Fig.1. Scheme of the PTEN/mTOR signaling pathway. In response to receptor tyrosine kinase (RTK) activation, PI3K phosphorylates and converts the lipid second messenger PIP₂ into PIP₃, which recruits and activates phosphatidylinositol-dependent kinase 1/2 (PDK1/2). PDK1/2, in turn, phosphorylates and activates Akt. PTEN catalyzes the conversion from PIP₃ to PIP₂. Thus, inactivation of PTEN results in the accumulation of PIP₃ and the activation of Akt. Akt controls a host of signaling molecules, including TSC1/2. Downstream of the TSC1/2 complex lies mTOR, which integrates various cellular signals, including nutrient availability to control protein translation, cell growth, and other processes. The ribosomal protein S6 kinase (RP-S6) and the eukaryotic initiation factor 4E (eIF-4E) binding protein 1 (4E-BP1) are the mTOR effector molecules executing these functions. Cellular stresses such as hypoxia induce expression of Redd1/2, which augments TSC1/2 activity and in turn suppress the mTOR activity.