G protein-coupled receptor adaptation mechanisms

Semin Cell Dev Biol. 1998 Apr;9(2):119-27. doi: 10.1006/scdb.1997.0216.


G protein-coupled receptors (GPCRs) transduce extracellular signals that modulate the activity of a wide variety of biological processes, such as neurotransmission, chemoattraction, cardiac function, olfaction, and vision. However, GPCR signalling desensitizes rapidly as the consequence of receptor phosphorylation. G protein-coupled receptor kinase-mediated receptor phosphorylation promotes the binding of beta-arrestin proteins, which not only uncouple GPCRs from their cognate heterotrimeric G protein, but also target them for endocytosis. The sequestration (endocytosis) of desensitized GPCRs to endosomes is required for their dephosphorylation and subsequent resensitization to their pre-ligand exposed state. This review concentrates on the mechanisms underlying GPCR desensitization and resensitization.

Publication types

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

MeSH terms

  • Adaptation, Physiological*
  • Animals
  • Arrestins / physiology
  • GTP-Binding Proteins / physiology*
  • Humans
  • Receptor Protein-Tyrosine Kinases / physiology
  • Receptors, Cell Surface / physiology*


  • Arrestins
  • Receptors, Cell Surface
  • Receptor Protein-Tyrosine Kinases
  • GTP-Binding Proteins