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:

Activation of the c-Abl tyrosine kinase in the stress response to DMA-damaging agents

Abstract

THE product of the c-abl gene is a non-receptor tyrosine kinase that is localized to the nucleus and cytoplasm. The precise function of c-Abl is unknown. Here we show that ionizing radiation activates c-Abl. Similar results were obtained with the alkylating agents cis-platinum and mitomycin C. We also demonstrate that cells deficient in c-Abl fail to activate Jun kinase (JNK/SAP kinase) after ionizing radiation or alkylating agent exposure and that reconstitution of c-Abl in these cells restores that response. In contrast, the stress response to tumour-necrosis factor is stimulated by a c-Abl-independent mechanism. These findings indicate that c-abl is involved in the stress response to DNA-damaging agents.

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. Feller, S. M., Knudsen, B. & Hanafusa, H. EMBO J. 13, 2341–2351 (1994).

    Article  CAS  Google Scholar 

  2. Ren, R., Ye, Z.-S. & Baltimore, D. Genes Dev. 8, 783–795 (1994).

    Article  CAS  Google Scholar 

  3. Songyang, Z. et al. Nature 373, 536–539 (1995).

    Article  ADS  CAS  Google Scholar 

  4. Sherman, S. E. & Lippard, S. J. Chem. Rev. 87, 1153–1181 (1987).

    Article  CAS  Google Scholar 

  5. Tomasz, M., Chawla, A. K. & Lipman, R. Biochemistry 27, 3182–3187 (1988).

    Article  CAS  Google Scholar 

  6. Pulverer, B. J., Kyriakis, J. M., Avruch, J., Nikolakaki, E. & Woodgett, J. R. Nature 353, 670–674 (1991).

    Article  ADS  CAS  Google Scholar 

  7. Kyriakis, J. M. et al. Nature 369, 156–160 (1994).

    Article  ADS  CAS  Google Scholar 

  8. Derijard, B. et al. Cell 76, 1025–1037 (1994).

    Article  CAS  Google Scholar 

  9. Engelberg, D., Klein, C., Martinetto, H., Struhl, K. & Karin, M. Cell 77, 381–390 (1994).

    Article  CAS  Google Scholar 

  10. Tybulewicz, V. L. J., Crawford, C. E., Jackson, P., Bronson, R. T. & Mulligan, R. C. Cell 65, 1153–1163 (1991).

    Article  CAS  Google Scholar 

  11. Welch, P. J. & Wang, J. Y. Cell 75, 779–790 (1993).

    Article  CAS  Google Scholar 

  12. Sawyers, C. L., McLaughlin, J., Goga, A., Havillk, M. & Witte, O. Cell 77, 121–131 (1994).

    Article  CAS  Google Scholar 

  13. Mattioni, T., Jackson, P. K., van Huijsduijnen, O. B.-H. & Picard, D. Oncogene 10, 1325–1333 (1995).

    CAS  PubMed  Google Scholar 

  14. Kipreos, E. T. & Wang, J. Y. J. Science 248, 217–220 (1990).

    Article  ADS  CAS  Google Scholar 

  15. Kipreos, E. T. & Wang, J. Y. J. Science 256, 382–385 (1992).

    Article  ADS  CAS  Google Scholar 

  16. Feller, S. M., Ren, R., Hanafusa, H. & Baltimore, D. Trends biochem. Sci. 19, 453–458 (1994).

    Article  CAS  Google Scholar 

  17. Saleem, A., Yuan, Z. M., Kufe, D. W. & Kharbanda, S. J. Immun. 154, 4150–4156 (1995).

    CAS  PubMed  Google Scholar 

  18. Morgenstern, J. P. & Land, H. Nucleic Acids Res. 18, 3587–3596 (1990).

    Article  CAS  Google Scholar 

  19. Pear, W. S., Nolan, G. P., Scott, M. L. & Baltimore, D. Proc. natn. Acad. Sci. U.S.A. 90, 8392–8396 (1993).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kharbanda, S., Ren, R., Pandey, P. et al. Activation of the c-Abl tyrosine kinase in the stress response to DMA-damaging agents. Nature 376, 785–788 (1995). https://doi.org/10.1038/376785a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/376785a0

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