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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