The mammalian c-H-, c-K- and N-Ras proto-oncogenes encode guanine nucleotide-binding proteins that are ubiquitously expressed in vertebrate cells. c-H- and c-K-Ras are cellular homologs of the v-H and v-K-Ras sequences originally isolated from the Harvey and Kirsten strains of rat sarcoma virus. Ras-encoded proteins bind GDP and GTP with high affinity and possess a low level intrinsic GTPase activity that can be stimulated over 100-fold by interaction with cytosolic GTPase activating protein (GAP), a potential effector for Ras p21 function. Point mutations at amino acids 12, 13, 59 and 61 within domains responsible for GTP binding and hydrolysis activate Ras proteins to their oncogenic form and block the ability of the GTPase activity to be stimulated by GAP. Several additional proteins with GAP activity have been identified and shown to interact with p21 Ras or other members of the Ras gene family.
