Glycogen synthase kinase-3 beta: Difference between revisions

GSK3B
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1GNG, 1H8F, 1I09, 1J1B, 1J1C, 1O6K, 1O6L, 1O9U, 1PYX, 1Q3D, 1Q3W, 1Q41, 1Q4L, 1Q5K, 1R0E, 1UV5, 2JDO, 2JDR, 2JLD, 2O5K, 2OW3, 2UW9, 2X39, 2XH5, 3CQU, 3CQW, 3DU8, 3E87, 3E88, 3E8D, 3F7Z, 3F88, 3GB2, 3I4B, 3L1S, 3M1S, 3MV5, 3OW4, 3PUP, 3Q3B, 3QKK, 3SAY, 3SD0, 3ZDI, 3ZRK, 3ZRL, 3ZRM, 4ACC, 4ACD, 4ACG, 4ACH, 4AFJ, 4B7T, 4DIT, 4EKK, 4IQ6, 4J1R, 4J71, 4NM0, 4NM3, 4NM5, 4NM7, 4PTC, 4PTE, 4PTG, 5F94, 5F95, 5HLP, 5HLN
Identifiers
Aliases	GSK3B, Gsk3b, 7330414F15Rik, 8430431H08Rik, C86142, GSK-3, GSK-3beta, GSK3, glycogen synthase kinase 3 beta
External IDs	OMIM: 605004; MGI: 1861437; HomoloGene: 55629; GeneCards: GSK3B; OMA:GSK3B - orthologs
EC number	2.7.11.1
Gene location (Human)
Chr.	Chromosome 3 (human)
End	120,094,994 bp
Gene location (Mouse)
Chr.	Chromosome 16 (mouse)
End	38,066,446 bp
RNA expression pattern
	Top expressed in
	Achilles tendon; ; epithelium of colon; ; sural nerve; ; buccal mucosa cell; ; skin of thigh; ; ventricular zone; ; ganglionic eminence; ; postcentral gyrus; ; left testis; ; right testis;
	Top expressed in
	spermatid; ; cumulus cell; ; ventromedial nucleus; ; lateral septal nucleus; ; lateral hypothalamus; ; mammillary body; ; retinal pigment epithelium; ; Rostral migratory stream; ; lateral geniculate nucleus; ; Region I of hippocampus proper;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	kinase activity; ATP binding; protein kinase activity; protein kinase A catalytic subunit binding; protein serine/threonine kinase activity; transferase activity; NF-kappaB binding; tau-protein kinase activity; protein binding; nucleotide binding; p53 binding; ubiquitin protein ligase binding; protease binding; beta-catenin binding; protein kinase binding; dynactin binding; tau protein binding;
Cellular component	cytoplasm; membrane; mitochondrion; nucleus; centrosome; plasma membrane; cytosol; beta-catenin destruction complex; postsynapse; Wnt signalosome; nucleoplasm; axon; dendrite; glutamatergic synapse;
Biological process	rhythmic process; negative regulation of type B pancreatic cell development; negative regulation of protein binding; negative regulation of glycogen (starch) synthase activity; glycogen metabolic process; superior temporal gyrus development; negative regulation of canonical Wnt signaling pathway; chemical synaptic transmission, postsynaptic; negative regulation of protein-containing complex assembly; positive regulation of protein export from nucleus; positive regulation of GTPase activity; protein autophosphorylation; cell differentiation; negative regulation of protein localization to nucleus; phosphorylation; positive regulation of cell-matrix adhesion; nervous system development; dopamine receptor signaling pathway; epithelial to mesenchymal transition; peptidyl-threonine phosphorylation; positive regulation of protein-containing complex assembly; positive regulation of neuron death; negative regulation of glycogen biosynthetic process; multicellular organism development; regulation of cellular response to heat; negative regulation of signal transduction; hippocampus development; beta-catenin destruction complex disassembly; proteasome-mediated ubiquitin-dependent protein catabolic process; Wnt signaling pathway; beta-catenin destruction complex assembly; protein phosphorylation; positive regulation of mitochondrion organization; intracellular signal transduction; positive regulation of protein catabolic process; negative regulation of dopaminergic neuron differentiation; ER overload response; circadian rhythm; peptidyl-serine phosphorylation; positive regulation of protein binding; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; regulation of microtubule-based process; cellular response to interleukin-3; negative regulation of apoptotic process; canonical Wnt signaling pathway; extrinsic apoptotic signaling pathway in absence of ligand; positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; carbohydrate metabolic process; neuron projection development; negative regulation of neuron death; positive regulation of gene expression; establishment of cell polarity; maintenance of cell polarity; regulation of axon extension; negative regulation of phosphoprotein phosphatase activity; regulation of dendrite morphogenesis; regulation of axonogenesis; excitatory postsynaptic potential; regulation of microtubule cytoskeleton organization; negative regulation of calcineurin-NFAT signaling cascade; extrinsic apoptotic signaling pathway; neuron projection retraction; negative regulation of protein acetylation; cellular response to amyloid-beta; positive regulation of protein localization to centrosome; regulation of synaptic vesicle exocytosis; neuron projection organization; positive regulation of autophagy; regulation of circadian rhythm; regulation of long-term synaptic potentiation; regulation of microtubule anchoring at centrosome;
	Sources:Amigo / QuickGO
Orthologs
	2932
	56637
	ENSG00000082701
	ENSMUSG00000022812
	P49841
	Q9WV60
	NM_001146156; NM_002093; NM_001354596
	NM_019827; NM_001347232
	NP_001139628; NP_002084; NP_001341525
	NP_001334161; NP_062801
	Wikidata
View/Edit Human	View/Edit Mouse

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Latest revision as of 16:52, 22 May 2024

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]

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.^[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.

Disease relevance

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]

Signaling pathways

Pharmacological inhibition of ERK1/2 restores GSK-3 beta activity and protein synthesis levels in a model of tuberous sclerosis.^[12]

Interactions

GSK3B has been shown to interact with:

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000082701 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022812 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Stambolic V, Woodgett JR (November 1994). "Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation". The Biochemical Journal. 303 (Pt 3): 701–4. doi:10.1042/bj3030701. PMC 1137602. PMID 7980435.
^ Lau KF, Miller CC, Anderton BH, Shaw PC (September 1999). "Molecular cloning and characterization of the human glycogen synthase kinase-3beta promoter". Genomics. 60 (2): 121–8. doi:10.1006/geno.1999.5875. PMID 10486203.
^ ^a ^b ^c Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR (July 2000). "Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation". Nature. 406 (6791): 86–90. Bibcode:2000Natur.406...86H. doi:10.1038/35017574. PMID 10894547. S2CID 205007364.
^ Luykx JJ, Boks MP, Terwindt AP, Bakker S, Kahn RS, Ophoff RA (June 2010). "The involvement of GSK3beta in bipolar disorder: integrating evidence from multiple types of genetic studies". European Neuropsychopharmacology. 20 (6): 357–68. doi:10.1016/j.euroneuro.2010.02.008. PMID 20226637. S2CID 43214075.
^ Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR (December 1992). "Glycogen synthase kinase-3: functions in oncogenesis and development". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1114 (2–3): 147–62. doi:10.1016/0304-419X(92)90012-N. PMID 1333807.
^ "Entrez Gene: GSK3B glycogen synthase kinase 3 beta".
^ Iwahashi K, Nishizawa D, Narita S, Numajiri M, Murayama O, Yoshihara E, et al. (2013). "Haplotype analysis of GSK-3β gene polymorphisms in bipolar disorder lithium responders and nonresponders". Clinical Neuropharmacology. 37 (4): 108–10. doi:10.1097/WNF.0000000000000039. PMC 4206383. PMID 24992082.
^ Pal R, Bondar VV, Adamski CJ, Rodney GG, Sardiello M (June 2017). "Inhibition of ERK1/2 Restores GSK3β Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis". Scientific Reports. 7 (1): 4174. Bibcode:2017NatSR...7.4174P. doi:10.1038/s41598-017-04528-5. PMC 5482840. PMID 28646232.
^ EMBL-EBI. "EMBL European Bioinformatics Institute". www.ebi.ac.uk. Retrieved 2017-04-26.
^ Gonnot F, Boulogne L, Brun C, Dia M, Gouriou Y, Bidaux G, et al. (June 2023). "SERCA2 phosphorylation at serine 663 is a key regulator of Ca²⁺ homeostasis in heart diseases". Nature Communications. 14 (1): 3346. doi:10.1038/s41467-023-39027-x. PMC 10250397. PMID 37291092.
^ ^a ^b Tanji C, Yamamoto H, Yorioka N, Kohno N, Kikuchi K, Kikuchi A (October 2002). "A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta". The Journal of Biological Chemistry. 277 (40): 36955–61. doi:10.1074/jbc.M206210200. PMID 12147701.
^ ^a ^b Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS (February 2003). "The tuberin-hamartin complex negatively regulates beta-catenin signaling activity". The Journal of Biological Chemistry. 278 (8): 5947–51. doi:10.1074/jbc.C200473200. PMID 12511557.
^ Nakamura T, Hamada F, Ishidate T, Anai K, Kawahara K, Toyoshima K, et al. (June 1998). "Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3beta and APC and reduces the beta-catenin level". Genes to Cells. 3 (6): 395–403. doi:10.1046/j.1365-2443.1998.00198.x. PMID 9734785. S2CID 10875463.
^ von Kries JP, Winbeck G, Asbrand C, Schwarz-Romond T, Sochnikova N, Dell'Oro A, et al. (September 2000). "Hot spots in beta-catenin for interactions with LEF-1, conductin and APC". Nature Structural Biology. 7 (9): 800–7. doi:10.1038/79039. PMID 10966653. S2CID 40432152.
^ Schwarz-Romond T, Asbrand C, Bakkers J, Kühl M, Schaeffer HJ, Huelsken J, et al. (August 2002). "The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling". Genes & Development. 16 (16): 2073–84. doi:10.1101/gad.230402. PMC 186448. PMID 12183362.
^ Wang L, Lin HK, Hu YC, Xie S, Yang L, Chang C (July 2004). "Suppression of androgen receptor-mediated transactivation and cell growth by the glycogen synthase kinase 3 beta in prostate cells". The Journal of Biological Chemistry. 279 (31): 32444–52. doi:10.1074/jbc.M313963200. PMID 15178691.
^ Davies G, Jiang WG, Mason MD (April 2001). "The interaction between beta-catenin, GSK3beta and APC after motogen induced cell-cell dissociation, and their involvement in signal transduction pathways in prostate cancer". International Journal of Oncology. 18 (4): 843–7. doi:10.3892/ijo.18.4.843. PMID 11251183.
^ Kishida S, Yamamoto H, Hino S, Ikeda S, Kishida M, Kikuchi A (June 1999). "DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability". Molecular and Cellular Biology. 19 (6): 4414–22. doi:10.1128/mcb.19.6.4414. PMC 104400. PMID 10330181.
^ Hong YR, Chen CH, Cheng DS, Howng SL, Chow CC (August 1998). "Human dynamin-like protein interacts with the glycogen synthase kinase 3beta". Biochemical and Biophysical Research Communications. 249 (3): 697–703. doi:10.1006/bbrc.1998.9253. PMID 9731200.
^ Wu X, Shen QT, Oristian DS, Lu CP, Zheng Q, Wang HW, et al. (February 2011). "Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3β". Cell. 144 (3): 341–52. doi:10.1016/j.cell.2010.12.033. PMC 3050560. PMID 21295697.
^ Li Y, Bharti A, Chen D, Gong J, Kufe D (December 1998). "Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin". Molecular and Cellular Biology. 18 (12): 7216–24. doi:10.1128/mcb.18.12.7216. PMC 109303. PMID 9819408.
^ Li Y, Kuwahara H, Ren J, Wen G, Kufe D (March 2001). "The c-Src tyrosine kinase regulates signaling of the human DF3/MUC1 carcinoma-associated antigen with GSK3 beta and beta-catenin". The Journal of Biological Chemistry. 276 (9): 6061–4. doi:10.1074/jbc.C000754200. PMID 11152665.
^ Guo X, Ramirez A, Waddell DS, Li Z, Liu X, Wang XF (January 2008). "Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling". Genes & Development. 22 (1): 106–20. doi:10.1101/gad.1590908. PMC 2151009. PMID 18172167.
^ Foltz DR, Santiago MC, Berechid BE, Nye JS (June 2002). "Glycogen synthase kinase-3beta modulates notch signaling and stability". Current Biology. 12 (12): 1006–11. Bibcode:2002CBio...12.1006F. doi:10.1016/S0960-9822(02)00888-6. PMID 12123574. S2CID 15884556.
^ Espinosa L, Inglés-Esteve J, Aguilera C, Bigas A (August 2003). "Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways". The Journal of Biological Chemistry. 278 (34): 32227–35. doi:10.1074/jbc.M304001200. PMID 12794074.
^ Watcharasit P, Bijur GN, Zmijewski JW, Song L, Zmijewska A, Chen X, et al. (June 2002). "Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damage". Proceedings of the National Academy of Sciences of the United States of America. 99 (12): 7951–5. Bibcode:2002PNAS...99.7951W. doi:10.1073/pnas.122062299. PMC 123001. PMID 12048243.
^ Dai F, Yu L, He H, Chen Y, Yu J, Yang Y, et al. (May 2002). "Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 through direct interaction". Biochemical and Biophysical Research Communications. 293 (4): 1191–6. doi:10.1016/S0006-291X(02)00349-2. PMID 12054501.
^ Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, et al. (September 2006). "TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth". Cell. 126 (5): 955–68. doi:10.1016/j.cell.2006.06.055. PMID 16959574. S2CID 16047397.

External links

PDBe-KB provides an overview of all the structure information available in the PDB for Human Glycogen synthase kinase-3 beta (GSK3B)

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000082701 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000022812 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid7980435-5] Stambolic V, Woodgett JR (November 1994). "Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation". The Biochemical Journal. 303 (Pt 3): 701–4. doi:10.1042/bj3030701. PMC 1137602. PMID 7980435.

[pmid10486203-6] Lau KF, Miller CC, Anderton BH, Shaw PC (September 1999). "Molecular cloning and characterization of the human glycogen synthase kinase-3beta promoter". Genomics. 60 (2): 121–8. doi:10.1006/geno.1999.5875. PMID 10486203.

[hoeflich2000-7] Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR (July 2000). "Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation". Nature. 406 (6791): 86–90. Bibcode:2000Natur.406...86H. doi:10.1038/35017574. PMID 10894547. S2CID 205007364.

[8] Luykx JJ, Boks MP, Terwindt AP, Bakker S, Kahn RS, Ophoff RA (June 2010). "The involvement of GSK3beta in bipolar disorder: integrating evidence from multiple types of genetic studies". European Neuropsychopharmacology. 20 (6): 357–68. doi:10.1016/j.euroneuro.2010.02.008. PMID 20226637. S2CID 43214075.

[pmid1333807-9] Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR (December 1992). "Glycogen synthase kinase-3: functions in oncogenesis and development". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1114 (2–3): 147–62. doi:10.1016/0304-419X(92)90012-N. PMID 1333807.

[10] "Entrez Gene: GSK3B glycogen synthase kinase 3 beta".

[11] Iwahashi K, Nishizawa D, Narita S, Numajiri M, Murayama O, Yoshihara E, et al. (2013). "Haplotype analysis of GSK-3β gene polymorphisms in bipolar disorder lithium responders and nonresponders". Clinical Neuropharmacology. 37 (4): 108–10. doi:10.1097/WNF.0000000000000039. PMC 4206383. PMID 24992082.

[pmid28646232-12] Pal R, Bondar VV, Adamski CJ, Rodney GG, Sardiello M (June 2017). "Inhibition of ERK1/2 Restores GSK3β Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis". Scientific Reports. 7 (1): 4174. Bibcode:2017NatSR...7.4174P. doi:10.1038/s41598-017-04528-5. PMC 5482840. PMID 28646232.

[13] EMBL-EBI. "EMBL European Bioinformatics Institute". www.ebi.ac.uk. Retrieved 2017-04-26.

[14] Gonnot F, Boulogne L, Brun C, Dia M, Gouriou Y, Bidaux G, et al. (June 2023). "SERCA2 phosphorylation at serine 663 is a key regulator of Ca²⁺ homeostasis in heart diseases". Nature Communications. 14 (1): 3346. doi:10.1038/s41467-023-39027-x. PMC 10250397. PMID 37291092.

[pmid12147701-15] Tanji C, Yamamoto H, Yorioka N, Kohno N, Kikuchi K, Kikuchi A (October 2002). "A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta". The Journal of Biological Chemistry. 277 (40): 36955–61. doi:10.1074/jbc.M206210200. PMID 12147701.

[pmid12511557-16] Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS (February 2003). "The tuberin-hamartin complex negatively regulates beta-catenin signaling activity". The Journal of Biological Chemistry. 278 (8): 5947–51. doi:10.1074/jbc.C200473200. PMID 12511557.

[pmid9734785-17] Nakamura T, Hamada F, Ishidate T, Anai K, Kawahara K, Toyoshima K, et al. (June 1998). "Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3beta and APC and reduces the beta-catenin level". Genes to Cells. 3 (6): 395–403. doi:10.1046/j.1365-2443.1998.00198.x. PMID 9734785. S2CID 10875463.

[pmid10966653-18] von Kries JP, Winbeck G, Asbrand C, Schwarz-Romond T, Sochnikova N, Dell'Oro A, et al. (September 2000). "Hot spots in beta-catenin for interactions with LEF-1, conductin and APC". Nature Structural Biology. 7 (9): 800–7. doi:10.1038/79039. PMID 10966653. S2CID 40432152.

[pmid12183362-19] Schwarz-Romond T, Asbrand C, Bakkers J, Kühl M, Schaeffer HJ, Huelsken J, et al. (August 2002). "The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling". Genes & Development. 16 (16): 2073–84. doi:10.1101/gad.230402. PMC 186448. PMID 12183362.

[pmid15178691-20] Wang L, Lin HK, Hu YC, Xie S, Yang L, Chang C (July 2004). "Suppression of androgen receptor-mediated transactivation and cell growth by the glycogen synthase kinase 3 beta in prostate cells". The Journal of Biological Chemistry. 279 (31): 32444–52. doi:10.1074/jbc.M313963200. PMID 15178691.

[pmid11251183-21] Davies G, Jiang WG, Mason MD (April 2001). "The interaction between beta-catenin, GSK3beta and APC after motogen induced cell-cell dissociation, and their involvement in signal transduction pathways in prostate cancer". International Journal of Oncology. 18 (4): 843–7. doi:10.3892/ijo.18.4.843. PMID 11251183.

[pmid10330181-22] Kishida S, Yamamoto H, Hino S, Ikeda S, Kishida M, Kikuchi A (June 1999). "DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability". Molecular and Cellular Biology. 19 (6): 4414–22. doi:10.1128/mcb.19.6.4414. PMC 104400. PMID 10330181.

[pmid9731200-23] Hong YR, Chen CH, Cheng DS, Howng SL, Chow CC (August 1998). "Human dynamin-like protein interacts with the glycogen synthase kinase 3beta". Biochemical and Biophysical Research Communications. 249 (3): 697–703. doi:10.1006/bbrc.1998.9253. PMID 9731200.

[24] Wu X, Shen QT, Oristian DS, Lu CP, Zheng Q, Wang HW, et al. (February 2011). "Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3β". Cell. 144 (3): 341–52. doi:10.1016/j.cell.2010.12.033. PMC 3050560. PMID 21295697.

[pmid9819408-25] Li Y, Bharti A, Chen D, Gong J, Kufe D (December 1998). "Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin". Molecular and Cellular Biology. 18 (12): 7216–24. doi:10.1128/mcb.18.12.7216. PMC 109303. PMID 9819408.

[pmid11152665-26] Li Y, Kuwahara H, Ren J, Wen G, Kufe D (March 2001). "The c-Src tyrosine kinase regulates signaling of the human DF3/MUC1 carcinoma-associated antigen with GSK3 beta and beta-catenin". The Journal of Biological Chemistry. 276 (9): 6061–4. doi:10.1074/jbc.C000754200. PMID 11152665.

[pmid18172167-27] Guo X, Ramirez A, Waddell DS, Li Z, Liu X, Wang XF (January 2008). "Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling". Genes & Development. 22 (1): 106–20. doi:10.1101/gad.1590908. PMC 2151009. PMID 18172167.

[pmid12123574-28] Foltz DR, Santiago MC, Berechid BE, Nye JS (June 2002). "Glycogen synthase kinase-3beta modulates notch signaling and stability". Current Biology. 12 (12): 1006–11. Bibcode:2002CBio...12.1006F. doi:10.1016/S0960-9822(02)00888-6. PMID 12123574. S2CID 15884556.

[pmid12794074-29] Espinosa L, Inglés-Esteve J, Aguilera C, Bigas A (August 2003). "Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways". The Journal of Biological Chemistry. 278 (34): 32227–35. doi:10.1074/jbc.M304001200. PMID 12794074.

[pmid12048243-30] Watcharasit P, Bijur GN, Zmijewski JW, Song L, Zmijewska A, Chen X, et al. (June 2002). "Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damage". Proceedings of the National Academy of Sciences of the United States of America. 99 (12): 7951–5. Bibcode:2002PNAS...99.7951W. doi:10.1073/pnas.122062299. PMC 123001. PMID 12048243.

[pmid12054501-31] Dai F, Yu L, He H, Chen Y, Yu J, Yang Y, et al. (May 2002). "Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 through direct interaction". Biochemical and Biophysical Research Communications. 293 (4): 1191–6. doi:10.1016/S0006-291X(02)00349-2. PMID 12054501.

[pmid16959574-32] Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, et al. (September 2006). "TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth". Cell. 126 (5): 955–68. doi:10.1016/j.cell.2006.06.055. PMID 16959574. S2CID 16047397.

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@@ Line 1: / Line 1: @@
+{{Short description|Protein-coding gene in the species Homo sapiens}}
-{{PBB|geneid=2932}}
+{{cs1 config|name-list-style=vanc|display-authors=6}}
-'''Glycogen synthase kinase 3 beta''', also known as '''GSK3B''', is an [[enzyme]] that in humans is encoded by the ''GSK3B'' [[gene]].<ref name="pmid7980435">{{cite journal | vauthors = Stambolic V, Woodgett JR | title = Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation | journal = The Biochemical Journal | volume = 303 ( Pt 3) | issue = Pt 3 | pages = 701–4 | date = Nov 1994 | pmid = 7980435 | pmc = 1137602 | doi =  }}</ref><ref name="pmid10486203">{{cite journal | vauthors = Lau KF, Miller CC, Anderton BH, Shaw PC | title = Molecular cloning and characterization of the human glycogen synthase kinase-3beta promoter | journal = Genomics | volume = 60 | issue = 2 | pages = 121–8 | date = Sep 1999 | pmid = 10486203 | doi = 10.1006/geno.1999.5875 }}</ref>  In mice, the enzyme is encoded by the GSK-3β gene.<ref name=hoeflich2000 /> Abnormal regulation and expression of GSK3β is associated with an increased susceptibility towards [[bipolar disorder]].<ref>{{cite journal | vauthors = Luykx JJ, Boks MP, Terwindt AP, Bakker S, Kahn RS, Ophoff RA | title = The involvement of GSK3beta in bipolar disorder: integrating evidence from multiple types of genetic studies | journal = European Neuropsychopharmacology | volume = 20 | issue = 6 | pages = 357–68 | date = Jun 2010 | pmid = 20226637 | doi = 10.1016/j.euroneuro.2010.02.008 | url = http://www-ncbi-nlm-nih-gov.proxy1.lib.uwo.ca/pubmed/20226637 }}</ref>
+{{Infobox_gene}}
+'''Glycogen synthase kinase-3 beta''', '''(GSK-3 beta)''', is an [[enzyme]] that in humans is encoded by the ''GSK3B'' [[gene]].<ref name="pmid7980435">{{cite journal | vauthors = Stambolic V, Woodgett JR | title = Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation | journal = The Biochemical Journal | volume = 303 | issue = Pt 3 | pages = 701–4 | date = November 1994 | pmid = 7980435 | pmc = 1137602 | doi = 10.1042/bj3030701 }}</ref><ref name="pmid10486203">{{cite journal | vauthors = Lau KF, Miller CC, Anderton BH, Shaw PC | title = Molecular cloning and characterization of the human glycogen synthase kinase-3beta promoter | journal = Genomics | volume = 60 | issue = 2 | pages = 121–8 | date = September 1999 | pmid = 10486203 | doi = 10.1006/geno.1999.5875 }}</ref>  In mice, the enzyme is encoded by the Gsk3b gene.<ref name=hoeflich2000 /> Abnormal regulation and expression of GSK-3 beta is associated with an increased susceptibility towards [[bipolar disorder]].<ref>{{cite journal | vauthors = Luykx JJ, Boks MP, Terwindt AP, Bakker S, Kahn RS, Ophoff RA | title = The involvement of GSK3beta in bipolar disorder: integrating evidence from multiple types of genetic studies | journal = European Neuropsychopharmacology | volume = 20 | issue = 6 | pages = 357–68 | date = June 2010 | pmid = 20226637 | doi = 10.1016/j.euroneuro.2010.02.008 | s2cid = 43214075 }}</ref>
 == Function ==
-Glycogen synthase kinase-3 ([[GSK-3]]) is a proline-directed [[Serine/threonine-specific protein kinase|serine-threonine kinase]] that was initially identified as a [[phosphorylation|phosphorylating]] and an inactivating agent of [[glycogen synthase]]. Two isoforms, alpha ([[GSK3A]]) and beta, show a high degree of amino acid homology.<ref name="pmid7980435">{{cite journal | vauthors = Stambolic V, Woodgett JR | title = Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation | journal = The Biochemical Journal | volume = 303 ( Pt 3) | issue = Pt 3 | pages = 701–4 | date = Nov 1994 | pmid = 7980435 | pmc = 1137602 }}</ref>  GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation.<ref name="pmid1333807">{{cite journal | vauthors = Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR | title = Glycogen synthase kinase-3: functions in oncogenesis and development | journal = Biochimica Et Biophysica Acta | volume = 1114 | issue = 2-3 | pages = 147–62 | date = Dec 1992 | pmid = 1333807 | doi = 10.1016/0304-419X(92)90012-N }}</ref><ref>{{cite web | title = Entrez Gene: GSK3B glycogen synthase kinase 3 beta| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2932| accessdate = }}</ref>
+Glycogen synthase kinase-3 ([[GSK-3]]) is a proline-directed [[Serine/threonine-specific protein kinase|serine-threonine kinase]] that was initially identified as a [[phosphorylation|phosphorylating]] and an inactivating agent of [[glycogen synthase]]. Two isoforms, alpha ([[GSK3A]]) and beta, show a high degree of amino acid homology.<ref name="pmid7980435" />  GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation.<ref name="pmid1333807">{{cite journal | vauthors = Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR | title = Glycogen synthase kinase-3: functions in oncogenesis and development | journal = Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | volume = 1114 | issue = 2–3 | pages = 147–62 | date = December 1992 | pmid = 1333807 | doi = 10.1016/0304-419X(92)90012-N }}</ref><ref>{{cite web | title = Entrez Gene: GSK3B glycogen synthase kinase 3 beta| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2932}}</ref> It might be a new therapeutic target for ischemic stroke.
+== Disease relevance ==
-== Loss of function mutations ==
-[[Homozygous]] disruption of the GSK-3β locus in mice results in embryonic lethality during mid-gestation.<ref name=hoeflich2000 />  This lethality phenotype could be rescued by inhibition of [[tumor necrosis factor]].<ref name=hoeflich2000 />
+[[Homozygous]] disruption of the Gsk3b locus in mice results in embryonic lethality during mid-gestation.<ref name=hoeflich2000 />  This lethality phenotype could be rescued by inhibition of [[tumor necrosis factor]].<ref name=hoeflich2000 />
+Two SNPs at this gene, rs334558 (-50T/C) and rs3755557 (-1727A/T), are associated with efficacy of [[lithium (medication)|lithium]] treatment in [[bipolar disorder]].<ref>{{cite journal | vauthors = Iwahashi K, Nishizawa D, Narita S, Numajiri M, Murayama O, Yoshihara E, Onozawa Y, Nagahori K, Fukamauchi F, Ikeda K, Ishigooka J | title = Haplotype analysis of GSK-3β gene polymorphisms in bipolar disorder lithium responders and nonresponders | journal = Clinical Neuropharmacology | volume = 37 | issue = 4 | pages = 108–10 | date = 2013 | pmid = 24992082 | pmc = 4206383 | doi = 10.1097/WNF.0000000000000039 }}</ref>
+== Signaling pathways ==
+Pharmacological inhibition of [[MAPK3|ERK1/2]] restores GSK-3 beta activity and protein synthesis levels in a model of [[tuberous sclerosis]].<ref name="pmid28646232">{{cite journal | vauthors = Pal R, Bondar VV, Adamski CJ, Rodney GG, Sardiello M | title = Inhibition of ERK1/2 Restores GSK3β Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 4174 | date = June 2017 | pmid = 28646232 | pmc = 5482840 | doi = 10.1038/s41598-017-04528-5 | bibcode = 2017NatSR...7.4174P }}</ref>
 == Interactions ==
 GSK3B has been shown to [[Protein-protein interaction|interact]] with:
+* [[KIAA1211L]]<ref>{{Cite web|url=http://www.ebi.ac.uk |title=EMBL European Bioinformatics Institute|last=EMBL-EBI|website=www.ebi.ac.uk.|language=en|access-date=2017-04-26}}</ref>
+* [[ATP2A2]]<ref>{{cite journal | vauthors = Gonnot F, Boulogne L, Brun C, Dia M, Gouriou Y, Bidaux G, Chouabe C, Crola Da Silva C, Ducreux S, Pillot B, Kaczmarczyk A, Leon C, Chanon S, Perret C, Sciandra F, Dargar T, Gache V, Farhat F, Sebbag L, Bochaton T, Thibault H, Ovize M, Paillard M, Gomez L | title = SERCA2 phosphorylation at serine 663 is a key regulator of Ca<sup>2+</sup> homeostasis in heart diseases | journal = Nature Communications | volume = 14 | issue = 1 | pages = 3346 | date = June 2023 | pmid = 37291092 | pmc = 10250397 | doi = 10.1038/s41467-023-39027-x }}</ref>
 {{div col|colwidth=20em}}
 * [[AKAP11]],<ref name = pmid12147701/>
-* [[AXIN1]],<ref name = pmid12511557/><ref name = pmid9734785>{{cite journal | vauthors = Nakamura T, Hamada F, Ishidate T, Anai K, Kawahara K, Toyoshima K, Akiyama T | title = Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3beta and APC and reduces the beta-catenin level | journal = Genes to Cells | volume = 3 | issue = 6 | pages = 395–403 | date = Jun 1998 | pmid = 9734785 | doi = 10.1046/j.1365-2443.1998.00198.x }}</ref>
+* [[AXIN1]],<ref name = pmid12511557/><ref name = pmid9734785>{{cite journal | vauthors = Nakamura T, Hamada F, Ishidate T, Anai K, Kawahara K, Toyoshima K, Akiyama T | title = Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3beta and APC and reduces the beta-catenin level | journal = Genes to Cells | volume = 3 | issue = 6 | pages = 395–403 | date = June 1998 | pmid = 9734785 | doi = 10.1046/j.1365-2443.1998.00198.x | s2cid = 10875463 | doi-access = free }}</ref>
-* [[AXIN2]],<ref name = pmid10966653>{{cite journal | vauthors = von Kries JP, Winbeck G, Asbrand C, Schwarz-Romond T, Sochnikova N, Dell'Oro A, Behrens J, Birchmeier W | title = Hot spots in beta-catenin for interactions with LEF-1, conductin and APC | journal = Nature Structural Biology | volume = 7 | issue = 9 | pages = 800–7 | date = Sep 2000 | pmid = 10966653 | doi = 10.1038/79039 }}</ref><ref name = pmid12183362>{{cite journal | vauthors = Schwarz-Romond T, Asbrand C, Bakkers J, Kühl M, Schaeffer HJ, Huelsken J, Behrens J, Hammerschmidt M, Birchmeier W | title = The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling | journal = Genes & Development | volume = 16 | issue = 16 | pages = 2073–84 | date = Aug 2002 | pmid = 12183362 | pmc = 186448 | doi = 10.1101/gad.230402 }}</ref>
+* [[AXIN2]],<ref name = pmid10966653>{{cite journal | vauthors = von Kries JP, Winbeck G, Asbrand C, Schwarz-Romond T, Sochnikova N, Dell'Oro A, Behrens J, Birchmeier W | title = Hot spots in beta-catenin for interactions with LEF-1, conductin and APC | journal = Nature Structural Biology | volume = 7 | issue = 9 | pages = 800–7 | date = September 2000 | pmid = 10966653 | doi = 10.1038/79039 | s2cid = 40432152 }}</ref><ref name = pmid12183362>{{cite journal | vauthors = Schwarz-Romond T, Asbrand C, Bakkers J, Kühl M, Schaeffer HJ, Huelsken J, Behrens J, Hammerschmidt M, Birchmeier W | title = The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling | journal = Genes & Development | volume = 16 | issue = 16 | pages = 2073–84 | date = August 2002 | pmid = 12183362 | pmc = 186448 | doi = 10.1101/gad.230402 }}</ref>
-* [[Androgen receptor|AR]],<ref name = pmid15178691>{{cite journal | vauthors = Wang L, Lin HK, Hu YC, Xie S, Yang L, Chang C | title = Suppression of androgen receptor-mediated transactivation and cell growth by the glycogen synthase kinase 3 beta in prostate cells | journal = The Journal of Biological Chemistry | volume = 279 | issue = 31 | pages = 32444–52 | date = Jul 2004 | pmid = 15178691 | doi = 10.1074/jbc.M313963200 }}</ref>
+* [[Androgen receptor|AR]],<ref name = pmid15178691>{{cite journal | vauthors = Wang L, Lin HK, Hu YC, Xie S, Yang L, Chang C | title = Suppression of androgen receptor-mediated transactivation and cell growth by the glycogen synthase kinase 3 beta in prostate cells | journal = The Journal of Biological Chemistry | volume = 279 | issue = 31 | pages = 32444–52 | date = July 2004 | pmid = 15178691 | doi = 10.1074/jbc.M313963200 | doi-access = free }}</ref>
-* [[Beta-catenin|CTNNB1]],<ref name = pmid11251183>{{cite journal | vauthors = Davies G, Jiang WG, Mason MD | title = The interaction between beta-catenin, GSK3beta and APC after motogen induced cell-cell dissociation, and their involvement in signal transduction pathways in prostate cancer | journal = International Journal of Oncology | volume = 18 | issue = 4 | pages = 843–7 | date = Apr 2001 | pmid = 11251183 | doi = 10.3892/ijo.18.4.843 }}</ref><ref name = pmid10330181>{{cite journal | vauthors = Kishida S, Yamamoto H, Hino S, Ikeda S, Kishida M, Kikuchi A | title = DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability | journal = Molecular and Cellular Biology | volume = 19 | issue = 6 | pages = 4414–22 | date = Jun 1999 | pmid = 10330181 | pmc = 104400 | doi =  }}</ref>
+* [[Beta-catenin|CTNNB1]],<ref name = pmid11251183>{{cite journal | vauthors = Davies G, Jiang WG, Mason MD | title = The interaction between beta-catenin, GSK3beta and APC after motogen induced cell-cell dissociation, and their involvement in signal transduction pathways in prostate cancer | journal = International Journal of Oncology | volume = 18 | issue = 4 | pages = 843–7 | date = April 2001 | pmid = 11251183 | doi = 10.3892/ijo.18.4.843 }}</ref><ref name = pmid10330181>{{cite journal | vauthors = Kishida S, Yamamoto H, Hino S, Ikeda S, Kishida M, Kikuchi A | title = DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability | journal = Molecular and Cellular Biology | volume = 19 | issue = 6 | pages = 4414–22 | date = June 1999 | pmid = 10330181 | pmc = 104400 | doi = 10.1128/mcb.19.6.4414 }}</ref>
-* [[DNM1L]],<ref name = pmid9731200>{{cite journal | vauthors = Hong YR, Chen CH, Cheng DS, Howng SL, Chow CC | title = Human dynamin-like protein interacts with the glycogen synthase kinase 3beta | journal = Biochemical and Biophysical Research Communications | volume = 249 | issue = 3 | pages = 697–703 | date = Aug 1998 | pmid = 9731200 | doi = 10.1006/bbrc.1998.9253 }}</ref>
+* [[DNM1L]],<ref name = pmid9731200>{{cite journal | vauthors = Hong YR, Chen CH, Cheng DS, Howng SL, Chow CC | title = Human dynamin-like protein interacts with the glycogen synthase kinase 3beta | journal = Biochemical and Biophysical Research Communications | volume = 249 | issue = 3 | pages = 697–703 | date = August 1998 | pmid = 9731200 | doi = 10.1006/bbrc.1998.9253 }}</ref>
-*[[MACF1]]<ref>{{cite journal | vauthors = Wu X, Shen QT, Oristian DS, Lu CP, Zheng Q, Wang HW, Fuchs E | title = Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3β | journal = Cell | volume = 144 | issue = 3 | pages = 341–52 | date = Feb 2011 | pmid = 21295697 | doi = 10.1016/j.cell.2010.12.033 }}</ref>
+*[[MACF1]]<ref>{{cite journal | vauthors = Wu X, Shen QT, Oristian DS, Lu CP, Zheng Q, Wang HW, Fuchs E | title = Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3β | journal = Cell | volume = 144 | issue = 3 | pages = 341–52 | date = February 2011 | pmid = 21295697 | pmc = 3050560 | doi = 10.1016/j.cell.2010.12.033 }}</ref>
-* [[MUC1]],<ref name = pmid9819408>{{cite journal | vauthors = Li Y, Bharti A, Chen D, Gong J, Kufe D | title = Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin | journal = Molecular and Cellular Biology | volume = 18 | issue = 12 | pages = 7216–24 | date = Dec 1998 | pmid = 9819408 | pmc = 109303 | doi =  }}</ref><ref name = pmid11152665>{{cite journal | vauthors = Li Y, Kuwahara H, Ren J, Wen G, Kufe D | title = The c-Src tyrosine kinase regulates signaling of the human DF3/MUC1 carcinoma-associated antigen with GSK3 beta and beta-catenin | journal = The Journal of Biological Chemistry | volume = 276 | issue = 9 | pages = 6061–4 | date = Mar 2001 | pmid = 11152665 | doi = 10.1074/jbc.C000754200 }}</ref>
+* [[MUC1]],<ref name = pmid9819408>{{cite journal | vauthors = Li Y, Bharti A, Chen D, Gong J, Kufe D | title = Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin | journal = Molecular and Cellular Biology | volume = 18 | issue = 12 | pages = 7216–24 | date = December 1998 | pmid = 9819408 | pmc = 109303 | doi = 10.1128/mcb.18.12.7216 }}</ref><ref name = pmid11152665>{{cite journal | vauthors = Li Y, Kuwahara H, Ren J, Wen G, Kufe D | title = The c-Src tyrosine kinase regulates signaling of the human DF3/MUC1 carcinoma-associated antigen with GSK3 beta and beta-catenin | journal = The Journal of Biological Chemistry | volume = 276 | issue = 9 | pages = 6061–4 | date = March 2001 | pmid = 11152665 | doi = 10.1074/jbc.C000754200 | doi-access = free }}</ref>
-* [[Mothers against decapentaplegic homolog 3|SMAD3]]<ref name = pmid18172167>{{cite journal | vauthors = Guo X, Ramirez A, Waddell DS, Li Z, Liu X, Wang XF | title = Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling | journal = Genes & Development | volume = 22 | issue = 1 | pages = 106–20 | date = Jan 2008 | pmid = 18172167 | pmc = 2151009 | doi = 10.1101/gad.1590908 }}</ref>
+* [[Mothers against decapentaplegic homolog 3|SMAD3]]<ref name = pmid18172167>{{cite journal | vauthors = Guo X, Ramirez A, Waddell DS, Li Z, Liu X, Wang XF | title = Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling | journal = Genes & Development | volume = 22 | issue = 1 | pages = 106–20 | date = January 2008 | pmid = 18172167 | pmc = 2151009 | doi = 10.1101/gad.1590908 }}</ref>
-* [[NOTCH1]],<ref name = pmid12123574>{{cite journal | vauthors = Foltz DR, Santiago MC, Berechid BE, Nye JS | title = Glycogen synthase kinase-3beta modulates notch signaling and stability | journal = Current Biology | volume = 12 | issue = 12 | pages = 1006–11 | date = Jun 2002 | pmid = 12123574 | doi = 10.1016/S0960-9822(02)00888-6 }}</ref>
+* [[NOTCH1]],<ref name = pmid12123574>{{cite journal | vauthors = Foltz DR, Santiago MC, Berechid BE, Nye JS | title = Glycogen synthase kinase-3beta modulates notch signaling and stability | journal = Current Biology | volume = 12 | issue = 12 | pages = 1006–11 | date = June 2002 | pmid = 12123574 | doi = 10.1016/S0960-9822(02)00888-6 | s2cid = 15884556 | doi-access = free | bibcode = 2002CBio...12.1006F }}</ref>
-* [[NOTCH2]],<ref name = pmid12794074>{{cite journal | vauthors = Espinosa L, Inglés-Esteve J, Aguilera C, Bigas A | title = Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways | journal = The Journal of Biological Chemistry | volume = 278 | issue = 34 | pages = 32227–35 | date = Aug 2003 | pmid = 12794074 | doi = 10.1074/jbc.M304001200 }}</ref>
+* [[NOTCH2]],<ref name = pmid12794074>{{cite journal | vauthors = Espinosa L, Inglés-Esteve J, Aguilera C, Bigas A | title = Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways | journal = The Journal of Biological Chemistry | volume = 278 | issue = 34 | pages = 32227–35 | date = August 2003 | pmid = 12794074 | doi = 10.1074/jbc.M304001200 | doi-access = free }}</ref>
-* [[P53]],<ref name = pmid12048243>{{cite journal | vauthors = Watcharasit P, Bijur GN, Zmijewski JW, Song L, Zmijewska A, Chen X, Johnson GV, Jope RS | title = Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damage | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 12 | pages = 7951–5 | date = Jun 2002 | pmid = 12048243 | pmc = 123001 | doi = 10.1073/pnas.122062299 }}</ref>
+* [[P53]],<ref name = pmid12048243>{{cite journal | vauthors = Watcharasit P, Bijur GN, Zmijewski JW, Song L, Zmijewska A, Chen X, Johnson GV, Jope RS | title = Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damage | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 12 | pages = 7951–5 | date = June 2002 | pmid = 12048243 | pmc = 123001 | doi = 10.1073/pnas.122062299 | bibcode = 2002PNAS...99.7951W | doi-access = free }}</ref>
-* [[PRKAR2A]],<ref name = pmid12147701>{{cite journal | vauthors = Tanji C, Yamamoto H, Yorioka N, Kohno N, Kikuchi K, Kikuchi A | title = A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta | journal = The Journal of Biological Chemistry | volume = 277 | issue = 40 | pages = 36955–61 | date = Oct 2002 | pmid = 12147701 | doi = 10.1074/jbc.M206210200 }}</ref>
+* [[PRKAR2A]],<ref name = pmid12147701>{{cite journal | vauthors = Tanji C, Yamamoto H, Yorioka N, Kohno N, Kikuchi K, Kikuchi A | title = A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta | journal = The Journal of Biological Chemistry | volume = 277 | issue = 40 | pages = 36955–61 | date = October 2002 | pmid = 12147701 | doi = 10.1074/jbc.M206210200 | doi-access = free }}</ref>
 * [[SGK3]],<ref name = pmid12054501>{{cite journal | vauthors = Dai F, Yu L, He H, Chen Y, Yu J, Yang Y, Xu Y, Ling W, Zhao S | title = Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 through direct interaction | journal = Biochemical and Biophysical Research Communications | volume = 293 | issue = 4 | pages = 1191–6 | date = May 2002 | pmid = 12054501 | doi = 10.1016/S0006-291X(02)00349-2 }}</ref>  and
-* [[TSC2]].<ref name = pmid12511557>{{cite journal | vauthors = Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS | title = The tuberin-hamartin complex negatively regulates beta-catenin signaling activity | journal = The Journal of Biological Chemistry | volume = 278 | issue = 8 | pages = 5947–51 | date = Feb 2003 | pmid = 12511557 | doi = 10.1074/jbc.C200473200 }}</ref><ref name = pmid16959574>{{cite journal | vauthors = Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, Wang CY, He X, MacDougald OA, You M, Williams BO, Guan KL | title = TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth | journal = Cell | volume = 126 | issue = 5 | pages = 955–68 | date = Sep 2006 | pmid = 16959574 | doi = 10.1016/j.cell.2006.06.055 }}</ref>
+* [[TSC2]].<ref name = pmid12511557>{{cite journal | vauthors = Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS | title = The tuberin-hamartin complex negatively regulates beta-catenin signaling activity | journal = The Journal of Biological Chemistry | volume = 278 | issue = 8 | pages = 5947–51 | date = February 2003 | pmid = 12511557 | doi = 10.1074/jbc.C200473200 | doi-access = free }}</ref><ref name = pmid16959574>{{cite journal | vauthors = Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, Wang CY, He X, MacDougald OA, You M, Williams BO, Guan KL | title = TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth | journal = Cell | volume = 126 | issue = 5 | pages = 955–68 | date = September 2006 | pmid = 16959574 | doi = 10.1016/j.cell.2006.06.055 | s2cid = 16047397 | doi-access = free }}</ref>
 {{Div col end}}
@@ Line 39: / Line 50: @@
 {{reflist|35em|refs=
-<ref name="hoeflich2000">{{cite journal | vauthors = Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR | title = Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation | journal = Nature | volume = 406 | issue = 6791 | pages = 86–90 | year = 2000 | pmid = 10894547 | doi = 10.1038/35017574 }}{{closed access}}</ref>
+<ref name="hoeflich2000">{{cite journal | vauthors = Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR | title = Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation | journal = Nature | volume = 406 | issue = 6791 | pages = 86–90 | date = July 2000 | pmid = 10894547 | doi = 10.1038/35017574 | bibcode = 2000Natur.406...86H | s2cid = 205007364 }}{{closed access}}</ref>
 }}
@@ Line 45: / Line 56: @@
 == Further reading ==
 {{refbegin|35em}}
-* {{cite journal | vauthors = Turenne GA, Price BD | title = Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53's transcriptional activity | journal = BMC Cell Biology | volume = 2 | pages = 12 | year = 2001 | pmid = 11483158 | pmc = 35361 | doi = 10.1186/1471-2121-2-12 | url = http://www.biomedcentral.com/1471-2121/2/12 }}
+* {{cite journal | vauthors = Turenne GA, Price BD | title = Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53's transcriptional activity | journal = BMC Cell Biology | volume = 2 | pages = 12 | year = 2001 | pmid = 11483158 | pmc = 35361 | doi = 10.1186/1471-2121-2-12 | doi-access = free }}
-* {{cite journal | vauthors = Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR | title = Glycogen synthase kinase-3: functions in oncogenesis and development | journal = Biochimica Et Biophysica Acta | volume = 1114 | issue = 2-3 | pages = 147–62 | date = Dec 1992 | pmid = 1333807 | doi = 10.1016/0304-419X(92)90012-N }}
+* {{cite journal | vauthors = Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR | title = Glycogen synthase kinase-3: functions in oncogenesis and development | journal = Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | volume = 1114 | issue = 2–3 | pages = 147–62 | date = December 1992 | pmid = 1333807 | doi = 10.1016/0304-419X(92)90012-N }}
-* {{cite journal | vauthors = Morishima-Kawashima M, Hasegawa M, Takio K, Suzuki M, Yoshida H, Watanabe A, Titani K, Ihara Y | title = Hyperphosphorylation of tau in PHF | journal = Neurobiology of Aging | volume = 16 | issue = 3 | pages = 365–71; discussion 371–80 | year = 1995 | pmid = 7566346 | doi = 10.1016/0197-4580(95)00027-C }}
+* {{cite journal | vauthors = Morishima-Kawashima M, Hasegawa M, Takio K, Suzuki M, Yoshida H, Watanabe A, Titani K, Ihara Y | title = Hyperphosphorylation of tau in PHF | journal = Neurobiology of Aging | volume = 16 | issue = 3 | pages = 365–71; discussion 371–80 | year = 1995 | pmid = 7566346 | doi = 10.1016/0197-4580(95)00027-C | s2cid = 22471158 }}
-* {{cite journal | vauthors = Jope RS, Bijur GN | title = Mood stabilizers, glycogen synthase kinase-3beta and cell survival | journal = Molecular Psychiatry | volume = 7 Suppl 1 | issue =  | pages = S35-45 | year = 2002 | pmid = 11986994 | doi = 10.1038/sj.mp.4001017 }}
+* {{cite journal | vauthors = Jope RS, Bijur GN | title = Mood stabilizers, glycogen synthase kinase-3beta and cell survival | journal = Molecular Psychiatry | volume = 7 | pages = S35-45 | year = 2002 | issue = Suppl 1 | pmid = 11986994 | doi = 10.1038/sj.mp.4001017 | doi-access = free }}
-* {{cite journal | vauthors = Bhat RV, Budd SL | title = GSK3beta signalling: casting a wide net in Alzheimer's disease | journal = Neuro-Signals | volume = 11 | issue = 5 | pages = 251–61 | year = 2003 | pmid = 12566926 | doi = 10.1159/000067423 }}
+* {{cite journal | vauthors = Bhat RV, Budd SL | title = GSK3beta signalling: casting a wide net in Alzheimer's disease | journal = Neuro-Signals | volume = 11 | issue = 5 | pages = 251–61 | year = 2003 | pmid = 12566926 | doi = 10.1159/000067423 | s2cid = 13650262 }}
-* {{cite journal | vauthors = Nadri C, Kozlovsky N, Agam G | title = [Schizophrenia, neurodevelopment and glycogen synthase kinase-3] | journal = Harefuah | volume = 142 | issue = 8-9 | pages = 636–42, 644 | date = Sep 2003 | pmid = 14518171 | doi =  }}
+* {{cite journal | vauthors = Wang W, Li M, Wang Y, Li Q, Deng G, Wan J, Yang Q, Chen Q, Wang J | title = GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats | journal = Molecular Neurobiology | volume = 53 | issue = 10 | pages = 7028–7036 | date = December 2016 | pmid = 26671619 | pmc = 4909586 | doi = 10.1007/s12035-015-9607-2 }}
-* {{cite journal | vauthors = Mulholland DJ, Dedhar S, Wu H, Nelson CC | title = PTEN and GSK3beta: key regulators of progression to androgen-independent prostate cancer | journal = Oncogene | volume = 25 | issue = 3 | pages = 329–37 | date = Jan 2006 | pmid = 16421604 | doi = 10.1038/sj.onc.1209020 }}
+* {{cite journal | vauthors = Nadri C, Kozlovsky N, Agam G | title = [Schizophrenia, neurodevelopment and glycogen synthase kinase-3] | journal = Harefuah | volume = 142 | issue = 8–9 | pages = 636–42, 644 | date = September 2003 | pmid = 14518171 }}
+* {{cite journal | vauthors = Mulholland DJ, Dedhar S, Wu H, Nelson CC | title = PTEN and GSK3beta: key regulators of progression to androgen-independent prostate cancer | journal = Oncogene | volume = 25 | issue = 3 | pages = 329–37 | date = January 2006 | pmid = 16421604 | doi = 10.1038/sj.onc.1209020 | doi-access = free }}
 {{refend}}
+== External links ==
+* [https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P49841 PDBe-KB] provides an overview of all the structure information available in the PDB for Human Glycogen synthase kinase-3 beta (GSK3B)
 {{PDB Gallery|geneid=2932}}
+{{Serine/threonine-specific protein kinases}}
+{{Enzymes}}
+{{Portal bar|Biology|border=no}}
 [[Category:Protein kinases]]
 [[Category:EC 2.7.11]]
-{{gene-3-stub}}

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)