Biased g protein-coupled receptor signaling: New player in modulating physiology and pathology

Zuzana Bologna, Jian Peng Teoh, Ahmed S. Bayoumi, Yaoliang Tang, Il Man Kim

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)12-25
Number of pages14
JournalBiomolecules and Therapeutics
Volume25
Issue number1
DOIs
StatePublished - Jan 2017
Externally publishedYes

Keywords

  • Biased signaling
  • G protein
  • G protein-coupled receptor
  • β-arrestin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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