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

Biochem J. 2003 Nov 1;375(Pt 3):503-15. doi: 10.1042/BJ20031076.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • ADP-Ribosylation Factor 6
  • Animals
  • Arrestins / physiology*
  • Biological Transport / physiology
  • Endocytosis / physiology
  • Humans
  • Models, Biological
  • Receptors, G-Protein-Coupled / physiology*
  • Signal Transduction / physiology
  • beta-Arrestins

Substances

  • ADP-Ribosylation Factor 6
  • Arrestins
  • Receptors, G-Protein-Coupled
  • beta-Arrestins
  • ARF6 protein, human