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AP Gilmore and LH Romer
Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill 27599, USA.
It has been proposed that the focal adhesion kinase (FAK) mediates focal adhesion formation through tyrosine phosphorylation during cell adhesion. We investigated the role of FAK in focal adhesion structure and function. Loading cells with a glutathione-S-transferase fusion protein (GST-Cterm) containing the FAK focal adhesion targeting sequence, but not the kinase domain, decreased the association of endogenous FAK with focal adhesions. This displacement of endogenous FAK in both BALB/c 3T3 cells and human umbilical vein endothelial cells loaded with GST-Cterm decreased focal adhesion phosphotyrosine content. Neither cell type, however, exhibited a reduction in focal adhesions after GST-Cterm loading. These results indicate that FAK mediates adhesion-associated tyrosine phosphorylation, but not the formation of focal adhesions. We then examined the effect of inhibiting FAK function on other adhesion-dependent cell behavior. Cells microinjected with GST- Cterm exhibited decreased migration. In addition, cells injected with GST-Cterm had decreased DNA synthesis compared with control-injected or noninjected cells. These findings suggest that FAK functions in the regulation of cell migration and cell proliferation.
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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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 F. Aoudjit and K. Vuori Engagement of the alpha 2beta 1 integrin inhibits Fas ligand expression and activation-induced cell death in T cells in a focal adhesion kinase-dependent manner Blood, March 15, 2000; 95(6): 2044 - 2051. [Abstract] [Full Text] [PDF]
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V. Petit, B. Boyer, D. Lentz, C. E. Turner, J. P. Thiery, and A. M. Valles Phosphorylation of Tyrosine Residues 31 and 118 on Paxillin Regulates Cell Migration through an Association with Crk in Nbt-II Cells J. Cell Biol., March 6, 2000; 148(5): 957 - 970. [Abstract] [Full Text] [PDF]
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M. J. Weyant, A. M. Carothers, M. E. Bertagnolli, and M. M. Bertagnolli Colon Cancer Chemopreventive Drugs Modulate Integrin-mediated Signaling Pathways Clin. Cancer Res., March 1, 2000; 6(3): 949 - 956. [Abstract] [Full Text]
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Y. Shen, P. Lyons, M. Cooley, D. Davidson, A. Veillette, R. Salgia, J. D. Griffin, and M. D. Schaller The Noncatalytic Domain of Protein-tyrosine Phosphatase-PEST Targets Paxillin for Dephosphorylation in Vivo J. Biol. Chem., January 14, 2000; 275(2): 1405 - 1413. [Abstract] [Full Text] [PDF]
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A. Asthagiri, C. Reinhart, A. Horwitz, and D. Lauffenburger The role of transient ERK2 signals in fibronectin- and insulin-mediated DNA synthesis J. Cell Sci., January 12, 2000; 113(24): 4499 - 4510. [Abstract] [PDF]
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J Zhao, C Zheng, and J Guan Pyk2 and FAK differentially regulate progression of the cell cycle J. Cell Sci., January 9, 2000; 113(17): 3063 - 3072. [Abstract] [PDF]
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M. Wassler and B. Shur Clustering of cell surface (beta)1,4-galactosyltransferase I induces transient tyrosine phosphorylation of focal adhesion kinase and loss of stress fibers J. Cell Sci., January 1, 2000; 113(2): 237 - 245. [Abstract] [PDF]
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J. W. Thomas, M. A. Cooley, J. M. Broome, R. Salgia, J. D. Griffin, C. R. Lombardo, and M. D. Schaller The Role of Focal Adhesion Kinase Binding in the Regulation of Tyrosine Phosphorylation of Paxillin J. Biol. Chem., December 17, 1999; 274(51): 36684 - 36692. [Abstract] [Full Text] [PDF]
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R. H. Palmer, L. I. Fessler, P. T. Edeen, S. J. Madigan, M. McKeown, and T. Hunter DFak56 Is a Novel Drosophila melanogaster Focal Adhesion Kinase J. Biol. Chem., December 10, 1999; 274(50): 35621 - 35629. [Abstract] [Full Text] [PDF]
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F. Wang, J. R. Van Brocklyn, L. Edsall, V. E. Nava, and S. Spiegel Sphingosine-1-phosphate Inhibits Motility of Human Breast Cancer Cells Independently of Cell Surface Receptors Cancer Res., December 1, 1999; 59(24): 6185 - 6191. [Abstract] [Full Text] [PDF]
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 B. M. FREY, B. F. X. REBER, B. S. VISHWANATH, G. ESCHER, and F. J. FREY Annexin I modulates cell functions by controlling intracellular calcium release FASEB J, December 1, 1999; 13(15): 2235 - 2245. [Abstract] [Full Text]
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 M. Tamura, J. Gu, H. Tran, and K. M. Yamada PTEN Gene and Integrin Signaling in Cancer J Natl Cancer Inst, November 3, 1999; 91(21): 1820 - 1828. [Abstract] [Full Text] [PDF]
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M. W. Renshaw, L. S. Price, and M. A. Schwartz Focal Adhesion Kinase Mediates the Integrin Signaling Requirement for Growth Factor Activation of Map Kinase J. Cell Biol., November 1, 1999; 147(3): 611 - 618. [Abstract] [Full Text] [PDF]
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E. P. Salazar and E. Rozengurt Bombesin and Platelet-derived Growth Factor Induce Association of Endogenous Focal Adhesion Kinase with Src in Intact Swiss 3T3 Cells J. Biol. Chem., October 1, 1999; 274(40): 28371 - 28378. [Abstract] [Full Text] [PDF]
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Y. Ohashi, S. Iwata, K. Kamiguchi, and C. Morimoto Tyrosine Phosphorylation of Crk-Associated Substrate Lymphocyte-Type Is a Critical Element in TCR- and {beta}1 Integrin-Induced T Lymphocyte Migration J. Immunol., October 1, 1999; 163(7): 3727 - 3734. [Abstract] [Full Text] [PDF]
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M. D. Schaller, J. D. Hildebrand, and J. T. Parsons Complex Formation with Focal Adhesion Kinase: A Mechanism to Regulate Activity and Subcellular Localization of Src Kinases Mol. Biol. Cell, October 1, 1999; 10(10): 3489 - 3505. [Abstract] [Full Text]
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J. S. Lymn, S. J. Rao, G. F. Clunn, K. L. Gallagher, C. O'Neil, N. T. Thompson, and A. D. Hughes Phosphatidylinositol 3-Kinase and Focal Adhesion Kinase Are Early Signals in the Growth Factor–Like Responses to Thrombospondin-1 Seen in Human Vascular Smooth Muscle Arterioscler Thromb Vasc Biol, September 1, 1999; 19(9): 2133 - 2140. [Abstract] [Full Text] [PDF]
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D. C. Han and J.-L. Guan Association of Focal Adhesion Kinase with Grb7 and Its Role in Cell Migration J. Biol. Chem., August 20, 1999; 274(34): 24425 - 24430. [Abstract] [Full Text] [PDF]
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Y. Shen and M. D. Schaller Focal Adhesion Targeting: The Critical Determinant of FAK Regulation and Substrate Phosphorylation Mol. Biol. Cell, August 1, 1999; 10(8): 2507 - 2518. [Abstract] [Full Text]
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J. Gu, M. Tamura, R. Pankov, E. H.J. Danen, T. Takino, K. Matsumoto, and K. M. Yamada Shc and Fak Differentially Regulate Cell Motility and Directionality Modulated by Pten J. Cell Biol., July 26, 1999; 146(2): 389 - 404. [Abstract] [Full Text] [PDF]
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M. Tamura, J. Gu, E. H. J. Danen, T. Takino, S. Miyamoto, and K. M. Yamada PTEN Interactions with Focal Adhesion Kinase and Suppression of the Extracellular Matrix-dependent Phosphatidylinositol 3-Kinase/Akt Cell Survival Pathway J. Biol. Chem., July 16, 1999; 274(29): 20693 - 20703. [Abstract] [Full Text] [PDF]
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J. D. Owen, P. J. Ruest, D. W. Fry, and S. K. Hanks Induced Focal Adhesion Kinase (FAK) Expression in FAK-Null Cells Enhances Cell Spreading and Migration Requiring Both Auto- and Activation Loop Phosphorylation Sites and Inhibits Adhesion-Dependent Tyrosine Phosphorylation of Pyk2 Mol. Cell. Biol., July 1, 1999; 19(7): 4806 - 4818. [Abstract] [Full Text] [PDF]
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M. Oktay, K. K. Wary, M. Dans, R. B. Birge, and F. G. Giancotti Integrin-mediated Activation of Focal Adhesion Kinase Is Required for Signaling to Jun NH2-terminal Kinase and Progression through the G1 Phase of the Cell Cycle J. Cell Biol., June 28, 1999; 145(7): 1461 - 1470. [Abstract] [Full Text] [PDF]
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M. S. Goligorsky, H. Abedi, E. Noiri, A. Takhtajan, S. Lense, V. Romanov, and I. Zachary Nitric oxide modulation of focal adhesions in endothelial cells Am J Physiol Cell Physiol, June 1, 1999; 276(6): C1271 - C1281. [Abstract] [Full Text] [PDF]
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J. L. Rodríguez-Fernández, M. Gómez, A. Luque, N. Hogg, F. Sánchez-Madrid, and C. Cabañas The Interaction of Activated Integrin Lymphocyte Function-associated Antigen 1 with Ligand Intercellular Adhesion Molecule 1 Induces Activation and Redistribution of Focal Adhesion Kinase and Proline-rich Tyrosine Kinase 2 in T Lymphocytes Mol. Biol. Cell, June 1, 1999; 10(6): 1891 - 1907. [Abstract] [Full Text]
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C. E. Turner, M. C. Brown, J. A. Perrotta, M.C. Riedy, S. N. Nikolopoulos, A. R. McDonald, S. Bagrodia, S. Thomas, and P. S. Leventhal Paxillin LD4 Motif Binds PAK and PIX through a Novel 95-kD Ankyrin Repeat, ARF-GAP Protein: A Role in Cytoskeletal Remodeling J. Cell Biol., May 17, 1999; 145(4): 851 - 863. [Abstract] [Full Text] [PDF]
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S. Manes, E. Mira, C. Gomez-Mouton, Z. J. Zhao, R. A. Lacalle, and C. Martinez-A. Concerted Activity of Tyrosine Phosphatase SHP-2 and Focal Adhesion Kinase in Regulation of Cell Motility Mol. Cell. Biol., April 1, 1999; 19(4): 3125 - 3135. [Abstract] [Full Text] [PDF]
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D.-Q. Zheng, A. S. Woodard, M. Fornaro, G. Tallini, and L. R. Languino Prostatic Carcinoma Cell Migration via {{alpha}}v{beta}3Integrin Is Modulated by a Focal Adhesion Kinase Pathway Cancer Res., April 1, 1999; 59(7): 1655 - 1664. [Abstract] [Full Text] [PDF]
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