Functional selectivity in GPCR signaling: understanding the full spectrum of receptor conformations

Mini Rev Med Chem. 2012 Aug;12(9):817-30. doi: 10.2174/138955712800959143.


The great versatility of G protein-coupled receptors (GPCRs), in terms of both their ability to bind different types of ligands and initiate a large number of distinct cellular signaling events, remains incompletely understood. In recent years, the classical view of the nature and consequences of ligand binding to GPCRs has dramatically changed. The notion of functional selectivity, achieved through both biased ligands and allosteric modulators, has brought substantial new insight into our comprehension of the pluridimensionality of signaling achieved by GPCRs. Moreover, receptor heterodimerization adds another important dimension to the diversity of cellular responses controlled by GPCRs. Here, we review these considerations and discuss how they will impact the design of improved therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allosteric Regulation
  • Allosteric Site
  • Biological Products / pharmacology*
  • Gastroesophageal Reflux / drug therapy
  • HIV Infections / drug therapy
  • Humans
  • Hyperparathyroidism, Secondary / drug therapy
  • Ligands
  • Protein Isoforms / agonists
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / physiology
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*


  • Biological Products
  • Ligands
  • Protein Isoforms
  • Receptors, G-Protein-Coupled