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KMID : 0606920170250010012
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Biomolecules & Therapeutics
2017 Volume.25 No. 1 p.12 ~ p.25
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Biased G Protein-Coupled Receptor Signaling: New Player in Modulating Physiology and Pathology
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Bologna Zuzana
Teoh Jian peng
Bayoumi Ahmed S.
Tang Yaoliang
Kim Il-man
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Abstract
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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 β-arrestins have important roles in internalization and desensitization of the receptor. Over the past decade, several novel functional aspects of β-arrestins in regulating GPCR signaling have been discovered. These previously unanticipated roles of β-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 β-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 β-arrestin-biased GPCR signaling and the effects of biased ligands on disease pathogenesis and regulation.
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KEYWORD
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β-arrestin, biased signaling, G protein-coupled receptor, G protein
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