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:

Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis

Nature volume 380, pages 75–79 (1996)Cite this article

Abstract

THE induction of programmed cell death, or apoptosis, involves activation of a signalling system, many elements of which remain unknown1. The sphingomyelin pathway, initiated by hydrolysis of the phospholipid sphingomyelin in the cell membrane to generate the second messenger ceramide2,3, is thought to mediate apoptosis in response to tumour-necrosis factor (TNF)-α2,3, to Fas ligand4 and to X-rays5. It is not known whether it plays a role in the stimulation of other forms of stress-induced apoptosis. Given that environmental stresses also stimulate a stress-activated protein kinase (SAPK/JNK) 6–12, the sphingomyelin and SAPK/ JNK signalling systems may be coordinated in induction of apoptosis. Here we report that ceramide initiates apoptosis through the SAPK cascade and provide evidence for a signalling mechanism that integrates cytokine- and stress-activated apoptosis.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Kerr, J. F. R. & Harmon, B. V. in Apoptosis: The Molecular Basis of Cell Death (eds Tomei, L. D. & Cope, F. O.) 5–29 (Cold Spring Harbor Laboratory Press, New York, 1991).

    Google Scholar 

  2. Pushkareva, M., Obeid, L. M. & Hannun, Y. A. Immun. Today 16, 294–297 (1995).

    Article  CAS  Google Scholar 

  3. Kolesnick, R. & Golde, D. W. Cell 77, 325–328 (1994).

    Article  CAS  Google Scholar 

  4. Gulbins, E. et al. Immunity 2, 341–351 (1995).

    Article  CAS  Google Scholar 

  5. Haimovitz-Friedman, A. et al. J. exp. Med. 180, 525–535 (1994).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  Google Scholar 

  8. Sluss, H. K., Barrett, T., Dérijard, B. & Davis, R. J. Molec. cell. Biol. 14, 8376–8384 (1994).

    Article  CAS  Google Scholar 

  9. Dérijard, B. et al. Science 267, 682–685 (1995).

    Article  ADS  Google Scholar 

  10. Sánchez, I. et al. Nature 372, 794–798 (1994).

    Article  ADS  Google Scholar 

  11. Yan, M. et al. Nature 372, 798–800 (1994).

    Article  ADS  CAS  Google Scholar 

  12. Lin, A. et al. Science 268, 286–290 (1995).

    Article  ADS  CAS  Google Scholar 

  13. Jarvis, W. D. et al. J. biol. Chem. 269, 31685–31692 (1994).

    CAS  Google Scholar 

  14. Oberhammer, F. A. et al. Proc. natn. Acad. Sci. U.S.A. 89, 5408–5412 (1992).

    Article  ADS  CAS  Google Scholar 

  15. Gavrieli, Y., Sherman, Y. & Ben-Sasson, S. A. J. Cell Biol. 119, 493–501 (1992).

    Article  CAS  Google Scholar 

  16. Westwick, J. K., Bielawska, A. E., Dbaibo, G., Hannun, Y. A. & Brenner, D. A. J. biol. Chem. 270, 22689–22692 (1995).

    Article  CAS  Google Scholar 

  17. Brown, P. H., Chen, T. K. & Birrer, M. J. Oncogene 9, 791–799 (1993).

    Google Scholar 

  18. Xia, Z., Dickens, M., Raingeaud, J., Davis, R. & Greenberg, M. E. Science 270, 1326–1331 (1995).

    Article  ADS  CAS  Google Scholar 

  19. Yao, B. et al. Nature 378, 307–310 (1995).

    Article  ADS  CAS  Google Scholar 

  20. Bruder, J. T., Heidecker, G. & Rapp, U. R. Genes Dev. 6, 545–556 (1992).

    Article  CAS  Google Scholar 

  21. Mansour, S. J. et al. Science 265, 966–970 (1994).

    Article  ADS  CAS  Google Scholar 

  22. Wiegmann, K., Schutze, S., Machleidt, T., Witte, D. & Krönke, M. Cell 78, 1005–1015 (1994).

    Article  CAS  Google Scholar 

  23. Ham, J. et al. Cell 14, 927–939 (1995).

    CAS  Google Scholar 

  24. Johnson, E. M. & Deckwarth, T. L. A. Rev. Neurosci. 16, 31–46 (1993).

    Article  CAS  Google Scholar 

  25. Martin, S. J. Trends Cell Biol. 3, 141–144 (1993).

    Article  CAS  Google Scholar 

  26. Karin, M. J. biol. Chem. 270, 16483–16486 (1995).

    Article  CAS  Google Scholar 

  27. Su, B. et al. Cell 77, 727–736 (1994).

    Article  Google Scholar 

  28. Kolesnick, R. & Fuks, Z. J. exp. Med. 181, 1949–1952 (1995).

    Article  CAS  Google Scholar 

  29. Alani, R. et al. Molec. cell. Biol. 11, 6286–6295 (1991).

    Article  CAS  Google Scholar 

  30. Kameshita, I. & Fujisawa, H. Analyt. Biochem. 183, 139–143 (1989).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Marcel Verheij

    Present address: Department of Radiation Therapy, Antoni v. Leeuwenhoekhuis/The Netherlands Cancer Institute, Amsterdam, The Netherlands

Authors and Affiliations

  1. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York, 10021, USA

    Marcel Verheij, Adriana Haimovitz-Friedman & Zvi Fuks

  2. Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York, 10021, USA

    Ron Bose, Xin Hua Lin, Bei Yao & Richard N. Kolesnick

  3. Department of Medicine, Division of Hematology–Oncology, Medical College of Virginia, 1101 East Marshall Street, Richmond, Virginia, 23298, USA

    W. David Jarvis & Steven Grant

  4. Biomarkers and Prevention Research Branch, Division of Cancer Prevention and Control, National Cancer Institute, 9610 Medical Center Drive, Rockville, Maryland, 20850, USA

    Michael J. Birrer & Eva Szabo

  5. Division of Hematology–Oncology, Children's Hospital and Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Howard Hughes Medical Institute, Children's Hospital, 300 Longwood Avenue, Enders 780, Boston, Massachusetts, 02115, USA

    Leonard I. Zon

  6. Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital East, 149 13th Street, Charlestown, Massachusetts, 02129, USA

    John M. Kyriakis

Authors
  1. Marcel Verheij
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Ron Bose
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Xin Hua Lin
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Bei Yao
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. W. David Jarvis
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Steven Grant
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Michael J. Birrer
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Eva Szabo
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Leonard I. Zon
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. John M. Kyriakis
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Adriana Haimovitz-Friedman
    View author publications

    You can also search for this author inPubMed Google Scholar

  12. Zvi Fuks
    View author publications

    You can also search for this author inPubMed Google Scholar

  13. Richard N. Kolesnick
    View author publications

    You can also search for this author inPubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Verheij, M., Bose, R., Hua Lin, X. et al. Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 380, 75–79 (1996). https://doi.org/10.1038/380075a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/380075a0

Search

Advanced 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