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Journal of Cell Science, Vol 109, Issue 7 1787-1794, Copyright © 1996 by Company of Biologists
JOURNAL ARTICLES |
LA Cary, JF Chang and JL Guan
Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Cellular interactions with the extracellular matrix proteins play important roles in a variety of biological processes. Recent studies suggest that integrin-mediated cell-matrix interaction can transduce biochemical signals across the plasma membrane to regulate cellular functions such as proliferation, differentiation and migration. These studies have implicated a critical role of focal adhesion kinase (FAK) in integrin-mediated signal transduction pathways. We report here that overexpression of FAK in CHO cells increased their migration on fibronectin. A mutation of the major autophosphorylation site Y397 in FAK abolished its ability to stimulate cell migration, while phosphorylation of Y397 in a kinase-defective FAK by endogenous FAK led to increased migration. We also find that the wild-type and the kinase-defective FAK were associated with Src and Fyn in CHO cells whereas the F397 mutant was not. These results directly demonstrate a functional role for FAK in integrin signaling leading to cell migration. They also provide evidence for the functional significance of FAK/Src complex formation in vivo.
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S. Abbi, H. Ueda, C. Zheng, L. A. Cooper, J. Zhao, R. Christopher, and J.-L. Guan Regulation of Focal Adhesion Kinase by a Novel Protein Inhibitor FIP200 Mol. Biol. Cell, September 1, 2002; 13(9): 3178 - 3191. [Abstract] [Full Text] [PDF]
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S. A. Wilcox-Adelman, F. Denhez, and P. F. Goetinck Syndecan-4 Modulates Focal Adhesion Kinase Phosphorylation J. Biol. Chem., August 30, 2002; 277(36): 32970 - 32977. [Abstract] [Full Text] [PDF]
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T.-L. Shen, D. C. Han, and J.-L. Guan Association of Grb7 with Phosphoinositides and Its Role in the Regulation of Cell Migration J. Biol. Chem., August 2, 2002; 277(32): 29069 - 29077. [Abstract] [Full Text] [PDF]
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G. Giannone, P. Ronde, M. Gaire, J. Haiech, and K. Takeda Calcium Oscillations Trigger Focal Adhesion Disassembly in Human U87 Astrocytoma Cells J. Biol. Chem., July 12, 2002; 277(29): 26364 - 26371. [Abstract] [Full Text] [PDF]
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 I. L. Szabo, R. Pai, M. K. Jones, G. R. Ehring, H. Kawanaka, and A. S. Tarnawski Indomethacin Delays Gastric Restitution: Association with the Inhibition of Focal Adhesion Kinase and Tensin Phosphorylation and Reduced Actin Stress Fibers Experimental Biology and Medicine, June 1, 2002; 227(6): 412 - 424. [Abstract] [Full Text] [PDF]
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S. Liu, W. B. Kiosses, D. M. Rose, M. Slepak, R. Salgia, J. D. Griffin, C. E. Turner, M. A. Schwartz, and M. H. Ginsberg A Fragment of Paxillin Binds the alpha 4 Integrin Cytoplasmic Domain (Tail) and Selectively Inhibits alpha 4-Mediated Cell Migration J. Biol. Chem., May 31, 2002; 277(23): 20887 - 20894. [Abstract] [Full Text] [PDF]
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D. Huang, A. T. Cheung, J. T. Parsons, and M. Bryer-Ash Focal Adhesion Kinase (FAK) Regulates Insulin-stimulated Glycogen Synthesis in Hepatocytes J. Biol. Chem., May 10, 2002; 277(20): 18151 - 18160. [Abstract] [Full Text] [PDF]
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T. P. Hecker, J. R. Grammer, G. Y. Gillespie, J. Stewart Jr., and C. L. Gladson Focal Adhesion Kinase Enhances Signaling through the Shc/Extracellular Signal-regulated Kinase Pathway in Anaplastic Astrocytoma Tumor Biopsy Samples Cancer Res., May 1, 2002; 62(9): 2699 - 2707. [Abstract] [Full Text] [PDF]
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L. A. Cary, R. A. Klinghoffer, C. Sachsenmaier, and J. A. Cooper Src Catalytic but Not Scaffolding Function Is Needed for Integrin-Regulated Tyrosine Phosphorylation, Cell Migration, and Cell Spreading Mol. Cell. Biol., April 15, 2002; 22(8): 2427 - 2440. [Abstract] [Full Text] [PDF]
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Q.-S. Du, X.-R. Ren, Y. Xie, Q. Wang, L. Mei, and W.-C. Xiong Inhibition of PYK2-induced actin cytoskeleton reorganization, PYK2 autophosphorylation and focal adhesion targeting by FAK J. Cell Sci., March 10, 2002; 114(16): 2977 - 2987. [Abstract] [Full Text] [PDF]
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G. W. McLean, K. Brown, M. I. Arbuckle, A. W. Wyke, T. Pikkarainen, E. Ruoslahti, and M. C. Frame Decreased Focal Adhesion Kinase Suppresses Papilloma Formation during Experimental Mouse Skin Carcinogenesis Cancer Res., December 1, 2001; 61(23): 8385 - 8389. [Abstract] [Full Text] [PDF]
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 H. M. ROSENFELDT, J. P. HOBSON, M. MACEYKA, A. OLIVERA, V. E. NAVA, S. MILSTIEN, and S. SPIEGEL EDG-1 links the PDGF receptor to Src and focal adhesion kinase activation leading to lamellipodia formation and cell migration FASEB J, December 1, 2001; 15(14): 2649 - 2659. [Abstract] [Full Text] [PDF]
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M. Ayaki, K. Komatsu, M. Mukai, K. Murata, M. Kameyama, S. Ishiguro, J. Miyoshi, M. Tatsuta, and H. Nakamura Reduced Expression of Focal Adhesion Kinase in Liver Metastases Compared with Matched Primary Human Colorectal Adenocarcinomas Clin. Cancer Res., October 1, 2001; 7(10): 3106 - 3112. [Abstract] [Full Text] [PDF]
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H.-B. Wang, M. Dembo, S. K. Hanks, and Y.-l. Wang Focal adhesion kinase is involved in mechanosensing during fibroblast migration PNAS, September 25, 2001; 98(20): 11295 - 11300. [Abstract] [Full Text] [PDF]
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 W. Thomas, G. D. Pullinger, A. J. Lax, and E. Rozengurt Escherichia coli Cytotoxic Necrotizing Factor and Pasteurella multocida Toxin Induce Focal Adhesion Kinase Autophosphorylation and Src Association Infect. Immun., September 1, 2001; 69(9): 5931 - 5935. [Abstract] [Full Text] [PDF]
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K. A. West, H. Zhang, M. C. Brown, S. N. Nikolopoulos, M.C. Riedy, A. F. Horwitz, and C. E. Turner The LD4 motif of paxillin regulates cell spreading and motility through an interaction with paxillin kinase linker (PKL) J. Cell Biol., July 9, 2001; 154(1): 161 - 176. [Abstract] [Full Text] [PDF]
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D. Ilic, O. Genbacev, F. Jin, E. Caceres, E. A. C. Almeida, V. Bellingard-Dubouchaud, E. M. Schaefer, C. H. Damsky, and S. J. Fisher Plasma Membrane-Associated pY397FAK Is a Marker of Cytotrophoblast Invasion in Vivo and in Vitro Am. J. Pathol., July 1, 2001; 159(1): 93 - 108. [Abstract] [Full Text] [PDF]
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Z. Lu, G. Jiang, P. Blume-Jensen, and T. Hunter Epidermal Growth Factor-Induced Tumor Cell Invasion and Metastasis Initiated by Dephosphorylation and Downregulation of Focal Adhesion Kinase Mol. Cell. Biol., June 15, 2001; 21(12): 4016 - 4031. [Abstract] [Full Text]
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 L. M. Gleeson, C. Chakraborty, T. McKinnon, and P. K. Lala Insulin-Like Growth Factor-Binding Protein 1 Stimulates Human Trophoblast Migration by Signaling through {{alpha}}5{beta}1 Integrin via Mitogen-Activated Protein Kinase Pathway J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2484 - 2493. [Abstract] [Full Text] [PDF]
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Y.-K. Wang, H.-H. Lin, and M.-J. Tang Collagen gel overlay induces two phases of apoptosis in MDCK cells Am J Physiol Cell Physiol, June 1, 2001; 280(6): C1440 - C1448. [Abstract] [Full Text] [PDF]
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X.-R. Ren, Q.-S. Du, Y.-Z. Huang, S.-Z. Ao, L. Mei, and W.-C. Xiong Regulation of CDC42 GTPase by Proline-rich Tyrosine Kinase 2 Interacting with PSGAP, a Novel Pleckstrin Homology and Src Homology 3 Domain Containing rhoGAP Protein J. Cell Biol., March 5, 2001; 152(5): 971 - 984. [Abstract] [Full Text] [PDF]
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E. A. Cox, S. K. Sastry, and A. Huttenlocher Integrin-mediated Adhesion Regulates Cell Polarity and Membrane Protrusion through the Rho Family of GTPases Mol. Biol. Cell, February 1, 2001; 12(2): 265 - 277. [Abstract] [Full Text]
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C. Buensuceso, D Woodside, J. Huff, G. Plopper, and T. O'Toole The WD protein Rack1 mediates protein kinase C and integrin-dependent cell migration J. Cell Sci., January 5, 2001; 114(9): 1691 - 1698. [Abstract] [PDF]
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 A. V. Kazansky and J. M. Rosen Signal Transducers and Activators of Transcription 5B Potentiates v-Src-mediated Transformation of NIH-3T3 Cells Cell Growth Differ., January 1, 2001; 12(1): 1 - 7. [Abstract] [Full Text]
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M. J. Weyant, A. M. Carothers, A. J. Dannenberg, and M. M. Bertagnolli (+)-Catechin Inhibits Intestinal Tumor Formation and Suppresses Focal Adhesion Kinase Activation in the Min/+ Mouse Cancer Res., January 1, 2001; 61(1): 118 - 125. [Abstract] [Full Text]
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M. R. Burnham, P. J. Bruce-Staskal, M. T. Harte, C. L. Weidow, A. Ma, S. A. Weed, and A. H. Bouton Regulation of c-SRC Activity and Function by the Adapter Protein CAS Mol. Cell. Biol., August 15, 2000; 20(16): 5865 - 5878. [Abstract] [Full Text]
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W. G. Cance, J. E. Harris, M. V. Iacocca, E. Roche, X. Yang, J. Chang, S. Simkins, and L. Xu Immunohistochemical Analyses of Focal Adhesion Kinase Expression in Benign and Malignant Human Breast and Colon Tissues: Correlation with Preinvasive and Invasive Phenotypes Clin. Cancer Res., June 1, 2000; 6(6): 2417 - 2423. [Abstract] [Full Text]
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H. Ueda, S. Abbi, C. Zheng, and J.-L. Guan Suppression of Pyk2 Kinase and Cellular Activities by FIP200 J. Cell Biol., April 17, 2000; 149(2): 423 - 430. [Abstract] [Full Text] [PDF]
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A. P. Gilmore, A. D. Metcalfe, L. H. Romer, and C. H. Streuli Integrin-mediated Survival Signals Regulate the Apoptotic Function of Bax through Its Conformation and Subcellular Localization J. Cell Biol., April 17, 2000; 149(2): 431 - 446. [Abstract] [Full Text] [PDF]
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J.-F. Wang, I.-W. Park, and J. E. Groopman Stromal cell-derived factor-1alpha stimulates tyrosine phosphorylation of multiple focal adhesion proteins and induces migration of hematopoietic progenitor cells: roles of phosphoinositide-3 kinase and protein kinase C Blood, April 15, 2000; 95(8): 2505 - 2513. [Abstract] [Full Text] [PDF]
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J.-F. Lai, S.-C. Kao, S.-T. Jiang, M.-J. Tang, P.-C. Chan, and H.-C. Chen Involvement of Focal Adhesion Kinase in Hepatocyte Growth Factor-induced Scatter of Madin-Darby Canine Kidney Cells J. Biol. Chem., March 10, 2000; 275(11): 7474 - 7480. [Abstract] [Full Text] [PDF]
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