Genetic mutagenesis has been used to study the roles of ras oncogenes and protooncogenes in cell transformation and normal cellular function. A very potent dominant negative ras mutant (asparagine-116 to tyrosine mutation of the v-H-ras) has been identified and characterized. This 116Y mutant strongly inhibits the c-H-ras proto-oncogene function. It suppresses transformation induced by over-expression of c-H-ras proto-oncogene function. It suppresses transformation by a group of retroviruses carrying a variety of protein-tyrosine kinase oncogenes, including v-abl, v- fes/flp, v-src and v-fms. Surprisingly, transformation by retroviruses carrying the homologous ras oncogenes, including v-H- ras, v-K-ras and v-bas, is not affected. These results suggest blocking of a c-ras proto-oncogene function upstream to transformation induced by the activated ras oncogenes.
