Deubiquitinases and their emerging roles in β-arrestin-mediated signaling.

Journal Article (Journal Article)

The two homologous mammalian proteins called β-arrestin1 (also known as arrestin2) and β-arrestin2 (also called arrestin3) are now widely accepted as endocytic and signaling adaptors for G protein-coupled receptors (GPCRs), growth factor receptors, and ion channels. The sustained interactions of β-arrestins with activated GPCRs have been shown to correlate with the agonist-induced ubiquitination on distinct domains in the β-arrestin molecule. Additionally, ubiquitination of β-arrestin promotes its interaction with proteins that mediate endocytosis (e.g., clathrin) and signaling (e.g., c-RAF). Recent studies have demonstrated that deubiquitination of β-arrestin by specific deubiquitinating enzymes (DUBs) acts as an important regulatory mechanism, which determines the stability of β-arrestin-GPCR binding and fine-tunes β-arrestin-dependent signaling to downstream kinases. Accordingly, ubiquitination/deubiquitination of β-arrestin can serve as an on/off switch for its signaling and endocytic functions. Moreover, by regulating the stability and localization of signalosomes, deubiquitination of β-arrestins by DUBs imparts spatial and temporal resolution in GPCR signaling.

Full Text

Duke Authors

Cited Authors

  • Shenoy, SK

Published Date

  • 2014

Published In

Volume / Issue

  • 535 /

Start / End Page

  • 351 - 370

PubMed ID

  • 24377933

Electronic International Standard Serial Number (EISSN)

  • 1557-7988

Digital Object Identifier (DOI)

  • 10.1016/B978-0-12-397925-4.00020-1


  • eng

Conference Location

  • United States