Multifaceted roles of beta-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling.


Journal Article (Review)

Beta-arrestins are cytosolic proteins that bind to activated and phosphorylated G-protein-coupled receptors [7MSRs (seven-membrane-spanning receptors)] and uncouple them from G-protein-mediated second messenger signalling pathways. The binding of beta-arrestins to 7MSRs also leads to new signals via activation of MAPKs (mitogen-activated protein kinases) such as JNK3 (c-Jun N-terminal kinase 3), ERK1/2 (extracellular-signal-regulated kinase 1/2) and p38 MAPKs. By binding to endocytic proteins [clathrin, AP2 (adapter protein 2), NSF (N -ethylmaleimide-sensitive fusion protein) and ARF6 (ADP-ribosylation factor 6)], beta-arrestins also serve as adapters to link the receptors to the cellular trafficking machinery. Agonist-promoted ubiquitination of beta-arrestins is a prerequisite for their role in receptor internalization, as well as a determinant of the differing trafficking patterns of distinct classes of receptors. Recently, beta-arrestins have also been implicated as playing novel roles in cellular chemotaxis and apoptosis. By virtue of their ability to bind, in a stimulus-dependent fashion, to 7MSRs as well as to different classes of cellular proteins, beta-arrestins serve as versatile adapter proteins that regulate the signalling and trafficking of the receptors.

Full Text

Duke Authors

Cited Authors

  • Shenoy, SK; Lefkowitz, RJ

Published Date

  • November 1, 2003

Published In

Volume / Issue

  • 375 / Pt 3

Start / End Page

  • 503 - 515

PubMed ID

  • 12959637

Pubmed Central ID

  • 12959637

Electronic International Standard Serial Number (EISSN)

  • 1470-8728

Digital Object Identifier (DOI)

  • 10.1042/BJ20031076


  • eng

Conference Location

  • England