G protein-coupled receptor kinase 2 activates radixin, regulating membrane protrusion and motility in epithelial cells.

Journal Article (Journal Article)

Ezrin/radixin/moesin (ERM) proteins are membrane-cytoskeleton linkers that also have roles in signal transduction. Here we show that G protein-coupled receptor kinase 2 (GRK2) regulates membrane protrusion and cell migration during wound closure in Madin-Darby canine kidney (MDCK) epithelial cell monolayers at least partly through activating phosphorylation of radixin on a conserved, regulatory C-terminal Thr residue. GRK2 phosphorylated radixin exclusively on Thr 564 in vitro. Expression of a phosphomimetic (Thr-564-to-Asp) mutant of radixin resulted in increased Rac1 activity, membrane protrusion and cell motility in MDCK cells, suggesting that radixin functions "upstream" of Rac1, presumably as a scaffolding protein. Phosphorylation of ERM proteins was highest during the most active phase of epithelial cell sheet migration over the course of wound closure. In view of these results, we explored the mode of action of quinocarmycin/quinocarcin analog DX-52-1, an inhibitor of cell migration and radixin function with considerable selectivity for radixin over the other ERM proteins, finding that its mechanism of inhibition of radixin does not appear to involve binding and antagonism at the site of regulatory phosphorylation.

Full Text

Duke Authors

Cited Authors

  • Kahsai, AW; Zhu, S; Fenteany, G

Published Date

  • February 2010

Published In

Volume / Issue

  • 1803 / 2

Start / End Page

  • 300 - 310

PubMed ID

  • 19913059

Pubmed Central ID

  • PMC2838949

International Standard Serial Number (ISSN)

  • 0006-3002

Digital Object Identifier (DOI)

  • 10.1016/j.bbamcr.2009.11.002


  • eng

Conference Location

  • Netherlands