GSK3A

This gene encodes a multifunctional Ser/Thr protein kinase that is implicated in the control of several regulatory proteins including glycogen synthase, and transcription factors, such as JUN. It also plays a role in the WNT and PI3K signaling pathways, as well as regulates the production of beta-amyloid peptides associated with Alzheimer's disease. [provided by RefSeq, Oct 2011]

Glycogen Synthase Kinase 3 Alpha

Constitutively active protein kinase that 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 (PubMed:11749387, PubMed:17478001, PubMed:19366350).

Requires primed phosphorylation of the majority of its substrates (PubMed:11749387, PubMed:17478001, PubMed:19366350).

Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:11749387, PubMed:17478001, PubMed:19366350).

Regulates glycogen metabolism in liver, but not in muscle (By similarity).

May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:10868943, PubMed:17478001).

In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin (PubMed:17229088).

Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease (PubMed:12761548).

May be involved in the regulation of replication in pancreatic beta-cells (By similarity).

Is necessary for the establishment of neuronal polarity and axon outgrowth (By similarity).

Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity).

Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899).

Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity).

Cardiac left ventricle morphogenesis Source: BHF-UCL
Cellular response to insulin stimulus Source: BHF-UCL
Cellular response to interleukin-3 Source: UniProtKB
Dopamine receptor signaling pathway Source: ParkinsonsUK-UCL
Excitatory postsynaptic potential Source: ParkinsonsUK-UCL
Extrinsic apoptotic signaling pathway Source: ARUK-UCL
Extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
Glycogen metabolic process Source: UniProtKB-KW
Insulin receptor signaling pathway Source: BHF-UCL
Negative regulation of canonical Wnt signaling pathway Source: GO_Central
Negative regulation of cell growth involved in cardiac muscle cell development Source: BHF-UCL
Negative regulation of glucose import Source: BHF-UCL
Negative regulation of glycogen (starch) synthase activity Source: UniProtKB
Negative regulation of glycogen biosynthetic process Source: UniProtKB
Negative regulation of glycogen synthase activity, transferring glucose-1-phosphate Source: BHF-UCL
Negative regulation of insulin receptor signaling pathway Source: BHF-UCL
Negative regulation of TOR signaling Source: BHF-UCL
Negative regulation of type B pancreatic cell development Source: UniProtKB
Negative regulation of UDP-glucose catabolic process Source: UniProtKB
Nervous system development Source: UniProtKB-KW
Peptidyl-threonine phosphorylation Source: ARUK-UCL
Positive regulation of adenylate cyclase-activating adrenergic receptor signaling pathway Source: BHF-UCL
Positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: BHF-UCL
Positive regulation of amyloid-beta formation Source: ARUK-UCL
Positive regulation of autophagy Source: UniProtKB
Positive regulation of gene expression Source: ARUK-UCL
Positive regulation of glycogen (starch) synthase activity Source: BHF-UCL
Positive regulation of heart contraction Source: BHF-UCL
Positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: UniProtKB
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: ARUK-UCL
Positive regulation of protein catabolic process Source: BHF-UCL
Positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
Positive regulation of protein ubiquitination Source: ARUK-UCL
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
Protein phosphorylation Source: BHF-UCL
Regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
Regulation of neuron projection development Source: GO_Central
Regulation of systemic arterial blood pressure Source: BHF-UCL
Signal transduction Source: GO_Central
Viral protein processing Source: Reactome
Wnt signaling pathway Source: UniProtKB-KW

Cytosol; Mitochondrion; Nucleus; Apical dendrite; Axon; Beta-catenin destruction complex; Cytoplasm; Neuronal cell body; Postsynapse; Proximal dendrite

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.
(Microbial infection) Dephosphorylated at Tyr-279 by M.tuberculosis PtpA, which leads to prevention of apoptosis during early stages of microbial infection.