FIGURE 2.

mTOR signaling pathway. mTOR is a critical downstream target of the PI3K signaling pathway. The insulin receptor substrate proteins (IRS) “transmit” signals from the insulin and insulin-like growth factor-1 receptors through PI3K and PDK1 (PI3K-dependent kinase 1), which phosphorylates Akt. mTOR forms two distinct protein complexes. mTORC1, which regulates translation, is sensitive to rapamycin and is defined by the scaffolding protein Raptor. mTORC1 phosphorylates 4E-BPs, S6K1, S6K2, and PRAS40. Akt can activate mTOR through phosphorylation and inhibition of TSC2 of the tuberous sclerosis complex. Phosphorylation of TSC2 leads to Rheb (Ras homolog enriched in brain) activation, which in turn activates mTOR. Cap-dependent translation through formation of the eIF4F complex can be regulated by mTORC1 inputs through 4E-BPs and S6Ks.