title: FAK phosphorylation at Tyr-925 regulates cross-talk between focal adhesion turnover and cell protrusion.
abstract: Cell migration is a highly complex process that requires the coordinated formation of membrane protrusion and focal adhesions (FAs). Focal adhesion kinase (FAK), a major signaling component of FAs, is involved in the disassembly process of FAs through phosphorylation and dephosphorylation of its tyrosine residues, but the role of such phosphorylations in nascent FA formation and turnover near the cell front and in cell protrusion is less well understood. In the present study, we demonstrate that, depending on the phosphorylation status of Tyr-925 residue, FAK modulates cell migration via two specific mechanisms. FAK⁻/⁻ mouse embryonic fibroblasts (MEFs) expressing nonphosphorylatable Y925F-FAK show increased interactions between FAK and unphosphorylated paxillin, which lead to FA stabilization and thus decreased FA turnover and reduced cell migration. Conversely, MEFs expressing phosphomimetic Y925E-FAK display unchanged FA disassembly rates, show increase in phosphorylated paxillin in FAs, and exhibit increased formation of nascent FAs at the cell leading edges. Moreover, Y925E-FAK cells present enhanced cell protrusion together with activation of the p130(CAS)/Dock180/Rac1 signaling pathway. Together, our results demonstrate that phosphorylation of FAK at Tyr-925 is required for FAK-mediated cell migration and cell protrusion.
authors.affiliation: Laboratoire de Biophotonique et Pharmacologie, Unité Mixte de Recherche 7213, Centre National de la Recherche Scientifique, and Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France.
authors.forename: Therese B
authors.initials: TB
authors.lastname: Deramaudt
authors.forename: Denis
authors.initials: D
authors.lastname: Dujardin
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Hamadi
authors.forename: Fanny
authors.initials: F
authors.lastname: Noulet
authors.forename: Kaouther
authors.initials: K
authors.lastname: Kolli
authors.forename: Jan
authors.initials: J
authors.lastname: De Mey
authors.forename: Kenneth
authors.initials: K
authors.lastname: Takeda
authors.forename: Philippe
authors.initials: P
authors.lastname: Rondé
mesh_terms: D000818:Animals; D022081:Cell Surface Extensions / Q000378:metabolism*; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; D051419:Paxillin; D014443:Tyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020830:rac1 GTP-Binding Protein