PerspectivePharmacology

Biasing GPCR Signaling from Inside

Science Signaling  28 Jan 2014:
Vol. 7, Issue 310, pp. pe3
DOI: 10.1126/scisignal.2005021

You are currently viewing the abstract.

View Full Text

Log in


Abstract

The discovery of “functional selectivity” or “biased signaling” through G protein–coupled receptors (GPCRs) has redefined the classical GPCR signaling paradigm. Moreover, the therapeutic potential of biased signaling by and biased ligands for GPCRs is changing the landscape of GPCR drug discovery. The concept of biased signaling has primarily been developed and discussed in the context of ligands that bind to the extracellular regions of GPCRs. However, two recent reports demonstrate that it is also possible to bias GPCR signaling from inside the cell by targeting intracellular regions of these receptors. These findings present a novel handle for delineating the functional outcomes of biased signaling by GPCRs. Moreover, these approaches also uncover a previously unexplored framework for biasing GPCR signaling for drug discovery.

View Full Text