Function and regulation of chemoattractant receptors.

Published

Journal Article (Review)

Phagocyte migration and activation at sites of inflammation is mediated through chemoattractant receptors that are coupled to G-proteins. Early studies from our laboratory demonstrated G-protein-mediated phospholipase C activation by chemoattractants. Recently, this laboratory developed cellular and animal models to allow biochemical, cell biological and molecular genetic approaches to be used in determining the mechanisms of chemoattractant receptor function, regulation, and cross regulation. These studies provided evidence that chemoattractant receptors activate distinct pathways for chemotaxis and exocytosis and cross-regulate each other's function at multiple levels. A major site of regulation is through phosphorylation of receptors by G-protein-coupled receptor kinases and by protein kinase C. In addition, the activation of phospholipase C by chemoattractants is also regulated at additional sites distal to receptor phosphorylation. These may include modulation of G-protein activation by regulators of G-protein signaling (RGS) and modification of phospholipase C. Phosphorylation of phospholipase Cbeta3 by both protein kinase A and protein kinase C has been demonstrated. The function and regulation of chemoattractant receptors are also being examined in mouse models. In these studies, mice deficient in leukotriene B4 receptors have been generated by targeted gene disruption. These mice displayed reduced neutrophil accumulation in certain inflammation models and sex-related differences in platelet-activating-factor induced anaphylaxis.

Full Text

Duke Authors

Cited Authors

  • Haribabu, B; Richardson, RM; Verghese, MW; Barr, AJ; Zhelev, DV; Snyderman, R

Published Date

  • 2000

Published In

Volume / Issue

  • 22 / 2-3

Start / End Page

  • 271 - 279

PubMed ID

  • 11339362

Pubmed Central ID

  • 11339362

International Standard Serial Number (ISSN)

  • 0257-277X

Digital Object Identifier (DOI)

  • 10.1385/IR:22:2-3:271

Language

  • eng

Conference Location

  • United States