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Cell Signal. 2013 Mar;25(3):707-16. doi: 10.1016/j.cellsig.2012.11.024. Epub 2012 Nov 29.

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

Author information

1
Department of Molecular Pharmacology and Therapeutics, Stritch School of Medicine, Loyola University Chicago, 2160 S. 1st Ave., Building 101, Room 2721, Maywood, IL 60153, USA. amarchese@lumc.edu

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 β-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, β-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.

PMID:
23201781
PMCID:
PMC3593103
DOI:
10.1016/j.cellsig.2012.11.024
[Indexed for MEDLINE]
Free PMC Article

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