Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference.
| dc.contributor.author | Ahn, Seungkirl | |
| dc.contributor.author | Nelson, Christopher D | |
| dc.contributor.author | Garrison, Tiffany Runyan | |
| dc.contributor.author | Miller, William E | |
| dc.contributor.author | Lefkowitz, Robert J | |
| dc.coverage.spatial | United States | |
| dc.date.accessioned | 2013-09-05T15:29:13Z | |
| dc.date.issued | 2003-02-18 | |
| 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.identifier | ||
| dc.identifier | 262789099 | |
| dc.identifier.issn | 0027-8424 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Proceedings of the National Academy of Sciences | |
| 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 | |
| duke.contributor.orcid | Ahn, Seungkirl|0000-0001-5681-3789 | |
| duke.contributor.orcid | Lefkowitz, Robert J|0000-0003-1472-7545 | |
| pubs.author-url | ||
| 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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