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http://dx.doi.org/10.4062/biomolther.2016.165

Biased G Protein-Coupled Receptor Signaling: New Player in Modulating Physiology and Pathology  

Bologna, Zuzana (Vascular Biology Center, Medical College of Georgia, Augusta University)
Teoh, Jian-peng (Vascular Biology Center, Medical College of Georgia, Augusta University)
Bayoumi, Ahmed S. (Vascular Biology Center, Medical College of Georgia, Augusta University)
Tang, Yaoliang (Vascular Biology Center, Medical College of Georgia, Augusta University)
Kim, Il-man (Vascular Biology Center, Medical College of Georgia, Augusta University)
Publication Information
Biomolecules & Therapeutics / v.25, no.1, 2017 , pp. 12-25 More about this Journal
Abstract
G protein-coupled receptors (GPCRs) are a family of cell-surface proteins that play critical roles in regulating a variety of pathophysiological processes and thus are targeted by almost a third of currently available therapeutics. It was originally thought that GPCRs convert extracellular stimuli into intracellular signals through activating G proteins, whereas ${\beta}$-arrestins have important roles in internalization and desensitization of the receptor. Over the past decade, several novel functional aspects of ${\beta}$-arrestins in regulating GPCR signaling have been discovered. These previously unanticipated roles of ${\beta}$-arrestins to act as signal transducers and mediators of G protein-independent signaling have led to the concept of biased agonism. Biased GPCR ligands are able to engage with their target receptors in a manner that preferentially activates only G protein- or ${\beta}$-arrestin-mediated downstream signaling. This offers the potential for next generation drugs with high selectivity to therapeutically relevant GPCR signaling pathways. In this review, we provide a summary of the recent studies highlighting G protein- or ${\beta}$-arrestin-biased GPCR signaling and the effects of biased ligands on disease pathogenesis and regulation.
Keywords
${\beta}$-arrestin; biased signaling; G protein-coupled receptor; G protein;
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