Biological Activity of a K-ras Mutant That Contains the 12R/59T/116Y Mutations.

The 12R/59T/116Y mutations have been shown to confer a dominant negative activity on H-ras oncogene (H-ras 116Y). To determine whether this event is unique for H-ras, we introduced the same mutations into K-ras oncogene. This mutant, K-ras 116Y, suppressed transformed phenotypes induced by overexpression of H-ras proto-oncogene. NIH3T3 cells expressing K-ras 116Y were resistant to transformation by v-fes oncogene. Analysis of chimaeras between H- and K-ras 116Y showed that the C-terminal variable region determines the level of suppressor activity. These results suggest that these mutations are applicable to other GDP/GTP binding proteins.