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

Publication ,  Journal Article
Kahsai, AW; Zhu, S; Fenteany, G
Published in: Biochim Biophys Acta
February 2010

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.

Duke Scholars

Published In

Biochim Biophys Acta

DOI

ISSN

0006-3002

Publication Date

February 2010

Volume

1803

Issue

2

Start / End Page

300 / 310

Location

Netherlands

Related Subject Headings

  • rac1 GTP-Binding Protein
  • cdc42 GTP-Binding Protein
  • Recombinant Fusion Proteins
  • Mutagenesis, Site-Directed
  • Membrane Proteins
  • Isoquinolines
  • Gene Silencing
  • G-Protein-Coupled Receptor Kinase 2
  • Epithelial Cells
  • Dogs
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kahsai, A. W., Zhu, S., & Fenteany, G. (2010). G protein-coupled receptor kinase 2 activates radixin, regulating membrane protrusion and motility in epithelial cells. Biochim Biophys Acta, 1803(2), 300–310. https://doi.org/10.1016/j.bbamcr.2009.11.002
Kahsai, Alem W., Shoutian Zhu, and Gabriel Fenteany. “G protein-coupled receptor kinase 2 activates radixin, regulating membrane protrusion and motility in epithelial cells.Biochim Biophys Acta 1803, no. 2 (February 2010): 300–310. https://doi.org/10.1016/j.bbamcr.2009.11.002.
Kahsai, Alem W., et al. “G protein-coupled receptor kinase 2 activates radixin, regulating membrane protrusion and motility in epithelial cells.Biochim Biophys Acta, vol. 1803, no. 2, Feb. 2010, pp. 300–10. Pubmed, doi:10.1016/j.bbamcr.2009.11.002.
Kahsai AW, Zhu S, Fenteany G. G protein-coupled receptor kinase 2 activates radixin, regulating membrane protrusion and motility in epithelial cells. Biochim Biophys Acta. 2010 Feb;1803(2):300–310.

Published In

Biochim Biophys Acta

DOI

ISSN

0006-3002

Publication Date

February 2010

Volume

1803

Issue

2

Start / End Page

300 / 310

Location

Netherlands

Related Subject Headings

  • rac1 GTP-Binding Protein
  • cdc42 GTP-Binding Protein
  • Recombinant Fusion Proteins
  • Mutagenesis, Site-Directed
  • Membrane Proteins
  • Isoquinolines
  • Gene Silencing
  • G-Protein-Coupled Receptor Kinase 2
  • Epithelial Cells
  • Dogs