CELLULAR-TRANSFORMATION AND GUANINE-NUCLEOTIDE EXCHANGE ACTIVITY ARE CATALYZED BY A COMMON DOMAIN ON THE DBL ONCOGENE PRODUCT

The dbl oncogene product contains a 238-amino acid domain, which is sh ared by an expanding family of growth regulatory proteins. These inclu de the Saccharomyces cerevisiae cell division cycle protein, CDC24, th e breakpoint cluster region protein, the ect2 and vav oncogene product s, and the brain GDP-releasing factor for Ras. Previous studies have p rovided evidence that oncogenic Dbl or an associated protein stimulate s GDP dissociation from the human species (Hs) homolog of CDC42. We sh ow here that Dbl specifically complexes with the GDP-bound forms of CD C42Hs and RhoA, but not Rac1 or TC10, and that this specificity correl ates with the ability of Dbl to act as a GDP-releasing factor. Small d eletions throughout the Dbl domain, which inactivate transformation, e liminated the ability of Dbl to stimulate GDP dissociation, whereas de letions outside of this domain did not impair either function. Finally , the Dbl domain itself, when expressed and purified as a recombinant protein, was shown to stimulate GDP dissociation from purified, recomb inant CDC42Hs. These findings establish that a minimal unit on Dbl tha t is critical to its transforming function directly regulates GDP-GTP exchange activity.