Characterization of functional domains of p21 ras by use of chimeric genes

Comparison of the predicted amino acid sequences of different members of the ras family in vertebrates has shown that the N-terminal 120 residues are highly conserved while the C terminus is variable. To test the possible role of the variable residues in cell transformation, chimeras were constructed containing the N-terminal 111 amino acids of the human Ha-ras EJ oncogene and the C terminus of two Drosophila ras genes. We show that one of these constructs which has only 20 conserved residues between positions 121 and 189, can transform rat-1 cells, and the transformed cells are capable of inducing lethal tumors in rats. The second construct containing the C terminus of another Drosophila ras gene exhibits a transforming capacity as well, but only after linkage to a viral transcriptional promoter. These results show that the majority of residues within the C terminus can be replaced without abolishing the transforming potential of p21 ras.