background:
Glycogen synthase kinase 3 alpha belongs to the Ser/Thr family of protein kinases, Cdc2/cdkx subfamily; GSK3 subsubfamily. It is implicated in the hormonal control of several regulatory proteins including glycogen synthase, myb, and the transcription factor c jun. GSK3 phosphorylates glycogen synthase and thereby inactivates it. Insulin stimulates the dephosphorylation of glycogen synthase at the sites phosphorylated by GSK3 and subsequently inhibits GSK3 acutely leading to the stimulation of glycogen synthesis. GSK3 signaling is performed by two isoforms, GSK3 alpha and GSK3 beta. The two isoforms share 97% sequence similarity within their catalytic domains. GSK3 has also been shown to play a role in protein synthesis, cell adhesion, cell proliferation, cell differentiation, microtubule dynamics and cell motility.
Function:
Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transctiption factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1. Requires primed phosphorylation of the majority of its substrates. 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.
Subunit:
Monomer. Interacts with ARRB2. Interacts with AXIN1 and CTNNB1/beta-catenin.
Post-translational modifications:
Phosphorylated by AKT1 at Ser-21: upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and desactivates GSK3A, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-279.
Similarity:
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.
Contains 1 protein kinase domain.
Database links:
Entrez Gene: 2931 Human
Entrez Gene: 606496 Mouse
Entrez Gene: 50686 Rat
Omim: 606784 Human
SwissProt: P49168 Human
SwissProt: Q2NL51 Mouse
SwissProt: P18265 Rat
Unigene: 466828 Human
Unigene: 294664 Mouse
Unigene: 7367 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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