Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma.

Journal Article (Journal Article)

The phosphorylation of heptahelical receptors by heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor kinases (GRKs) is a universal regulatory mechanism that leads to desensitization of G protein signaling and to the activation of alternative signaling pathways. We determined the crystallographic structure of bovine GRK2 in complex with G protein beta1gamma2 subunits. Our results show how the three domains of GRK2-the RGS (regulator of G protein signaling) homology, protein kinase, and pleckstrin homology domains-integrate their respective activities and recruit the enzyme to the cell membrane in an orientation that not only facilitates receptor phosphorylation, but also allows for the simultaneous inhibition of signaling by Galpha and Gbetagamma subunits.

Full Text

Duke Authors

Cited Authors

  • Lodowski, DT; Pitcher, JA; Capel, WD; Lefkowitz, RJ; Tesmer, JJG

Published Date

  • May 23, 2003

Published In

Volume / Issue

  • 300 / 5623

Start / End Page

  • 1256 - 1262

PubMed ID

  • 12764189

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1082348


  • eng

Conference Location

  • United States