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dc.contributor.authorKadaré, Gress
dc.contributor.authorGervasi, Nicolas
dc.contributor.authorBrami-Cherrier, Karen
dc.contributor.authorBlockus, Heike
dc.contributor.authorEl Messari, Said
dc.contributor.authorArold, Stefan T.
dc.contributor.authorGirault, Jean-Antoine
dc.date.accessioned2015-06-12T06:30:36Z
dc.date.available2015-06-12T06:30:36Z
dc.date.issued2014-11-12
dc.identifier.citationConformational Dynamics of the Focal Adhesion Targeting Domain Control Specific Functions of Focal Adhesion Kinase in Cells 2015, 290 (1):478 Journal of Biological Chemistry
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.pmid25391654
dc.identifier.doi10.1074/jbc.M114.593632
dc.identifier.urihttp://hdl.handle.net/10754/556843
dc.description.abstractFocal adhesion (FA) kinase (FAK) regulates cell survival and motility by transducing signals from membrane receptors. The C-terminal FA targeting (FAT) domain of FAK fulfils multiple functions, including recruitment to FAs through paxillin binding. Phosphorylation of FAT on Tyr925 facilitates FA disassembly and connects to the MAPK pathway through Grb2 association, but requires dissociation of the first helix (H1) of the four-helix bundle of FAT. We investigated the importance of H1 opening in cells by comparing the properties of FAK molecules containing wild-type or mutated FAT with impaired or facilitated H1 openings. These mutations did not alter the activation of FAK, but selectively affected its cellular functions, including self-association, Tyr925 phosphorylation, paxillin binding, and FA targeting and turnover. Phosphorylation of Tyr861, located between the kinase and FAT domains, was also enhanced by the mutation that opened the FAT bundle. Similarly phosphorylation of Ser910 by ERK in response to bombesin was increased by FAT opening. Although FAK molecules with the mutation favoring FAT opening were poorly recruited at FAs, they efficiently restored FA turnover and cell shape in FAK-deficient cells. In contrast, the mutation preventing H1 opening markedly impaired FAK function. Our data support the biological importance of conformational dynamics of the FAT domain and its functional interactions with other parts of the molecule.
dc.publisherAmerican Society for Biochemistry & Molecular Biology (ASBMB)
dc.relation.urlhttp://www.jbc.org/lookup/doi/10.1074/jbc.M114.593632
dc.rightsThis research was originally published in Journal of Biological Chemistry. Kadaré, Gress, Nicolas Gervasi, Karen Brami-Cherrier, Heike Blockus, Said El Messari, Stefan T. Arold, and Jean-Antoine Girault. "Conformational Dynamics of the Focal Adhesion Targeting Domain Control specific functions of focal adhesion kinase in cells." Journal of Biological Chemistry 290, no. 1 (2015): 478-491. © the American Society for Biochemistry and Molecular Biology
dc.subjectTyrosine-Protein Kinase (Tyrosine Kinase)
dc.subjectProtein Structure
dc.subjectProtein Kinase
dc.subjectFocal Adhesions
dc.subjectConformational change
dc.titleConformational Dynamics of the Focal Adhesion Targeting Domain Control Specific Functions of Focal Adhesion Kinase in Cells
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentComputational Bioscience Research Center (CBRC)
dc.identifier.journalJournal of Biological Chemistry
dc.identifier.pmcidPMC4281750
dc.eprint.versionPost-print
dc.contributor.institutionINSERM, UMR-S 839, F-75005 Paris, France
dc.contributor.institutionUniversité Pierre & Marie Curie (UPMC), Sorbonne Universités, F-75005 Paris, France
dc.contributor.institutionInstitut du Fer à Moulin, F-75005 Paris, France
dc.contributor.institutionCentre de Biochimie Structurale, CNRS UMR5048, INSERM U1054, Université de Montpellier I & II, Montpellier, France
kaust.personArold, Stefan T.
refterms.dateFOA2016-01-02T00:00:00Z
dc.date.published-online2014-11-12
dc.date.published-print2015-01-02


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