Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference.
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.
Type
Journal articleSubject
ArrestinsBase Sequence
Blotting, Western
Cell Line
DNA Primers
Endocytosis
Enzyme Activation
Humans
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
Molecular Sequence Data
Phosphorylation
RNA, Small Interfering
Signal Transduction
beta-Arrestins
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https://hdl.handle.net/10161/7800Published Version (Please cite this version)
10.1073/pnas.262789099Publication Info
Ahn, Seungkirl; Nelson, Christopher D; Garrison, Tiffany Runyan; Miller, William E;
& Lefkowitz, Robert J (2003). Desensitization, internalization, and signaling functions of beta-arrestins demonstrated
by RNA interference. Proc Natl Acad Sci U S A, 100(4). pp. 1740-1744. 10.1073/pnas.262789099. Retrieved from https://hdl.handle.net/10161/7800.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Seungkirl Ahn
Assistant Professor in Medicine
Robert J. Lefkowitz
The Chancellor's Distinguished Professor of Medicine
Dr. Lefkowitz’s memoir, A Funny Thing Happened on the Way to Stockholm, recounts his
early career as a cardiologist and his transition to biochemistry, which led to his
Nobel Prize win.
Robert J. Lefkowitz, M.D. is Chancellor’s Distinguished Professor of Medicine and
Professor of Biochemistry and Chemistry at the Duke University Medical Center. He
has bee
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