Glycogen synthase kinase 3

The chapter provides a short summary of the structure, substrate specificity, functions, and regulation of glycogen synthase kinase 3 protein. Glycogen synthase kinase 3 (GSK3) is a protein that phosphorylates and inhibits glycogen synthase, the enzyme that catalyzes the transfer of glucose from UDPG to glycogen. GSK3 is a key player in two distinct signal transduction pathways: the phosphatidylinositol-3-kinase-dependent pathway that is triggered by insulin and growth factors, and the Wnt signaling pathway that is required for embryonic development. Insulin induces the activation of glycogen synthase, mainly by stimulating the dephosphorylation of the serine residues in glycogen synthase that are targeted by GSK3, and stimulates the activation of eIF2B by promoting the dephosphorylation of Ser535. GSK3 appears to play a role in the insulin-regulated transcription of the genes. Inhibitors of GSK3 may lower the levels of blood glucose in vivo by suppressing the production of glucose as well as by enhancing the conversion of glucose to glycogen. There is considerable evidence that the inhibition of GSK3 triggered by growth factors contributes to the anti-apoptotic effects of these signals. It is a therapeutic target for the design of inhibitory drugs to treat diseases such as head trauma, stroke, epilepsy, and motor neuron disease. GSK3 plays a key role in embryonic development as a central player in the Wnt signaling pathway. It mimics the Wnt signaling pathway and stimulates the accumulation of ß-catenin.