The mammalian target of rapamycin (mTOR) signaling pathway allows cells to monitor environmental signals like nutrient availability and oxygen levels. mTOR is a phosphoinositide 3-kinase (PI3K)-related protein that assembles into large protein complexes (mTORC1 and mTORC2) capable of regulating cell metabolism, growth, and proliferation. mTOR complexes can be stimulated by extracellular growth factors such through the insulin and Ras signaling pathways as well as by intracellular signals such as the ratio of ATP:ADP within the cell or by amino acid levels. The tuberous sclerosis complex (TSC) is an important sensor module that integrates many of these signals and activates or inhibits mTOR accordingly. TSC acts as a GTPase-activating protein (GAP) for Rheb (Ras homolog enriched in brain), a direct interactor of the mTOR complex. GTP bound Rheb stimulates mTOR activity. However TSC negatively...








