a constitutively active proline-directed protein kinase of the GSK family. A negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubule. Phosphorylates and inactivates glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1. Generally requires primed phosphorylation sites C-terminal to the targeted serine or threonine residues in its substrate. Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. Regulates glycogen metabolism in liver, but not in muscle. May also mediate the development of insulin resistance by regulating activation of transcription factors. In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin. Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease. May be involved in the regulation of replication in pancreatic beta-cells. Is necessary for the establishment of neuronal polarity and axon outgrowth. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factor deprivation. A GSK3 promoter SNP effects progression of bipolar disorder. The GSK3 inhibitor, lithium, is used to treat bipolar disorder and is seen to block plaque formation. GSK3 generally opposes the action of insulin, and GSK3 hyperactivity is thought to contribute to insulin resistant (type II) diabetes. GSK3 also negatively regulates cardiac hypertrophy. A tumor suppressor role is indicated by the oncogenic potential of stabilized b-catenin mutants that lack GSK3 phosphorylation sites. Note: This description may include information from UniProtKB.
Protein type: CMGC group; EC 18.104.22.168; EC 22.214.171.124; GSK family; GSK subfamily; Kinase, protein; Protein kinase, CMGC; Protein kinase, Ser/Thr (non-receptor)