Abstract
THE interaction of cells with the extracellular matrix regulates cell shape, motility, growth, survival, differentiation and gene expression, through integrin-mediated signal transduction1–3. We used a two-hybrid screen to isolate genes encoding proteins that interact with the β1-integrin cytoplasmic domain. The most frequently isolated complementary DNA encoded a new, 59K serine/threonine protein kinase, containing four ankyrin-like repeats. We report here that this integrin-linked kinase (ILK) phosphorylated a β1-integrin cytoplasmic domain peptide in vitro and coimmunoprecipitated with β1 in lysates of mammalian cells. Endogenous ILK kinase activity was reduced in response to fibronectin. Overexpression of p59ILK disrupted epithelial cell architecture and inhibited adhesion to integrin substrates, while inducing anchorage-independent growth. We propose that ILK is a receptor-proximal protein kinase regulating integrin-mediated signal transduction.
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References
Damsky, C. H. & Werb, Z. Curr. Opin. Cell Biol. 4, 772–781 (1992).
Hynes, R. O. Cell 69, 11–25 (1992).
Clark, E. A. & Brugge, J. S. Science 268, 233–239 (1995).
Fields, S. & Song, O. Nature 340, 245–246 (1989).
Lux, S. E., John, K. M. & Bennett, V. Nature 344, 36–42 (1990).
Inoue, J.-I. et al. Proc. natn. Acad. Sci. U.S.A. 89, 4333–4337 (1992).
Lukas, J. et al. Nature 375, 503–506 (1993).
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, 8481–8491 (1992).
Dedhar, S., Saulnier, R., Nagle, R. & Overall, C. M. Clin. exp. Metastasis 11, 391–400 (1993).
Chen, Y.-P. et al. J. biol. Chem. 269, 18307–18310 (1994).
Filmus, J. et al. Oncogene 9, 3627–3633 (1994).
O'Toole, T. E. et al. J. Cell Biol. 124, 1047–1059 (1994).
Kapron-Bras, C., Fitz-Gibbon, L., Jeevaratnam, P., Wilkins, J. & Dedhar, S. J. biol. Chem. 268, 20701–20704 (1993).
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 (1994).
Kozak, M. Cell 44, 283–292 (1986).
Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. J. molec. Biol. 215, 403–410 (1990).
Hanks, S. K., Quinn, A. M. & Hunter T. Science 241, 42–52 (1988).
Zervos, A. S., Gyuris, J. & Brent, R. Cell 72, 223–232 (1993).
Argraves, W. S. et al. J. Cell Biol. 105, 1183–1190 (1987).
Gietz, D., St Jean, A., Woods, R. A. & Schiestl, R. H. Nucleic Acids Res. 20, 1425(1992).
Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning; A Laboratory Manual 2nd edn (Cold Spring Harbor Laboratory Press, New York, 1989).
Otey, C. A., Pavalko, F. M. & Burridge, K. J. Cell Biol. 111, 721–729 (1990).
Cooper, J. A., Sefton, B. M. & Hunter, T. Meth. Enzym. 99, 387–402 (1983).
Stephens, L. C., Sonne, J. E., Fitzgerald, M. L. & Damsky, C. H. J. Cell Biol. 123, 1607–1620 (1993).
Harlow, E. & Lane, D. Antibodies: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1988).
Leung-Hagesteijn, C. Y., Milankov, K., Michalak, M., Wilkins, J. & Dedhar, S. J. Cell Sci. 107, 589–600 (1994).
Buick, R. N., Filmus, J. & Quaroni, A. Expl Cell Res. 170, 300–309 (1987).
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Hannigan, G., Leung-Hagesteijn, C., Fitz-Gibbon, L. et al. Regulation of cell adhesion and anchorage-dependent growth by a new β1-integrin-linked protein kinase. Nature 379, 91–96 (1996). https://doi.org/10.1038/379091a0
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DOI: https://doi.org/10.1038/379091a0
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