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Provides a good overview of the early studies on FAK.
Ilic, D. et al. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377, 539–544 (1995).
Shows that null mutation of FAK results in defects in embryonic morphogenesis, and that FAK-null cells show enhanced focal-contact formation and cell motility defects in culture.
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Provides evidence that FAK promotes cell polarization through the stabilization of microtubules at leading edges of motile cells.
Ren, X. et al. Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. J. Cell Sci. 113, 3673–3678 (2000).
Agochiya, M. et al. Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells. Oncogene 18, 5646–5653 (1999).
Bhattacharjee, A. et al. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc. Natl Acad. Sci. USA 98, 13790–13795 (2001).
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This reference, together with reference 69, shows that constitutively active Src can bypass the need for FAK in promoting the turnover of focal contacts.
Schlaepfer, D. D., Mitra, S. K. & Ilic, D. Control of motile and invasive cell phenotypes by focal adhesion kinase. Biochim. Biophys. Acta 1692, 77–102 (2004).
Provides a solid review on the role of FAK during embryonic development.
Yano, H. et al. Roles played by a subset of integrin signaling molecules in cadherin-based cell–cell adhesion. J. Cell Biol. 166, 283–295 (2004).
Katsumi, A., Orr, A. W., Tzima, E. & Schwartz, M. A. Integrins in mechanotransduction. J. Biol. Chem. 279, 12001–12004 (2004).
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Hauck, C. R. et al. Inhibition of focal adhesion kinase expression or activity disrupts epidermal growth factor-stimulated signaling promoting the migration of invasive human carcinoma cells. Cancer Res. 61, 7079–7090 (2001).
Sieg, D. J. et al. FAK integrates growth-factor and integrin signals to promote cell migration. Nature Cell Biol. 2, 249–256 (2000).
Streblow, D. N. et al. Human cytomegalovirus chemokine receptor US28-induced smooth muscle cell migration is mediated by focal adhesion kinase and Src. J. Biol. Chem. 278, 50456–50465 (2003).
Together with reference 23, this paper shows that the FAK FERM domain has important roles in promoting growth-factor-stimulated and G-protein-stimulated cell motility.
Chen, R. et al. Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain. Nature Cell Biol. 3, 439–444 (2001).
Poullet, P. et al. Ezrin interacts with focal adhesion kinase and induces its activation independently of cell–matrix adhesion. J. Biol. Chem. 276, 37686–37691 (2001).
Kadare, G. et al. PIAS1-mediated sumoylation of focal adhesion kinase activates its autophosphorylation. J. Biol. Chem. 278, 47434–47440 (2003).
Shows that sumoylation of FAK within the FERM domain is associated with catalytic activation and preferential nuclear localization.
Jones, G. & Stewart, G. Nuclear import of N-terminal FAK by activation of the FcεRI receptor in RBL-2H3 cells. Biochem. Biophys. Res. Comm. 314, 39–45 (2004).
McKean, D. M. et al. FAK induces expression of Prx1 to promote tenascin-C-dependent fibroblast migration. J. Cell Biol. 161, 393–402 (2003).
Zhao, J. et al. Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression. Mol. Cell 11, 1503–1515 (2003).
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Chodniewicz, D. & Klemke, R. L. Regulation of integrin-mediated cellular responses through assembly of a CAS/Crk scaffold. Biochim. Biophys. Acta. 1692, 63–76 (2004).
Schaller, M. D. Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim. Biophys. Acta. 1540, 1–21 (2001).
Zhai, J. et al. Direct interaction of focal adhesion kinase with p190RhoGEF. J. Biol. Chem. 278, 24865–24873 (2003).
Together with reference 79, shows that FAK can directly activate Rho through binding and phosphorylation of a GEF, and that this activation regulates axonal branching.
Toutant, M. et al. Alternative splicing controls the mechanisms of FAK autophosphorylation. Mol. Cell. Biol. 22, 7731–7743 (2002).
Liu, E., Cote, J. F. & Vuori, K. Negative regulation of FAK signaling by SOCS proteins. EMBO J. 22, 5036–5046 (2003).
This paper established a link between FAK activation, phosphorylation of Tyr397 and subsequent degradation of FAK.
Avraham, H., Park, S. Y., Schinkmann, K. & Avraham, S. RAFTK/Pyk2-mediated cellular signalling. Cell. Signal 12, 123–133 (2000).
Klingbeil, C. K. et al. Targeting Pyk2 to β1-integrin-containing focal contacts rescues fibronectin-stimulated signaling and haptotactic motility defects of focal adhesion kinase-null cells. J. Cell Biol. 152, 97–110 (2001).
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Nowakowski, J. et al. Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography. Structure (Camb.) 10, 1659–1667 (2002).
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Shows that selected β-integrin subunits can bind and activate Src in the absence of a contribution from FAK.
Turner, C. E. Paxillin and focal adhesion signalling. Nature Cell Biol. 2, 231–236 (2000).
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References 53, 54, 55 and 57 provide structural analyses of the FAK FAT domain and the paxillin LD peptide binding, and show that Tyr925 phosphorylation might require conformational alterations in the FAT domain.
Ma, A., Richardson, A., Schaefer, E. M. & Parsons, J. T. Serine phosphorylation of focal adhesion kinase in interphase and mitosis: a possible role in modulating binding to p130Cas. Mol. Biol. Cell 12, 1–12 (2001).
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Together with reference 67, this study shows that null mutation of SHP2 results in FAK hyperactivation, elevated α-actinin phosphorylation, and the failure to promote the maturation of integrin–cytoskeletal linkages.
Moissoglu, K. & Gelman, I. H. v-Src rescues actin-based cytoskeletal architecture and cell motility and induces enhanced anchorage independence during oncogenic transformation of focal adhesion kinase-null fibroblasts. J. Biol. Chem. 278, 47946–47959 (2003).
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Together with references 91 and 92, this reference shows that FAK–Src phosphorylation events function to control the composition of membrane lipids and the dynamics of focal contacts.
Wheelock, M. J. & Johnson, K. R. Cadherins as modulators of cellular phenotype. Ann. Rev. Cell Dev. Biol. 19, 207–235 (2003).
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Shows that FAK functions as an important environmental biosensor in promoting directional motility signals in response to changes in substrate flexibility.
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References 103 and 104 show that FAK has crucial roles in promoting 3D-matrix assembly and/or remodelling during development and in cell culture model systems.
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Shows that null mutation of the FAK-related kinase PYK2 results in integrin and chemokine-stimulated motility defects of macrophages that are not functionally compensated by FAK expression.
Watson, J. M. et al. Inhibition of the calcium-dependent tyrosine kinase (CADTK) blocks monocyte spreading and motility. J. Biol. Chem. 276, 3536–3542 (2001).
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