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:

Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbloncogene product

Abstract

THE superfamily of low molecular mass GTP-binding proteins, for which the ras proteins are prototypes, has been implicated in the regulation of diverse biological activities including protein trafficking, secretion, and cell growth and differentiation1–3. One member of this family, CDC42Hs (originally referred to as Gp or G25K)4,5, seems to be the human homologue of the Saccharomyces cerevisiae cell-division-cycle protein, CDC42Sc(refs 6–9). A second S. cerevisiae protein, CDC24 (ref. 10), which is known from complementation studies to act with CDC42Sc to regulate the development of normal cell shape and the selection of nonran-dom budding sites in yeast, contains a region with sequence similarity to the dbl oncogene product11–14. Here we show that dbl specifically catalyses the dissociation of GDP from CDC42Hsand thereby qualifies as a highly selective guanine nucleotide exchange factor for the GTP-binding protein. Although guanine nucleotide exchange activities have been previously described for other members of the Ras-related GTP-binding protein family15–17, this is the first demonstration, to our knowledge, of the involvement of a human oncogenic protein in catalysing exchange activity.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  1. Hall, A. Science 249, 635–640 (1990).

    Article  ADS  CAS  Google Scholar 

  2. Bourne, H. R., Sanders, D. A. & McCormick, F. Nature 348, 125–132 (1990).

    Article  ADS  CAS  Google Scholar 

  3. Evans, T., Hart, M. J. & Cerione, R. A. Curr. Opinion Cell Biol. 3, 185–191 (1991).

    Article  CAS  Google Scholar 

  4. Evans, T., Brown, M. L., Fraser, E. D. & Northup, J. K. J. biol. Chem. 261, 7052–7056 (1986).

    CAS  PubMed  Google Scholar 

  5. Polakis, P. G., Snyderman, R. & Evans, T. Biochem. biophys. Res. Commun. 160, 25–32 (1989).

    Article  CAS  Google Scholar 

  6. Adams, A. E. M., Johnson, D. I., Longnecker, R. M., Sloat, B. F. & Pringle, J. R. J. Cell Biol. 111, 131–142 (1990).

    Article  CAS  Google Scholar 

  7. Johnson, D. I. & Pringle, J. R. J. Cell Biol. 111, 143–152 (1990).

    Article  CAS  Google Scholar 

  8. Munemitsu, S. et al. Molec. cell. Biol. 10, 5977–5982 (1990).

    Article  CAS  Google Scholar 

  9. Shinjo, K. et al. Proc. natn. Acad. Sci. U.S.A. 87, 9853–9857 (1990).

    Article  ADS  CAS  Google Scholar 

  10. Sloat, B. F., Adams, A. & Pringle, J. R. J. Cell Biol. 89, 395–405 (1981).

    Article  CAS  Google Scholar 

  11. Eva, A. & Aaronson, S. A. Nature 316, 273–275 (1985).

    Article  ADS  CAS  Google Scholar 

  12. Ron, D., Tronick, S. R., Aaronson, S. A. & Eva, A. EMBO J. 7, 2465–2473 (1988).

    Article  CAS  Google Scholar 

  13. Eva, A., Vecchio, G., Rao, C. D., Tronick, S. R. & Aaronson, S. A. Proc. natn. Acad. Sci. U.S.A. 85, 2061–2065 (1988).

    Article  ADS  CAS  Google Scholar 

  14. Ron, D. et al. New Biologist, 3, 372–379 (1991).

    CAS  Google Scholar 

  15. Wolfman, A. & Macara, I. G. Science 248, 67–69 (1990).

    Article  ADS  CAS  Google Scholar 

  16. Huang, Y. K., Kung, H.-F. & Kamata, T. Proc. natn. Acad. Sci. U.S.A. 87, 8008–8012 (1990).

    Article  ADS  CAS  Google Scholar 

  17. Yamamoto, T. et al. J. biol. Chem. 265, 16626–16634 (1990).

    CAS  PubMed  Google Scholar 

  18. Graziani, G., Nebreda, A., Srivastava, S. K., Santos, E. & Eva, A. Oncogene (in the press).

  19. Hart, M. J., Shinjo, K., Hall, A., Evans, T. & Cerione, R. A. J. biol. Chem. (in the press).

  20. Graziani, G., Ron, D., Eva, A. & Srivastava, S. K. Oncogene 4, 823–829 (1989).

    CAS  PubMed  Google Scholar 

  21. Hart, M. J., Polakis, P. G., Evans, T. & Cerione, R. A. J. biol. Chem. 265, 5990–6001 (1990).

    CAS  Google Scholar 

  22. Polakis, P. G. et al. J. biol. Chem. 264, 16378–16382 (1989).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hart, M., Eva, A., Evans, T. et al. Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbloncogene product. Nature 354, 311–314 (1991). https://doi.org/10.1038/354311a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/354311a0

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