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

Bologna, Zuzana; Teoh, Jian-peng; Bayoumi, Ahmed S.; Tang, Yaoliang; Kim, Il-man

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저자정보: 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)

저널정보: 한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제25권 제1호

발행연도: 2017.1

수록면: 12 - 25 (14page)

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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 ${\beta}$-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.

#${beta}$-arrestin #biased signaling #G protein-coupled receptor #G protein

참고문헌 (147)

참고문헌 신청

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Alonso, N. / 2015 / Physiological implications of biased signaling at histamine H2 receptors / Front. Pharmacol 6:45

Angers, S. / 2000 / Detection of β2-adrenergic receptor dimerization in living cells using bioluminescence resonance energy transfer (BRET) / Proc. Natl. Acad. Sci. U.S.A 97:3684~3689

Aplin, M. / 2007 / The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and Langendorff-perfused hearts / Basic Clin. Pharmacol. Toxicol 100:289~295

Aurora, A. B. / 2012 / MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca2+ overload and cell death / J. Clin. Invest 122:1222~1232

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