Desensitization of the mouse thromboxane A2 receptor (TP) by G protein-coupled receptor kinases (Grks).

Journal Article (Journal Article)

GRKs play a key role in regulating G protein-coupled receptor (GPCR) responsiveness. To investigate the role of GRKs in desensitization of TP, we replaced threonines with favorable phosphorylation motifs for GRKs (positions 226 and 230) with alanine. Mutant and wild-type receptors were expressed in cell culture models and clones expressing similar numbers of receptors were studied. We found that: (1) affinity and specificity of thromboxane A2 (TxA2) binding to mutant TP were identical to the wild-type, (2) replacement of threonines 226 and 230 with alanines delayed the onset of agonist-induced desensitization, and (3) inhibition of endogenous GRK activity with a dominant-negative construct inhibited agonist-induced phosphorylation and enhanced responsiveness of wild-type TP but had little effect on responsiveness of the receptor mutant. These data are consistent with the notion that GRKs contribute to desensitization of TP.

Full Text

Duke Authors

Cited Authors

  • Flannery, PJ; Spurney, RF

Published Date

  • September 2002

Published In

Volume / Issue

  • 70 / 1-2

Start / End Page

  • 79 - 90

PubMed ID

  • 12428680

International Standard Serial Number (ISSN)

  • 1098-8823

Digital Object Identifier (DOI)

  • 10.1016/s0090-6980(02)00013-8


  • eng

Conference Location

  • United States