Glycogen synthase kinase-3 beta

Glycogen synthase kinase-3 beta, (GSK-3 beta), is an enzyme that in humans is encoded by the GSK3B gene. In mice, the enzyme is encoded by the Gsk3b gene. Abnormal regulation and expression of GSK-3 beta is associated with an increased susceptibility towards bipolar disorder.

Function
Glycogen synthase kinase-3 (GSK-3) is a proline-directed serine-threonine kinase that was initially identified as a phosphorylating and an inactivating agent of glycogen synthase. Two isoforms, alpha (GSK3A) and beta, show a high degree of amino acid homology. GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation. It might be a new therapeutic target for ischemic stroke.

Disease relevance
Homozygous disruption of the Gsk3b locus in mice results in embryonic lethality during mid-gestation. This lethality phenotype could be rescued by inhibition of tumor necrosis factor.

Two SNPs at this gene, rs334558 (-50T/C) and rs3755557 (-1727A/T), are associated with efficacy of lithium treatment in bipolar disorder.

Signaling pathways
Pharmacological inhibition of ERK1/2 restores GSK-3 beta activity and protein synthesis levels in a model of tuberous sclerosis.

Interactions
GSK3B has been shown to interact with:
 * KIAA1211L
 * ATP2A2


 * AKAP11,
 * AXIN1,
 * AXIN2,
 * AR,
 * CTNNB1,
 * DNM1L,
 * MACF1
 * MUC1,
 * SMAD3
 * NOTCH1,
 * NOTCH2,
 * P53,
 * PRKAR2A,
 * SGK3, and
 * TSC2.