Glycogen synthase kinase-3 beta, (GSK-3 beta), is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

that in humans is encoded by the ''GSK3B''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. 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 Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...

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 Glycogen synthase (UDP-glucose-glycogen glucosyltransferase) is a key enzyme in glycogenesis, the conversion of glucose into glycogen. It is a glycosyltransferase () that catalyses the reaction of UDP-glucose and (1,4--D-glucosyl)n to yield UDP ...

. 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 Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

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 Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologo ...

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

lithium Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid ...

treatment in

Signaling pathways

Pharmacological inhibition of ERK1/2 restores GSK-3 beta activity and protein synthesis levels in a model of

tuberous sclerosis Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combinatio ...

Interactions

GSK3B has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizat ...

with: * KIAA1211L * AKAP11, * AXIN1, * AXIN2, * AR, *

CTNNB1 Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene. Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcript ...

, *

DNM1L Dynamin-1-like protein is a GTPase that regulates mitochondrial fission. In humans, dynamin-1-like protein, which is typically referred to as dynamin-related protein 1 (Drp1), is encoded by the ''DNM1L'' gene and is part of the dynamin superfamily ...

, * MACF1 *

MUC1 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 e ...

, *

SMAD3 Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene. SMAD3 is a member of the SMAD family of proteins. It acts as a mediator of the signals initiated by t ...

* NOTCH1, *

NOTCH2 Neurogenic locus notch homolog protein 2 (Notch 2) is a protein that in humans is encoded by the ''NOTCH2'' gene. NOTCH2 is associated with Alagille syndrome and Hajdu–Cheney syndrome. Function Notch 2 is a member of the notch family. Member ...

, * P53, * PRKAR2A, *

SGK3 Serine/threonine-protein kinase Sgk3 is an enzyme that in humans is encoded by the ''SGK3'' gene. Function This gene is a member of the serine/threonine protein kinase family and encodes a phosphoprotein with a PX (phox homology) domain. The ...

, and *

TSC2 Tuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the ''TSC2'' gene. Function Mutations in this gene lead to tuberous sclerosis. Its gene product is believed to be a tumor suppressor and is a ...

References

External links

PDBe-KB
provides an overview of all the structure information available in the PDB for Human Glycogen synthase kinase-3 beta (GSK3B) {{Portal bar, Biology, border=no Protein kinases EC 2.7.11