Mouse Glycogen synthase kinase-3 Alpha,Gsk3a ELI

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:15791206, PubMed:17908561).

Requires primed phosphorylation of the majority of its substrates (PubMed:22539723).

Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:15791206, PubMed:17908561).

Regulates glycogen metabolism in liver, but not in muscle (PubMed:17908561).

May also mediate the development of insulin resistance by regulating activation of transcription factors (By similarity).

In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin (PubMed:15791206).

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

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 (PubMed:17391670).

Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (PubMed:16543145).

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:22539723).

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).

{ECO:0000250|UniProtKB:P49840, ECO:0000250|UniProtKB:P49841, ECO:0000269|PubMed:15791206, ECO:0000269|PubMed:16543145, ECO:0000269|PubMed:17391670, ECO:0000269|PubMed:17908561, ECO:0000269|PubMed:22539723}.