Last updated
Available structures
PDB Ortholog search: PDBe RCSB
Aliases GSK3B , Gsk3b, 7330414F15Rik, 8430431H08Rik, C86142, GSK-3, GSK-3beta, GSK3, glycogen synthase kinase 3 beta
External IDs MGI: 1861437 HomoloGene: 55629 GeneCards: GSK3B
EC number
Gene location (Human)
Chr. Chromosome 3 (human) [1]
Band 3q13.33Start119,821,323 bp [1]
End120,094,417 bp [1]
RNA expression pattern
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 3: 119.82 – 120.09 Mb Chr 16: 38.09 – 38.25 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

Glycogen synthase kinase 3 beta, also known as GSK3B, is an enzyme that in humans is encoded by the GSK3B gene. [5] [6] In mice, the enzyme is encoded by the GSK-3β gene. [7] Abnormal regulation and expression of GSK3β 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.

Loss of function mutations

Homozygous disruption of the GSK-3β locus in mice results in embryonic lethality during mid-gestation. [7] This lethality phenotype could be rescued by inhibition of tumor necrosis factor. [7]

Signaling pathways

Pharmacological inhibition of ERK1/2 restores GSK3β activity and protein synthesis levels in a model of tuberous sclerosis. [11]


GSK3B has been shown to interact with:

Overview of signal transduction pathways involved in apoptosis.

See also


  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000082701 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022812 - Ensembl, May 2017
  3. "Human PubMed Reference:".
  4. "Mouse PubMed Reference:".
  5. 1 2 Stambolic V, Woodgett JR (Nov 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 Freely accessible. PMID   7980435.
  6. Lau KF, Miller CC, Anderton BH, Shaw PC (Sep 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.
  7. 1 2 3 Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR (2000). "Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation". Nature. 406 (6791): 86–90. doi:10.1038/35017574. PMID   10894547.
  8. Luykx JJ, Boks MP, Terwindt AP, Bakker S, Kahn RS, Ophoff RA (Jun 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.
  9. Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR (Dec 1992). "Glycogen synthase kinase-3: functions in oncogenesis and development". Biochimica et Biophysica Acta. 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. Pal R, Bondar VV, Adamski CJ, Rodney GG, Sardiello M (2017). "Inhibition of ERK1/2 Restores GSK3β Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis". Sci. Rep. 7 (1): 4174. doi:10.1038/s41598-017-04528-5. PMC   5482840 Freely accessible. PMID   28646232.
  12. EMBL-EBI. "EMBL European Bioinformatics Institute" Check |url= value (help). Retrieved 2017-04-26.
  13. 1 2 Tanji C, Yamamoto H, Yorioka N, Kohno N, Kikuchi K, Kikuchi A (Oct 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.
  14. 1 2 Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS (Feb 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.
  15. Nakamura T, Hamada F, Ishidate T, Anai K, Kawahara K, Toyoshima K, Akiyama T (Jun 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.
  16. von Kries JP, Winbeck G, Asbrand C, Schwarz-Romond T, Sochnikova N, Dell'Oro A, Behrens J, Birchmeier W (Sep 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.
  17. Schwarz-Romond T, Asbrand C, Bakkers J, Kühl M, Schaeffer HJ, Huelsken J, Behrens J, Hammerschmidt M, Birchmeier W (Aug 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 Freely accessible. PMID   12183362.
  18. Wang L, Lin HK, Hu YC, Xie S, Yang L, Chang C (Jul 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.
  19. Davies G, Jiang WG, Mason MD (Apr 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.
  20. Kishida S, Yamamoto H, Hino S, Ikeda S, Kishida M, Kikuchi A (Jun 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 Freely accessible. PMID   10330181.
  21. Hong YR, Chen CH, Cheng DS, Howng SL, Chow CC (Aug 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.
  22. Wu X, Shen QT, Oristian DS, Lu CP, Zheng Q, Wang HW, Fuchs E (Feb 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 Freely accessible. PMID   21295697.
  23. Li Y, Bharti A, Chen D, Gong J, Kufe D (Dec 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 Freely accessible. PMID   9819408.
  24. Li Y, Kuwahara H, Ren J, Wen G, Kufe D (Mar 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.
  25. Guo X, Ramirez A, Waddell DS, Li Z, Liu X, Wang XF (Jan 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 Freely accessible. PMID   18172167.
  26. Foltz DR, Santiago MC, Berechid BE, Nye JS (Jun 2002). "Glycogen synthase kinase-3beta modulates notch signaling and stability". Current Biology. 12 (12): 1006–11. doi:10.1016/S0960-9822(02)00888-6. PMID   12123574.
  27. Espinosa L, Inglés-Esteve J, Aguilera C, Bigas A (Aug 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.
  28. Watcharasit P, Bijur GN, Zmijewski JW, Song L, Zmijewska A, Chen X, Johnson GV, Jope RS (Jun 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. doi:10.1073/pnas.122062299. PMC   123001 Freely accessible. PMID   12048243.
  29. Dai F, Yu L, He H, Chen Y, Yu J, Yang Y, Xu Y, Ling W, Zhao S (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.
  30. 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 (Sep 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.

Further reading