Figure 9 of Biswas, Mol Vis 2009; 15:1599-1610.

Figure 9. Schematic showing imatinib dysregulation of PI 3-kinase/Akt signaling in RGCs. PI 3-kinase is a heterodimer consisting of p85 regulatory and p110 catalytic subunits. Imatinib inhibition of PDGFR tyrosine kinase abrogates PDGF-induced PDGFR tyrosine phosphorylation, p85 regulatory subunit recruitment, PI 3-kinase activity, and the phosphorylation of downstream effectors such as Akt, GSK-3β, and p70S6kinase. In contrast, imatinib exposure maintains insulin receptor-mediated IRS-associated PI 3-kinase activity and the downstream phosphorylation of Akt, GSK-3β, and p70S6kinase. Thus, an imbalance between receptor- and IRS-associated PI 3-kinase activity attenuates coordinated increases in phosphatidylinositol 3,4,5-trisphosphate (PIP3) lipids. The resultant diminutions in the overall phosphorylation of Akt, GSK-3β, and p70S6kinase increase the propensity toward apoptotic cell death.