Fig. 1. As a major downstream effector of receptor tyrosine kinase (RTK) and G protein-coupled receptors, PI3K activates various downstream effectors by generating phospholipids, transducing signals of various growth factors and cytokines into intracellular information.

The main lipid substrate of PTEN is PIP 3 and indeed PTEN acts as a negative regulator of PI3K/AKT signaling. Among the upstream signaling networks, Akt inactivate TSC1/2 and activate mTORC1. mTORC2 directly phosphorylates Akt at S473 residue leading to its complete activation. This activation of the PI3K/Akt pathway is opposed by PTEN.