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Cell Growth Regulation by PI3‐kinase, Ras and mTOR Signal Integration

Growth factor and oncogene‐regulated PI3 kinase‐ and Ras‐activated signaling pathways converge upon the nutrient‐ and energy‐sensing mTOR pathway to modulate cell growth, survival and proliferation in many cell types. In human cancer, components of these pathways are often amplified or mutated resulting in inappropriate cell growth. Rapamycin, a specific inhibitor of mTOR, has emerged as a drug with potential anticancer therapeutic efficacy alone or in combination therapy. The molecular basis of how mTOR and its effector, S6 kinase 1 regulate cell growth through translation initiation is not understood. How components of the translation initiation complex act as a scaffold to coordinate a series of protein‐protein interactions regulated by ordered phosphorylation events will be discussed.