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

1996; American Association for the Advancement of Science; Volume: 271; Issue: 5247 Linguagem: Inglês

10.1126/science.271.5247.363

1095-9203

Stephen S. G. Ferguson, William E. Downey, Anne-Marie Colapietro, Larry S. Barak, Luc Ménard, Marc G. Caron,

Pharmacogenetics and Drug Metabolism

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 β 2 -adrenergic receptor (β 2 AR) mutants defective in their ability to sequester, an effect enhanced by simultaneous overexpression of β-adrenergic receptor kinase 1. Wild-type β 2 AR 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.