The pathway begins with the activation of PI3K, which generates phosphatidylinositol (3,4,5)-trisphosphate (PIP3) on the inner leaflet of the plasma membrane. PIP3 serves as a docking site for proteins with pleckstrin homology (PH) domains, including Akt and its upstream kinase, PDK1 (phosphoinositide-dependent kinase-1). Upon binding to PIP3, Akt is phosphorylated at two key residues: Thr308 by PDK1 and Ser473 by the mTORC2 complex, leading to its full activation.
