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The role of GSK3beta in the development of the central nervous system

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Frontiers in Biology

Abstract

Glycogen synthase kinase 3β (GSK3β) is a multifunctional serine/threonine kinase. It is particularly abundant in the developing central nervous system (CNS). Since GSK3β has diverse substrates ranging from metabolic/signaling proteins and structural proteins to transcription factors, it is involved in many developmental events in the immature brain, such as neurogenesis, neuronal migration, differentiation and survival. The activity of GSK3β is developmentally regulated and is affected by various environmental/cellular insults, such as deprivation of nutrients/trophic factors, oxidative stress and endoplasmic reticulum stress. Abnormalities in GSK3β activity may disrupt CNS development. Therefore, GSK3β is a critical signaling protein that regulates brain development. It may also determine neuronal susceptibility to damages caused by various environmental insults.

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References

  • Arévalo J C, Chao M V (2005). Axonal growth: where neurotrophins meet Wnts. Curr Opin Cell Biol, 17(2): 112–115

    Article  PubMed  Google Scholar 

  • Asada N, Sanada K (2010). LKB1-mediated spatial control of GSK3beta and adenomatous polyposis coli contributes to centrosomal forward movement and neuronal migration in the developing neocortex. J Neurosci, 30(26): 8852–8865

    Article  PubMed  CAS  Google Scholar 

  • Baltzis D, Pluquet O, Papadakis A I, Kazemi S, Qu L K, Koromilas A E (2007). The eIF2alpha kinases PERK and PKR activate glycogen synthase kinase 3 to promote the proteasomal degradation of p53. J Biol Chem, 282(43): 31675–31687

    Article  PubMed  CAS  Google Scholar 

  • Barth A I, Caro-Gonzalez H Y, Nelson WJ (2008). Role of adenomatous polyposis coli (APC) and microtubules in directional cell migration and neuronal polarization. Semin Cell Dev Biol, 19(3): 245–251

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Beurel E, Jope R S (2006). The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways. Prog Neurobiol, 79(4): 173–189

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Bhat R V, Shanley J, Correll MP, Fieles WE, Keith R A, Scott CW, Lee C M (2000). Regulation and localization of tyrosine216 phosphorylation of glycogen synthase kinase-3beta in cellular and animal models of neuronal degeneration. Proc Natl Acad Sci USA, 97(20): 11074–11079

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Bianchi M, De Lucchini S, Marin O, Turner D L, Hanks S K, Villa-Moruzzi E (2005). Regulation of FAK Ser-722 phosphorylation and kinase activity by GSK3 and PP1 during cell spreading and migration. Biochem J, 391(2): 359–370

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Bijur G N, De Sarno P, Jope R S (2000). Glycogen synthase kinase-3beta facilitates staurosporine- and heat shock-induced apoptosis. Protection by lithium. J Biol Chem, 275(11): 7583–7590

    Article  PubMed  CAS  Google Scholar 

  • Boku S, Nakagawa S, Masuda T, Nishikawa H, Kato A, Kitaichi Y, Inoue T, Koyama T (2009). Glucocorticoids and lithium reciprocally regulate the proliferation of adult dentate gyrus-derived neural precursor cells through GSK-3beta and beta-catenin/TCF pathway. Neuropsychopharmacology, 34(3): 805–815

    Article  PubMed  CAS  Google Scholar 

  • Brewster J L, Linseman D A, Bouchard R J, Loucks F A, Precht T A, Esch E A, Heidenreich K A (2006). 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. Mol Cell Neurosci, 32(3): 242–253

    Article  PubMed  CAS  Google Scholar 

  • Carter J J, Tong M, Silbermann E, Lahousse S A, Ding F F, Longato L, Roper N, Wands J R, de la Monte S M (2008). Ethanol impaired neuronal migration is associated with reduced aspartyl-asparaginylbeta-hydroxylase expression. Acta Neuropathol, 116(3): 303–315

    Article  PubMed  CAS  Google Scholar 

  • Castelo-Branco G, Rawal N, Arenas E (2004). GSK-3beta inhibition/beta-catenin stabilization in ventral midbrain precursors increases differentiation into dopamine neurons. J Cell Sci, 117(24): 5731–5737

    Article  PubMed  CAS  Google Scholar 

  • Chen G, Bower K A, Ma C, Fang S, Thiele C J, Luo J (2004). Glycogen synthase kinase 3beta (GSK3beta) mediates 6-hydroxydopamineinduced neuronal death. FASEB J, 18(10): 1162–1164

    PubMed  CAS  Google Scholar 

  • Chen G, Bower K A, Xu M, Ding M, Shi X, Ke Z J, Luo J (2009b). Cyanidin-3-glucoside reverses ethanol-induced inhibition of neurite outgrowth: role of glycogen synthase kinase 3 beta. Neurotox Res, 15(4): 321–331

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Chen Z L, Haegeli V, Yu H, Strickland S (2009a). Cortical deficiency of laminin gamma1 impairs the AKT/GSK-3beta signaling pathway and leads to defects in neurite outgrowth and neuronal migration. Dev Biol, 327(1): 158–168

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Cheng T S, Hsiao Y L, Lin C C, Yu C T, Hsu C M, Chang M S, Lee C I, Huang C Y, Howng S L, Hong Y R (2007). Glycogen synthase kinase 3beta interacts with and phosphorylates the spindle-associated protein astrin. J Biol Chem, 283(4): 2454–2464

    Article  PubMed  Google Scholar 

  • Ciani L, Salinas P C (2007). c-Jun N-terminal kinase (JNK) cooperates with Gsk3beta to regulate Dishevelled-mediated microtubule stability. BMC Cell Biol, 8(1): 27

    Article  PubMed  PubMed Central  Google Scholar 

  • Cole A, Frame S, Cohen P (2004). Further evidence that the tyrosine phosphorylation of glycogen synthase kinase-3 (GSK3) in mammalian cells is an autophosphorylation event. Biochem J, 377(1): 249–255

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Coyle-Rink J, Del Valle L, Sweet T, Khalili K, Amini S (2002). Developmental expression of Wnt signaling factors in mouse brain. Cancer Biol Ther, 1(6): 640–645

    PubMed  CAS  Google Scholar 

  • Crowder R J, Freeman R S (2000). Glycogen synthase kinase-3 beta activity is critical for neuronal death caused by inhibiting phosphatidylinositol 3-kinase or Akt but not for death caused by nerve growth factor withdrawal. J Biol Chem, 275(44): 34266–34271

    Article  PubMed  CAS  Google Scholar 

  • Cui H, Meng Y, Bulleit R F (1998). Inhibition of glycogen synthase kinase 3beta activity regulates proliferation of cultured cerebellar granule cells. Brain Res Dev Brain Res, 111(2): 177–188

    Article  PubMed  CAS  Google Scholar 

  • D’Mello S R, Anelli R, Calissano P (1994). Lithium induces apoptosis in immature cerebellar granule cells but promotes survival of mature neurons. Exp Cell Res, 211(2): 332–338

    Article  PubMed  Google Scholar 

  • Diehl J A, Cheng M, Roussel M F, Sherr C J (1998). Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev, 12(22): 3499–3511

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Dill J, Wang H, Zhou F, Li S (2008). Inactivation of glycogen synthase kinase 3 promotes axonal growth and recovery in the CNS. J Neurosci, 28(36): 8914–8928

    Article  PubMed  CAS  Google Scholar 

  • Doble BW, Woodgett J R (2003). GSK-3: tricks of the trade for a multitasking kinase. J Cell Sci, 116(7): 1175–1186

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Eom T Y, Roth K A, Jope R S (2007). Neural precursor cells are protected from apoptosis induced by trophic factor withdrawal or genotoxic stress by inhibitors of glycogen synthase kinase 3. J Biol Chem, 282(31): 22856–22864

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Etienne-Manneville S, Hall A (2003). Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity. Nature, 421(6924): 753–756

    Article  PubMed  CAS  Google Scholar 

  • Gärtner A, Huang X, Hall A (2006). Neuronal polarity is regulated by glycogen synthase kinase-3 (GSK-3beta) independently of Akt/PKB serine phosphorylation. J Cell Sci, 119(19): 3927–3934

    Article  PubMed  Google Scholar 

  • Gonzalez-Billault C, Avila J, Cáceres A (2001). Evidence for the role of MAP1B in axon formation. Mol Biol Cell, 12(7): 2087–2098

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • González-Billault C, Del Río J A, Ureña J M, Jiménez-Mateos E M, Barallobre M J, Pascual M, Pujadas L, Simó S, Torre A L, Gavin R, Wandosell F, Soriano E, Avila J (2004). A role of MAP1B in Reelin-dependent neuronal migration. Cereb Cortex, 15(8): 1134–1145

    Article  PubMed  Google Scholar 

  • Goold R G, Gordon-Weeks P R (2001). Microtubule-associated protein 1B phosphorylation by glycogen synthase kinase 3beta is induced during PC12 cell differentiation. J Cell Sci, 114(Pt 23): 4273–4284

    PubMed  CAS  Google Scholar 

  • Goold R G, Gordon-Weeks P R (2005). The MAP kinase pathway is upstream of the activation of GSK3beta that enables it to phosphorylate MAP1B and contributes to the stimulation of axon growth. Mol Cell Neurosci, 28(3): 524–534

    Article  PubMed  CAS  Google Scholar 

  • Grimes C A, Jope R S (2001). The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Prog Neurobiol, 65(4): 391–426

    Article  PubMed  CAS  Google Scholar 

  • Guo W, Murthy A C, Zhang L, Johnson E B, Schaller E G, Allan A M, Zhao X (2011). Inhibition of GSK3 Improves Hippocampus-dependent Learning and Rescues Neurogenesis in a Mouse Model of Fragile X Syndrome. Hum Mol Genet

  • Hanks S K, Ryzhova L, Shin N Y, Brábek J (2003). Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility. Front Biosci, 8(1–3): d982–d996

    Article  PubMed  CAS  Google Scholar 

  • Hartigan J A, Johnson G V (1999). Transient increases in intracellular calcium result in prolonged site-selective increases in Tau phosphorylation through a glycogen synthase kinase 3beta-dependent pathway. J Biol Chem, 274(30): 21395–21401

    Article  PubMed  CAS  Google Scholar 

  • Hartigan J A, Xiong W C, Johnson G V (2001). Glycogen synthase kinase 3beta is tyrosine phosphorylated by PYK2. Biochem Biophys Res Commun, 284(2): 485–489

    Article  PubMed  CAS  Google Scholar 

  • Hetman M, Cavanaugh J E, Kimelman D, Xia Z (2000). Role of glycogen synthase kinase-3beta in neuronal apoptosis induced by trophic withdrawal. J Neurosci, 20(7): 2567–2574

    PubMed  CAS  Google Scholar 

  • Hongisto V, Smeds N, Brecht S, Herdegen T, Courtney M J, Coffey E T (2003). Lithium blocks the c-Jun stress response and protects neurons via its action on glycogen synthase kinase 3. Mol Cell Biol, 23(17): 6027–6036

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hoshi M, Takashima A, Noguchi K, Murayama M, Sato M, Kondo S, Saitoh Y, Ishiguro K, Hoshino T, Imahori K (1996). Regulation of mitochondrial pyruvate dehydrogenase activity by tau protein kinase I/glycogen synthase kinase 3beta in brain. Proc Natl Acad Sci USA, 93(7): 2719–2723

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Huang W, Chang H Y, Fei T, Wu H, Chen Y G (2007). GSK3 beta mediates suppression of cyclin D2 expression by tumor suppressor PTEN. Oncogene, 26(17): 2471–2482

    Article  PubMed  CAS  Google Scholar 

  • Hur EM, Zhou F Q (2010). GSK3 signalling in neural development. Nat Rev Neurosci, 11(8): 539–551

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Ille F, Sommer L (2005). Wnt signaling: multiple functions in neural development. Cell Mol Life Sci, 62(10): 1100–1108

    Article  PubMed  CAS  Google Scholar 

  • Jiang H, Guo W, Liang X, Rao Y (2005). Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3beta and its upstream regulators. Cell, 120(1): 123–135

    PubMed  CAS  Google Scholar 

  • Jin L, Hu X, Feng L (2005). NT3 inhibits FGF2-induced neural progenitor cell proliferation via the PI3K/GSK3 pathway. J Neurochem, 93(5): 1251–1261

    Article  PubMed  CAS  Google Scholar 

  • Jope R S, Yuskaitis C J, Beurel E (2007). Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics. Neurochem Res, 32(4–5): 577–595

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kaytor M D, Orr H T (2002). The GSK3 beta signaling cascade and neurodegenerative disease. Curr Opin Neurobiol, 12(3): 275–278

    Article  PubMed  CAS  Google Scholar 

  • Ke Z, Liu Y, Wang X, Fan Z, Chen G, Xu M, Bower K A, Frank J A, Ou X, Shi X, Luo J (2011). Cyanidin-3-glucoside ameliorates ethanol neurotoxicity in the developing brain. J Neurosci Res, 89(10): 1676–1684

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Knoepfler P S, Kenney A M (2006). Neural precursor cycling at sonic speed: N-Myc pedals, GSK-3 brakes. Cell Cycle, 5(1): 47–52

    Article  PubMed  CAS  Google Scholar 

  • Koh S H, Lee Y B, Kim K S, Kim H J, Kim M, Lee Y J, Kim J, Lee KW, Kim S H (2005). Role of GSK-3beta activity in motor neuronal cell death induced by G93A or A4V mutant hSOD1 gene. Eur J Neurosci, 22(2): 301–309

    Article  PubMed  Google Scholar 

  • Lee K Y, Koh S H, Noh M Y, Park K W, Lee Y J, Kim S H (2007). Glycogen synthase kinase-3beta activity plays very important roles in determining the fate of oxidative stress-inflicted neuronal cells. Brain Res, 1129(1): 89–99

    Article  PubMed  CAS  Google Scholar 

  • Leroy K, Brion J P (1999). Developmental expression and localization of glycogen synthase kinase-3beta in rat brain. J Chem Neuroanat, 16(4): 279–293

    Article  PubMed  CAS  Google Scholar 

  • Lesort M, Jope R S, Johnson G V (1999). Insulin transiently increases tau phosphorylation: involvement of glycogen synthase kinase-3beta and Fyn tyrosine kinase. J Neurochem, 72(2): 576–584

    Article  PubMed  CAS  Google Scholar 

  • Linseman D A, Butts B D, Precht T A, Phelps R A, Le S S, Laessig T A, Bouchard R J, Florez-McClure M L, Heidenreich K A (2004). Glycogen synthase kinase-3beta phosphorylates Bax and promotes its mitochondrial localization during neuronal apoptosis. J Neurosci, 24(44): 9993–10002

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Chen G, Ma C, Bower K A, Xu M, Fan Z, Shi X, Ke Z J, Luo J (2009). Over-expression of GSK3 beta sensitizes neuronal cells to ethanol toxicity. J Neurosci Res, 87(12): 2793–2802

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Lossi L, Merighi A (2003). In vivo cellular and molecular mechanisms of neuronal apoptosis in the mammalian CNS. Prog Neurobiol, 69(5): 287–312

    Article  PubMed  CAS  Google Scholar 

  • Lucas J J, Hernández F, Gómez-Ramos P, Morán M A, Hen R, Avila J (2001). Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. EMBO J, 20(1): 27–39

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Luo J (2009a). Glycogen synthase kinase 3beta (GSK3beta) in tumorigenesis and cancer chemotherapy. Cancer Lett, 273(2): 194–200

    Article  PubMed  CAS  Google Scholar 

  • Luo J (2009b). GSK3beta in ethanol neurotoxicity. Mol Neurobiol, 40(2): 108–121

    Article  PubMed  CAS  Google Scholar 

  • Ma C, Wang J, Gao Y, Gao T W, Chen G, Bower K A, Odetallah M, Ding M, Ke Z, Luo J (2007). The role of glycogen synthase kinase 3beta in the transformation of epidermal cells. Cancer Res, 67(16): 7756–7764

    Article  PubMed  CAS  Google Scholar 

  • Madalosso S H, Pérez-Villegas E M, Armengol J A (2005). Naturally occurring neuronal death during the postnatal development of Purkinje cells and their precerebellar afferent projections. Brain Res Brain Res Rev, 49(2): 267–279

    Article  PubMed  CAS  Google Scholar 

  • Malaterre J, Ramsay R G, Mantamadiotis T (2007). Wnt-Frizzled signalling and the many paths to neural development and adult brain homeostasis. Front Biosci, 12(1): 492–506

    Article  PubMed  CAS  Google Scholar 

  • Manoukian A S, Woodgett J R (2002). Role of glycogen synthase kinase-3 in cancer: regulation by Wnts and other signaling pathways. Adv Cancer Res, 84: 203–229

    Article  PubMed  CAS  Google Scholar 

  • Maurer M H, Brömme J O, Feldmann R E Jr, Järve A, Sabouri F, Bürgers H F, Schelshorn DW, Krüger C, Schneider A, Kuschinsky W (2007). Glycogen synthase kinase 3beta (GSK3beta) regulates differentiation and proliferation in neural stem cells from the rat subventricular zone. J Proteome Res, 6(3): 1198–1208

    Article  PubMed  CAS  Google Scholar 

  • Meares G P, Jope R S (2007). Resolution of the nuclear localization mechanism of glycogen synthase kinase-3: functional effects in apoptosis. J Biol Chem, 282(23): 16989–17001

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Mishra R, Barthwal M K, Sondarva G, Rana B, Wong L, Chatterjee M, Woodgett J R, Rana A (2007). Glycogen synthase kinase-3beta induces neuronal cell death via direct phosphorylation of mixed lineage kinase 3. J Biol Chem, 282(42): 30393–30405

    Article  PubMed  CAS  Google Scholar 

  • Muñoz-Montaño J R, Lim F, Moreno F J, Avila J, Díaz-Nido J (1999). Glycogen synthase kinase-3 modulates neurite outgrowth in cultured neurons: possible implications for neurite pathology in Alzheimer’s disease. J Alzheimers Dis, 1(6): 361–378

    PubMed  Google Scholar 

  • Nedachi T, Kawai T, Matsuwaki T, Yamanouchi K, Nishihara M (2011). Progranulin enhances neural progenitor cell proliferation through glycogen synthase kinase 3β phosphorylation. Neuroscience, 185: 106–115

    Article  PubMed  CAS  Google Scholar 

  • Orme M H, Giannini A L, Vivanco M D, Kypta R M (2003). Glycogen synthase kinase-3 and Axin function in a beta-catenin-independent pathway that regulates neurite outgrowth in neuroblastoma cells. Mol Cell Neurosci, 24(3): 673–686

    Article  PubMed  CAS  Google Scholar 

  • Owen R, Gordon-Weeks P R (2003). Inhibition of glycogen synthase kinase 3beta in sensory neurons in culture alters filopodia dynamics and microtubule distribution in growth cones. Mol Cell Neurosci, 23(4): 626–637

    Article  PubMed  CAS  Google Scholar 

  • Pap M, Cooper G M (1998). Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-Kinase/Akt cell survival pathway. J Biol Chem, 273(32): 19929–19932

    Article  PubMed  CAS  Google Scholar 

  • Pap M, Cooper G M (2002). Role of translation initiation factor 2B in control of cell survival by the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3beta signaling pathway. Mol Cell Biol, 22(2): 578–586

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Patapoutian A, Reichardt L F (2000). Roles of Wnt proteins in neural development and maintenance. Curr Opin Neurobiol, 10(3): 392–399

    Article  PubMed  CAS  Google Scholar 

  • Saito M, Chakraborty G, Mao R F, Paik S M, Vadasz C, Saito M (2010). Tau phosphorylation and cleavage in ethanol-induced neurodegeneration in the developing mouse brain. Neurochem Res, 35(4): 651–659

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Sayas C L, Ariaens A, Ponsioen B, Moolenaar W H (2006). GSK-3 is activated by the tyrosine kinase Pyk2 during LPA1-mediated neurite retraction. Mol Biol Cell, 17(4): 1834–1844

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Seng S, Avraham H K, Jiang S, Venkatesh S, Avraham S (2006). KLHL1/MRP2 mediates neurite outgrowth in a glycogen synthase kinase 3beta-dependent manner. Mol Cell Biol, 26(22): 8371–8384

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Shimizu T, Kagawa T, Inoue T, Nonaka A, Takada S, Aburatani H, Taga T (2008). Stabilized beta-catenin functions through TCF/LEF proteins and the Notch/RBP-Jkappa complex to promote proliferation and suppress differentiation of neural precursor cells. Mol Cell Biol, 28(24): 7427–7441

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Song L, De Sarno P, Jope R S (2002). Central role of glycogen synthase kinase-3beta in endoplasmic reticulum stress-induced caspase-3 activation. J Biol Chem, 277(47): 44701–44708

    Article  PubMed  CAS  Google Scholar 

  • Spittaels K, Van den Haute C, Van Dorpe J, Geerts H, Mercken M, Bruynseels K, Lasrado R, Vandezande K, Laenen I, Boon T, Van Lint J, Vandenheede J, Moechars D, Loos R, Van Leuven F (2000). Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human fourrepeat tau transgenic mice. J Biol Chem, 275(52): 41340–41349

    Article  PubMed  CAS  Google Scholar 

  • Spittaels K, Van den Haute C, Van Dorpe J, Terwel D, Vandezande K, Lasrado R, Bruynseels K, Irizarry M, Verhoye M, Van Lint J, Vandenheede J R, Ashton D, Mercken M, Loos R, Hyman B, Van der Linden A, Geerts H, Van Leuven F (2002). Neonatal neuronal overexpression of glycogen synthase kinase-3 beta reduces brain size in transgenic mice. Neuroscience, 113(4): 797–808

    Article  PubMed  CAS  Google Scholar 

  • Sui Z, Sniderhan L F, Fan S, Kazmierczak K, Reisinger E, Kovács A D, Potash M J, Dewhurst S, Gelbard H A, Maggirwar S B (2006). Human immunodeficiency virus-encoded Tat activates glycogen synthase kinase-3beta to antagonize nuclear factor-kappaB survival pathway in neurons. Eur J Neurosci, 23(10): 2623–2634

    Article  PubMed  Google Scholar 

  • Sun Y, Kim N H, Yang H, Kim S H, Huh S O (2011). Lysophosphatidic acid induces neurite retraction in differentiated neuroblastoma cells via GSK-3β activation. Mol Cells, 31(5): 483–489

    Article  PubMed  CAS  Google Scholar 

  • Takadera T, Fujibayashi M, Kaniyu H, Sakota N, Ohyashiki T (2007). Caspase-dependent apoptosis induced by thapsigargin was prevented by glycogen synthase kinase-3 inhibitors in cultured rat cortical neurons. Neurochem Res, 32(8): 1336–1342

    Article  PubMed  CAS  Google Scholar 

  • Takahashi M, Tomizawa K, Ishiguro K (2000). Distribution of tau protein kinase I/glycogen synthase kinase-3beta, phosphatases 2A and 2B, and phosphorylated tau in the developing rat brain. Brain Res, 857(1–2): 193–206

    Article  PubMed  CAS  Google Scholar 

  • Takahashi M, Yasutake K, Tomizawa K (1999). Lithium inhibits neurite growth and tau protein kinase I/glycogen synthase kinase-3betadependent phosphorylation of juvenile tau in cultured hippocampal neurons. J Neurochem, 73(5): 2073–2083

    PubMed  CAS  Google Scholar 

  • Takahashi-Yanaga F, Shiraishi F, Hirata M, Miwa Y, Morimoto S, Sasaguri T (2004). Glycogen synthase kinase-3beta is tyrosinephosphorylated by MEK1 in human skin fibroblasts. Biochem Biophys Res Commun, 316(2): 411–415

    Article  PubMed  CAS  Google Scholar 

  • Tong N, Sanchez J F, Maggirwar S B, Ramirez S H, Guo H, Dewhurst S, Gelbard H A (2001). Activation of glycogen synthase kinase 3 beta (GSK-3beta) by platelet activating factor mediates migration and cell death in cerebellar granule neurons. Eur J Neurosci, 13(10): 1913–1922

    Article  PubMed  CAS  Google Scholar 

  • Trivedi N, Marsh P, Goold R G, Wood-Kaczmar A, Gordon-Weeks P R (2005). Glycogen synthase kinase-3beta phosphorylation of MAP1B at Ser1260 and Thr1265 is spatially restricted to growing axons. J Cell Sci, 118(5): 993–1005

    Article  PubMed  CAS  Google Scholar 

  • Tsukane M, Yoshizaki C, Yamauchi T (2007). Development and specific induction of apoptosis of cultured cell models overexpressing human tau during neural differentiation: Implication in Alzheimer’s disease. Anal Biochem, 360(1): 114–122

    Article  PubMed  CAS  Google Scholar 

  • Valerio A, Ghisi V, Dossena M, Tonello C, Giordano A, Frontini A, Ferrario M, Pizzi M, Spano P, Carruba M O, Nisoli E (2006). Leptin increases axonal growth cone size in developing mouse cortical neurons by convergent signals inactivating glycogen synthase kinase-3beta. J Biol Chem, 281(18): 12950–12958

    Article  PubMed  CAS  Google Scholar 

  • Vohra B P, Fu M, Heuckeroth R O (2007). Protein kinase Czeta and glycogen synthase kinase-3beta control neuronal polarity in developing rodent enteric neurons, whereas SMAD specific E3 ubiquitin protein ligase 1 promotes neurite growth but does not influence polarity. J Neurosci, 27(35): 9458–9468

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Wang H Y, Juo L I, Lin Y T, Hsiao M, Lin J T, Tsai C H, Tzeng Y H, Chuang Y C, Chang N S, Yang C N, Lu P J (2011). WW domain-containing oxidoreductase promotes neuronal differentiation via negative regulation of glycogen synthase kinase 3β. Cell Death Differ, Online Available December 23, 2011

    Google Scholar 

  • Watcharasit P, Bijur G N, Song L, Zhu J, Chen X, Jope R S (2003). Glycogen synthase kinase-3beta (GSK3beta) binds to and promotes the actions of p53. J Biol Chem, 278(49): 48872–48879

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Woodgett J R (1990). Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J, 9(8): 2431–2438

    PubMed  CAS  PubMed Central  Google Scholar 

  • Yeste-Velasco M, Folch J, Trullàs R, Abad M A, Enguita M, Pallàs M, Camins A (2007). Glycogen synthase kinase-3 is involved in the regulation of the cell cycle in cerebellar granule cells. Neuropharmacology, 53(2): 295–307

    Article  PubMed  CAS  Google Scholar 

  • Yoshimura T, Kawano Y, Arimura N, Kawabata S, Kikuchi A, Kaibuchi K (2005). GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Cell, 120(1): 137–149

    Article  PubMed  CAS  Google Scholar 

  • Yuskaitis C J, Jope R S (2009). Glycogen synthase kinase-3 regulates microglial migration, inflammation, and inflammation-induced neurotoxicity. Cell Signal, 21(2): 264–273

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Zhang W, Smith A, Liu J P, Cheung N S, Zhou S, Liu K, Li Q T, Duan W (2009). GSK3beta modulates PACAP-induced neuritogenesis in PC12 cells by acting downstream of Rap1 in a caveolae-dependent manner. Cell Signal, 21(2): 237–245

    Article  PubMed  CAS  Google Scholar 

  • Zhou F, Zhang L, Wang A, Song B, Gong K, Zhang L, Hu M, Zhang X, Zhao N, Gong Y (2008). The association of GSK3 beta with E2F1 facilitates nerve growth factor-induced neural cell differentiation. J Biol Chem, 283(21): 14506–14515

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY, 40536, USA

    Jia Luo

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Luo, J. The role of GSK3beta in the development of the central nervous system. Front. Biol. 7, 212–220 (2012). https://doi.org/10.1007/s11515-012-1222-2

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  • DOI: https://doi.org/10.1007/s11515-012-1222-2

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