Figure 1.

The PI3-K/Akt/mTOR signaling cascade. Stimulation of receptor tyrosine kinases (RTK) and G-protein-coupled receptors (GPCR) leads to activation of PI3-K, which then synthesizes PIP₃ in the membrane. Subsequently, Akt is recruited to the membrane and phosphorylated by PDK-1 and mTORC2. The activated Akt kinase phosphorylates various substrates such as PRAS40, which is then inactivated and releases mTORC1. In addition, TSC2 is inhibited so that the downstream GTPase Rheb remains GTP-bound and can activate mTORC1. The fully activated mTORC1 complex then activates proteins of the translation machinery by phosphorylating S6K-1 or 4E-BP1 [adapted from Manning et al. 23).