Arrestins and protein ubiquitination.


Journal Article (Review)

The adaptor proteins, β-arrestins 1 and 2, were originally identified as inhibitors of G protein signaling at the seven-transmembrane receptors (7TMRs, also called G protein-coupled receptors or GPCRs). Subsequent studies have established β-arrestins as critical multifunctional 7TMR adaptors that mediate receptor trafficking and activate G protein-independent signaling pathways. 7TMR activation leads not only to the recruitment of arrestin proteins upon phosphorylation by GPCR kinases but also to β-arrestin ubiquitination. This posttranslational modification of β-arrestin is appended by specific E3 ubiquitin ligases and reversed by deubiquitinases, which are also recruited in a receptor- and agonist-specific manner. β-Arrestin ubiquitination allows it to form protein complexes with activated 7TMRs, endocytic proteins such as clathrin, and phosphorylated ERK1/2. β-Arrestin ubiquitination is dependent on its activated conformation and likely regulates timing and subcellular localization of various protein interactions during receptor trafficking and signaling. β-Arrestins also serve as adaptors that escort E3 ubiquitin ligases to mediate ubiquitination of a wide list of substrate proteins including 7TMRs and provide an added layer of regulation for defining substrate specificity in the cellular ubiquitination pathway.

Full Text

Duke Authors

Cited Authors

  • Kommaddi, RP; Shenoy, SK

Published Date

  • 2013

Published In

Volume / Issue

  • 118 /

Start / End Page

  • 175 - 204

PubMed ID

  • 23764054

Pubmed Central ID

  • 23764054

Electronic International Standard Serial Number (EISSN)

  • 1878-0814

Digital Object Identifier (DOI)

  • 10.1016/B978-0-12-394440-5.00007-3


  • eng

Conference Location

  • Netherlands