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Glycogen synthase kinase 3 beta, also known as GSK3B, is an enzyme that in humans is encoded by the GSK3B gene.[1][2] In mice, the enzyme is encoded by the GSK-3β gene.[3] Abnormal regulation and expression of GSK3β is associated with an increased susceptibility towards bipolar disorder.[4]


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.[1] GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation.[5][6] 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.[3] This lethality phenotype could be rescued by inhibition of tumor necrosis factor.[3]

Signaling pathways

Pharmacological inhibition of ERK1/2 restores GSK3β activity and protein synthesis levels in a model of tuberous sclerosis.[7]


GSK3B has been shown to interact with:

Overview of signal transduction pathways involved in apoptosis.

See also


  1. 1.0 1.1 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. PMID 7980435.
  2. 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.
  3. 3.0 3.1 3.2 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.closed access publication – behind paywall
  4. 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.
  5. 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.
  6. "Entrez Gene: GSK3B glycogen synthase kinase 3 beta".
  7. 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. PMID 28646232.
  8. EMBL-EBI. "EMBL European Bioinformatics Institute" Check |url= value (help). Retrieved 2017-04-26.
  9. 9.0 9.1 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.
  10. 10.0 10.1 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.
  11. 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.
  12. 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.
  13. 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. PMID 12183362.
  14. 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.
  15. 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.
  16. 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. PMID 10330181.
  17. 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.
  18. 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. PMID 21295697.
  19. 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. PMID 9819408.
  20. 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.
  21. 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. PMID 18172167.
  22. 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.
  23. 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.
  24. 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. PMID 12048243.
  25. 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.
  26. 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