Figure 1. Simplified scheme of mTOR pathway activation.

Akt activation releases Rheb from the inhibitory effects of TSC1/2 thus allowing mTOR activation. Signaling defects upstream of mTOR in the PI3K/Akt/mTOR pathway (mutations in PTEN, PI3K, Akt and TSCs) lead to mTOR deregulation. Akt can also be a downstream effector of mTOR, due to mTOR association with different protein partners to form two functionally distinct signaling complexes, mTORC1 and mTORC2.