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 substrates, and the enzyme converts the substrates into different molecules known as products ...

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 (mood), depression and periods of abnormally elevated Mood (psychology), mood that last from days to weeks each. If the elevat ...

Function

Glycogen synthase kinase-3 (

GSK-3 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 ...

) 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 ...

. 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 homolog ...

. 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 soli ...

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 combination ...

Interactions

GSK3B has been shown to

interact Advocates for Informed Choice, doing business as, 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 trai ...

with: *

KIAA1211L KIAA1211L is a protein that in humans is encoded by the KIAA1211L gene. It is highly expressed in the brain (Cerebral Cortex). Furthermore, it is localized to the microtubules and the centrosomes and is subcellularly located in the nucleus. Finally ...

AKAP11 A-kinase anchor protein 11 is an enzyme that in humans is encoded by the ''AKAP11'' gene. Function The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory s ...

, *

AXIN1 Axin-1 is a protein that in humans is encoded by the ''AXIN1'' gene. Function This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded prote ...

, * AXIN2, * AR, * CTNNB1, *

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 Microtubule-actin cross-linking factor 1, isoforms 1/2/3/5 is a protein that in humans is encoded by the ''MACF1'' gene. MACF1 encodes a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. MACF1 is a member of a fami ...

* MUC1, * SMAD3 *

NOTCH1 Neurogenic locus notch homolog protein 1 (Notch 1) is a protein encoded in humans by the ''NOTCH1'' gene. Notch 1 is a single-pass transmembrane receptor. Function This gene encodes a member of the Notch family. Members of this Type 1 trans ...

, *

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. Membe ...

, *

P53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

, * 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