Role of β-Arrestin in Mediating Agonist-Promoted G Protein-Coupled Receptor Internalization

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Science  19 Jan 1996:
Vol. 271, Issue 5247, pp. 363-366
DOI: 10.1126/science.271.5247.363


β-Arrestins are proteins that bind phosphorylated heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) and contribute to the desensitization of GPCRs by uncoupling the signal transduction process. Resensitization of GPCR responsiveness involves agonist-mediated receptor sequestration. Overexpression of β-arrestins in human embryonic kidney cells rescued the sequestration of β2-adrenergic receptor (β2AR) mutants defective in their ability to sequester, an effect enhanced by simultaneous overexpression of β-adrenergic receptor kinase 1. Wild-type β2AR sequestration was inhibited by the overexpression of two β-arrestin mutants. These findings suggest that β-arrestins play an integral role in GPCR internalization and thus serve a dual role in the regulation of GPCR function.

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