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:

Cross-talk between cellular signalling pathways suggested by phorbol-ester-induced adenylate cyclase phosphorylation

Abstract

Receptor-mediated activation of both adenylate cyclase and phosphatidylinositide hydrolysis systems occurs through guanine nucleotide regulatory proteins and ultimately leads to specific activation of either cyclic AMP-dependent protein kinase A or Ca2+/phospholipid-dependent protein kinase C1,2. Given the remarkable diversity of agents that influence cellular metabolism through these pathways and the similarities of their components, interactions between the two signalling systems could occur. In fact, stimulation of cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA), a phorbol ester that activates protein kinase C3,4, influences hormone-sensitive adenylate cyclase. In some cells TPA induces desensitization of receptor-mediated stimulation of adenylate cyclase5,6, whereas in others, such as frog erythrocytes, phorbol ester treatment results in increased agonist-stimulated as well as basal, guanine nucleotide- and fluoride ion-stimulated adenylate cyclase activities7,8. We show here that TPA produces phosphorylation of the catalytic unit of adenylate cyclase in frog erythrocytes. Moreover, purified protein kinase C can directly phosphorylate in vitro the catalytic unit of adenylate cyclase purified from bovine brain. These results suggest that phosphorylation of the catalytic unit of adenylate cyclase by protein kinase C may be involved in the phorbol ester-induced enhancement of adenylate cyclase activity. In addition to providing the first direct demonstration of a covalent modification of the catalytic unit of adenylate cyclase, these results provide a potential biochemical mechanism for a regulatory link between the two major transmembrane signalling systems.

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. 1. Nishizuka, Y. Nature 308, 693–698 (1984). 2. M. Berridge & Irvine, R. F. Nature 312, 315–321 (1984). 3. Castagna, M. et al. J. biol. Chem. 257, 7849–7857 (1982). 4. Kikkawa, U., Takai, Y., Tanaka, Y., Miyake, R. & Nishizuka, Y. J. biol Chem. 258, 11442–11445 (1983). 5. Sibley, D. R., Nambi, P., Peters, J. R. & Lefkowitz, R. J. biochem., Biophys. Res. Commun 121,973–979 (1984). 6. Kelleher, D. J., Pessin, J. E., Ruoho, A. & Johnson, G. L. Proc. natn. Acad. Sci. U.S.A. 81, 4316–4320 (1984). 7. Sibley, D. R., Jeffs, R. A., Daniel, K., Nambi, P., & Lefkowitz, R. J. Archs Biochem. Biophys. 244, 373–381 (1986). 8. Bell, J. D., Buxton, I. L. & Brunton, L. L. /. biol. Chem. 260, 2625–2628 (1985). 9. Seamon, K. B., Padgett, W. & Daly, J. W. Proc. natn. Acad. Sci. U.S.A. 78, 3363–3367 (1981). 10. Bender, J. L. & Neer, E. J. /. biol Chem. 258, 2432–2439 (1983). 11. Yoshimasa, T. et al. J. biol. Chem. (submitted). 12. Pfeuffer, E., Drehev, R.–M., Metzfer, H. & Pfeuffer, T. Proc. natn. Acad. Sci. U.S.A. 82, 3086–3090 (1985). 13. Cousson, F., Haiech, J., D'Alayer, J. & Monneron, A. Proc. natn. Acad. Sci. U.S.A. 82, 6736–6740 (1985). 14. Pfeuffer, E., Mollner, S. & Pfeuffer, T. EMBO J. 4, 3675–3679. 15. Yeager, R. E., Heideman, W., Rosenberg, G. B. & Storm, D. R. Biochemistry 24, 3776–3783 (1985). 16. Smigel, M. D. / biol. Chem. 261, 1976–1982 (1986). 17. Seamon, K. B., Vaillancourt, R., Edwards, M. & Daly, J. W. Proc. natn. Acad. Sci. U.S.A. 81, 5081–5085 (1984). 18. Sibley, D. R., Strasser, R. H., Caron, M. G. & Lefkowitz, R. J. /. biol. Chem. 260, 3883–3886 (1985). 19. Jakobs, K. H., Bauer, S. & Watanabe, Y. Eur. J. Biochem. 151, 425–430 (1985). 20. Katada, T., Oilman, A. G., Watanabe, Y., Bauder, S. & Jakobs, K. H. Eur. J. Biochem. 151, 431–437 (1985). 21. Olianas, M. C. & Onali, P. /. Neurochem. 47, 890–897 (1986). 22. Sugden, D., Vanecek, J., Klein, D. C., Thomas, T. P. & Anderson, W. B. Nature 314, 359–361 (1985). 23. Nabika, T., Nara, Y., Yamori, Y., Lovenberg, W. & Endo, J. Biochem. biophys. Res. Commun. 131, 30–36 (1985). 24. Sibley, D. R. & Lefkowitz, R. J. Nature 317, 124–129 (1985). 25. Laemmli, U. K. Nature 227, 680–685 (1970). 26. Bolton, A. E. & Hunter, W. M. Biochem. J. 133, 529–530 (1973). 27. Uchida, T. & Filburn, C. R. J. biol. Chem. 258, 12311–12314 (1984).

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoshimasa, T., Sibley, D., Bouvier, M. et al. Cross-talk between cellular signalling pathways suggested by phorbol-ester-induced adenylate cyclase phosphorylation. Nature 327, 67–70 (1987). https://doi.org/10.1038/327067a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/327067a0

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