GSK3B

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Glycogen synthase kinase 3 beta
Protein GSK3B PDB 1gng.png
PDB rendering based on 1gng.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbol GSK3B
External IDs OMIM605004 MGI1861437 HomoloGene55629 ChEMBL: 262 GeneCards: GSK3B Gene
EC number 2.7.11.1, 2.7.11.26
RNA expression pattern
PBB GE GSK3B 209945 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2932 56637
Ensembl ENSG00000082701 ENSMUSG00000022812
UniProt P49841 Q9WV60
RefSeq (mRNA) NM_001146156 NM_019827
RefSeq (protein) NP_001139628 NP_062801
Location (UCSC) Chr 3:
119.54 – 119.81 Mb
Chr 16:
38.09 – 38.25 Mb
PubMed search [1] [2]

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]

Function[edit]

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.[4][5]

Loss of function mutations[edit]

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]

Interactions[edit]

GSK3B has been shown to interact with:

Overview of signal transduction pathways involved in apoptosis.

See also[edit]


References[edit]

  1. ^ a b Stambolic V, Woodgett JR (November 1994). "Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation". Biochem. J. 303 (Pt 3): 701–4. PMC 1137602. PMID 7980435. 
  2. ^ 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. 
  3. ^ a b c 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
  4. ^ Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR (December 1992). "Glycogen synthase kinase-3: functions in oncogenesis and development". Biochim. Biophys. Acta 1114 (2–3): 147–62. doi:10.1016/0304-419X(92)90012-N. PMID 1333807. 
  5. ^ "Entrez Gene: GSK3B glycogen synthase kinase 3 beta". 
  6. ^ a b Tanji C, Yamamoto H, Yorioka N, Kohno N, Kikuchi K, Kikuchi A (2002). "A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta". J. Biol. Chem. 277 (40): 36955–61. doi:10.1074/jbc.M206210200. PMID 12147701. 
  7. ^ a b Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS (2003). "The tuberin-hamartin complex negatively regulates beta-catenin signaling activity". J. Biol. Chem. 278 (8): 5947–51. doi:10.1074/jbc.C200473200. PMID 12511557. 
  8. ^ Nakamura T, Hamada F, Ishidate T, Anai K, Kawahara K, Toyoshima K, Akiyama T (1998). "Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3beta and APC and reduces the beta-catenin level". Genes Cells 3 (6): 395–403. doi:10.1046/j.1365-2443.1998.00198.x. PMID 9734785. 
  9. ^ von Kries JP, Winbeck G, Asbrand C, Schwarz-Romond T, Sochnikova N, Dell'Oro A, Behrens J, Birchmeier W (2000). "Hot spots in beta-catenin for interactions with LEF-1, conductin and APC". Nat. Struct. Biol. 7 (9): 800–7. doi:10.1038/79039. PMID 10966653. 
  10. ^ Schwarz-Romond T, Asbrand C, Bakkers J, Kühl M, Schaeffer HJ, Huelsken J, Behrens J, Hammerschmidt M, Birchmeier W (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 Dev. 16 (16): 2073–84. doi:10.1101/gad.230402. PMC 186448. PMID 12183362. 
  11. ^ Wang L, Lin HK, Hu YC, Xie S, Yang L, Chang C (2004). "Suppression of androgen receptor-mediated transactivation and cell growth by the glycogen synthase kinase 3 beta in prostate cells". J. Biol. Chem. 279 (31): 32444–52. doi:10.1074/jbc.M313963200. PMID 15178691. 
  12. ^ Davies G, Jiang WG, Mason MD (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". Int. J. Oncol. 18 (4): 843–7. doi:10.3892/ijo.18.4.843. PMID 11251183. 
  13. ^ Kishida S, Yamamoto H, Hino S, Ikeda S, Kishida M, Kikuchi A (1999). "DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability". Mol. Cell. Biol. 19 (6): 4414–22. PMC 104400. PMID 10330181. 
  14. ^ Hong YR, Chen CH, Cheng DS, Howng SL, Chow CC (1998). "Human dynamin-like protein interacts with the glycogen synthase kinase 3beta". Biochem. Biophys. Res. Commun. 249 (3): 697–703. doi:10.1006/bbrc.1998.9253. PMID 9731200. 
  15. ^ Wu, Xiaoyang; Shen QT; Oristian DS; Lu CP; Zheng Q; Wang HW; Fuchs E (2011). "Skin Stem Cells Orchestrate Directional Migration by Regulating Microtubule-ACF7 Connections through GSK3b". Cell 144. doi:10.1016/j.cell.2010.12.033. 
  16. ^ Li Y, Bharti A, Chen D, Gong J, Kufe D (1998). "Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin". Mol. Cell. Biol. 18 (12): 7216–24. PMC 109303. PMID 9819408. 
  17. ^ Li Y, Kuwahara H, Ren J, Wen G, Kufe D (2001). "The c-Src tyrosine kinase regulates signaling of the human DF3/MUC1 carcinoma-associated antigen with GSK3 beta and beta-catenin". J. Biol. Chem. 276 (9): 6061–4. doi:10.1074/jbc.C000754200. PMID 11152665. 
  18. ^ Guo X, Ramirez A, Waddell DS, Li Z, Liu X, Wang XF (2008). "Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling". Genes Dev. 22 (1): 106–20. doi:10.1101/gad.1590908. PMC 2151009. PMID 18172167. 
  19. ^ Foltz DR, Santiago MC, Berechid BE, Nye JS (2002). "Glycogen synthase kinase-3beta modulates notch signaling and stability". Curr. Biol. 12 (12): 1006–11. doi:10.1016/S0960-9822(02)00888-6. PMID 12123574. 
  20. ^ Espinosa L, Inglés-Esteve J, Aguilera C, Bigas A (2003). "Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways". J. Biol. Chem. 278 (34): 32227–35. doi:10.1074/jbc.M304001200. PMID 12794074. 
  21. ^ Watcharasit P, Bijur GN, Zmijewski JW, Song L, Zmijewska A, Chen X, Johnson GV, Jope RS (2002). "Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damage". Proc. Natl. Acad. Sci. U.S.A. 99 (12): 7951–5. doi:10.1073/pnas.122062299. PMC 123001. PMID 12048243. 
  22. ^ Dai F, Yu L, He H, Chen Y, Yu J, Yang Y, Xu Y, Ling W, Zhao S (2002). "Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 through direct interaction". Biochem. Biophys. Res. Commun. 293 (4): 1191–6. doi:10.1016/S0006-291X(02)00349-2. PMID 12054501. 
  23. ^ 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 (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[edit]