Gene Symbol: GSK3beta
Description: glycogen synthase kinase 3 beta
Alias: glycogen synthase kinase-3 beta, GSK-3 beta, GSK3beta isoform, serine/threonine-protein kinase GSK3B
Species: human
Products:     GSK3beta

Top Publications

  1. Diehl J, Cheng M, Roussel M, Sherr C. Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 1998;12:3499-511 pubmed
    ..Therefore, phosphorylation and proteolytic turnover of cyclin D1 and its subcellular localization during the cell division cycle are linked through the action of GSK-3beta. ..
  2. Li M, Mo Y, Luo X, Xiao X, Shi L, Peng Y, et al. Genetic association and identification of a functional SNP at GSK3? for schizophrenia susceptibility. Schizophr Res. 2011;133:165-71 pubmed publisher
    ..Our findings suggest that GSK3? is likely a risk gene for schizophrenia, and its expression alteration caused by the risk SNP in the promoter region may contribute to the etiology of schizophrenia. ..
  3. Tang Q, Xie X, Wang J, Chen Q, Han A, Zou C, et al. Glycogen synthase kinase-3?, NF-?B signaling, and tumorigenesis of human osteosarcoma. J Natl Cancer Inst. 2012;104:749-63 pubmed publisher
    ..2 months). GSK-3? activity may promote osteosarcoma tumor growth, and therapeutic targeting of the GSK-3? and/or NF-?B pathways may be an effective way to enhance the therapeutic activity of anticancer drugs against osteosarcoma. ..
  4. Darrington R, Campa V, Walker M, Bengoa Vergniory N, Gorroño Etxebarria I, Uysal Onganer P, et al. Distinct expression and activity of GSK-3? and GSK-3? in prostate cancer. Int J Cancer. 2012;131:E872-83 pubmed publisher
  5. Li V, Ng S, Boersema P, Low T, Karthaus W, Gerlach J, et al. Wnt signaling through inhibition of ?-catenin degradation in an intact Axin1 complex. Cell. 2012;149:1245-56 pubmed publisher
    ..Subsequently, newly synthesized ?-catenin can accumulate in a free cytosolic form and engage nuclear TCF transcription factors. ..
  6. Berwick D, Harvey K. The importance of Wnt signalling for neurodegeneration in Parkinson's disease. Biochem Soc Trans. 2012;40:1123-8 pubmed
    ..This suggests the prospect of targeting Wnt signalling pathways to modify PD progression. ..
  7. Lang U, Kocabayoglu P, Cheng G, Ghiassi Nejad Z, Muñoz U, Vetter D, et al. GSK3? phosphorylation of the KLF6 tumor suppressor promotes its transactivation of p21. Oncogene. 2013;32:4557-64 pubmed publisher
    ..This interaction may account for the growth-promoting effects of cancer-derived KLF6 mutants that lack tumor suppressor activity. ..
  8. Kitano A, Shimasaki T, Chikano Y, Nakada M, Hirose M, Higashi T, et al. Aberrant glycogen synthase kinase 3? is involved in pancreatic cancer cell invasion and resistance to therapy. PLoS ONE. 2013;8:e55289 pubmed publisher
    ..The targeting of GSK3? represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer. ..
  9. Gao Y, Liu Z, Zhang X, He J, Pan Y, Hao F, et al. Inhibition of cytoplasmic GSK-3? increases cisplatin resistance through activation of Wnt/?-catenin signaling in A549/DDP cells. Cancer Lett. 2013;336:231-9 pubmed publisher
    ..In conclusion, activation of the Wnt/?-catenin signaling pathway and upregulated survivin expression due to cytoplasmic GSK-3? inhibition might lead to cisplatin resistance in NSCLC. ..

More Information

Publications161 found, 100 shown here

  1. Grassilli E, Narloch R, Federzoni E, Ianzano L, Pisano F, Giovannoni R, et al. Inhibition of GSK3B bypass drug resistance of p53-null colon carcinomas by enabling necroptosis in response to chemotherapy. Clin Cancer Res. 2013;19:3820-31 pubmed publisher
    ..a kinase-directed short hairpin RNA library and HCT116p53KO drug-resistant colon carcinoma cells, glycogen synthase kinase 3 beta (GSK3B) was identified as a target whose silencing bypasses drug resistance due to loss of p53...
  2. Feng L, Zhang D, Fan C, Ma C, Yang W, Meng Y, et al. ER stress-mediated apoptosis induced by celastrol in cancer cells and important role of glycogen synthase kinase-3? in the signal network. Cell Death Dis. 2013;4:e715 pubmed publisher
    ..On the basis of the results of the present study, possible signal network of celastrol activated by celastrol leading to apoptosis was predicted. ..
  3. Numajiri M, Nishizawa D, Ikeda K, Yoshihara E, Iwahashii K. [The relationship between glycogen synthase kinase - 3beta -1727A/T x -50T/C genetic polymorphisms and nicotine dependence]. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2013;48:293-9 pubmed
    ..There was significantly lower T-allele frequency in the smokers than controls (chi2 (2) = 23.42, P = 0.01; chi2 (1) = 12.17, P = 0.01). ..
  4. Tanioka T, Tamura Y, Fukaya M, Shinozaki S, Mao J, Kim M, et al. Inducible nitric-oxide synthase and nitric oxide donor decrease insulin receptor substrate-2 protein expression by promoting proteasome-dependent degradation in pancreatic beta-cells: involvement of glycogen synthase kinase-3beta. J Biol Chem. 2011;286:29388-96 pubmed publisher
    ..Our findings suggest that iNOS-mediated decreased IRS-2 expression may contribute to the progression and/or exacerbation of ?-cell failure in diabetes. ..
  5. Cheng Y, Huang W, Chen C, Tsai C, Wang C, Chiu W, et al. Increased galectin-3 facilitates leukemia cell survival from apoptotic stimuli. Biochem Biophys Res Commun. 2011;412:334-40 pubmed publisher
    ..We found that GSK-3? upregulated galectin-3 and stabilized anti-apoptotic Bcl-2 family proteins, which is important for the escape of leukemia cells from apoptotic stimuli. ..
  6. Kawakami F, Suzuki M, Shimada N, Kagiya G, Ohta E, Tamura K, et al. Stimulatory effect of ?-synuclein on the tau-phosphorylation by GSK-3?. FEBS J. 2011;278:4895-904 pubmed publisher
    ..These results suggest that the cellular level of Hsp70 may be a novel therapeutic target to counteract ?-SN-mediated tau phosphorylation in the initial stage of neurodegenerative disease. ..
  7. Chou C, Chou A, Lin C, Chen W, Wei C, Yang M, et al. GSK3? regulates Bcl2L12 and Bcl2L12A anti-apoptosis signaling in glioblastoma and is inhibited by LiCl. Cell Cycle. 2012;11:532-42 pubmed publisher
    ..These findings suggest that LiCl may be a prospective therapeutic agent against GBM. ..
  8. Liu Z, Fu Z, Song J, Zhang J, Wei Y, Chu J, et al. Bip enhanced the association of GSK-3? with tau during ER stress both in vivo and in vitro. J Alzheimers Dis. 2012;29:727-40 pubmed publisher
    ..All these data suggest an essential role of Bip in GSK-3? dependent tau hyperphosphorylation in ER stress by promoting the binding of GSK-3? to tau. ..
  9. Lin S, Li T, Liu Q, Zhang C, Li X, Chen Y, et al. GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy. Science. 2012;336:477-81 pubmed publisher
    ..These findings uncover an activating pathway that integrates protein phosphorylation and acetylation to connect growth factor deprivation to autophagy. ..
  10. Benedetti F, Bollettini I, Barberi I, Radaelli D, Poletti S, Locatelli C, et al. Lithium and GSK3-? promoter gene variants influence white matter microstructure in bipolar disorder. Neuropsychopharmacology. 2013;38:313-27 pubmed publisher
  11. Wu Z, Li X, Hu C, Ford M, Kleer C, Weiss S. Canonical Wnt signaling regulates Slug activity and links epithelial-mesenchymal transition with epigenetic Breast Cancer 1, Early Onset (BRCA1) repression. Proc Natl Acad Sci U S A. 2012;109:16654-9 pubmed publisher
    ..Together, these findings establish unique functional links between canonical Wnt signaling, Slug expression, EMT, and BRCA1 regulation. ..
  12. Yuan Y, Tong Q, Zhou X, Zhang R, Qi Z, Zhang K. The association between glycogen synthase kinase 3 beta polymorphisms and Parkinson's disease susceptibility: a meta-analysis. Gene. 2013;524:133-8 pubmed publisher
    Previous studies on the association between glycogen synthase kinase 3 beta (GSK3-?) polymorphisms (rs334558 and rs6438552) and Parkinson's disease (PD) susceptibility remained inconsistent...
  13. Kwok J, Hallupp M, Loy C, Chan D, Woo J, Mellick G, et al. GSK3B polymorphisms alter transcription and splicing in Parkinson's disease. Ann Neurol. 2005;58:829-39 pubmed
    ..64; p = 0.007; (H1/H1 individuals: odds ratio, 0.68; p < 0.001). Ours results suggest GSK3B polymorphisms alter transcription and splicing and interact with Tau haplotypes to modify disease risk in PD. ..
  14. Mai W, Kawakami K, Shakoori A, Kyo S, Miyashita K, Yokoi K, et al. Deregulated GSK3{beta} sustains gastrointestinal cancer cells survival by modulating human telomerase reverse transcriptase and telomerase. Clin Cancer Res. 2009;15:6810-9 pubmed publisher
    Glycogen synthase kinase-3beta (GSK3beta) regulates multiple cell signaling pathways and has been implicated in glucose intolerance, neurodegenerative disorders, and inflammation...
  15. Miyashita K, Kawakami K, Nakada M, Mai W, Shakoori A, Fujisawa H, et al. Potential therapeutic effect of glycogen synthase kinase 3beta inhibition against human glioblastoma. Clin Cancer Res. 2009;15:887-97 pubmed publisher
    ..We investigated the expression, activity, and putative pathologic role of glycogen synthase kinase 3beta (GSK3beta), an emerging therapeutic target for neurodegenerative diseases, in human glioblastoma...
  16. Al Khouri A, Ma Y, Togo S, Williams S, Mustelin T. Cooperative phosphorylation of the tumor suppressor phosphatase and tensin homologue (PTEN) by casein kinases and glycogen synthase kinase 3beta. J Biol Chem. 2005;280:35195-202 pubmed
    ..Here we showed that CK2 does not phosphorylate all sites in PTEN and that glycogen synthase kinase 3beta (GSK3beta) also participates in PTEN phosphorylation...
  17. Rottmann S, Wang Y, Nasoff M, Deveraux Q, Quon K. A TRAIL receptor-dependent synthetic lethal relationship between MYC activation and GSK3beta/FBW7 loss of function. Proc Natl Acad Sci U S A. 2005;102:15195-200 pubmed screening a kinase-directed library of small inhibitory RNAs, we identify glycogen synthase kinase 3beta (GSK3beta) as a gene whose inactivation potentiates TNF-related apoptosis-inducing ligand death receptor-mediated apoptosis ..
  18. Jho E, Lomvardas S, Costantini F. A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression. Biochem Biophys Res Commun. 1999;266:28-35 pubmed
    Upon binding of a Wnt to its receptor, GSK3beta is inhibited through an unknown mechanism involving Dishevelled (Dsh), resulting in the dephosphorylation and stabilization of beta-catenin, which translocates to the nucleus and interacts ..
  19. Castellone M, Teramoto H, Williams B, Druey K, Gutkind J. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science. 2005;310:1504-10 pubmed
    ..These findings may provide a molecular framework for the future evaluation of chemopreventive strategies for colorectal cancer. ..
  20. Naderi S, Gutzkow K, Låhne H, Lefdal S, Ryves W, Harwood A, et al. cAMP-induced degradation of cyclin D3 through association with GSK-3beta. J Cell Sci. 2004;117:3769-83 pubmed
    ..These results demonstrate how cAMP enhances degradation of cyclin D3. Furthermore, we provide evidence for a novel mechanism by which GSK-3beta might phosphorylate unprimed substrates in vivo. ..
  21. von Kries J, Winbeck G, Asbrand C, Schwarz Romond T, Sochnikova N, Dell Oro A, et al. Hot spots in beta-catenin for interactions with LEF-1, conductin and APC. Nat Struct Biol. 2000;7:800-7 pubmed
    ..Binding of APC to conductin/axin activates the latter and occurs between their SAMP and RGS domains, respectively. ..
  22. Ban K, Singh H, Krishnan R, Seow H. GSK-3beta phosphorylation and alteration of beta-catenin in hepatocellular carcinoma. Cancer Lett. 2003;199:201-8 pubmed
    ..This result differed from HCC in geographical areas with high aflatoxin exposure. ..
  23. Zhou B, Deng J, Xia W, Xu J, Li Y, Gunduz M, et al. Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol. 2004;6:931-40 pubmed
    ..Furthermore, inhibition of GSK-3beta results in the upregulation of Snail and downregulation of E-cadherin in vivo. Thus, Snail and GSK-3beta together function as a molecular switch for many signalling pathways that lead to EMT. ..
  24. Hua F, Zhou J, Liu J, Zhu C, Cui B, Lin H, et al. Glycogen synthase kinase-3beta negatively regulates TGF-beta1 and Angiotensin II-mediated cellular activity through interaction with Smad3. Eur J Pharmacol. 2010;644:17-23 pubmed publisher
    Glycogen synthase kinase-3beta (GSK3beta) is a major negative modulator of cardiac hypertrophy. Here we report that GSK3beta physically and functionally interacts with Smad3...
  25. Watson R, Spalding A, Zielske S, Morgan M, Kim A, Bommer G, et al. GSK3beta and beta-catenin modulate radiation cytotoxicity in pancreatic cancer. Neoplasia. 2010;12:357-65 pubmed
    ..Irradiation inhibits glycogen synthase kinase 3beta (GSK3beta) by phosphorylation at serine 9...
  26. Hur E, Zhou F. GSK3 signalling in neural development. Nat Rev Neurosci. 2010;11:539-51 pubmed publisher
  27. Mohamed J, Lopez M, Boriek A. Mechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3?. J Biol Chem. 2010;285:29336-47 pubmed publisher
    ..Overall, as a first time, our study unveils that miR-26a is a mechanosensitive gene, and it plays an important role in the regulation of HASMC hypertrophy. ..
  28. Stein J, Milewski W, Hara M, Steiner D, Dey A. GSK-3 inactivation or depletion promotes ?-cell replication via down regulation of the CDK inhibitor, p27 (Kip1). Islets. 2011;3:21-34 pubmed
    ..Altogether our findings indicate that p27 levels in ?-cells are stabilized by GSK-3 and thus p27 down regulation following GSK-3 depletion / inactivation plays a critical role in promoting ?-cell replication. ..
  29. Bijur G, Jope R. Proapoptotic stimuli induce nuclear accumulation of glycogen synthase kinase-3 beta. J Biol Chem. 2001;276:37436-42 pubmed
    ..Thus, the intracellular distribution of GSK-3 beta is dynamically regulated by signaling cascades, and apoptotic stimuli cause increased nuclear levels of GSK-3 beta, which facilitates interactions with nuclear substrates. ..
  30. Lee Y, Seo M, Kim Y, Kim S, Kang U, Kim Y, et al. Membrane depolarization induces the undulating phosphorylation/dephosphorylation of glycogen synthase kinase 3beta, and this dephosphorylation involves protein phosphatases 2A and 2B in SH-SY5Y human neuroblastoma cells. J Biol Chem. 2005;280:22044-52 pubmed
  31. Gong R, Ge Y, Chen S, Liang E, Esparza A, Sabo E, et al. Glycogen synthase kinase 3beta: a novel marker and modulator of inflammatory injury in chronic renal allograft disease. Am J Transplant. 2008;8:1852-63 pubmed publisher
    ..synthase kinase (GSK) 3beta is an indispensable element of NF-kappaB activation, however, the exact role of GSK3beta in the pathogenesis of inflammatory kidney diseases like CRAD is uncertain and was examined...
  32. Wilson W, Baldwin A. Maintenance of constitutive IkappaB kinase activity by glycogen synthase kinase-3alpha/beta in pancreatic cancer. Cancer Res. 2008;68:8156-63 pubmed publisher
    ..These data provide new insight into GSK-3-dependent NF-kappaB regulation and further establish GSK-3 and IKK as potential therapeutic targets for pancreatic cancer. ..
  33. Nagao M, Hayashi H. Glycogen synthase kinase-3beta is associated with Parkinson's disease. Neurosci Lett. 2009;449:103-7 pubmed publisher
    ..Our results suggest that GSK-3beta plays a role in the pathogenesis of PD but not in that of MSA. ..
  34. Hughes K, Nikolakaki E, Plyte S, Totty N, Woodgett J. Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation. EMBO J. 1993;12:803-8 pubmed
    ..However, unlike MAP kinases, GSK-3 is highly phosphorylated on tyrosine and thus active in resting cells. ..
  35. Clifford R, Deacon K, Knox A. Novel regulation of vascular endothelial growth factor-A (VEGF-A) by transforming growth factor (beta)1: requirement for Smads, (beta)-CATENIN, AND GSK3(beta). J Biol Chem. 2008;283:35337-53 pubmed publisher
    ..These results provide new insight into the molecular regulation of VEGF by two interacting pathways necessary for vascular development, maintenance, and disease. ..
  36. Cole A, Causeret F, Yadirgi G, Hastie C, McLauchlan H, McManus E, et al. Distinct priming kinases contribute to differential regulation of collapsin response mediator proteins by glycogen synthase kinase-3 in vivo. J Biol Chem. 2006;281:16591-8 pubmed
    ..This is the first GSK3 substrate found to be regulated in this manner and may explain the hyperphosphorylation of CRMP2 observed in Alzheimer's disease. ..
  37. Bachelder R, Yoon S, Franci C, De Herreros A, Mercurio A. Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition. J Cell Biol. 2005;168:29-33 pubmed
    ..These findings indicate that epithelial cells must sustain activation of a specific kinase to impede a mesenchymal transition. ..
  38. Lee K, Ahn Y, Joo E, Jeong S, Chang J, Kim S, et al. No association of two common SNPs at position -1727 A/T, -50 C/T of GSK-3 beta polymorphisms with schizophrenia and bipolar disorder of Korean population. Neurosci Lett. 2006;395:175-8 pubmed
    ..In conclusion, these results suggest that the GSK-3 beta is not associated with the development of schizophrenia and bipolar disorder in Korean population. ..
  39. Dajani R, Fraser E, Roe S, Yeo M, Good V, Thompson V, et al. Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex. EMBO J. 2003;22:494-501 pubmed
    Glycogen synthase kinase 3beta (GSK3beta) is a serine/threonine kinase involved in insulin, growth factor and Wnt signalling...
  40. Meares G, Zmijewska A, Jope R. HSP105 interacts with GRP78 and GSK3 and promotes ER stress-induced caspase-3 activation. Cell Signal. 2008;20:347-58 pubmed
    ..Thus, HSP105 appears to chaperone the responses to ER stress through its interactions with GRP78 and GSK3, and without HSP105 cell death following ER stress proceeds by a non-caspase-3-dependent process. ..
  41. Beals C, Sheridan C, Turck C, Gardner P, Crabtree G. Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3. Science. 1997;275:1930-4 pubmed
    ..Because GSK-3 responds to signals initiated by Wnt and other ligands, NF-AT family members could be effectors of these pathways. ..
  42. Hart M, de los Santos R, Albert I, Rubinfeld B, Polakis P. Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr Biol. 1998;8:573-81 pubmed
    ..This suggests a possible link between Axin, the Wnt-1 signaling components beta-catenin and glycogen synthase kinase 3 beta (GSK3 beta), and APC...
  43. Lachman H, Pedrosa E, Petruolo O, Cockerham M, Papolos A, Novak T, et al. Increase in GSK3beta gene copy number variation in bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:259-65 pubmed
    ..One such gene is GSK3beta, which codes for glycogen synthase kinase, a key component of the Wnt signaling pathway and a target of lithium ..
  44. Stambolic V, Woodgett J. Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation. Biochem J. 1994;303 ( Pt 3):701-4 pubmed
    ..Since p90rsk-1 is directly activated by mitogen-activated protein kinases, agonists of this pathway, such as insulin, repress GSK-3 function. ..
  45. Cao Q, Lu X, Feng Y. Glycogen synthase kinase-3beta positively regulates the proliferation of human ovarian cancer cells. Cell Res. 2006;16:671-7 pubmed
    ..Our findings thus suggest that GSK-3beta activity is important for the proliferation of ovarian cancer cells, implicating this kinase as a potential therapeutic target in ovarian cancer. ..
  46. Ougolkov A, Fernandez Zapico M, Bilim V, Smyrk T, Chari S, Billadeau D. Aberrant nuclear accumulation of glycogen synthase kinase-3beta in human pancreatic cancer: association with kinase activity and tumor dedifferentiation. Clin Cancer Res. 2006;12:5074-81 pubmed
  47. Plyte S, Hughes K, Nikolakaki E, Pulverer B, Woodgett J. Glycogen synthase kinase-3: functions in oncogenesis and development. Biochim Biophys Acta. 1992;1114:147-62 pubmed
    ..The challenge is to co-ordinate these two approaches, a strategy currently being employed to further unravel the biological role of GSK-3. ..
  48. Kang T, Wei Y, Honaker Y, Yamaguchi H, Appella E, Hung M, et al. GSK-3 beta targets Cdc25A for ubiquitin-mediated proteolysis, and GSK-3 beta inactivation correlates with Cdc25A overproduction in human cancers. Cancer Cell. 2008;13:36-47 pubmed publisher
    ..Importantly, a strong correlation between Cdc25A overproduction and GSK-3beta inactivation was observed in human tumor tissues, indicating that GSK-3beta inactivation may account for Cdc25A overproduction in a subset of human tumors. ..
  49. Wang Q, Fiol C, DePaoli Roach A, Roach P. Glycogen synthase kinase-3 beta is a dual specificity kinase differentially regulated by tyrosine and serine/threonine phosphorylation. J Biol Chem. 1994;269:14566-74 pubmed
    ..Phosphorylation at different residues differentially controls enzyme activity, Ser/Thr phosphorylation causing inactivation and Tyr phosphorylation resulting in increased activity. ..
  50. Lau K, Miller C, Anderton B, Shaw P. Molecular cloning and characterization of the human glycogen synthase kinase-3beta promoter. Genomics. 1999;60:121-8 pubmed
    ..CP2 has recently been shown to interact with the Alzheimer disease amyloid precursor protein binding protein Fe65. The significance of these results with respect to Alzheimer disease pathogenesis are discussed. ..
  51. Kim M, Chia I, Costantini F. SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability. FASEB J. 2008;22:3785-94 pubmed publisher
    ..Therefore, some other specific property of the C6 motif seems to reduce the interaction of Axin with Dvl-1. ..
  52. Turenne G, Price B. Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53's transcriptional activity. BMC Cell Biol. 2001;2:12 pubmed
    ..The 2 isoforms of GSK3, GSK3alpha and GSK3beta, phosphorylate the sequence Ser-X-X-X-Ser(P) when the C-terminal serine residue is already phosphorylated...
  53. Shakoori A, Ougolkov A, Yu Z, Zhang B, Modarressi M, Billadeau D, et al. Deregulated GSK3beta activity in colorectal cancer: its association with tumor cell survival and proliferation. Biochem Biophys Res Commun. 2005;334:1365-73 pubmed
    Glycogen synthase kinase 3beta (GSK3beta) reportedly has opposing roles, repressing Wnt/beta-catenin signaling on the one hand but maintaining cell survival and proliferation through the NF-kappaB pathway on the other...
  54. Yook J, Li X, Ota I, Hu C, Kim H, Kim N, et al. A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells. Nat Cell Biol. 2006;8:1398-406 pubmed
    ..Axin2 regulates EMT by acting as a nucleocytoplasmic chaperone for GSK3beta, the dominant kinase responsible for controlling Snail1 protein turnover and activity...
  55. Kim J, Lee J, Kim M, Cho E, Cho S, Choi E. Glycogen synthase kinase 3 beta is a natural activator of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1). J Biol Chem. 2003;278:13995-4001 pubmed
    ..Ectopic expression of GSK3 beta increased both basal and tumor necrosis factor alpha-stimulated activities of MEKK1 in GSK3 beta(-/-) cells. Together, these observations suggest that GSK3 beta functions as a natural activator of MEKK1. ..
  56. Bachar Dahan L, Goltzmann J, Yaniv A, Gazit A. Engrailed-1 negatively regulates beta-catenin transcriptional activity by destabilizing beta-catenin via a glycogen synthase kinase-3beta-independent pathway. Mol Biol Cell. 2006;17:2572-80 pubmed
    ..Moreover, because En-1-mediated beta-catenin degradation is also Siah independent, our data imply that En-1 exerts its repressive effect by a novel mechanism negatively controlling the level of beta-catenin. ..
  57. Greco S, Sarkar S, Casadesus G, Zhu X, Smith M, Ashford J, et al. Leptin inhibits glycogen synthase kinase-3beta to prevent tau phosphorylation in neuronal cells. Neurosci Lett. 2009;455:191-4 pubmed publisher
    ..These studies provide further insight into Leptin's mechanism of action in suppressing AD-related pathways. ..
  58. Wood Kaczmar A, Kraus M, Ishiguro K, Philpott K, Gordon Weeks P. An alternatively spliced form of glycogen synthase kinase-3beta is targeted to growing neurites and growth cones. Mol Cell Neurosci. 2009;42:184-94 pubmed publisher
    ..We conclude that the alternatively spliced isoform of GSK-3beta, GSK-3beta2, is neuron-specific and has overlapping activities with GSK-3beta1. ..
  59. Kobayashi T, Hino S, Oue N, Asahara T, Zollo M, Yasui W, et al. Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions. Mol Cell Biol. 2006;26:898-911 pubmed
    ..These results suggest that GSK-3 and h-prune cooperatively regulate the disassembly of focal adhesions to promote cell migration and that h-prune is useful as a marker for tumor aggressiveness. ..
  60. Cai X, Li M, Vrana J, Schaller M. Glycogen synthase kinase 3- and extracellular signal-regulated kinase-dependent phosphorylation of paxillin regulates cytoskeletal rearrangement. Mol Cell Biol. 2006;26:2857-68 pubmed
    ..Hence, phosphorylation of paxillin on serines 126 and 130, which is mediated by an ERK/GSK-3 dual-kinase mechanism, plays an important role in cytoskeletal rearrangement. ..
  61. Mazor M, Kawano Y, Zhu H, Waxman J, Kypta R. Inhibition of glycogen synthase kinase-3 represses androgen receptor activity and prostate cancer cell growth. Oncogene. 2004;23:7882-92 pubmed
    ..Finally, inhibition of GSK-3 reduced the growth of AR-expressing prostate cancer cell lines. Our observations suggest a potential new therapeutic application for GSK-3 inhibitors in prostate cancer...
  62. Chou H, Howng S, Cheng T, Hsiao Y, Lieu A, Loh J, et al. GSKIP is homologous to the Axin GSK3beta interaction domain and functions as a negative regulator of GSK3beta. Biochemistry. 2006;45:11379-89 pubmed
    ..Using a yeast two-hybrid screen, we identified a novel protein, GSK3beta interaction protein (GSKIP), which binds to GSK3beta...
  63. Schütz S, Cronauer M, Rinnab L. Inhibition of glycogen synthase kinase-3beta promotes nuclear export of the androgen receptor through a CRM1-dependent mechanism in prostate cancer cell lines. J Cell Biochem. 2010;109:1192-200 pubmed publisher
    ..The results suggest that GSK-3beta is an important element not only in AR stability but also significantly alters nuclear translocation of the AR, thereby modulating the androgenic response of human PCa cells. ..
  64. Fang J, Lei W, Huang X, Li P, Chen X, Zhu X, et al. Expression of mismatch repair gene PMS2 in nasopharyngeal carcinoma and regulation by glycogen synthase kinase-3β in vivo and in vitro. Auris Nasus Larynx. 2012;39:71-6 pubmed publisher
  65. Fumoto K, Lee P, Saya H, Kikuchi A. AIP regulates stability of Aurora-A at early mitotic phase coordinately with GSK-3beta. Oncogene. 2008;27:4478-87 pubmed publisher
    ..These results suggest that GSK-3beta modulates the early mitotic Aurora-A level through binding and phosphorylating AIP. ..
  66. Oinuma I, Katoh H, Negishi M. R-Ras controls axon specification upstream of glycogen synthase kinase-3beta through integrin-linked kinase. J Biol Chem. 2007;282:303-18 pubmed
    ..In addition, membrane targeting of ILK was sufficient to inactivate GSK-3beta and to form multiple axons. Our study demonstrates a novel role of R-Ras and ILK upstream of GSK-3beta in the regulation of neuronal polarity. ..
  67. Zhou F, Zhang L, Wang A, Song B, Gong K, Zhang L, et al. The association of GSK3 beta with E2F1 facilitates nerve growth factor-induced neural cell differentiation. J Biol Chem. 2008;283:14506-15 pubmed publisher
    It is widely acknowledged that E2F1 and GSK3beta are both involved in the process of cell differentiation. However, the relationship between E2F1 and GSK3beta in cell differentiation has yet to be discovered...
  68. Nakamura T, Hamada F, Ishidate T, Anai K, Kawahara K, Toyoshima K, et al. Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3beta and APC and reduces the beta-catenin level. Genes Cells. 1998;3:395-403 pubmed
    ..Axin interacts with beta-catenin, GSK-3beta and APC, and negatively regulates the Wnt signalling pathway, presumably by regulating the level of beta-catenin. ..
  69. Bax B, Carter P, Lewis C, Guy A, Bridges A, Tanner R, et al. The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation. Structure. 2001;9:1143-52 pubmed
    ..Pre-phosphorylated substrate peptides can be modeled into the active site of the enzyme, with the P1 residue occupying a pocket partially formed by phosphotyrosine 216 and the P4 phosphoserine occupying the 'primed' binding site. ..
  70. Wang Z, Smith K, Murphy M, Piloto O, Somervaille T, Cleary M. Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy. Nature. 2008;455:1205-9 pubmed publisher
    ..Inhibition of GSK3 in a preclinical murine model of MLL leukaemia provides promising evidence of efficacy and earmarks GSK3 as a candidate cancer drug target. ..
  71. Liang M, Chuang D. Differential roles of glycogen synthase kinase-3 isoforms in the regulation of transcriptional activation. J Biol Chem. 2006;281:30479-84 pubmed
    ..The development of GSK-3 isoform-specific inhibitors is thus crucial for therapeutic intervention of GSK-3-related neuropathological conditions. ..
  72. Goode N, Hughes K, Woodgett J, Parker P. Differential regulation of glycogen synthase kinase-3 beta by protein kinase C isotypes. J Biol Chem. 1992;267:16878-82 pubmed
    ..Phosphorylation of GSK-3 beta by PKC results in its specific inactivation. These results are consistent with a model in which activation of PKC stimulates c-Jun DNA binding by inhibiting its phosphorylation by GSK-3 beta. ..
  73. Zhang N, Jiang Y, Zou J, Yu Q, Zhao W. Structural basis for the complete loss of GSK3beta catalytic activity due to R96 mutation investigated by molecular dynamics study. Proteins. 2009;75:671-81 pubmed publisher
    ..Presently, the similarity of activation loop between two crystal complexes, i.e. glycogen synthase kinase 3beta (GSK3beta)-AMPNP and GSK3beta-sulfate ion complex, indicates that the activation segment of GSK3beta is preformed requiring ..
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    ..Our study establishes GSK-3 as a specific in vivo modulator of HSC activity, and suggests that administration of GSK-3 inhibitors may provide a clinical means to directly enhance the repopulating capacity of transplanted HSCs. ..
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    Glycogen synthase kinase 3beta (GSK3beta), a multifunctional serine/threonine kinase found in all eukaryotes, had been initially identified as a key regulator of insulin-dependent glycogen synthesis...
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    ..Interestingly, expression of glycogen synthase kinase 3 beta (GSK3beta), which was found to be consistently expressed in primary GBM, also declined...
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    ..Together, our data demonstrated that GSK3 beta may function as a repressor to suppress AR-mediated transactivation and cell growth, which may provide a new strategy to modulate the AR-mediated prostate cancer growth. ..
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    ..These results imply that GSK-3beta may function in transporting centrosomal proteins to the centrosome by stabilizing the BICD1 and dynein complex, resulting in the regulation of a focused microtubule organization. ..
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    ..Thus, cyclin E turnover is controlled by multiple biological inputs and cannot be understood in terms of autophosphorylation alone. ..
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    ..The results demonstrate that the control of MCL-1 stability by GSK-3 is an important mechanism for the regulation of apoptosis by growth factors, PI3K, and AKT. ..
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    ..Further studies with larger sample sizes and different populations are needed. ..
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    ..These data suggest that in MM cells GSK-3? and ? i) play distinct roles in cell survival and ii) modulate the sensitivity to proteasome inhibitors. ..
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    ..383, P=0.013). Our findings suggest that the functional polymorphisms in GSK3B promoter may be involved in the risk of developing sporadic LOAD in Han Chinese. ..
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    ..This may explain how the essential cellular functions of GSK3 can continue, despite the suppression of beta-catenin phosphorylation. ..
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    ..of PKB regulation, we determined the crystal structures of activated kinase domains of PKB in complex with a GSK3beta-peptide substrate and an ATP analog...
  88. Liao X, Zhang L, Thrasher J, Du J, Li B. Glycogen synthase kinase-3beta suppression eliminates tumor necrosis factor-related apoptosis-inducing ligand resistance in prostate cancer. Mol Cancer Ther. 2003;2:1215-22 pubmed
  89. Deng J, Xia W, Miller S, Wen Y, Wang H, Hung M. Crossregulation of NF-kappaB by the APC/GSK-3beta/beta-catenin pathway. Mol Carcinog. 2004;39:139-46 pubmed
    ..Thus, APC/GSK-3beta, through beta-catenin, may crossregulate NF-kappaB signaling pathway. ..
  90. Yoshimura T, Kawano Y, Arimura N, Kawabata S, Kikuchi A, Kaibuchi K. GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Cell. 2005;120:137-49 pubmed
    ..Knockdown of CRMP-2 inhibited NT-3-induced axon outgrowth. These results suggest that NT-3 decreases phosphorylated CRMP-2 and increases nonphosphorylated active CRMP-2, thereby promoting axon outgrowth. ..
  91. Badorff C, Seeger F, Zeiher A, Dimmeler S. Glycogen synthase kinase 3beta inhibits myocardin-dependent transcription and hypertrophy induction through site-specific phosphorylation. Circ Res. 2005;97:645-54 pubmed
    Cardiomyocyte hypertrophy is transcriptionally controlled and inhibited by glycogen synthase kinase 3beta (GSK3beta). Myocardin is a muscle-specific transcription factor with yet unknown relation to hypertrophy...