Conservation and divergence of RAS protein function during evolution

The ras genes were first isolated as the transforming genes of Harvey and Kirsten sarcoma virus (Ellis et al. 1981). At least three different ras genes, Ha-ras, Ki-ras, and N-ras, exist in mammals and code for three very similar 21-kD proteins (Shimizu et al. 1983b). The ras proteins are localized in the plasma membrane (Willingham et al. 1980), bind guanine nucleotides (Shih et al. 1980, 1982), and have weak GTPase activity (Gibbs et al. 1984; McGrath et al. 1984; Sweet et al. 1984). A large number of tumor cells contain structurally mutated ras genes that are capable of tumorigenic transformation of NIH-3T3 cells upon DNA-mediated gene transfer (Reddy et al. 1982; Tabin et al. 1982; Taparowsky et al. 1982; Capon et al. 1983; Shimizu et al. 1983a; Yuasa et al. 1983