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.

The stress-activated protein kinase subfamily of c-Jun kinases

Abstract

THE mitogen-activated protein (MAP) kinases Erk-1 and Erk-2 are proline-directed kinases that are themselves activated through concomitant phosphorylation of tyrosine and threonine residues1–4. The kinase p54 (Mr 54,000), which was first isolated from cycloheximide-treated rats, is proline-directed like Erks-1/2, and requires both Tyr and Ser/Thr phosphorylation3,5,6 for activity. p54 is, however, distinct from Erks-1/2 in its substrate specificity, being unable to phosphon late pp90rsk but more active in phosphor-ylating the c-Jun transactivation domain5,7,8. Molecular cloning of p54 reveals a unique subfamily of extracellularly regulated kinases. Although they are 40–45% identical in sequence to Erks-1/2, unlike Erks-1/2 the p54s are only poorly activated in most cells by mitogens or phorbol esters. However, p54s are the principal c-Jun N-terminal kinases activated by cellular stress and tumour necrosis factor (TNF)-α, hence they are designated stress-activated protein kinases, or SAPKs. SAPKs are also activated by sphingo-myelinase, which elicits a subset of cellular responses to TNF-α (ref. 9). SAPKs therefore define a new TNF-α and stress-activated signalling pathway, possibly initiated by sphingomyelin-based second messengers, which regulates the activity of c-Jun.

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

References

  1. Boulton, T. G. et al. Cell 65, 663–675 (1991).

    Article  CAS  Google Scholar 

  2. Alvarez, E. et al. J. biol. Chem. 266, 15277–15285 (1991).

    CAS  Google Scholar 

  3. Mukhopadhyay, N. K. et al. J. biol. Chem. 267, 3325–3335 (1992).

    CAS  PubMed  Google Scholar 

  4. Anderson, N. G., Maller, J. L., Tonks, N. K. & Sturgill, T. W. Nature 343, 651–653 (1990).

    Article  ADS  CAS  Google Scholar 

  5. Kyriakis, J. M. & Avruch, J. J. biol. Chem. 265, 17355–17363 (1990).

    CAS  PubMed  Google Scholar 

  6. Kyriakis, J. M., Brautigan, D. L., Ingebritsen, T. S. & Avruch, J. J. blol. Chem. 266, 10043–10046 (1991).

    CAS  Google Scholar 

  7. Pulverer, B. J. et al. Nature 353, 670–673 (1992).

    Article  ADS  Google Scholar 

  8. Sturgill, T. W., Ray, L. B., Erikson, E. & Maller, J. L. Nature 334, 715–718 (1988).

    Article  ADS  CAS  Google Scholar 

  9. Hannun, Y. A. J. biol. Chem. 269, 3125–3128 (1994).

    CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  11. Courchesne, W. E., Kunisawa, R. & Thorner, J. Cell 58, 1107–1119 (1989).

    Article  CAS  Google Scholar 

  12. Brewster, J. L. et al. Science 259, 1760–1763 (1993).

    Article  ADS  CAS  Google Scholar 

  13. Levin, D. E. & Errede, B. A. J. NIH Res. 5, 49–52 (1993).

    Google Scholar 

  14. Elion, E. A., Grisafi, P. L. & Fink, G. R. Cell 60, 649–664 (1990).

    Article  CAS  Google Scholar 

  15. Payne, D. M. et al. EMBO J. 10, 885–892 (1991).

    Article  CAS  Google Scholar 

  16. Ahn, N. G. et al. J. blol. Chem. 266, 4220–4227 (1991).

    CAS  Google Scholar 

  17. Gómez, N. & Cohen, P. Nature 253, 170–173 (1991).

    Article  ADS  Google Scholar 

  18. Nakielny, S., Cohen, P., Wu, J. & Sturgill, T. W. EMBO J. 11, 2123–2129 (1992).

    Article  CAS  Google Scholar 

  19. Beutler, B. & Cerami, A. A. Rev. Biochem. 57, 505–517 (1988).

    Article  CAS  Google Scholar 

  20. Goeddel D. V. et al. Cold Spring Harbor Symp. quant. Biol. 51, 597–609 (1986).

    Article  CAS  Google Scholar 

  21. Brenner, D. A. et al. Nature 337, 661–663 (1989).

    Article  ADS  CAS  Google Scholar 

  22. Binétruy, B., Smeal, T. & Karin, M. Nature 351, 122–127 (1991).

    Article  ADS  Google Scholar 

  23. Smeal, T. et al. Nature 354, 494–496 (1991).

    Article  ADS  CAS  Google Scholar 

  24. Adler, V., Franklin, C. C. & Kraft, A. S. Proc. natn. Acad. Sci. U.S.A. 89, 5341–5345 (1992).

    Article  ADS  CAS  Google Scholar 

  25. Hibi, M. et al. Genes Dev. 7, 2135–2148 (1993).

    Article  CAS  Google Scholar 

  26. Kyriakis, J. M. & Avruch, J. in Frontiers in Molecular Biology (ed. Woodgett, J. R.) (Oxford University Press, London, in the press).

  27. Devary, Y., Gottleib, R., Smeal, T. & Karin, M. Cell 71, 1081–1091 (1992).

    Article  CAS  Google Scholar 

  28. Pulverer, B. J. et al. Oncogene 8, 407–415 (1993).

    CAS  PubMed  Google Scholar 

  29. Dressler, K. A., Mathias, S. & Kolesnik, R. N. Science 255, 1715–1718 (1992).

    Article  ADS  CAS  Google Scholar 

  30. Kyriakis, J. M. et al. Nature 358, 417–421 (1992).

    Article  ADS  CAS  Google Scholar 

  31. Dérijard, B. et al. Cell 76, 1025–1037 (1994).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kyriakis, J., Banerjee, P., Nikolakaki, E. et al. The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369, 156–160 (1994). https://doi.org/10.1038/369156a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/369156a0

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