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

Biochimica Et Biophysica Acta
Alem W KahsaiGabriel Fenteany

Abstract

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.

References

Nov 24, 1995·The Journal of Biological Chemistry·S BagrodiaR A Cerione
Sep 29, 1995·The Journal of Biological Chemistry·S BagrodiaR A Cerione
Aug 8, 1997·The Journal of Biological Chemistry·C RoyP Mangeat
Nov 5, 1997·European Journal of Biochemistry·K Palczewski
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·A M AragayF Mayor
Apr 29, 1998·The Journal of Biological Chemistry·S F PietromonacoL Elias
Aug 1, 1998·The Journal of Biological Chemistry·C V CarmanJ L Benovic
Aug 26, 1998·European Journal of Biochemistry·K HagaH Murofushi
Nov 24, 1999·The Journal of Biological Chemistry·C V CarmanT Kozasa
Jan 15, 2000·The Journal of Biological Chemistry·L Y BourguignonY W Chen
May 19, 2000·The Journal of Biological Chemistry·R VaiskunaiteT A Voyno-Yasenetskaya
Jun 15, 2000·The Journal of Biological Chemistry·A N ProninJ L Benovic
Jul 8, 2000·The Journal of Biological Chemistry·A Ruiz-GómezF Mayor
Aug 18, 2000·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·N NakamuraK Kaibuchi
Oct 14, 2000·Annual Review of Cell and Developmental Biology·A BretscherD Reczek
Oct 19, 2000·Methods in Enzymology·A MammotoY Takai
Nov 9, 2000·Biology of the Cell·S Louvet-Vallée
Aug 3, 2002·Nature Reviews. Molecular Cell Biology·Anthony BretscherRichard G Fehon
Oct 31, 2002·Chembiochem : a European Journal of Chemical Biology·Kevin T Mc HenryGabriel Fenteany
Jun 13, 2003·Molecular Biology of the Cell·Philippe PujuguetMonique Arpin
Jan 6, 2004·Nature Medicine·Chand KhannaLee J Helman
May 19, 2004·Immunology·Aleksandar Ivetic, Anne J Ridley
Jul 31, 2004·Proceedings of the National Academy of Sciences of the United States of America·Anuwat DinudomDavid I Cook
Aug 18, 2004·The International Journal of Biochemistry & Cell Biology·Klaus P Hoeflich, Mitsuhiko Ikura
Apr 23, 2005·Science·Robert J Lefkowitz, Sudha K Shenoy

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Citations

Mar 28, 2013·High Blood Pressure & Cardiovascular Prevention : the Official Journal of the Italian Society of Hypertension·Gaetano SantulliGuido Iaccarino
May 13, 2014·FEBS Letters·Daisuke AsaiJeong-Hun Kang
Jul 16, 2013·Biochimica Et Biophysica Acta·Mohamad AdadaLina M Obeid
Jan 27, 2012·Trends in Pharmacological Sciences·Tama EvronMarc G Caron
Sep 10, 2011·Pharmacology & Therapeutics·Eugenia V GurevichVsevolod V Gurevich
Mar 18, 2016·Journal of Biomedical Science·Godwin A Ponuwei
Aug 1, 2015·Genes and Immunity·N Packiriswamy, N Parameswaran
Jan 15, 2013·Neurobiology of Disease·Cora H NijboerAnnemieke Kavelaars
Oct 31, 2012·The Biochemical Journal·K Alexa Orr GandyLina M Obeid
Feb 24, 2011·Cell Adhesion & Migration·Monique ArpinIngrid Zwaenepoel
Apr 1, 2014·Current Opinion in Cell Biology·Petronila PenelaFederico Mayor
May 8, 2016·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Maneesh BhargavaChris H Wendt
Jul 1, 2016·Journal of Medicinal Chemistry·Manuela GuccioneSilvana Grasso
Jan 9, 2013·Journal of Toxicology and Environmental Health. Part a·Adriana J LaGierJanice A Dye
Oct 18, 2016·Nature Communications·Kan Xing WuJustin Jang Hann Chu
Mar 23, 2019·Journal of Biomechanical Engineering·Shan SunMichael Cho
Nov 30, 2016·Molecular Pharmacology·Laura NoguésFederico Mayor
Aug 23, 2019·Cellular and Molecular Life Sciences : CMLS·Petronila PenelaFederico Mayor
May 1, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·K Alexa Orr GandyLina M Obeid
Dec 29, 2020·Communications Biology·Sonal PrasadAnders Fridberger
Apr 4, 2021·International Journal of Molecular Sciences·Preeti Kumari Chaudhary, Soochong Kim

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