Here, we review recent developments in our understanding of how ubiquitin regulates GPCR trafficking within the endocytic pathway. Recent studies have revealed a mechanistic link between GPCR phosphorylation, β-arrestins, and ubiquitination. Ubiquitination has now emerged as an important posttranslational modification that has multiple roles, either directly or indirectly, in governing GPCR trafficking. Classically, GPCR signaling is tightly regulated by GPCR kinases and β-arrestins, which act in a concerted fashion to govern GPCR desensitization and also GPCR trafficking. Despite the role of GPCR signaling in health and disease, the molecular mechanisms governing GPCR signaling remain poorly understanding. In addition, GPCRs are also the largest class of target for many drugs used to treat a variety of diseases. G protein-coupled receptor (GPCR)-promoted signaling mediates cellular responses to a variety of stimuli involved in diverse physiological processes. Kennedy, Adriano Marchese, in Progress in Molecular Biology and Translational Science, 2015 Abstract This chapter will focus on the importance of GIPs along the GPCR life cycle and discuss the dynamics and molecular organization of GPCR/GIP complexes. Interfering with a GPCR/GIP interaction might become a new strategy for specific therapeutic intervention. Differential expression of GIPs and rapid alterations of GPCR/GIP interaction networks are efficient means to regulate GPCR function in a tissue-specific and spatiotemporal manner to trigger appropriate cellular responses. Along their life cycle, GPCRs are accompanied by a range of specialized GPCR-interacting proteins (GIPs) to assist nascent receptors in proper folding, to target them to the appropriate subcellular compartments and to fulfill their signaling tasks. Receptor activation triggers several processes such as signaling and receptor endocytosis. GPCRs are synthesized in the endoplasmatic reticulum and are then transported to the cell surface where they are typically activated. They are responding to a plethora of ligands and are involved in the transmission of extracellular signals inside the cell. G protein-coupled receptors (GPCRs) are, with approximately 800 members, among the most abundant membrane proteins in humans. Ralf Jockers, in Advances in Pharmacology, 2011 Abstract
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