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.

Tools of the trade: use of dominant-inhibitory mutants of Ras-family GTPases

Abstract

One of the most powerful ways of studying the function of a protein is to specifically block its activity within cells. Over the past decade, dominant-inhibitory proteins have emerged as popular tools with which to accomplish this task; these mutated proteins interfere with the function of their normal cellular counterparts or with proteins that interact with them. This approach has been used extensively in the elucidation of signal-transduction cascades, such as those involving Ras-family proteins. Here I discuss the power and potential pitfalls of using dominant-inhibitory Ras proteins.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: How dominant-inhibitory Ras17N suppresses Ras activation in cells.

References

  1. Lowry, D. R. & Willumsen, B. M. Annu. Rev. Biochem. 62, 851–891 (1993).

    Article  Google Scholar 

  2. Katz, M. E. & McCormick, F. Curr. Opin. Genet. Dev. 7, 75–79 (1997).

    Article  CAS  PubMed  Google Scholar 

  3. Sigal, I. et al. Proc. Natl Acad. Sci. USA 83, 952– 956 (1996).

    Article  Google Scholar 

  4. Feig, L. A. & Cooper, G. M. Mol. Cell. Biol. 8 , 3235–3243 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Powers, S. K., O'Neill, K. & Wigler, M. Mol. Cell. Biol. 9, 390– 395 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Quilliam, L. A. et al. Mol. Cell. Biol. 14, 1113– 1121 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Crechet, J. B. et al. J. Biol. Chem. 271, 17234– 17240 (1996).

    Article  CAS  PubMed  Google Scholar 

  8. Farnsworth, C. L. & Feig, L. A. Mol. Cell. Biol. 11, 4822–4829 ( 1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. John, J. et al. J. Biol. Chem. 268, 923– 929 (1993).

    CAS  PubMed  Google Scholar 

  10. Goody, R. S. et al. Phil. Trans. R. Soc. Lond. B 336, 3 –10 (1992).

    Article  CAS  Google Scholar 

  11. Stacey, D. W. et al. Mol. Cell. Biol. 11, 4053– 4064 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Peterson, S. N. et al. J. Biol. Chem. 271, 29903– 29908 (1996).

    Article  CAS  PubMed  Google Scholar 

  13. Lenzen, C., Cool, R. H., Prinz, H., Kuhlmann, J. & Wittinghofer, A. Biochemistry 37, 7420– 7430 (1998).

    Article  CAS  PubMed  Google Scholar 

  14. Lai, C.-C., Boguski, M., Broek, D. & Powers, S. Mol. Cell. Biol. 13, 1345–1352 ( 1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Farnsworth, C. L., Marshal, M. S., Gibbs, J. B., Stacey, D. W. & Feig, L. A. Cell 64, 625–633 (1991).

    Article  CAS  PubMed  Google Scholar 

  16. Graham, S. M. et al. Mol. Cell. Biol. 16, 6132– 6140 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Rosario, M., Paterson, H. F. & Marshall, C. J. EMBO J. 18, 1270– 1279 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gotoh, T. et al. J. Biol. Chem. 272, 18602– 18607 (1997).

    Article  CAS  PubMed  Google Scholar 

  19. Zheng, Y., Hart, M. J. & Cerione, R. A. Methods Enzymol. 256, 77– 84 (1995).

    Article  CAS  PubMed  Google Scholar 

  20. Mott, H. R., Carpenter, J. W. & Campbell, S. L. Biochemistry 36, 3640– 3644 (1997).

    Article  CAS  PubMed  Google Scholar 

  21. Downward, J., Graves, J. D., Warne, P. H., Rayter, S. & Cantrell, D. A. Nature 346, 719–723 (1990).

    Article  CAS  PubMed  Google Scholar 

  22. Marais, R. et al. Science 280, 109–112 (1998).

    Article  CAS  PubMed  Google Scholar 

  23. Szeberenyi, J., Cai, H. & Cooper, G. M. Mol. Cell. Biol. 10, 5324– 5332 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. van den Berghe, N., Cool, R. H., Horn, G. & Wittinghofer, A. Oncogene 15, 845–850 ( 1997).

    Article  CAS  PubMed  Google Scholar 

  25. Noel, J. P. Nature 366, 654–663 ( 1993).

    Article  CAS  PubMed  Google Scholar 

  26. Hildebrandt, J., Day, R., Farnsworth, C. L. & Feig, L. A. Mol. Cell. Biol. 11, 4830–4838 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

I thank A. Wittinghofer, R. Cool, D. Bar-Sagi, A. Polzin, S. Klinz, G. Rusanescu, R.l Buchsbaum, D. Cullis and T. Gotoh for helpful suggestions on the content and preparation of this commentary.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Larry A. Feig.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Feig, L. Tools of the trade: use of dominant-inhibitory mutants of Ras-family GTPases. Nat Cell Biol 1, E25–E27 (1999). https://doi.org/10.1038/10018

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/10018

This article is cited by

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