Ras-A Molecular Switch Involved in Tumor Formation

Ras, a GTP-hydrolyzing protein, is the product of a proto-oncogene found mutated in about 20-30 % of human tumors. It binds GDP/GTP with high affinity and in the presence of a GTPase-activating protein (GAP) has high GTP-hydrolyzing activity. The proto-oncogenic "normal" Ras functions as a regulated molecular switch cycling between a GDP-bound OFF and a GTP-bound ON state and is involved in signal transduction pathways controling cell growth, differentiation, apoptosis, and other events. The oncogenic versions of Ras contain point mutations which block the GTPase activity in the presence and absence of GAP. This process in turn inhibits the cycling of the switch and leads to the accumulation of Ras in the active form and contributes to tumor formation. Substantial effort has been devoted towards understanding the molecular basis for the switch function of Ras proteins and developing Ras-directed antitumor drugs.