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.

Growth factor-like action of phosphatidic acid

Abstract

Phosphatidic acid (PA), an intriguing phospholipid that is rapidly produced during receptor-stimulated breakdown of phosphoinosi-tides, has often been proposed to function as a Ca2+ ionophore in activated cells11–5. The PA-ionophore hypothesis is supported by the fact that exogenously applied PA stimulates Ca2+ uptake in various cells4–6 and can evoke Ca2+-mediated physiological responses2–5, but it is not known whether PA accumulation affects cytoplasmic free Ca2+ concentration ([Ca2+]i). Here we report that PA elicits a transient rise in [Ca2+]i in cultured cells, not by stimulating Ca2+ influx, but, surprisingly, by releasing Ca2+ from intracellular stores. We further show that PA evokes growth factor-like effects in that it raises cytoplasmic pH, induces expression of the c-fos and c-myc proto-oncogenes and stimulates DNA synthesis. Our results indicate that, unlike an ionophore, PA acts by triggering the hydrolysis of phosphoinositides, with consequent formation of second messengers such as inositol trisphosphate signalling Ca2+ release. Furthermore, our data strengthen the notion that any Cai2+-mobilizing stimulus acting through phospholipase C may ultimately function as a growth factor.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. Salmon, D. M. & Honeyman, T. W. Nature 284, 344–345 (1980).

    ADS  CAS  Article  Google Scholar 

  2. Putney, J. W., Weiss, S. J., Van De Walle, C. M. & Haddas, R. A. Nature 284, 345–347 (1980).

    ADS  CAS  Article  Google Scholar 

  3. Harris, R. A., Schmidt, J., Hitzemann, B. A. & Hitzemann, R. J. Science 212, 1290–1291 (1981).

    ADS  CAS  Article  Google Scholar 

  4. Ohsako, S. & Deguchi, T. J. biol. Chem. 256, 10945–10948 (1981).

    CAS  PubMed  Google Scholar 

  5. Barrit, G. J., Dalton, K. A. & Whiting, J.A. FEBS Lett. 125, 137–140 (1981).

    Article  Google Scholar 

  6. Ohsako, S. & Deguchi, T. FEBS Lett. 152, 62–66 (1983).

    CAS  Article  Google Scholar 

  7. Sawyer, S. T. & Cohen, S. Biochemistry 20, 6280–6286 (1981).

    CAS  Article  Google Scholar 

  8. Bravo, R., Burckhardt, J., Curran, T. & Müllet, R. EMBO J. 4, 1193–1198 (1985).

    CAS  Article  Google Scholar 

  9. Moolenaar, W. H., Aerts, R. J., Tertoolen, L. J. G. & de Laat, S. W. J. biol. Chem. 261, 279–284 (1986).

    CAS  PubMed  Google Scholar 

  10. Prentki, M. et al. Nature 309, 562–564 (1984).

    ADS  CAS  Article  Google Scholar 

  11. Somlyo, A. P. Nature 309, 516–517 (1984).

    ADS  CAS  Article  Google Scholar 

  12. Imamura, S. & Horiuti, Y. J. Biochem., Tokyo 85, 79–95 (1979).

    CAS  Article  Google Scholar 

  13. Berridge, M. J. & Irvine, R. F. Nature 312, 315–321 (1984).

    ADS  CAS  Article  Google Scholar 

  14. Moolenaar, W. H. A. Rev. Physiol. 48, 363–376 (1986).

    CAS  Article  Google Scholar 

  15. Kelly, K., Cochran, B. H., Stiles, C. D. & Leder, P. Cell 35, 603–610 (1983).

    CAS  Article  Google Scholar 

  16. Kruijer, W., Cooper, J., Hunter, T. & Verma, I. M. Nature 312, 711–716 (1984).

    ADS  CAS  Article  Google Scholar 

  17. Müller, R., Bravo, R., Burckhardt, J. & Curran, T. Nature 312, 716–720 (1984).

    ADS  Article  Google Scholar 

  18. Cockroft, S. & Gomperts, B. D. Nature 314, 534–536 (1985).

    ADS  Article  Google Scholar 

  19. Galla, H.-J. & Sackmann, E. Biochim. biophys. Acta. 401, 509–529 (1975).

    CAS  Article  Google Scholar 

  20. Papahadjopoulos, D., Vail, W. J., Pangborn, W. A. & Poste, G. Biochim. biophys. Acta 448, 265–283 (1976).

    CAS  Article  Google Scholar 

  21. Massari, S. & Pascolini, D. Biochemistry 16, 1189–1195 (1977).

    CAS  Article  Google Scholar 

  22. Verkleij, A. J., de Maagd, R., Leunissen-Bijvelt, J. & de Kruijf, B. Biochim. biophys. Acta 684, 255–262 (1982).

    CAS  Article  Google Scholar 

  23. Dawson, R. M. C., Irvine, R. F., Bray, J. & Quinn, P. J. Biochem. biophys. Res. Commun. 125, 836–842 (1984).

    CAS  Article  Google Scholar 

  24. Irvine, R. F., Letcher, A. J. & Dawson, R. M. C. Biochem. J. 218, 177–185 (1984).

    CAS  Article  Google Scholar 

  25. Moolenaar, W. H., Tsien, R. Y., van der Saag, P. T. & de Laat, S. W. Nature 304, 645–648 (1983).

    ADS  CAS  Article  Google Scholar 

  26. Berridge, M. J., Dawson, R. M. C., Downes, C. P., Heslop, J. P. & Irvine, R. F. Biochem. J. 212, 473–482 (1983).

    CAS  Article  Google Scholar 

  27. Irvine, R. F., Anggard, E. E., Letcher, A. J. & Downes, C. P. Biochem. J. 229, 505–511 (1985).

    CAS  Article  Google Scholar 

  28. Burgess, G. M., McKinney, J. S., Irvine, R. F. & Putney, J. W. Biochem. J. 232, 237–243 (1985).

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Moolenaar, W., Kruijer, W., Tilly, B. et al. Growth factor-like action of phosphatidic acid. Nature 323, 171–173 (1986). https://doi.org/10.1038/323171a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/323171a0

Further reading

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