Details

Autor(en) / Beteiligte

• Ahn, Seungkirl
• Nelson, Christopher D.
• Garrison, Tiffany Runyan
• Miller, William E.
• Lefkowitz, Robert J.

Titel

Desensitization, Internalization, and Signaling Functions of β-Arrestins Demonstrated by RNA Interference

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2003-02, Vol.100 (4), p.1740-1744

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2003

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• β-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 β-arrestins, we have developed and validated a generally applicable interfering RNA approach for selectively suppressing β-arrestins 1 or 2 expression by up to 95%. β-Arrestin depletion in HEK293 cells leads to enhanced cAMP generation in response to β2-adrenergic receptor stimulation, markedly reduced β2-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.