Glycogen synthase kinase-3 beta, (GSK-3 beta), is an enzyme that in humans is encoded by the GSK3B gene. [5] [6] In mice, the enzyme is encoded by the Gsk3b gene. [7] Abnormal regulation and expression of GSK-3 beta is associated with an increased susceptibility towards bipolar disorder. [8]
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. [5] GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation. [9] [10] It might be a new therapeutic target for ischemic stroke.
Homozygous disruption of the Gsk3b locus in mice results in embryonic lethality during mid-gestation. [7] This lethality phenotype could be rescued by inhibition of tumor necrosis factor. [7]
Two SNPs at this gene, rs334558 (-50T/C) and rs3755557 (-1727A/T), are associated with efficacy of lithium treatment in bipolar disorder. [11]
Pharmacological inhibition of ERK1/2 restores GSK-3 beta activity and protein synthesis levels in a model of tuberous sclerosis. [12]
GSK3B has been shown to interact with:
Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues. First discovered in 1980 as a regulatory kinase for its namesake, glycogen synthase (GS), GSK-3 has since been identified as a protein kinase for over 100 different proteins in a variety of different pathways. In mammals, including humans, GSK-3 exists in two isozymes encoded by two homologous genes GSK-3α (GSK3A) and GSK-3β (GSK3B). GSK-3 has been the subject of much research since it has been implicated in a number of diseases, including type 2 diabetes, Alzheimer's disease, inflammation, cancer, addiction and bipolar disorder.
The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.
Adenomatous polyposis coli (APC) also known as deleted in polyposis 2.5 (DP2.5) is a protein that in humans is encoded by the APC gene. The APC protein is a negative regulator that controls beta-catenin concentrations and interacts with E-cadherin, which are involved in cell adhesion. Mutations in the APC gene may result in colorectal cancer and desmoid tumors.
Frzb is a Wnt-binding protein especially important in embryonic development. It is a competitor for the cell-surface G-protein receptor Frizzled.
Catenin beta-1, also known as β-catenin (beta-catenin), is a protein that in humans is encoded by the CTNNB1 gene.
The Casein kinase 1 family of protein kinases are serine/threonine-selective enzymes that function as regulators of signal transduction pathways in most eukaryotic cell types. CK1 isoforms are involved in Wnt signaling, circadian rhythms, nucleo-cytoplasmic shuttling of transcription factors, DNA repair, and DNA transcription.
Protein kinase C delta type is an enzyme that in humans is encoded by the PRKCD gene.
Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene.
Mucin short variant S1, also called polymorphic epithelial mucin (PEM) or epithelial membrane antigen (EMA), is a mucin encoded by the MUC1 gene in humans. Mucin short variant S1 is a glycoprotein with extensive O-linked glycosylation of its extracellular domain. Mucins line the apical surface of epithelial cells in the lungs, stomach, intestines, eyes and several other organs. Mucins protect the body from infection by pathogen binding to oligosaccharides in the extracellular domain, preventing the pathogen from reaching the cell surface. Overexpression of MUC1 is often associated with colon, breast, ovarian, lung and pancreatic cancers. Joyce Taylor-Papadimitriou identified and characterised the antigen during her work with breast and ovarian tumors.
Axin-1 is a protein that in humans is encoded by the AXIN1 gene.
In enzymology, a tau-protein kinase is an enzyme that catalyzes the chemical reaction
Segment polarity protein dishevelled homolog DVL-1 is a protein that in humans is encoded by the DVL1 gene.
Serine/threonine-protein kinase Sgk3 is an enzyme that in humans is encoded by the SGK3 gene.
Serine/threonine-protein kinase D3 (PKD3) or PKC-nu is an enzyme that in humans is encoded by the PRKD3 gene.
Low-density lipoprotein receptor-related protein 6 is a protein that in humans is encoded by the LRP6 gene. LRP6 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway.
Serine/threonine-protein kinase MARK1 is an enzyme that in humans is encoded by the MARK1 gene.
Axin-2, also known as axin-like protein (Axil), axis inhibition protein 2 (AXIN2), or conductin, is a protein that in humans is encoded by the AXIN2 gene.
Proto-oncogene FRAT1 is a protein that in humans is encoded by the FRAT1 gene.
A-kinase anchor protein 11 is an enzyme that in humans is encoded by the AKAP11 gene.
GSK-3-binding protein FRAT2 is a protein that in humans is encoded by the FRAT2 gene.
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