Fig. 2.

PI3K-mTOR autophagy pathway utilizes PIP3 lipid signaling. PI3K converts the lipid PIP2 to PIP3. PIP3 mediates the phosphorylation of PDK1 causing the activation of AKT. AKT inhibits the activation of the TSC1/2 complex by phosphorylating TSC2. The inhibition of the TSC1/2 complex results in inhibition of Rheb GTPase which in turn activates mTORC1. MTORC1 inhibits the activation of the ULK activation complex leading to an inhibition of autophagy. Inversely, phosphatase activity of PTEN converts PIP3 to PIP2 which suppresses the activation of PDK1 and downstream AKT. Inhibited AKT cannot suppress the TSC1/2 complex allowing Rheb GTPase to remain active. An active Rheb results in inhibition of mTORC1 and an activation of the ULK1 complex