Deubiquitinases and their emerging roles in β-arrestin-mediated signaling.
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.
Mesh Terms:
Arrestins, Enzyme Activation, Enzyme Assays, Extracellular Signal-Regulated MAP Kinases, HEK293 Cells, Humans, Kinetics, Protein Interaction Mapping, Signal Transduction, Ubiquitin Thiolesterase, Ubiquitination
Arrestins, Enzyme Activation, Enzyme Assays, Extracellular Signal-Regulated MAP Kinases, HEK293 Cells, Humans, Kinetics, Protein Interaction Mapping, Signal Transduction, Ubiquitin Thiolesterase, Ubiquitination
Meth. Enzymol.
Date: Jan. 01, 2014
PubMed ID: 24377933
View in: Pubmed Google Scholar
Download Curated Data For This Publication
166866
Switch View:
- Interactions 3
- PTM Genes 1