Glycogen synthase kinase-3 beta
Glycogen synthase kinase-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 is a proline-directed serine-threonine kinase that was initially identified as a phosphorylating and an inactivating agent of glycogen synthase. Two isoforms, alpha and beta, show a high degree of amino acid homology.GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation.
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 and rs3755557, 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.