Ubiquitin-dependent regulation of G protein-coupled receptor trafficking and signaling Journal Article

Authors: Marchese, A; Trejo, J.
Article Title: Ubiquitin-dependent regulation of G protein-coupled receptor trafficking and signaling
Abstract: G protein-coupled receptors (GPCRs) belong to one of the largest family of signaling receptors in the mammalian genome [1]. GPCRs elicit cellular responses to multiple diverse stimuli and play essential roles in human health and disease. GPCRs have important clinical implications in various diseases and are the targets of approximately 25-50% of all marketed drugs [2,3]. Understanding how GPCRs are regulated is essential to delineating their role in normal physiology and in the pathophysiology of several diseases. Given the vast number and diversity of GPCRs, it is likely that multiple mechanisms exist to regulate GPCR function. While GPCR signaling is typically regulated by desensitization and endocytosis mediated by phosphorylation and beta-arrestins, it can also be modulated by ubiquitination. Ubiquitination is emerging an important regulatory process that may have unique roles in governing GPCR trafficking and signaling. Recent studies have revealed a mechanistic link between GPCR phosphorylation, beta-arrestins and ubiquitination that may be applicable to some GPCRs but not others. While the function of ubiquitination is generally thought to promote receptor endocytosis and endosomal sorting, recent studies have revealed that ubiquitination also plays an important role in positive regulation of GPCR signaling. Here, we will review recent developments in our understanding of how ubiquitin regulates GPCR endocytic trafficking and how it contributes to signal transduction induced by GPCR activation.
Journal Title: Cellular signalling
Volume: 25
Issue: 3
ISSN: 1873-3913; 0898-6568
Publisher: Elsevier Inc  
Journal Place: England
Date Published: 2013
Start Page: 707
End Page: 716
Language: eng
Notes: ID: 13129; CI: Copyright (c) 2012; GR: R01 GM075159/GM/NIGMS NIH HHS/United States; JID: 8904683; NIHMS437798; OID: NLM: NIHMS437798 [Available on 03/01/14]; OID: NLM: PMC3593103 [Available on 03/01/14]; PMCR: 2014/03/01 00:00; 2012/11/12 [received]; 2012/11/25 [accepted]; 2012/11/29 [aheadofprint]; ppublish