PDK1, one of the missing links in insulin signal transduction?1

摘要: The initial steps in insulin signal transduction occur at the plasma membrane and lead to activation of phosphatidylinositide (PtdIns) 3-kinase formation PtdIns(3,4,5,)P3 inner leaflet which is then converted PtdIns(3,4)P2 by a specific phosphatase. Inhibitors PtdIns suppress nearly all metabolic actions indicating that PtdIns(3,4,5)P3 and/or are key 'second messengers' for this hormone. A major effect its ability stimulate synthesis glycogen skeletal muscle. By 'working backwards' from synthesis, we have dissected an insulin-stimulated protein kinase cascade triggered 3-kinase. first enzyme termed 3-phosphoinositide-dependent (PDK1), because it only active presence or PtdIns(3,4)P2. PDK1 activates B (PKB) which, turn, inactivates synthase kinase-3 (GSK3), leading dephosphorylation hence acceleration synthesis. We review evidence indicates phosphorylation other proteins PKB GSK3 likely mediate many intracellular insulin.