Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Regulation of cell adhesion and anchorage-dependent growth by a new β1-integrin-linked protein kinase

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Damsky, C. H. & Werb, Z. Curr. Opin. Cell Biol. 4, 772–781 (1992).

    Article  CAS  Google Scholar 

  2. Hynes, R. O. Cell 69, 11–25 (1992).

    Article  CAS  Google Scholar 

  3. Clark, E. A. & Brugge, J. S. Science 268, 233–239 (1995).

    Article  ADS  CAS  Google Scholar 

  4. Fields, S. & Song, O. Nature 340, 245–246 (1989).

    Article  ADS  CAS  Google Scholar 

  5. Lux, S. E., John, K. M. & Bennett, V. Nature 344, 36–42 (1990).

    Article  ADS  CAS  Google Scholar 

  6. Inoue, J.-I. et al. Proc. natn. Acad. Sci. U.S.A. 89, 4333–4337 (1992).

    Article  ADS  CAS  Google Scholar 

  7. Lukas, J. et al. Nature 375, 503–506 (1993).

    Article  ADS  Google Scholar 

  8. Schaller, M. D. et al. Proc. natn. Acad. Sci. U.S.A. 89, 5192–5196 (1992).

    Article  ADS  CAS  Google Scholar 

  9. Hanks, S. K., Calalb, M. B., Harper, M. C. & Patel, S. K. Proc. natn. Acad. Sci. U.S.A. 89, 8481–8491 (1992).

    Article  ADS  Google Scholar 

  10. Dedhar, S., Saulnier, R., Nagle, R. & Overall, C. M. Clin. exp. Metastasis 11, 391–400 (1993).

    Article  CAS  Google Scholar 

  11. Chen, Y.-P. et al. J. biol. Chem. 269, 18307–18310 (1994).

    CAS  PubMed  Google Scholar 

  12. Filmus, J. et al. Oncogene 9, 3627–3633 (1994).

    CAS  PubMed  Google Scholar 

  13. O'Toole, T. E. et al. J. Cell Biol. 124, 1047–1059 (1994).

    Article  CAS  Google Scholar 

  14. Kapron-Bras, C., Fitz-Gibbon, L., Jeevaratnam, P., Wilkins, J. & Dedhar, S. J. biol. Chem. 268, 20701–20704 (1993).

    CAS  PubMed  Google Scholar 

  15. Chen, Q., Kinch, M. S., Lin, T. H., Burridge, K. & Juliano, R. L. J. biol. Chem. 269, 26602–26605 (1994).

    CAS  PubMed  Google Scholar 

  16. Schlaepfer, D. D., Hanks, S. K., Hunter, T. & van der Geer, P. Nature 372, 786–791 (1994).

    Article  ADS  CAS  Google Scholar 

  17. Kozak, M. Cell 44, 283–292 (1986).

    Article  CAS  Google Scholar 

  18. Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. J. molec. Biol. 215, 403–410 (1990).

    Article  CAS  Google Scholar 

  19. Hanks, S. K., Quinn, A. M. & Hunter T. Science 241, 42–52 (1988).

    Article  ADS  CAS  Google Scholar 

  20. Zervos, A. S., Gyuris, J. & Brent, R. Cell 72, 223–232 (1993).

    Article  CAS  Google Scholar 

  21. Argraves, W. S. et al. J. Cell Biol. 105, 1183–1190 (1987).

    Article  CAS  Google Scholar 

  22. Gietz, D., St Jean, A., Woods, R. A. & Schiestl, R. H. Nucleic Acids Res. 20, 1425(1992).

    Article  Google Scholar 

  23. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning; A Laboratory Manual 2nd edn (Cold Spring Harbor Laboratory Press, New York, 1989).

    Google Scholar 

  24. Otey, C. A., Pavalko, F. M. & Burridge, K. J. Cell Biol. 111, 721–729 (1990).

    Article  CAS  Google Scholar 

  25. Cooper, J. A., Sefton, B. M. & Hunter, T. Meth. Enzym. 99, 387–402 (1983).

    Article  CAS  Google Scholar 

  26. Stephens, L. C., Sonne, J. E., Fitzgerald, M. L. & Damsky, C. H. J. Cell Biol. 123, 1607–1620 (1993).

    Article  CAS  Google Scholar 

  27. Harlow, E. & Lane, D. Antibodies: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1988).

    Google Scholar 

  28. Leung-Hagesteijn, C. Y., Milankov, K., Michalak, M., Wilkins, J. & Dedhar, S. J. Cell Sci. 107, 589–600 (1994).

    CAS  PubMed  Google Scholar 

  29. Buick, R. N., Filmus, J. & Quaroni, A. Expl Cell Res. 170, 300–309 (1987).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/379091a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing