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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.

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References

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  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).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  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).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  Google Scholar 

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

    Article  ADS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  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).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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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

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