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| Subject Categories: Cell & Tissue Architecture |
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| The EMBO Journal
(2008) 27, 38–50, doi:10.1038/sj.emboj.7601943 Published online 29 November 2007 |
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| Spatial recruitment and activation of the Fes kinase by ezrin promotes HGF-induced cell scattering |
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| Alexandra Naba1, 2, Céline Reverdy3, Daniel Louvard1, 2 and Monique Arpin1, 2 |
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1 Centre National de la Recherche Scientifique (CNRS), UMR 144, Paris, France 2 Institut Curie, Centre de Recherche, Paris, France 3 Hybrigenics, Paris, France To whom correspondence should be addressed Monique Arpin, Corresponding author. Institut Curie, Centre National de la Recherche Scientifique (CNRS), UMR 144, 26, rue d'Ulm, Paris 75248, France. Tel.: +33 1 42 34 63 68; Fax: +33 1 42 34 63 77; E-mail: marpin@curie.fr Received 16 February 2007; Accepted 9 November 2007; Published online 29 November 2007. |
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| Abstract |
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| The remodeling of epithelial monolayers induced by hepatocyte growth factor (HGF) results in the reorganization of actin cytoskeleton and cellular junctions. We previously showed that the membrane–cytoskeleton linker ezrin plays a major role in HGF-induced morphogenic effects. Here we identified a novel partner of phosphorylated ezrin, the Fes kinase, that acts downstream of ezrin in HGF-mediated cell scattering. We found that Fes interacts directly, through its SH2 domain, with ezrin phosphorylated at tyrosine 477. We show that in epithelial cells, activated Fes localizes either to focal adhesions or cell–cell contacts depending on cell confluency. The recruitment and the activation of Fes to the cell–cell contacts in confluent cells depend on its interaction with ezrin. When this interaction is impaired, Fes remains in focal adhesions and as a consequence the cells show defective spreading and scattering in response to HGF stimulation. Altogether, these results provide a novel mechanism whereby ezrin/Fes interaction at cell–cell contacts plays an essential role in HGF-induced cell scattering and implicates Fes in the cross-talk between cell–cell and cell–matrix adhesion. |
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| Keywords: cell scattering, ERM proteins, fps/fes, HGF, Src kinases |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHIncreased CCR4 Expression in Cutaneous T Cell Lymphoma Journal of Investigative Dermatology Original Article Spatial recruitment and activation of the Fes kinase by ezrin promotes HGF-induced cell scattering The EMBO Journal Article Hepatocyte growth factor in renal failure: Promise and reality Kidney International Original Article Nature Medicine Article (01 Feb 2004) |
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