Constitutive desensitization: a new paradigm for g protein-coupled receptor regulation.

Journal Article (Journal Article;Review)

GPCRs are a large family of cell-surface proteins that regulate many important biochemical pathways and physiological responses. The isolation and characterization of GPCRs represent one of the more remarkable success stories that occurred during the revolution in biology of the last quarter century. Of the many discoveries that originated in the laboratory of Robert Lefkowitz at Duke University concerning GPCR regulation, none is more fundamental than the elucidation of the families of GRKs and arrestin proteins that terminate GPCR signaling. In this essay, we will discuss how advances in microscopy and biology have made the visualization of GPCR, GRK, and arrestin activity possible in single cells. Additionally, we will discuss how imaging studies using arrestins and a naturally occurring mutant of the vasopressin receptor led to the recognition of a novel phenotypic receptor behavior, in which the receptor desensitizes in the absence of agonist. We have termed this process constitutive desensitization, and this unexpected receptor property suggests that it may be possible to develop novel classes of signal-inhibiting drugs distinct from conventional antagonists.

Full Text

Duke Authors

Cited Authors

  • Barak, LS; Wilbanks, AM; Caron, MG

Published Date

  • April 2003

Published In

Volume / Issue

  • 1 / 2

Start / End Page

  • 339 - 346

PubMed ID

  • 15090199

International Standard Serial Number (ISSN)

  • 1540-658X

Digital Object Identifier (DOI)

  • 10.1089/15406580360545152


  • eng

Conference Location

  • United States