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.

GTPase inhibiting mutations activate the α chain of Gs and stimulate adenylyl cyclase in human pituitary tumours

Nature volume 340, pages 692–696 (1989)Cite this article

Abstract

A subset of growth hormone-secreting human pituitary tumours carries somatic mutations that inhibit GTPase activity of a G protein α chain, αs. The resulting activation of adenylyl cyclase bypasses the cells' normal requirement for trophic hormone. Amino acids substituted in the putative gsp oncogene identify a domain of G protein α-chains required for intrinsic ability to hydrolyse GTP. This domain may serve as a built-in counter-part of the separate GTPase-activating proteins required for GTP hydrolysis by small GTP-binding proteins such as p21ras.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

  1. Dumont, J. E., Jauniaux, J. C. & Roger, P. P. Trends biochem. Sci. 14, 67–71 (1989).

    CAS  Article  Google Scholar 

  2. Rozengurt, E. Science 234, 161–166 (1986).

    ADS  CAS  Article  Google Scholar 

  3. Stryer, L. & Bourne, H. R. A. Rev. Cell Biol. 2, 391–419 (1986).

    CAS  Article  Google Scholar 

  4. Neer, E. J. & Clapham, D. E. Nature 333, 129–134 (1988).

    ADS  CAS  Article  Google Scholar 

  5. Casey, P. J. & Gilman, A. G. J. biol. Chem. 263, 2577–2580 (1988).

    CAS  PubMed  Google Scholar 

  6. Birnbaumer, L. et al. Kidney Internatl (Suppl.) 32, S14–S37 (1987).

    Google Scholar 

  7. Bourne, H. R. Nature 330, 517–518 (1987).

    ADS  CAS  Article  Google Scholar 

  8. Vallar, L., Spada, A. & Giannattasio, G. Nature 330, 566–568 (1987).

    ADS  CAS  Article  Google Scholar 

  9. Trahey, M. & McCormick, F. Science 238, 542–545 (1987).

    ADS  CAS  Article  Google Scholar 

  10. McCormick, F. Cell 56, 5–8 (1989).

    CAS  Article  Google Scholar 

  11. Billestrup, N., Swanson, L. W. & Vale, W. Proc. natn. Acad. Sci. U.S.A. 83, 6854–6857 (1986).

    ADS  CAS  Article  Google Scholar 

  12. Saiki, R. K. et al. Science 239, 487–491 (1988).

    ADS  CAS  Article  Google Scholar 

  13. Van Dop, C., Tsubokawa, M., Bourne, H. R. & Ramachandran, J. J. biol. Chem. 259, 696–698 (1984).

    CAS  PubMed  Google Scholar 

  14. Cassel, D. & Selinger, Z. Proc. natn. Acad. Sci. U.S.A. 74, 3307–3311 (1977).

    ADS  CAS  Article  Google Scholar 

  15. Masters, S. B., Stroud, R. M. & Bourne, H. R. Protein Engng 1, 47–54 (1986).

    CAS  Article  Google Scholar 

  16. Der, C. J., Finkel, T. & Cooper, G. M. Cell 44, 167–176 (1986).

    CAS  Article  Google Scholar 

  17. Jones, D. T. & Reed, R. R. J. biol. Chem. 262, 14241–14249 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Sullivan, K. A. et al. Nature 330, 758–760 (1987).

    ADS  CAS  Article  Google Scholar 

  19. Miller, R. T., Masters, S. B., Sullivan, K. A., Beiderman, B. & Bourne, H. R. Nature 334, 712–715 (1988).

    ADS  CAS  Article  Google Scholar 

  20. Masters, S. B. et al. Science 241, 448–451 (1988).

    ADS  CAS  Article  Google Scholar 

  21. Masters, S. B. et al. J. biol. Chem., in the press.

  22. Graziano, M. & Gilman, A. G. J. biol. Chem., in the press.

  23. Holbrook, S. R. & Kim, S. H. Proc. natn. Acad. Sci. U.S.A. 86, 1751–1755 (1989).

    ADS  CAS  Article  Google Scholar 

  24. Barbacid, M. A. Rev. Biochem. 56, 779–827 (1987).

    CAS  Article  Google Scholar 

  25. Cassel, D., Eckstein, F., Lowe, M. & Selinger, Z. J. biol. Chem. 254, 9835–9838 (1979).

    CAS  PubMed  Google Scholar 

  26. Moss, J. & Vaughan, M. J. biol. chem. 252, 2455–2457 (1977).

    CAS  PubMed  Google Scholar 

  27. Graziano, M. P., Freissmuth, M. & Gilman, A. G. J. biol. Chem. 264, 409–418 (1989).

    CAS  PubMed  Google Scholar 

  28. Neal, S. E., Eccleston, J. F., Hall, A. & Webb, M. R. J. biol. Chem. 263, 19718–19722 (1988).

    CAS  PubMed  Google Scholar 

  29. Thompson, R. C., Dix, D. B. & Karim, A. M. J. biol. Chem. 261, 4868–4874 (1986).

    CAS  PubMed  Google Scholar 

  30. Sigal, I. S., Gibbs, J. B., D'Alonzo, J. S. & Scolnick, E. M. Proc. natn. Acad. Sci. U.S.A. 83, 4725–4729 (1986).

    ADS  CAS  Article  Google Scholar 

  31. Adari, H., Lowy, D. R., Willumsen, B. M., Der, C. J. & McCormick, F. Science 240, 518–521 (1988).

    ADS  CAS  Article  Google Scholar 

  32. Varmus, H. E. A. Rev. Genet. 18, 553–612 (1984).

    CAS  Article  Google Scholar 

  33. Gilman, A. G. A. Rev. Biochem. 56, 615–649 (1987).

    CAS  Article  Google Scholar 

  34. Fong, H. K. W., Yoshimoto, K. K., Eversole-Cire, P. & Simon, M. I. Proc. natn. Acad. Sci. U.S.A. 85, 3066–3070 (1988).

    ADS  CAS  Article  Google Scholar 

  35. Matsuoka, M., Itoh, H., Kozasa, T. & Kaziro, Y. Proc. natn. Acad. Sci. U.S.A. 85, 5384–5388 (1988).

    ADS  CAS  Article  Google Scholar 

  36. Chomczynski, P. & Sacchi, N. Analyt. Biochem. 162, 156–159 (1987).

    CAS  Article  Google Scholar 

  37. Kozasa, T., Itoh, H., Tsukamoto, T. & Kaziro, Y. Proc. natn. Acad. Sci. U.S.A. 85, 2081–2085 (1988).

    ADS  CAS  Article  Google Scholar 

  38. Gyllensten, U. B. & Erlich, H. A. Proc. natn. Acad. Sci. U.S.A. 85, 7652–7656 (1988).

    ADS  CAS  Article  Google Scholar 

  39. Kunkel, T. A. Proc. natn. Acad. Sci. U.S.A. 82, 488–492 (1985).

    ADS  CAS  Article  Google Scholar 

Download references

Author information

Affiliations

  1. Departments of Pharmacology and Medicine and the Cardiovascular Research Institute, University of California, San Francisco, California, 94143, USA

    Claudia A. Landis, Susan B. Masters, Ann M. Pace & Henry R. Bourne

  2. University of California, San Francisco, California, 94143, USA

    Claudia A. Landis, Susan B. Masters, Ann M. Pace & Henry R. Bourne

  3. Renal Division, Department of Medicine, University of California, San Francisco, California, 94143, USA

    Claudia A. Landis

  4. Department of Endocrinology, School of Medicine, University of Milan, Italy

    Anna Spada

  5. Department of Pharmacology, CNR Center of Cytopharmacology, Scientific Institute San Raffaele, University of Milan, Italy

    Lucia Vallar

Authors
  1. Claudia A. Landis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan B. Masters
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Spada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ann M. Pace
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Henry R. Bourne
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lucia Vallar
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Landis, C., Masters, S., Spada, A. et al. GTPase inhibiting mutations activate the α chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature 340, 692–696 (1989). https://doi.org/10.1038/340692a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/340692a0

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

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