期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：4
页码：1740-1744
DOI：10.1073/pnas.262789099
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：{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.
