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词条 GSK3B
释义

  1. Function

  2. Loss of function mutations

  3. Signaling pathways

  4. Interactions

  5. See also

  6. References

  7. Further reading

{{Infobox_gene}}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. Abnormal regulation and expression of GSK3β is associated with an increased susceptibility towards bipolar disorder.[3]

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.[4][5] 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. This lethality phenotype could be rescued by inhibition of tumor necrosis factor.

Signaling pathways

Pharmacological inhibition of ERK1/2 restores GSK3β activity and protein synthesis levels in a model of tuberous sclerosis.[6]

Interactions

GSK3B has been shown to interact with:

  • KIAA1211L[7]
{{div col|colwidth=20em}}
  • AKAP11,[12]
  • AXIN1,[13][8]
  • AXIN2,[9][10]
  • AR,[11]
  • CTNNB1,[12][13]
  • DNM1L,[14]
  • MACF1[15]
  • MUC1,[16][17]
  • SMAD3[18]
  • NOTCH1,[19]
  • NOTCH2,[20]
  • P53,[21]
  • PRKAR2A,[22]
  • SGK3,[23] and
  • TSC2.[24][25]
{{Div col end}}

See also

  • Glycogen synthase kinase 3
{{Clear}}

References

1. ^1 {{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 = Nov 1994 | pmid = 7980435 | pmc = 1137602 | doi = 10.1042/bj3030701}}
2. ^{{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 }}
3. ^{{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 | doi = 10.1016/j.euroneuro.2010.02.008 | pmid = 20226637 }}
4. ^{{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 }}
5. ^{{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| accessdate = }}
6. ^{{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 = Sci. Rep. | volume = 7 | issue = 1 | pages = 4174 | year = 2017 | pmid = 28646232 | doi = 10.1038/s41598-017-04528-5 | pmc=5482840}}
7. ^{{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}}
8. ^{{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 }}
9. ^{{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 }}
10. ^{{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 }}
11. ^{{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 }}
12. ^{{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 }}
13. ^{{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 = 10.1128/mcb.19.6.4414}}
14. ^{{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 }}
15. ^{{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 | pmc=3050560}}
16. ^{{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 = 10.1128/mcb.18.12.7216}}
17. ^{{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 }}
18. ^{{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 }}
19. ^{{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 }}
20. ^{{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 }}
21. ^{{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 }}
22. ^1 {{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 }}
23. ^{{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 }}
24. ^1 {{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 }}
25. ^{{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 }}
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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 = 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 = 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 = 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 = 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 = Wang W, Li M, Wang Y, Li Q, et al.| 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 = Mol Neurobiol | volume = 53 | issue = 10 | pages = 7028-7036 | year = 2016 | pmid = 26671619 | doi = 10.1007/s12035-015-9607-2 | pmc = 4909586 }}
  • {{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 = 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 }}
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2 : Protein kinases|EC 2.7.11
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