Biased G Protein-Coupled Receptor Signaling: New Player in Modulating Physiology and Pathology.
10.4062/biomolther.2016.165
- Author:
Zuzana BOLOGNA
1
;
Jian Peng TEOH
;
Ahmed S BAYOUMI
;
Yaoliang TANG
;
Il man KIM
Author Information
1. Vascular Biology Center, Medical College of Georgia, Augusta University, GA 30912, USA. ILKIM@augusta.edu
- Publication Type:Review
- Keywords:
β-arrestin;
biased signaling;
G protein-coupled receptor;
G protein
- MeSH:
Bias (Epidemiology)*;
Felodipine;
GTP-Binding Proteins;
Humans;
Ligands;
Pathology*;
Physiology*;
Transducers
- From:Biomolecules & Therapeutics
2017;25(1):12-25
- CountryRepublic of Korea
- Language:English
-
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 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.
