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. Author manuscript; available in PMC: 2012 Jul 1.
Published in final edited form as: Semin Hematol. 2011 Jul;48(3):214–226. doi: 10.1053/j.seminhematol.2011.05.001

Figure 2. Targeting the PI3K/AKT/mTOR pathway.

Figure 2

PI3 kinases, heterodimers composed of p85 regulatory and p110 catalytic subunits, phosphorylate phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3), which leads to recruitment and activation of AKT. AKT activation requires both phosphorylation at threonine 308(P*) and at serine 473(P**) in order to activate mTOR-containing complexes mTORC1 and mTORC2 and HDM2 or inhibit FOXO, GSK3β, and BAD. Several small molecules targeting the PI3K/AKT/mTOR pathway at different levels are currently in clinical testing.