Abstract
THE intracellular protein tyrosine kinase FAK (focal adhesion kinase) was originally identified by its high level of tyrosine phosphorylation in v-src-transformed cells1á¤-4. FAK is also highly phosphorylated during early development5,6. In cultured cells it is localized to focal adhesion contacts and becomes phosphorylated and activated in response to integrin-mediated binding of cells to the extracellular matrix, suggesting an important role in cell adhesion and/or migration. We have generated FAK-deficient mice by gene targeting to examine the role of FAK during development. Mutant embryos displayed a general defect of mesoderm development, and cells from these embryos had reduced mobilityin vitro. Surprisingly, the number of focal adhesions was increased in FAK-deficient cells, suggesting that FAK may be involved in the turnover of focal adhesion contacts during cell migration.
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References
Kanner, S. B., Reynolds, A. B., Vines, R. R. & Parsons, J. T. Proc. natn. Acad. Sci. U.S.A. 87, 3328–3332 (1990).
Schaller, M. D. et al. Proc. natn. Acad. Sci. U.S.A. 89, 5192–5196 (1992).
Hanks, S. K., Calalb, M. B., Harper, M. C. & Patel, S. K. Proc. natn. Acad. Sci. U.S.A. 89, 8487–8491 (1992).
Hanks, S. & Hunter, T. FASEB J. 9, 576–596 (1995).
Polte, T. R., Naftilan, A. J. & Hanks, S. K. J. cell. Biochem. 55, 106–119 (1994).
Burridge, K., Turner, C. E. & Romer, L. H. J. Cell Biol. 119, 893–903 (1992).
Ilić, D. et al. Biochem. biophys. Res. Commun. 209, 300–309 (1995).
Schaller, M. D., Borgman, C. A. & Parsons, J. T. Molec. cell. Biol. 13, 785–791 (1993).
Furuta, Y. et al. Oncogene (in the press).
George, E. L., Georges-Labouesse, E. N., Patel-King, R. S., Rayburn, H. & Hynes, R. O. Development 119, 1079–1091 (1993).
Hashimoto, K., Fujimoto, H. & Nakatsuji, N. Development 100, 587–598 (1987).
Klemke, R. L., Yebra, M., Bayna, E. M. & Cheresh, D. A. J. Cell Biol. 127, 859–866 (1994).
Geiger, B. Biochem. biophys. Acta 737, 305–341 (1983).
Rinnerthaler, G., Geiger, B. & Small, J. V. J. Cell Biol. 106, 747–760 (1988).
Wu, H. & Parsons, J. T. J. Cell Biol. 120, 1417–1426 (1993).
Parsons, J. T. et al. J. Cell Sci. (suppl.) 18, 109–113 (1994).
Izzard, C. S. & Lochner, L. R. J. Cell Sci. 21, 129–159 (1976).
Nakamura, N., Tanaka, J. & Sobue, K. J. Cell Sci. 106, 1057–1069 (1993).
Kanner, S. B., Aruffo, A. & Chan, P.-Y. Proc. natn. Acad. Sci. U.S.A. 91, 10484–10487 (1994).
Reynolds, A. B., Roesel, D. J., Kanner, S. B. & Parsons, J. T. Molec. cell. Biol. 9, 629–638 (1989).
Blake, T. J., Heath, K. G. & Langdon, W. Y. EMBO J. 12, 2017–2026 (1993).
Conrad, P. A. et al. J. Cell Biol. 120, 1381–1391 (1993).
Thomas, S. M., Soriano, P. & Imamoto, A. Nature 376, 267–271 (1995).
Chen, Q., Kinch, M. S., Lin, T. H., Burridge, K. & Juliano, R. L. J. biol. Chem. 269, 26602–26605 (1994).
Schlaepfer, D. D., Hanks, S. K., Hunter, T. & van der Geer, P. Nature 372, 786–791 (1995).
Yagi T. et al. Analyt. Biochem. 214, 70–76 (1994).
Nada, S. et al. Cell 73, 1125–1135 (1993).
Tsukada, T. et al. Oncogene 8, 3313–3322 (1993).
Rudnicki, M. A. & McBurney, M. in Teratocarcinomas and Embryonic Stem Cells, A Practical Approach (ed. Robertson, E. J.) 37–49 (IRL, Oxford, 1987).
Bockholt, S. M. & Burridge, K. J. biol. Chem. 268, 14565–14567 (1993).
Kanazawa, S., Ilić, D., Nomura, T., Yamamoto, T. & Aizawa, S. Biochem. biophys. Res. Commun. (in the press).
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llić, D., Furuta, Y., Kanazawa, S. et al. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377, 539–544 (1995). https://doi.org/10.1038/377539a0
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DOI: https://doi.org/10.1038/377539a0