Research ArticleGPCR SIGNALING

Distinct profiles of functional discrimination among G proteins determine the actions of G protein–coupled receptors

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Science Signaling  01 Dec 2015:
Vol. 8, Issue 405, pp. ra123
DOI: 10.1126/scisignal.aab4068

Fingerprinting GPCRs

G protein–coupled receptors (GPCRs) influence most aspects of physiology and are targeted by many clinically used drugs. The physiological functions of this large family of proteins are thought to be mediated by highly specific G protein interactions (see the Focus by Smrcka). Masuho et al. devised a bioluminescence-based assay in transfected cells to examine the G protein–coupling specificities of different GPCRs for 13 different G proteins, generating fingerprint-like profiles for each receptor. These assays revealed unexpected use of G proteins by certain GPCRs, biased G protein usage by a given GPCR in response to different agonists, and G protein activation by a ligand thought to be an antagonist, findings that were verified in relevant cells. Given the clinical importance of this family of receptors, assays such as this one aid in understanding the physiological effects of currently used drugs, as well as in designing better therapeutics and limiting their potential side effects.