Summary of Talk
Class I phosphoinositide 3-kinases (PI3K) are central signal transduction hubs in mammalian cells. These lipid kinases catalyze the production of phosphatidylinositol-3,4,5-trisphosphate (PIP3) to activate intracellular signaling, including via Akt and mTOR pathways. While homozygous genetic inactivation of the respective catalytic subunit (p110) of PI3Kβ/δ/γ is viable, systemic deletion/inactivation of p110α results in early embryonic lethality. This significantly limited investigations of the specific functions of PI3Kα in adult tissues. Pharmacological approaches present additional challenges. Despite improved biochemical selectivity for PI3Kα, isoform-selective inhibitors require high systemic exposure in preclinical models which can impact the function of other class I isoforms.