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Gene Review

Gsk3b  -  glycogen synthase kinase 3 beta

Rattus norvegicus

Synonyms: FA, Factor A, GSK-3 beta, Glycogen synthase kinase-3 beta, Serine/threonine-protein kinase GSK3B
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Disease relevance of Gsk3b

  • To mimic phosphorylation-induced inhibition of GSK-3 beta activity, SB-216763 (SB), a GSK-3 beta inhibitor, was administered before ischemia or 5 min before reperfusion [1].
  • Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy [2].
  • Pinealectomy stimulated tumor growth, LA uptake and metabolism to 13-HODE, and FA storage in hepatoma 7288CTC, whereas melatonin administration (200 microg/day) was inhibitory in vivo [3].
  • These inhibitory effects of melatonin on tumor FA uptake and 13-HODE release were completely reversed by perfusion of tumors in situ with melatonin receptor antagonist S-20928, pertussis toxin, forskolin, or 8-bromo-cAMP [3].
  • Advanced recipient age was associated with reduced creatinine clearance, more severe histologic injuries, including extended glomerular sclerosis, interstitial fibrosis, and vascular lesions, more pronounced cellular infiltration, and greater expression of transforming growth factor-beta and platelet-derived growth factor A and B chains [4].

High impact information on Gsk3b


Chemical compound and disease context of Gsk3b

  • RESULTS: Testosterone treatment resulted in an increased proteinuria as well as profound glomerulosclerosis, tubulointerstitial fibrosis, and mononuclear cell infiltration that paralleled enhanced intragraft mRNA levels of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-A and -B chain (PDGF-A and -B) [9].
  • CONCLUSION: Multiglycosidorum tripterygii is superior to cyclosporine in prevention and attenuation of graft coronary arteriosclerosis and this efficacy is probably associated with the depressed expression of graft platelet-derived growth factor A mRNA in the multiglycosidorum tripterygii-treated groups [10].

Biological context of Gsk3b


Anatomical context of Gsk3b


Associations of Gsk3b with chemical compounds

  • PUGNAc did not significantly alter insulin-stimulated phosphorylation of Akt (serine and threonine) or its substrates glycogen synthase kinase (GSK)3 alpha and GSK3 beta [15].
  • In undifferentiated F9 cells, which are refractory to cAMP induction, transfected GSK-3 beta kinase induces a 60-fold increase in cyclic AMP response element-dependent transcription, mediated via the endogenous CREB protein [17].
  • These results support a novel mechanism of tumor growth inhibition by melatonin involving a melatonin receptor-mediated suppression of cAMP levels, resulting in diminished tumor FA transport, possibly via decreased FATP function [3].
  • When receptor molecules from nonlabeled PC12 cells were immunoprecipitated and then incubated in vitro with [gamma-32P]ATP and the cAMP-independent protein kinase FA/GSK-3, phosphorylation occurred predominantly on serine and to a lesser extent on threonine [18].
  • These results demonstrate that the kinase that phosphorylates and inhibits the pro-survival function of MEF2D in cerebellar granule neurons is a novel lithium target distinct from GSK-3 beta [19].

Enzymatic interactions of Gsk3b

  • In addition, 4R did not enhance total phospho-ERK-1/2 but increased the amount of total Akt/PKB phosphorylated on the activation site and of glycogen synthase kinase 3-beta phosphorylated on the inhibitory site [20].

Regulatory relationships of Gsk3b


Other interactions of Gsk3b


Analytical, diagnostic and therapeutic context of Gsk3b


  1. Erythropoietin affords additional cardioprotection to preconditioned hearts by enhanced phosphorylation of glycogen synthase kinase-3 beta. Nishihara, M., Miura, T., Miki, T., Sakamoto, J., Tanno, M., Kobayashi, H., Ikeda, Y., Ohori, K., Takahashi, A., Shimamoto, K. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  2. Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy. Negoro, N., Kanayama, Y., Haraguchi, M., Umetani, N., Nishimura, M., Konishi, Y., Iwai, J., Okamura, M., Inoue, T., Takeda, T. J. Clin. Invest. (1995) [Pubmed]
  3. Melatonin inhibition of cancer growth in vivo involves suppression of tumor fatty acid metabolism via melatonin receptor-mediated signal transduction events. Blask, D.E., Sauer, L.A., Dauchy, R.T., Holowachuk, E.W., Ruhoff, M.S., Kopff, H.S. Cancer Res. (1999) [Pubmed]
  4. Recipient age and weight affect chronic renal allograft rejection in rats. Liu, S., Lutz, J., Antus, B., Yao, Y., Baik, S., Illies, F., Heemann, U. J. Am. Soc. Nephrol. (2001) [Pubmed]
  5. Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells. Naftilan, A.J., Pratt, R.E., Dzau, V.J. J. Clin. Invest. (1989) [Pubmed]
  6. Molecular cloning and expression of glycogen synthase kinase-3/factor A. Woodgett, J.R. EMBO J. (1990) [Pubmed]
  7. Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1. Piantadosi, C.A., Suliman, H.B. J. Biol. Chem. (2006) [Pubmed]
  8. Blood lipid mediator sphingosine 1-phosphate potently stimulates platelet-derived growth factor-A and -B chain expression through S1P1-Gi-Ras-MAPK-dependent induction of Kruppel-like factor 5. Usui, S., Sugimoto, N., Takuwa, N., Sakagami, S., Takata, S., Kaneko, S., Takuwa, Y. J. Biol. Chem. (2004) [Pubmed]
  9. Contribution of androgens to chronic allograft nephropathy is mediated by dihydrotestosterone. Antus, B., Yao, Y., Liu, S., Song, E., Lutz, J., Heemann, U. Kidney Int. (2001) [Pubmed]
  10. Multiglycosidorum tripterygii, a new immunosuppressant, supresses coronary arteriosclerosis after heart transplantation. Hachida, M., Zhang, X., Lu, H., Hoshi, H., Koyanagi, H. J. Heart Lung Transplant. (1999) [Pubmed]
  11. Glycogen synthase kinase 3 beta is identical to tau protein kinase I generating several epitopes of paired helical filaments. Ishiguro, K., Shiratsuchi, A., Sato, S., Omori, A., Arioka, M., Kobayashi, S., Uchida, T., Imahori, K. FEBS Lett. (1993) [Pubmed]
  12. Evidence for a role of glycogen synthase kinase-3 beta in rodent spermatogenesis. Guo, T.B., Chan, K.C., Hakovirta, H., Xiao, Y., Toppari, J., Mitchell, A.P., Salameh, W.A. J. Androl. (2003) [Pubmed]
  13. Different localization of tau protein kinase I/glycogen synthase kinase-3 beta from glycogen synthase kinase-3 alpha in cerebellum mitochondria. Hoshi, M., Sato, M., Kondo, S., Takashima, A., Noguchi, K., Takahashi, M., Ishiguro, K., Imahori, K. J. Biochem. (1995) [Pubmed]
  14. Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor A-chain expression. Rao, G.N., Corson, M.A., Berk, B.C. J. Biol. Chem. (1991) [Pubmed]
  15. Prolonged incubation in PUGNAc results in increased protein O-Linked glycosylation and insulin resistance in rat skeletal muscle. Arias, E.B., Kim, J., Cartee, G.D. Diabetes (2004) [Pubmed]
  16. Endoplasmic reticulum stress and trophic factor withdrawal activate distinct signaling cascades that induce glycogen synthase kinase-3 beta and a caspase-9-dependent apoptosis in cerebellar granule neurons. Brewster, J.L., Linseman, D.A., Bouchard, R.J., Loucks, F.A., Precht, T.A., Esch, E.A., Heidenreich, K.A. Mol. Cell. Neurosci. (2006) [Pubmed]
  17. A secondary phosphorylation of CREB341 at Ser129 is required for the cAMP-mediated control of gene expression. A role for glycogen synthase kinase-3 in the control of gene expression. Fiol, C.J., Williams, J.S., Chou, C.H., Wang, Q.M., Roach, P.J., Andrisani, O.M. J. Biol. Chem. (1994) [Pubmed]
  18. Phosphorylation of nerve growth factor receptor proteins in sympathetic neurons and PC12 cells. In vitro phosphorylation by the cAMP-independent protein kinase FA/GSK-3. Taniuchi, M., Johnson, E.M., Roach, P.J., Lawrence, J.C. J. Biol. Chem. (1986) [Pubmed]
  19. A myocyte enhancer factor 2D (MEF2D) kinase activated during neuronal apoptosis is a novel target inhibited by lithium. Linseman, D.A., Cornejo, B.J., Le, S.S., Meintzer, M.K., Laessig, T.A., Bouchard, R.J., Heidenreich, K.A. J. Neurochem. (2003) [Pubmed]
  20. Tobacco cembranoids protect the function of acute hippocampal slices against NMDA by a mechanism mediated by alpha4beta2 nicotinic receptors. Ferchmin, P.A., Hao, J., Perez, D., Penzo, M., Maldonado, H.M., Gonzalez, M.T., Rodriguez, A.D., de Vellis, J. J. Neurosci. Res. (2005) [Pubmed]
  21. Glycogen synthase kinase-3beta is involved in the process of myocardial hypertrophy stimulated by insulin-like growth factor-1. Seimi, S.K., Seinosuke, K., Tsuyoshi, S., Tomomi, U., Tetsuaki, H., Miki, K., Ryuji, T., Kenji, I., Mitsuhiro, Y. Circ. J. (2004) [Pubmed]
  22. Altered adhesion features and signal transduction in NRK-49F cells transformed by down-regulation of lysyl oxidase. Giampuzzi, M., Oleggini, R., Di Donato, A. Biochim. Biophys. Acta (2003) [Pubmed]
  23. Impact of a novel cardioprotective agent on the ischaemia-reperfusion-induced Akt kinase activation. Toth, A., Kovacs, K., Deres, P., Halmosi, R., Czopf, L., Hanto, K., Kalai, T., Hideg, K., Sumegi, B., Toth, K. Biochem. Pharmacol. (2003) [Pubmed]
  24. Growth factor transcripts in rat renal transplants. Paul, L.C., Saito, K., Davidoff, A., Benediktsson, H. Am. J. Kidney Dis. (1996) [Pubmed]
  25. Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture. Bermudez, E., Everitt, J., Walker, C. Exp. Cell Res. (1990) [Pubmed]
  26. A specific immunoprecipitation assay for the protein kinase FA/glycogen synthase kinase 3. Van Lint, J., Khandelwal, R.L., Merlevede, W., Vandenheede, J.R. Anal. Biochem. (1993) [Pubmed]
  27. Enhanced synthesis of platelet-derived growth factor following injury induced by 6-hydroxydopamine in rat brain. Funa, K., Yamada, N., Brodin, G., Pietz, K., Ahgren, A., Wictorin, K., Lindvall, O., Odin, P. Neuroscience (1996) [Pubmed]
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