Glycogen synthase kinase-3 alpha is an enzyme that in humans is encoded by the GSK3A gene. It acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1. GSK3 alpha requires primed phosphorylation of the majority of its substrates. It contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. GSK3 alpha regulates glycogen metabolism in liver, but not in muscle. It may also mediate the development of insulin resistance by regulating activation of transcription factors. In Wnt signaling, GSK3 alpha regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin.
