Letter | Published:

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

Nature volume 354, pages 311314 (28 November 1991) | Download Citation

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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.

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Author information

Affiliations

  1. Department of Biochemistry, Cellular and Molecular Biology, and Department of Pharmacology, Cornell University, Ithaca, New York 14853, USA

    • Matthew J. Hart
    •  & Richard A. Cerione
  2. Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, USA.

    • Alessandra Eva
    •  & Stuart A. Aaronson
  3. Department of Cell Biology, Genentech Inc., 460 Pt San Bruno Boulevard, South San Francisco, California 94080, USA

    • Tony Evans

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

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