subject Signal Transduction
dc.subject beta-Arrestins
dc.title Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/12582207
pubs.begin-page 1740
pubs.end-page 1744
pubs.issue 4
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 100


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