Growth factors, insulin, nutrients and energy status regulate the activation of the PI3K/Akt/mTOR signaling network. Protein synthesis, cell growth and proliferation, and metabolic functions are regulated by downstream effectors of the pathway, such as 4E-BP1 and S6K. Boxes indicate therapies targeting the pathway. Arrows represent activation and bars represent inhibition. Abbreviations: 4E-BP1, eukaryotic translation initiation factor 4E-binding protein 1; AMPK, adenosine monophosphate-activated protein kinase; ASK1, apoptosis signalregulating kinase 1; ATP, adenosine-5’-triphosphate; BAD, BCL2-associated agonist of cell death; FKBP-12, FK506-binding protein, 12 kD; FoxO, forkhead box O; GDP, guanosine diphosphate; GSK3, glycogen synthase kinase 3; GTP, guanosine-5’-triphosphate; IRS1, insulin receptor substrate 1; MAP4K3, mitogen-activated protein kinase kinase kinase kinase 3; mLST8, mTOR associated protein, LST8 homolog; mTOR, mammalian target of rapamycin; mTORC1, mTOR complex 1; mTORC2, mTOR complex 2; PDK-1, phosphoinositide-dependent kinase 1; PI3K, phosphatidylinositol 3-kinase; PIP2, phosphatidylinositol (,) biphosphate; PIP3, phosphatidylinositol (,,) triphosphate; PRAS40, proline-rich Akt1 substrate 40; PTEN, phosphatase and tensin homolog deleted from chromosome 10; Rheb, Ras homolog enriched in brain; RTK, receptor tyrosine kinase; S6K, ribosomal protein S6 kinase; SIN1, stress-activated mitogen-activated protein kinase associated protein 1; TSC1, tuberous sclerosis complex 1; TSC2, tuberous sclerosis complex 2.