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
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hall, A. Science 249, 635–640 (1990).
Bourne, H. R., Sanders, D. A. & McCormick, F. Nature 348, 125–132 (1990).
Evans, T., Hart, M. J. & Cerione, R. A. Curr. Opinion Cell Biol. 3, 185–191 (1991).
Evans, T., Brown, M. L., Fraser, E. D. & Northup, J. K. J. biol. Chem. 261, 7052–7056 (1986).
Polakis, P. G., Snyderman, R. & Evans, T. Biochem. biophys. Res. Commun. 160, 25–32 (1989).
Adams, A. E. M., Johnson, D. I., Longnecker, R. M., Sloat, B. F. & Pringle, J. R. J. Cell Biol. 111, 131–142 (1990).
Johnson, D. I. & Pringle, J. R. J. Cell Biol. 111, 143–152 (1990).
Munemitsu, S. et al. Molec. cell. Biol. 10, 5977–5982 (1990).
Shinjo, K. et al. Proc. natn. Acad. Sci. U.S.A. 87, 9853–9857 (1990).
Sloat, B. F., Adams, A. & Pringle, J. R. J. Cell Biol. 89, 395–405 (1981).
Eva, A. & Aaronson, S. A. Nature 316, 273–275 (1985).
Ron, D., Tronick, S. R., Aaronson, S. A. & Eva, A. EMBO J. 7, 2465–2473 (1988).
Eva, A., Vecchio, G., Rao, C. D., Tronick, S. R. & Aaronson, S. A. Proc. natn. Acad. Sci. U.S.A. 85, 2061–2065 (1988).
Ron, D. et al. New Biologist, 3, 372–379 (1991).
Wolfman, A. & Macara, I. G. Science 248, 67–69 (1990).
Huang, Y. K., Kung, H.-F. & Kamata, T. Proc. natn. Acad. Sci. U.S.A. 87, 8008–8012 (1990).
Yamamoto, T. et al. J. biol. Chem. 265, 16626–16634 (1990).
Graziani, G., Nebreda, A., Srivastava, S. K., Santos, E. & Eva, A. Oncogene (in the press).
Hart, M. J., Shinjo, K., Hall, A., Evans, T. & Cerione, R. A. J. biol. Chem. (in the press).
Graziani, G., Ron, D., Eva, A. & Srivastava, S. K. Oncogene 4, 823–829 (1989).
Hart, M. J., Polakis, P. G., Evans, T. & Cerione, R. A. J. biol. Chem. 265, 5990–6001 (1990).
Polakis, P. G. et al. J. biol. Chem. 264, 16378–16382 (1989).
Author information
Authors and Affiliations
Rights 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
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.