Figure 1. Receptor-mediated activation of phosphatidylinositol 3′-kinase (PI3K) and activation of Akt.
The example shown is insulin binding to the insulin receptor, which leads to the phosphorylation of insulin receptor substrates (IRS) that can bind, and thus activate, PI3K. In turn, activated PI3K phosphorylates phosphatidylinositol (PI)-4,5-bisphosphate (PtdIns(4,5)P2), thereby creating PI-3,4,5-triphosphate (PtdIns(3,4,5)P3) at the plasma membrane. Both Akt and phosphoinositide-dependent protein kinase 1 (PDK1) can be recruited to the membrane by binding PtdIns(3,4,5)P3. This positions PDK1 and Akt such that PDK1 can phosphorylate, and thus activate, Akt on threonine 308 (T308). PTEN, phosphatase and tensin homologue.
