Biology:GSK3B

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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]

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.[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.

Disease relevance

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]

Two SNPs at this gene, rs334558 (-50T/C) and rs3755557 (-1727A/T), are associated with efficacy of lithium treatment in bipolar disorder.[7]

Signaling pathways

Pharmacological inhibition of ERK1/2 restores GSK3β activity and protein synthesis levels in a model of tuberous sclerosis.[8]

Interactions

GSK3B has been shown to interact with:


Overview of signal transduction pathways involved in apoptosis.

See also

  • Glycogen synthase kinase 3

References

  1. ↑ 1.0 1.1 "Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation". The Biochemical Journal 303 (Pt 3): 701–4. November 1994. doi:10.1042/bj3030701. PMID 7980435. 
  2. ↑ "Molecular cloning and characterization of the human glycogen synthase kinase-3beta promoter". Genomics 60 (2): 121–8. September 1999. doi:10.1006/geno.1999.5875. PMID 10486203. 
  3. ↑ 3.0 3.1 3.2 "Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation". Nature 406 (6791): 86–90. July 2000. doi:10.1038/35017574. PMID 10894547. Bibcode: 2000Natur.406...86H. closed access
  4. ↑ "The involvement of GSK3beta in bipolar disorder: integrating evidence from multiple types of genetic studies". European Neuropsychopharmacology 20 (6): 357–68. June 2010. doi:10.1016/j.euroneuro.2010.02.008. PMID 20226637. 
  5. ↑ "Glycogen synthase kinase-3: functions in oncogenesis and development". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1114 (2–3): 147–62. December 1992. doi:10.1016/0304-419X(92)90012-N. PMID 1333807. 
  6. ↑ "Entrez Gene: GSK3B glycogen synthase kinase 3 beta". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2932. 
  7. ↑ "Haplotype analysis of GSK-3β gene polymorphisms in bipolar disorder lithium responders and nonresponders". Clinical Neuropharmacology 37 (4): 108–10. 2013. doi:10.1097/WNF.0000000000000039. PMID 24992082. 
  8. ↑ "Inhibition of ERK1/2 Restores GSK3β Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis". Scientific Reports 7 (1): 4174. June 2017. doi:10.1038/s41598-017-04528-5. PMID 28646232. Bibcode: 2017NatSR...7.4174P. 
  9. ↑ EMBL-EBI. "EMBL European Bioinformatics Institute" (in en). http://www.ebi.ac.uk.. 
  10. ↑ 10.0 10.1 "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. October 2002. doi:10.1074/jbc.M206210200. PMID 12147701. 
  11. ↑ 11.0 11.1 "The tuberin-hamartin complex negatively regulates beta-catenin signaling activity". The Journal of Biological Chemistry 278 (8): 5947–51. February 2003. doi:10.1074/jbc.C200473200. PMID 12511557. 
  12. ↑ "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. June 1998. doi:10.1046/j.1365-2443.1998.00198.x. PMID 9734785. 
  13. ↑ "Hot spots in beta-catenin for interactions with LEF-1, conductin and APC". Nature Structural Biology 7 (9): 800–7. September 2000. doi:10.1038/79039. PMID 10966653. 
  14. ↑ "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. August 2002. doi:10.1101/gad.230402. PMID 12183362. 
  15. ↑ "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. July 2004. doi:10.1074/jbc.M313963200. PMID 15178691. 
  16. ↑ "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. April 2001. doi:10.3892/ijo.18.4.843. PMID 11251183. 
  17. ↑ "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. June 1999. doi:10.1128/mcb.19.6.4414. PMID 10330181. 
  18. ↑ "Human dynamin-like protein interacts with the glycogen synthase kinase 3beta". Biochemical and Biophysical Research Communications 249 (3): 697–703. August 1998. doi:10.1006/bbrc.1998.9253. PMID 9731200. 
  19. ↑ "Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3β". Cell 144 (3): 341–52. February 2011. doi:10.1016/j.cell.2010.12.033. PMID 21295697. 
  20. ↑ "Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin". Molecular and Cellular Biology 18 (12): 7216–24. December 1998. doi:10.1128/mcb.18.12.7216. PMID 9819408. 
  21. ↑ "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. March 2001. doi:10.1074/jbc.C000754200. PMID 11152665. 
  22. ↑ "Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling". Genes & Development 22 (1): 106–20. January 2008. doi:10.1101/gad.1590908. PMID 18172167. 
  23. ↑ "Glycogen synthase kinase-3beta modulates notch signaling and stability". Current Biology 12 (12): 1006–11. June 2002. doi:10.1016/S0960-9822(02)00888-6. PMID 12123574. 
  24. ↑ "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. August 2003. doi:10.1074/jbc.M304001200. PMID 12794074. 
  25. ↑ "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. June 2002. doi:10.1073/pnas.122062299. PMID 12048243. Bibcode: 2002PNAS...99.7951W. 
  26. ↑ "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. May 2002. doi:10.1016/S0006-291X(02)00349-2. PMID 12054501. 
  27. ↑ "TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth". Cell 126 (5): 955–68. September 2006. doi:10.1016/j.cell.2006.06.055. PMID 16959574. 

Further reading

External links

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




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