title: Deubiquitinases and their emerging roles in β-arrestin-mediated signaling.
abstract: 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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. Electronic address: sudha@receptor-biol.duke.edu.
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Shenoy
mesh_terms: D019390:Arrestins / Q000378:metabolism*; D004789:Enzyme Activation; D057075:Enzyme Assays; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D043222:Ubiquitin Thiolesterase / Q000302:isolation & purification / Q000378:metabolism*; D054875:Ubiquitination; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D000071557:beta-Arrestins; D048049:Extracellular Signal-Regulated MAP Kinases; C449799:USP33 protein, human; D043222:Ubiquitin Thiolesterase
keywords: Arrestin; Deubiquitination; G protein-coupled receptors; Kinases; Signaling; Ubiquitin