The proteins encoded by ras genes serve as essential transducers of diverse physiological signals, and mutationally altered ras products represent import ant contributors to the neoplastic phenotype. Analyses ofRas protein structure, function, and regulation have revealed important relationships between Ras and diverse areas of investigation, resulting in intensive scrutiny of these molecules by investigators from many fields. The viral oncogenes of certain acute transforming retroviruses were the first ras genes (v-ras) to be identified. The recognition that retroviral oncogenes, including v-ras, are derived from normal cellular genes, was followed by the demonstration that many of the transforming genes identified through the NIH 3T3 cell transformation assay represented cellular genes (c-ras) that had been activated by point mutation (1). As reviewed elsewhere, activated c-ras genes have repeatedly been implicated in many types of human cancer (2, 3) as well as in experimental tumors induced by chemical and physical agents (4). In addition to this role in neoplasia, normal ras genes, which are present in all eukaryotes including yeasts, are critical regulators of numerous physiological functions, including cell growth and differentiation. These normal activities of Ras appear to be mediated through its position as a key intermediate of signal transduction pathways.

The biological importance of ras genes has led to a systematic analysis of their encoded proteins. The discovery that Ras proteins bind guanine nucleotides (GTP and GDP) with high affinity and possess intrinsic GTPase activity suggested, by analogy with other guanine nucleotide-binding proteins, a mechanism by which Ras activity is regulated. Ras, which migrates as a 2I-kDa protein (p21), has also served as a prototype for what has been termed the superfamily of Ras-related proteins, a group of 20-25-kDa guanine nucleotide-binding proteins that share structural homol ogy with Ras (5-7). Mutational and crystallographic analyses of mammalian Ras protein have provided considerable insight into the structure of Ras and other members of the superfamily, which share many biochemical properties with p2I. The identification of factors that positively and negatively regulate Ras activity, the involvement of these factors in physiological signalling and in tumors, and the recognition that other members of the Ras superfamily are regulated by analogous factors have further expanded interest in Ras. Studies on the posttranslational modifications of Ras that involve products of the sterol synthesis pathway represent yet another area that involves Ras proteins (8).