Skip to main content
SpringerLink
Log in

Glycogen Synthase Kinase-3 in Neurological Diseases

  • Protocol
  • First Online:
Protein Kinase Technologies

Part of the book series: Neuromethods ((NM,volume 68))

  • 1025 Accesses

Abstract

Glycogen synthase kinase-3 (GSK-3) occupies an unusual niche in cellular regulation via its negative regulation of a series of important cellular target proteins coupled with its own sensitivity to several major signaling pathways including the Wnt, Notch, Hedgehog, and insulin systems. This protein kinase thus has multiple physiological functions depending on the cell or tissue type. Mouse genetic models in which the two mammalian isoforms (known as GSK-3a and GSK-3b) have been globally or tissue-specifically inactivated or activated have revealed roles in behavior, neurodegenerative diseases, and cognition. The activity of the protein kinase is also influenced directly or indirectly by a series of neuroactive drugs including lithium and psychotropic agents. In this review, we describe the modes of regulation, the molecular targets lying downstream and the association of dysfunction of GSK-3 in various neurological disorders including bipolar disorder, schizophrenia, and neurodegeneration as well as discuss possible strategies that may target GSK-3 for therapeutic benefit.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kannan N, Neuwald AF (2004) Evolutionary constraints associated with functional specificity of the CMGC protein kinases MAPK, CDK, GSK, SRPK, DYRK, and CK2alpha. Protein Sci 13(8):2059–2077

    PubMed  CAS  Google Scholar 

  2. Embi N, Rylatt DB, Cohen P (1980) Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem/FEBS 107(2):519–527

    CAS  Google Scholar 

  3. Rylatt DB, Aitken A, Bilham T, Condon GD, Embi N, Cohen P (1980) Glycogen synthase from rabbit skeletal muscle. Amino acid sequence at the sites phosphorylated by glycogen synthase kinase-3, and extension of the N-terminal sequence containing the site phosphorylated by phosphorylase kinase. Eur J Biochem/FEBS 107(2):529–537

    CAS  Google Scholar 

  4. Vandenheede JR, Yang SD, Goris J, Merlevede W (1980) ATP x Mg-dependent protein phosphatase from rabbit skeletal muscle. II. Purification of the activating factor and its characterization as a bifunctional protein also displaying synthase kinase activity. J Biol chem 255(24):11768–11774

    PubMed  CAS  Google Scholar 

  5. Larner J (1972) Insulin and glycogen synthase. Diabetes 21(2 Suppl):428–438

    PubMed  CAS  Google Scholar 

  6. Rosell-Perez M, Larner J (1964) Studies on Udpg: alpha-1.4-glucan alpha-4-glucosyltransferase. Vi. Specificity and structural requirements for the activator of the D form of the dog muscle enzyme. Biochemistry 3:773–778

    PubMed  CAS  Google Scholar 

  7. Schlender KK, Wei SH, Villar-Palasi C (1969) UDP-glucose:glycogen alpha-4-glucosyltransferase I kinase activity of purified muscle protein kinase. Cyclic nucleotide specificity. Biochim Biophys Acta 191(2):272–278

    PubMed  CAS  Google Scholar 

  8. Roach PJ, DePaoli-Roach AA, Larner J (1978) Ca2+-stimulated phosphorylation of muscle glycogen synthase by phosphorylase b kinase. J Cyclic Nucleotide Res 4(4):245–257

    PubMed  CAS  Google Scholar 

  9. Embi N, Rylatt DB, Cohen P (1979) Glycogen synthase kinase-2 and phosphorylase kinase are the same enzyme. Eur J Biochem/FEBS 100(2):339–347

    CAS  Google Scholar 

  10. DePaoli-Roach AA, Roach PJ, Larner J (1979) Rabbit skeletal muscle phosphorylase kinase. Comparison of glycogen synthase and phosphorylase as substrates. J Biol chem 254(10):4212–4219

    PubMed  CAS  Google Scholar 

  11. Soderling TR, Srivastava AK, Bass MA, Khatra BS (1979) Phosphorylation and inactivation of glycogen synthase by phosphorylase kinase. Proc Natl Acad Sci U S A 76(6):2536–2540

    PubMed  CAS  Google Scholar 

  12. Parker PJ, Caudwell FB, Cohen P (1983) Glycogen synthase from rabbit skeletal muscle; effect of insulin on the state of phosphorylation of the seven phosphoserine residues in vivo. Eur J Biochem/FEBS 130(1):227–234

    CAS  Google Scholar 

  13. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA (1995) Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378(6559):785–789

    PubMed  CAS  Google Scholar 

  14. Welsh GI, Proud CG (1993) Glycogen synthase kinase-3 is rapidly inactivated in response to insulin and phosphorylates eukaryotic initiation factor eIF-2B. Biochem J 294(Pt 3): 625–629

    PubMed  CAS  Google Scholar 

  15. Welsh GI, Miller CM, Loughlin AJ, Price NT, Proud CG (1998) Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin. FEBS Lett 421(2):125–130

    PubMed  CAS  Google Scholar 

  16. Siegfried E, Perkins LA, Capaci TM, Perrimon N (1990) Putative protein kinase product of the Drosophila segment-polarity gene zeste-white3. Nature 345(6278):825–829

    PubMed  CAS  Google Scholar 

  17. Bourouis M, Moore P, Ruel L, Grau Y, Heitzler P, Simpson P (1990) An early embryonic product of the gene shaggy encodes a serine/threonine protein kinase related to the CDC28/cdc2+ subfamily. EMBO J 9(9): 2877–2884

    PubMed  CAS  Google Scholar 

  18. Siegfried E, Chou TB, Perrimon N (1992) wingless signaling acts through zeste-white 3, the Drosophila homolog of glycogen synthase kinase-3, to regulate engrailed and establish cell fate. Cell 71(7):1167–1179

    PubMed  CAS  Google Scholar 

  19. Pierce SB, Kimelman D (1995) Regulation of Spemann organizer formation by the intracellular kinase Xgsk-3. Development 121(3):755–765

    PubMed  CAS  Google Scholar 

  20. He X, Saint-Jeannet JP, Woodgett JR, Varmus HE, Dawid IB (1995) Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos. Nature 374(6523):617–622

    PubMed  CAS  Google Scholar 

  21. Kao KR, Masui Y, Elinson RP (1986) Lithium-induced respecification of pattern in Xenopus laevis embryos. Nature 322(6077):371–373

    PubMed  CAS  Google Scholar 

  22. Klein PS, Melton DA (1996) A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A 93(16): 8455–8459

    PubMed  CAS  Google Scholar 

  23. Stambolic V, Ruel L, Woodgett JR (1996) Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol 6(12):1664–1668

    PubMed  CAS  Google Scholar 

  24. Ali A, Hoeflich KP, Woodgett JR (2001) Glycogen synthase kinase-3: properties, functions, and regulation. Chem Rev 101(8):2527–2540

    PubMed  CAS  Google Scholar 

  25. Woodgett JR (1991) cDNA cloning and properties of glycogen synthase kinase-3. Methods Enzymol 200:564–577

    PubMed  CAS  Google Scholar 

  26. Ruel L, Bourouis M, Heitzler P, Pantesco V, Simpson P (1993) Drosophila shaggy kinase and rat glycogen synthase kinase-3 have conserved activities and act downstream of Notch. Nature 362(6420):557–560

    PubMed  CAS  Google Scholar 

  27. Kassir Y, Rubin-Bejerano I, Mandel-Gutfreund Y (2006) The Saccharomyces cerevisiae GSK-3 beta homologs. Curr Drug Targets 7(11):1455–1465

    PubMed  CAS  Google Scholar 

  28. Alon LT, Pietrokovski S, Barkan S, Avrahami L, Kaidanovich-Beilin O, Woodgett JR, Barnea A, Eldar-Finkelman H (2011) Selective loss of glycogen synthase kinase-3alpha in birds reveals distinct roles for GSK-3 isozymes in tau phosphorylation. FEBS Lett 585(8):1158–1162

    PubMed  CAS  Google Scholar 

  29. Hemmings BA, Aitken A, Cohen P, Rymond M, Hofmann F (1982) Phosphorylation of the type-II regulatory subunit of cyclic-AMP-dependent protein kinase by glycogen synthase kinase 3 and glycogen synthase kinase 5. Eur J Biochem/FEBS 127(3):473–481

    CAS  Google Scholar 

  30. Woodgett JR, Cohen P (1984) Multisite phosphorylation of glycogen synthase. Molecular basis for the substrate specificity of glycogen synthase kinase-3 and casein kinase-II (glycogen synthase kinase-5). Biochim Biophys Acta 788(3):339–347

    PubMed  CAS  Google Scholar 

  31. Tung HY, Reed LJ (1989) Purification and characterization of protein phosphatase 1I activating kinase from bovine brain cytosolic and particulate fractions. J Biol Chem 264(5):2985–2990

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  33. Dajani R, Fraser E, Roe SM, Young N, Good V, Dale TC, Pearl LH (2001) Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell 105(6):721–732

    PubMed  CAS  Google Scholar 

  34. MacAulay K, Doble BW, Patel S, Hansotia T, Sinclair EM, Drucker DJ, Nagy A, Woodgett JR (2007) Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism. Cell Metab 6(4):329–337

    PubMed  CAS  Google Scholar 

  35. Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR (2000) Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature 406(6791):86–90

    PubMed  CAS  Google Scholar 

  36. Perez-Costas E, Gandy JC, Melendez-Ferro M, Roberts RC, Bijur GN (2010) Light and electron microscopy study of glycogen synthase kinase-3beta in the mouse brain. PLoS One 5(1):e8911

    PubMed  Google Scholar 

  37. Yao HB, Shaw PC, Wong CC, Wan DC (2002) Expression of glycogen synthase kinase-3 isoforms in mouse tissues and their transcription in the brain. J Chem Neuroanat 23(4):291–297

    PubMed  CAS  Google Scholar 

  38. Ferrer I, Barrachina M, Puig B (2002) Glycogen synthase kinase-3 is associated with neuronal and glial hyperphosphorylated tau deposits in Alzheimer’s disease, Pick’s disease, progressive supranuclear palsy and corticobasal degeneration. Acta Neuropathol 104(6):583–591

    PubMed  CAS  Google Scholar 

  39. Pandey GN, Dwivedi Y, Rizavi HS, Teppen T, Gaszner GL, Roberts RC, Conley RR (2009) GSK-3beta gene expression in human postmortem brain: regional distribution, effects of age and suicide. Neurochem Res 34(2):274–285

    PubMed  CAS  Google Scholar 

  40. Hanks SK, Hunter T (1995) Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J 9(8):576–596

    PubMed  CAS  Google Scholar 

  41. Mukai F, Ishiguro K, Sano Y, Fujita SC (2002) Alternative splicing isoform of tau protein kinase I/glycogen synthase kinase 3beta. J Neurochem 81(5):1073–1083

    PubMed  CAS  Google Scholar 

  42. Lau KF, Miller CC, Anderton BH, Shaw PC (1999) Expression analysis of glycogen synthase kinase-3 in human tissues. J Pept Res 54(1):85–91

    PubMed  CAS  Google Scholar 

  43. Schaffer B, Wiedau-Pazos M, Geschwind DH (2003) Gene structure and alternative splicing of glycogen synthase kinase 3 beta (GSK-3beta) in neural and non-neural tissues. Gene 302(1–2):73–81

    PubMed  CAS  Google Scholar 

  44. Kwok JB, Hallupp M, Loy CT, Chan DK, Woo J, Mellick GD, Buchanan DD, Silburn PA, Halliday GM, Schofield PR (2005) GSK3B polymorphisms alter transcription and splicing in Parkinson’s disease. Ann Neurol 58(6):829–839

    PubMed  CAS  Google Scholar 

  45. Takahashi M, Tomizawa K, Kato R, Sato K, Uchida T, Fujita SC, Imahori K (1994) Localization and developmental changes of tau protein kinase I/glycogen synthase kinase-3 beta in rat brain. J Neurochem 63(1):245–255

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  47. Wood-Kaczmar A, Kraus M, Ishiguro K, Philpott KL, Gordon-Weeks PR (2009) An alternatively spliced form of glycogen synthase kinase-3beta is targeted to growing neurites and growth cones. Mol Cell Neurosci 42(3):184–194

    PubMed  CAS  Google Scholar 

  48. Bijur GN, Jope RS (2001) Proapoptotic stimuli induce nuclear accumulation of glycogen synthase kinase-3 beta. J Biol Chem 276(40):37436–37442

    PubMed  CAS  Google Scholar 

  49. Bijur GN, Jope RS (2003) Glycogen synthase kinase-3 beta is highly activated in nuclei and mitochondria. Neuroreport 14(18): 2415–2419

    PubMed  CAS  Google Scholar 

  50. Goold RG, Gordon-Weeks PR (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 

  51. Stambolic V, Woodgett JR (1994) Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation. Biochem J 303(Pt 3):701–704

    PubMed  CAS  Google Scholar 

  52. Sutherland C, Leighton IA, Cohen P (1993) Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new kinase connections in insulin and growth-factor signalling. Biochem J 296(Pt 1):15–19

    PubMed  CAS  Google Scholar 

  53. Woodgett JR (1994) Regulation and functions of the glycogen synthase kinase-3 subfamily. Semin Cancer Biol 5(4):269–275

    PubMed  CAS  Google Scholar 

  54. Kockeritz L, Doble B, Patel S, Woodgett JR (2006) Glycogen synthase kinase-3 – an overview of an over-achieving protein kinase. Curr Drug Targets 7(11):1377–1388

    PubMed  CAS  Google Scholar 

  55. Doble BW, Woodgett JR (2003) GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci 116(Pt 7):1175–1186

    PubMed  CAS  Google Scholar 

  56. Frame S, Cohen P (2001) GSK3 takes centre stage more than 20 years after its discovery. Biochem J 359(Pt 1):1–16

    PubMed  CAS  Google Scholar 

  57. Jope RS, Johnson GV (2004) The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci 29(2):95–102

    PubMed  CAS  Google Scholar 

  58. McNeill H, Woodgett JR (2010) When pathways collide: collaboration and connivance among signalling proteins in development. Nat Rev Mol Cell Biol 11(6):404–413

    PubMed  CAS  Google Scholar 

  59. Hughes K, Nikolakaki E, Plyte SE, Totty NF, Woodgett JR (1993) Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation. EMBO J 12(2):803–808

    PubMed  CAS  Google Scholar 

  60. Lochhead PA, Kinstrie R, Sibbet G, Rawjee T, Morrice N, Cleghon V (2006) A chaperone-dependent GSK3beta transitional intermediate mediates activation-loop autophosphorylation. Mol Cell 24(4):627–633

    PubMed  CAS  Google Scholar 

  61. Sutherland C, Cohen P (1994) The alpha-isoform of glycogen synthase kinase-3 from rabbit skeletal muscle is inactivated by p70 S6 kinase or MAP kinase-activated protein kinase-1 in vitro. FEBS Lett 338(1):37–42

    PubMed  CAS  Google Scholar 

  62. Bax B, Carter PS, Lewis C, Guy AR, Bridges A, Tanner R, Pettman G, Mannix C, Culbert AA, Brown MJ, Smith DG, Reith AD (2001) The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation. Structure 9(12):1143–1152

    PubMed  CAS  Google Scholar 

  63. Wang X, Liu XT, Dunn R, Ohl DA, Smith GD (2003) Glycogen synthase kinase-3 regulates mouse oocyte homologue segregation. Mol Reprod Dev 64(1):96–105

    PubMed  Google Scholar 

  64. 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(Pt 1):249–255

    PubMed  CAS  Google Scholar 

  65. Kim L, Liu J, Kimmel AR (1999) The novel tyrosine kinase ZAK1 activates GSK3 to direct cell fate specification. Cell 99(4):399–408

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  67. Plyte SE, O’Donovan E, Woodgett JR, Harwood AJ (1999) Glycogen synthase kinase-3 (GSK-3) is regulated during Dictyostelium development via the serpentine receptor cAR3. Development 126(2):325–333

    PubMed  CAS  Google Scholar 

  68. Kim L, Harwood A, Kimmel AR (2002) Receptor-dependent and tyrosine phosphatase-mediated inhibition of GSK3 regulates cell fate choice. Dev Cell 3(4):523–532

    PubMed  Google Scholar 

  69. Lochhead PA, Sibbet G, Morrice N, Cleghon V (2005) Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs. Cell 121(6):925–936

    PubMed  CAS  Google Scholar 

  70. Zhang F, Phiel CJ, Spece L, Gurvich N, Klein PS (2003) Inhibitory phosphorylation of glycogen synthase kinase-3 (GSK-3) in response to lithium. Evidence for autoregulation of GSK-3. J Biol Chem 278(35):33067–33077

    PubMed  CAS  Google Scholar 

  71. Grimes CA, Jope RS (2001) CREB DNA binding activity is inhibited by glycogen synthase kinase-3 beta and facilitated by lithium. J Neurochem 78(6):1219–1232

    PubMed  CAS  Google Scholar 

  72. Frame S, Cohen P, Biondi RM (2001) A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation. Mol Cell 7(6):1321–1327

    PubMed  CAS  Google Scholar 

  73. Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P, Hemmings BA (1996) Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 15(23):6541–6551

    PubMed  CAS  Google Scholar 

  74. Li M, Wang X, Meintzer MK, Laessig T, Birnbaum MJ, Heidenreich KA (2000) Cyclic AMP promotes neuronal survival by phosphorylation of glycogen synthase kinase 3beta. Mol Cell Biol 20(24):9356–9363

    PubMed  CAS  Google Scholar 

  75. Svenningsson P, Tzavara ET, Carruthers R, Rachleff I, Wattler S, Nehls M, McKinzie DL, Fienberg AA, Nomikos GG, Greengard P (2003) Diverse psychotomimetics act through a common signaling pathway. Science 302(5649):1412–1415

    PubMed  CAS  Google Scholar 

  76. Eldar-Finkelman H, Krebs EG (1997) Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action. Proc Natl Acad Sci U S A 94(18):9660–9664

    PubMed  CAS  Google Scholar 

  77. Sharfi H, Eldar-Finkelman H (2008) Sequential phosphorylation of insulin receptor substrate-2 by glycogen synthase kinase-3 and c-Jun NH2-terminal kinase plays a role in hepatic insulin signaling. Am J Physiol 294(2):E307–E315

    CAS  Google Scholar 

  78. Shaw M, Cohen P (1999) Role of protein kinase B and the MAP kinase cascade in mediating the EGF-dependent inhibition of glycogen synthase kinase 3 in Swiss 3T3 cells. FEBS Lett 461(1–2):120–124

    PubMed  CAS  Google Scholar 

  79. Brady MJ, Bourbonais FJ, Saltiel AR (1998) The activation of glycogen synthase by insulin switches from kinase inhibition to phosphatase activation during adipogenesis in 3T3-L1 cells. J Biol Chem 273(23):14063–14066

    PubMed  CAS  Google Scholar 

  80. Saito Y, Vandenheede JR, Cohen P (1994) The mechanism by which epidermal growth factor inhibits glycogen synthase kinase 3 in A431 cells. Biochem J 303(Pt 1):27–31

    PubMed  CAS  Google Scholar 

  81. Armstrong JL, Bonavaud SM, Toole BJ, Yeaman SJ (2001) Regulation of glycogen synthesis by amino acids in cultured human muscle cells. J Biol Chem 276(2):952–956

    PubMed  CAS  Google Scholar 

  82. Krause U, Bertrand L, Maisin L, Rosa M, Hue L (2002) Signalling pathways and combinatory effects of insulin and amino acids in isolated rat hepatocytes. Eur J Biochem/FEBS 269(15):3742–3750

    CAS  Google Scholar 

  83. Terruzzi I, Allibardi S, Bendinelli P, Maroni P, Piccoletti R, Vesco F, Samaja M, Luzi L (2002) Amino acid- and lipid-induced insulin resistance in rat heart: molecular mechanisms. Mol Cell Endocrinol 190(1–2):135–145

    PubMed  CAS  Google Scholar 

  84. Fang X, Yu SX, Lu Y, Bast RC Jr, Woodgett JR, Mills GB (2000) Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. Proc Natl Acad Sci U S A 97(22):11960–11965

    PubMed  CAS  Google Scholar 

  85. Tanji C, Yamamoto H, Yorioka N, Kohno N, Kikuchi K, Kikuchi A (2002) A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta. J Biol Chem 277(40): 36955–36961

    PubMed  CAS  Google Scholar 

  86. Ballou LM, Tian PY, Lin HY, Jiang YP, Lin RZ (2001) Dual regulation of glycogen synthase kinase-3beta by the alpha1A-­adrenergic receptor. J Biol Chem 276(44):40910–40916

    PubMed  CAS  Google Scholar 

  87. Fang X, Yu S, Tanyi JL, Lu Y, Woodgett JR, Mills GB (2002) Convergence of multiple signaling cascades at glycogen synthase kinase 3: Edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase C-dependent intracellular pathway. Mol Cell Biol 22(7):2099–2110

    PubMed  CAS  Google Scholar 

  88. Goode N, Hughes K, Woodgett JR, Parker PJ (1992) Differential regulation of glycogen synthase kinase-3 beta by protein kinase C isotypes. J Biol Chem 267(24):16878–16882

    PubMed  CAS  Google Scholar 

  89. Lee E, Salic A, Kruger R, Heinrich R, Kirschner MW (2003) The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway. PLoS Biol 1(1):E10

    PubMed  Google Scholar 

  90. Benchabane H, Hughes EG, Takacs CM, Baird JR, Ahmed Y (2008) Adenomatous polyposis coli is present near the minimal level required for accurate graded responses to the Wingless morphogen. Development 135(5): 963–971

    PubMed  CAS  Google Scholar 

  91. Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL III, Lee JJ, Tilghman SM, Gumbiner BM, Costantini F (1997) The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell 90(1):181–192

    PubMed  CAS  Google Scholar 

  92. Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, Kikuchi A (1998) Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J 17(5):1371–1384

    PubMed  CAS  Google Scholar 

  93. Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P (1998) Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr Biol 8(10):573–581

    PubMed  CAS  Google Scholar 

  94. Amit S, Hatzubai A, Birman Y, Andersen JS, Ben-Shushan E, Mann M, Ben-Neriah Y, Alkalay I (2002) Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev 16(9):1066–1076

    PubMed  CAS  Google Scholar 

  95. Hagen T, Vidal-Puig A (2002) Characterisation of the phosphorylation of beta-catenin at the GSK-3 priming site Ser45. Biochem Biophys Res Commun 294(2):324–328

    PubMed  CAS  Google Scholar 

  96. Hagen T, Di Daniel E, Culbert AA, Reith AD (2002) Expression and characterization of GSK-3 mutants and their effect on beta-catenin phosphorylation in intact cells. J Biol Chem 277(26):23330–23335

    PubMed  CAS  Google Scholar 

  97. Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X (2002) Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108(6):837–847

    PubMed  CAS  Google Scholar 

  98. Sakanaka C (2002) Phosphorylation and regulation of beta-catenin by casein kinase I epsilon. J Biochem 132(5):697–703

    PubMed  CAS  Google Scholar 

  99. Yanagawa S, Matsuda Y, Lee JS, Matsubayashi H, Sese S, Kadowaki T, Ishimoto A (2002) Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila. EMBO J 21(7):1733–1742

    PubMed  CAS  Google Scholar 

  100. Aberle H, Bauer A, Stappert J, Kispert A, Kemler R (1997) beta-catenin is a target for the ubiquitin-proteasome pathway. EMBO J 16(13):3797–3804

    PubMed  CAS  Google Scholar 

  101. Miller JR (2002) The Wnts. Genome Biol 3(1):REVIEWS3001

    PubMed  Google Scholar 

  102. Polakis P (2000) Wnt signaling and cancer. Genes Dev 14(15):1837–1851

    PubMed  CAS  Google Scholar 

  103. Smalley MJ, Dale TC (1999) Wnt signalling in mammalian development and cancer. Cancer Metastasis Rev 18(2):215–230

    PubMed  CAS  Google Scholar 

  104. Mi K, Dolan PJ, Johnson GV (2006) The low density lipoprotein receptor-related protein 6 interacts with glycogen synthase kinase 3 and attenuates activity. J Biol Chem 281(8): 4787–4794

    PubMed  CAS  Google Scholar 

  105. Zeng X, Huang H, Tamai K, Zhang X, Harada Y, Yokota C, Almeida K, Wang J, Doble B, Woodgett J, Wynshaw-Boris A, Hsieh JC, He X (2008) Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions. Development 135(2):367–375

    PubMed  CAS  Google Scholar 

  106. Niehrs C, Shen J (2010) Regulation of Lrp6 phosphorylation. Cell Mol Life Sci 67(15):2551–2562

    PubMed  CAS  Google Scholar 

  107. Bilic J, Huang YL, Davidson G, Zimmermann T, Cruciat CM, Bienz M, Niehrs C (2007) Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation. Science 316(5831):1619–1622

    PubMed  CAS  Google Scholar 

  108. Blitzer JT, Nusse R (2006) A critical role for endocytosis in Wnt signaling. BMC Cell Biol 7:28

    PubMed  Google Scholar 

  109. Yamamoto H, Komekado H, Kikuchi A (2006) Caveolin is necessary for Wnt-3a-dependent internalization of LRP6 and accumulation of beta-catenin. Dev Cell 11(2):213–223

    PubMed  CAS  Google Scholar 

  110. Jho E, Lomvardas S, Costantini F (1999) A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression. Biochem Biophys Res Commun 266(1):28–35

    PubMed  CAS  Google Scholar 

  111. Yamamoto H, Kishida S, Kishida M, Ikeda S, Takada S, Kikuchi A (1999) Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability. J Biol Chem 274(16):10681–10684

    PubMed  CAS  Google Scholar 

  112. Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P (1996) Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science 272(5264):1023–1026

    PubMed  CAS  Google Scholar 

  113. Doble BW, Patel S, Wood GA, Kockeritz LK, Woodgett JR (2007) Functional redundancy of GSK-3alpha and GSK-3beta in Wnt/beta-catenin signaling shown by using an allelic series of embryonic stem cell lines. Dev Cell 12(6):957–971

    PubMed  CAS  Google Scholar 

  114. Kimelman D, Xu W (2006) beta-catenin destruction complex: insights and questions from a structural perspective. Oncogene 25(57):7482–7491

    PubMed  CAS  Google Scholar 

  115. Cselenyi CS, Jernigan KK, Tahinci E, Thorne CA, Lee LA, Lee E (2008) LRP6 transduces a canonical Wnt signal independently of Axin degradation by inhibiting GSK3’s phosphorylation of beta-catenin. Proc Natl Acad Sci U S A 105(23):8032–8037

    PubMed  CAS  Google Scholar 

  116. Piao S, Lee SH, Kim H, Yum S, Stamos JL, Xu Y, Lee SJ, Lee J, Oh S, Han JK, Park BJ, Weis WI, Ha NC (2008) Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling. PLoS One 3(12):e4046

    PubMed  Google Scholar 

  117. Wu G, Huang H, Garcia Abreu J, He X (2009) Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6. PLoS One 4(3):e4926

    PubMed  Google Scholar 

  118. Taelman VF, Dobrowolski R, Plouhinec JL, Fuentealba LC, Vorwald PP, Gumper I, Sabatini DD, De Robertis EM (2010) Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. Cell 143(7):1136–1148

    PubMed  CAS  Google Scholar 

  119. Thornton TM, Pedraza-Alva G, Deng B, Wood CD, Aronshtam A, Clements JL, Sabio G, Davis RJ, Matthews DE, Doble B, Rincon M (2008) Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation. Science 320(5876):667–670

    PubMed  CAS  Google Scholar 

  120. Cohen P (1982) The role of protein phosphorylation in neural and hormonal control of cellular activity. Nature 296(5858):613–620

    PubMed  CAS  Google Scholar 

  121. DePaoli-Roach AA, Ahmad Z, Camici M, Lawrence JC Jr, Roach PJ (1983) Multiple phosphorylation of rabbit skeletal muscle glycogen synthase. Evidence for interactions among phosphorylation sites and the resolution of electrophoretically distinct forms of the subunit. J Biol chem 258(17):10702–10709

    PubMed  CAS  Google Scholar 

  122. Picton C, Woodgett J, Hemmings B, Cohen P (1982) Multisite phosphorylation of glycogen synthase from rabbit skeletal muscle. Phosphorylation of site 5 by glycogen synthase kinase-5 (casein kinase-II) is a prerequisite for phosphorylation of sites 3 by glycogen synthase kinase-3. FEBS Lett 150(1):191–196

    PubMed  CAS  Google Scholar 

  123. ter Haar E, Coll JT, Austen DA, Hsiao HM, Swenson L, Jain J (2001) Structure of GSK3beta reveals a primed phosphorylation mechanism. Nat Struct Biol 8(7):593–596

    PubMed  Google Scholar 

  124. Fiol CJ, Mahrenholz AM, Wang Y, Roeske RW, Roach PJ (1987) Formation of protein kinase recognition sites by covalent modification of the substrate. Molecular mechanism for the synergistic action of casein kinase II and glycogen synthase kinase 3. J Biol Chem 62(29):14042–14048

    Google Scholar 

  125. Fiol CJ, Wang A, Roeske RW, Roach PJ (1990) Ordered multisite protein phosphorylation. Analysis of glycogen synthase kinase 3 action using model peptide substrates. J Biol Chem 265(11):6061–6065

    PubMed  CAS  Google Scholar 

  126. Cole AR, Causeret F, Yadirgi G, Hastie CJ, McLauchlan H, McManus EJ, Hernandez F, Eickholt BJ, Nikolic M, Sutherland C (2006) Distinct priming kinases contribute to differential regulation of collapsin response mediator proteins by glycogen synthase kinase-3 in vivo. J Biol Chem 281(24):16591–16598

    PubMed  CAS  Google Scholar 

  127. Li T, Hawkes C, Qureshi HY, Kar S, Paudel HK (2006) Cyclin-dependent protein kinase 5 primes microtubule-associated protein tau site-specifically for glycogen synthase kinase 3beta. Biochemistry 45(10):3134–3145

    PubMed  CAS  Google Scholar 

  128. Noble W, Olm V, Takata K, Casey E, Mary O, Meyerson J, Gaynor K, LaFrancois J, Wang L, Kondo T, Davies P, Burns M, Veeranna, Nixon R, Dickson D, Matsuoka Y, Ahlijanian M, Lau LF, Duff K (2003) Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron 38(4):555–565

    PubMed  CAS  Google Scholar 

  129. Sengupta A, Wu Q, Grundke-Iqbal I, Iqbal K, Singh TJ (1997) Potentiation of GSK-3-catalyzed Alzheimer-like phosphorylation of human tau by cdk5. Mol Cell Biochem 167(1–2):99–105

    PubMed  CAS  Google Scholar 

  130. Nishimura I, Yang Y, Lu B (2004) PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila. Cell 116(5):671–682

    PubMed  CAS  Google Scholar 

  131. Singh TJ, Zaidi T, Grundke-Iqbal I, Iqbal K (1995) Modulation of GSK-3-catalyzed phosphorylation of microtubule-associated protein tau by non-proline-dependent protein kinases. FEBS Lett 358(1):4–8

    PubMed  CAS  Google Scholar 

  132. Thomas GM, Frame S, Goedert M, Nathke I, Polakis P, Cohen P (1999) A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin. FEBS Lett 458(2):247–251

    PubMed  CAS  Google Scholar 

  133. Boyle WJ, Smeal T, Defize LH, Angel P, Woodgett JR, Karin M, Hunter T (1991) Activation of protein kinase C decreases phosphorylation of c-Jun at sites that negatively regulate its DNA-binding activity. Cell 64(3):573–584

    PubMed  CAS  Google Scholar 

  134. Saksela K, Makela TP, Hughes K, Woodgett JR, Alitalo K (1992) Activation of protein kinase C increases phosphorylation of the L-myc trans-activator domain at a GSK-3 target site. Oncogene 7(2):347–353

    PubMed  CAS  Google Scholar 

  135. Diehl JA, Cheng M, Roussel MF, Sherr CJ (1998) Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev 12(22):3499–3511

    PubMed  CAS  Google Scholar 

  136. Sears R, Nuckolls F, Haura E, Taya Y, Tamai K, Nevins JR (2000) Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability. Genes Dev 14(19):2501–2514

    PubMed  CAS  Google Scholar 

  137. Yost C, Torres M, Miller JR, Huang E, Kimelman D, Moon RT (1996) The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. Genes Dev 10(12):1443–1454

    PubMed  CAS  Google Scholar 

  138. Kang T, Wei Y, Honaker Y, Yamaguchi H, Appella E, Hung MC, Piwnica-Worms H (2008) GSK-3 beta targets Cdc25A for ubiquitin-mediated proteolysis, and GSK-3 beta inactivation correlates with Cdc25A overproduction in human cancers. Cancer Cell 13(1):36–47

    PubMed  CAS  Google Scholar 

  139. Ding Q, He X, Hsu JM, Xia W, Chen CT, Li LY, Lee DF, Liu JC, Zhong Q, Wang X, Hung MC (2007) Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Mol Cell Biol 27(11):4006–4017

    PubMed  CAS  Google Scholar 

  140. Fuentealba LC, Eivers E, Ikeda A, Hurtado C, Kuroda H, Pera EM, De Robertis EM (2007) Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal. Cell 131(5):980–993

    PubMed  CAS  Google Scholar 

  141. Kerkela R, Kockeritz L, Macaulay K, Zhou J, Doble BW, Beahm C, Greytak S, Woulfe K, Trivedi CM, Woodgett JR, Epstein JA, Force T, Huggins GS (2008) Deletion of GSK-3beta in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation. J Clin Invest 118(11): 3609–3618

    PubMed  CAS  Google Scholar 

  142. Kaidanovich-Beilin O, Lipina TV, Takao K, van Eede M, Hattori S, Laliberte C, Khan M, Okamoto K, Chambers JW, Fletcher PJ, MacAulay K, Doble BW, Henkelman M, Miyakawa T, Roder J, Woodgett JR (2009) Abnormalities in brain structure and behavior in GSK-3alpha mutant mice. Mol Brain 2:35

    PubMed  Google Scholar 

  143. Liang MH, Chuang DM (2006) Differential roles of glycogen synthase kinase-3 isoforms in the regulation of transcriptional activation. J Biol Chem 281(41):30479–30484

    PubMed  CAS  Google Scholar 

  144. Liang MH, Chuang DM (2007) Regulation and function of glycogen synthase kinase-3 isoforms in neuronal survival. J Biol Chem 282(6):3904–3917

    PubMed  CAS  Google Scholar 

  145. Wang QM, Park IK, Fiol CJ, Roach PJ, DePaoli-Roach AA (1994) Isoform differences in substrate recognition by glycogen synthase kinases 3 alpha and 3 beta in the phosphorylation of phosphatase inhibitor 2. Biochemistry 33(1):143–147

    PubMed  CAS  Google Scholar 

  146. Phiel CJ, Wilson CA, Lee VM, Klein PS (2003) GSK-3alpha regulates production of Alzheimer’s disease amyloid-beta peptides. Nature 423(6938):435–439

    PubMed  CAS  Google Scholar 

  147. Force T, Woodgett JR (2009) Unique and overlapping functions of GSK-3 isoforms in cell differentiation and proliferation and cardiovascular development. J Biol Chem 284(15):9643–9647

    PubMed  CAS  Google Scholar 

  148. Chen L, Salinas GD, Li X (2009) Regulation of serotonin 1B receptor by glycogen synthase kinase-3. Mol Pharmacol 76(6):1150–1161

    PubMed  CAS  Google Scholar 

  149. Lucas FR, Goold RG, Gordon-Weeks PR, Salinas PC (1998) Inhibition of GSK-3beta leading to the loss of phosphorylated MAP-1B is an early event in axonal remodelling induced by WNT-7a or lithium. J Cell Sci 111(Pt 10):1351–1361

    PubMed  CAS  Google Scholar 

  150. Lucas FR, Salinas PC (1997) WNT-7a induces axonal remodeling and increases synapsin I levels in cerebellar neurons. Dev Biol 192(1):31–44

    PubMed  CAS  Google Scholar 

  151. Eickholt BJ, Walsh FS, Doherty P (2002) An inactive pool of GSK-3 at the leading edge of growth cones is implicated in Semaphorin 3A signaling. J Cell Biol 157(2):211–217

    PubMed  CAS  Google Scholar 

  152. Packard M, Mathew D, Budnik V (2003) Wnts and TGF beta in synaptogenesis: old friends signalling at new places. Nat Rev 4(2):113–120

    CAS  Google Scholar 

  153. Guan RJ, Khatra BS, Cohlberg JA (1991) Phosphorylation of bovine neurofilament proteins by protein kinase FA (glycogen synthase kinase 3). J Biol Chem 266(13):8262–8267

    PubMed  CAS  Google Scholar 

  154. Berling B, Wille H, Roll B, Mandelkow EM, Garner C, Mandelkow E (1994) Phosphorylation of microtubule-associated proteins MAP2a, b and MAP2c at Ser136 by proline-directed kinases in vivo and in vitro. Eur J Cell Biol 64(1):120–130

    PubMed  CAS  Google Scholar 

  155. Guidato S, Tsai LH, Woodgett J, Miller CC (1996) Differential cellular phosphorylation of neurofilament heavy side-arms by glycogen synthase kinase-3 and cyclin-dependent kinase-5. J Neurochem 66(4):1698–1706

    PubMed  CAS  Google Scholar 

  156. Garcia-Perez J, Avila J, Diaz-Nido J (1998) Implication of cyclin-dependent kinases and glycogen synthase kinase 3 in the phosphorylation of microtubule-associated protein 1B in developing neuronal cells. J Neurosci Res 52(4):445–452

    PubMed  CAS  Google Scholar 

  157. Mackie K, Sorkin BC, Nairn AC, Greengard P, Edelman GM, Cunningham BA (1989) Identification of two protein kinases that phosphorylate the neural cell-adhesion molecule, N-CAM. J Neurosci 9(6):1883–1896

    PubMed  CAS  Google Scholar 

  158. 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 U S A 93(7):2719–2723

    PubMed  CAS  Google Scholar 

  159. Peineau S, Bradley C, Taghibiglou C, Doherty A, Bortolotto ZA, Wang YT, Collingridge GL (2008) The role of GSK-3 in synaptic plasticity. Br J Pharmacol 153(Suppl 1):S428–S437

    PubMed  CAS  Google Scholar 

  160. Peineau S, Nicolas CS, Bortolotto ZA, Bhat RV, Ryves WJ, Harwood AJ, Dournaud P, Fitzjohn SM, Collingridge GL (2009) A systematic investigation of the protein kinases involved in NMDA receptor-dependent LTD: evidence for a role of GSK-3 but not other serine/threonine kinases. Mol Brain 2(1):22

    PubMed  Google Scholar 

  161. Zhu LQ, Wang SH, Liu D, Yin YY, Tian Q, Wang XC, Wang Q, Chen JG, Wang JZ (2007) Activation of glycogen synthase kinase-3 inhibits long-term potentiation with synapse-associated impairments. J Neurosci 27(45):12211–12220

    PubMed  CAS  Google Scholar 

  162. Hooper C, Markevich V, Plattner F, Killick R, Schofield E, Engel T, Hernandez F, Anderton B, Rosenblum K, Bliss T, Cooke SF, Avila J, Lucas JJ, Giese KP, Stephenson J, Lovestone S (2007) Glycogen synthase kinase-3 inhibition is integral to long-term potentiation. Eur J Neurosci 25(1):81–86

    PubMed  Google Scholar 

  163. Beaulieu JM, Sotnikova TD, Yao WD, Kockeritz L, Woodgett JR, Gainetdinov RR, Caron MG (2004) Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proc Natl Acad Sci U S A 101(14):5099–5104

    PubMed  CAS  Google Scholar 

  164. Beaulieu JM, Zhang X, Rodriguiz RM, Sotnikova TD, Cools MJ, Wetsel WC, Gainetdinov RR, Caron MG (2008) Role of GSK3 beta in behavioral abnormalities induced by serotonin deficiency. Proc Natl Acad Sci U S A 105(4):1333–1338

    PubMed  CAS  Google Scholar 

  165. Li X, Zhu W, Roh MS, Friedman AB, Rosborough K, Jope RS (2004) In vivo regulation of glycogen synthase kinase-3beta (GSK3beta) by serotonergic activity in mouse brain. Neuropsychopharmacology 29(8):1426–1431

    PubMed  CAS  Google Scholar 

  166. Yin L, Wang J, Klein PS, Lazar MA (2006) Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock. Science 311(5763):1002–1005

    PubMed  CAS  Google Scholar 

  167. Iitaka C, Miyazaki K, Akaike T, Ishida N (2005) A role for glycogen synthase kinase-3beta in the mammalian circadian clock. J Biol Chem 280(33):29397–29402

    PubMed  CAS  Google Scholar 

  168. Hur EM, Zhou FQ (2010) GSK3 signalling in neural development. Nat Rev 11(8):539–551

    CAS  Google Scholar 

  169. Espinosa L, Ingles-Esteve J, Aguilera C, Bigas A (2003) Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways. J Biol Chem 278(34):32227–32235

    PubMed  CAS  Google Scholar 

  170. Uemura K, Kuzuya A, Shimozono Y, Aoyagi N, Ando K, Shimohama S, Kinoshita A (2007) GSK3beta activity modifies the localization and function of presenilin 1. J Biol Chem 282(21):15823–15832

    PubMed  CAS  Google Scholar 

  171. Jin YH, Kim H, Oh M, Ki H, Kim K (2009) Regulation of Notch1/NICD and Hes1 expressions by GSK-3alpha/beta. Mol Cells 27(1):15–19

    PubMed  CAS  Google Scholar 

  172. Kim WY, Wang X, Wu Y, Doble BW, Patel S, Woodgett JR, Snider WD (2009) GSK-3 is a master regulator of neural progenitor homeostasis. Nat Neurosci 12(11):1390–1397

    PubMed  CAS  Google Scholar 

  173. Wei W, Jin J, Schlisio S, Harper JW, Kaelin WG Jr (2005) The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase. Cancer cell 8(1):25–33

    PubMed  CAS  Google Scholar 

  174. Gregory MA, Qi Y, Hann SR (2003) Phosphorylation by glycogen synthase kinase-3 controls c-myc proteolysis and subnuclear localization. J Biol Chem 278(51):51606–51612

    PubMed  CAS  Google Scholar 

  175. Beals CR, Sheridan CM, Turck CW, Gardner P, Crabtree GR (1997) Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3. Science 275(5308):1930–1934

    PubMed  CAS  Google Scholar 

  176. Ma YC, Song MR, Park JP, Henry HO HY, Hu L, Kurtev MV, Zieg J, Ma Q, Pfaff SL, Greenberg ME (2008) Regulation of motor neuron specification by phosphorylation of neurogenin 2. Neuron 58(1):65–77

    PubMed  CAS  Google Scholar 

  177. Zumbrunn J, Kinoshita K, Hyman AA, Nathke IS (2001) Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3 beta phosphorylation. Curr Biol 11(1):44–49

    PubMed  CAS  Google Scholar 

  178. Kumar P, Lyle KS, Gierke S, Matov A, Danuser G, Wittmann T (2009) GSK3beta phosphorylation modulates CLASP-microtubule association and lamella microtubule attachment. J Cell Biol 184(6):895–908

    PubMed  CAS  Google Scholar 

  179. 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

    PubMed  CAS  Google Scholar 

  180. Goold RG, Owen R, Gordon-Weeks PR (1999) Glycogen synthase kinase 3beta phosphorylation of microtubule-associated protein 1B regulates the stability of microtubules in growth cones. J Cell Sci 112(Pt 19): 3373–3384

    PubMed  CAS  Google Scholar 

  181. Stoothoff WH, Johnson GV (2005) Tau phosphorylation: physiological and pathological consequences. Biochim Biophys Acta 1739(2–3):280–297

    PubMed  CAS  Google Scholar 

  182. van Diepen MT, Parsons M, Downes CP, Leslie NR, Hindges R, Eickholt BJ (2009) MyosinV controls PTEN function and neuronal cell size. Nat Cell Biol 11(10):1191–1196

    PubMed  Google Scholar 

  183. Morfini G, Szebenyi G, Elluru R, Ratner N, Brady ST (2002) Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility. EMBO J 21(3):281–293

    PubMed  CAS  Google Scholar 

  184. 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 (2006) TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell 126(5):955–968

    PubMed  CAS  Google Scholar 

  185. Mao Y, Ge X, Frank CL, Madison JM, Koehler AN, Doud MK, Tassa C, Berry EM, Soda T, Singh KK, Biechele T, Petryshen TL, Moon RT, Haggarty SJ, Tsai LH (2009) Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3-beta/beta-catenin signaling. Cell 136(6):1017–1031

    PubMed  CAS  Google Scholar 

  186. McManus EJ, Sakamoto K, Armit LJ, Ronaldson L, Shpiro N, Marquez R, Alessi DR (2005) Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis. EMBO J 24(8):1571–1583

    PubMed  CAS  Google Scholar 

  187. Eom TY, Jope RS (2009) Blocked inhibitory serine-phosphorylation of glycogen synthase kinase-3alpha/beta impairs in vivo neural precursor cell proliferation. Biol Psychiatry 66(5):494–502

    PubMed  CAS  Google Scholar 

  188. Duman RS (2002) Structural alterations in depression: cellular mechanisms underlying pathology and treatment of mood disorders. CNS Spectr 7(2):140-142

    Google Scholar 

  189. Jacobs BL, van Praag H, Gage FH (2000) Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry 5(3):262–269

    PubMed  CAS  Google Scholar 

  190. Kempermann G (2002) Regulation of adult hippocampal neurogenesis – implications for novel theories of major depression. Bipolar Disord 4(1):17–33

    PubMed  Google Scholar 

  191. Schloesser RJ, Chen G, Manji HK (2007) Neurogenesis and neuroenhancement in the pathophysiology and treatment of bipolar disorder. Int Rev Neurobiol 77:143–178

    PubMed  CAS  Google Scholar 

  192. Reif A, Fritzen S, Finger M, Strobel A, Lauer M, Schmitt A, Lesch KP (2006) Neural stem cell proliferation is decreased in schizophrenia, but not in depression. Mol Psychiatry 11(5): 514–522

    PubMed  CAS  Google Scholar 

  193. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20(24):9104–9110

    PubMed  CAS  Google Scholar 

  194. Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, Bartolomucci A, Fuchs E (2001) Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci U S A 98(22): 12796–12801

    PubMed  CAS  Google Scholar 

  195. Manev H, Uz T, Smalheiser NR, Manev R (2001) Antidepressants alter cell proliferation in the adult brain in vivo and in neural cultures in vitro. Eur J Pharmacol 411(1–2):67–70

    PubMed  CAS  Google Scholar 

  196. Banasr M, Soumier A, Hery M, Mocaer E, Daszuta A (2006) Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Biol Psychiatry 59(11):1087–1096

    PubMed  CAS  Google Scholar 

  197. Warner-Schmidt JL, Duman RS (2007) VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. Proc Natl Acad Sci U S A 104(11): 4647–4652

    PubMed  CAS  Google Scholar 

  198. Scott BW, Wojtowicz JM, Burnham WM (2000) Neurogenesis in the dentate gyrus of the rat following electroconvulsive shock seizures. Exp Neurol 165(2):231–236

    PubMed  CAS  Google Scholar 

  199. Madsen TM, Treschow A, Bengzon J, Bolwig TG, Lindvall O, Tingstrom A (2000) Increased neurogenesis in a model of electroconvulsive therapy. Biol Psychiatry 47(12):1043–1049

    PubMed  CAS  Google Scholar 

  200. Segi-Nishida E, Warner-Schmidt JL, Duman RS (2008) Electroconvulsive seizure and VEGF increase the proliferation of neural stem-like cells in rat hippocampus. Proc Natl Acad Sci U S A 105(32):11352–11357

    PubMed  CAS  Google Scholar 

  201. Warner-Schmidt JL, Madsen TM, Duman RS (2008) Electroconvulsive seizure restores neurogenesis and hippocampus-dependent fear memory after disruption by irradiation. Eur J Neurosci 27(6):1485–1493

    PubMed  Google Scholar 

  202. Chen G, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji HK (2000) Enhancement of hippocampal neurogenesis by lithium. J Neurochem 75(4):1729–1734

    PubMed  CAS  Google Scholar 

  203. Hashimoto R, Senatorov V, Kanai H, Leeds P, Chuang DM (2003) Lithium stimulates progenitor proliferation in cultured brain neurons. Neuroscience 117(1):55–61

    PubMed  CAS  Google Scholar 

  204. Shimomura A, Nomura R, Senda T (2003) Lithium inhibits apoptosis of mouse neural progenitor cells. Neuroreport 14(14):1779–1782

    PubMed  CAS  Google Scholar 

  205. Dawirs RR, Hildebrandt K, Teuchert-Noodt G (1998) Adult treatment with haloperidol increases dentate granule cell proliferation in the gerbil hippocampus. J Neural Transm 105(2–3):317–327

    PubMed  CAS  Google Scholar 

  206. Wakade CG, Mahadik SP, Waller JL, Chiu FC (2002) Atypical neuroleptics stimulate neurogenesis in adult rat brain. J Neurosci Res 69(1):72–79

    PubMed  CAS  Google Scholar 

  207. Wang HD, Dunnavant FD, Jarman T, Deutch AY (2004) Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat. Neuropsychopharmacology 29(7):1230–1238

    PubMed  CAS  Google Scholar 

  208. Newton SS, Duman RS (2007) Neurogenic actions of atypical antipsychotic drugs and therapeutic implications. CNS Drugs 21(9):715–725

    PubMed  CAS  Google Scholar 

  209. Mai L, Jope RS, Li X (2002) BDNF-mediated signal transduction is modulated by GSK3beta and mood stabilizing agents. J Neurochem 82(1):75–83

    PubMed  CAS  Google Scholar 

  210. Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA (2004) Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat Genet 36(2):131–137

    PubMed  CAS  Google Scholar 

  211. Li X, Rosborough KM, Friedman AB, Zhu W, Roth KA (2007) Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics. Int J Neuropsychopharmacol 10(1):7–19

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  213. Jin Z, El-Deiry WS (2005) Overview of cell death signaling pathways. Cancer Biol Ther 4(2):139–163

    PubMed  CAS  Google Scholar 

  214. Bhat RV, Shanley J, Correll MP, Fieles WE, Keith RA, Scott CW, Lee CM (2000) Regulation and localization of tyrosine216 phosphorylation of glycogen synthase kinase-3beta in cellular and animal models of neuronal degeneration. Proc Natl Acad Sci U S A 97(20):11074–11079

    PubMed  CAS  Google Scholar 

  215. Hetman M, Cavanaugh JE, 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 

  216. Lucas JJ, Hernandez F, Gomez-Ramos P, Moran MA, Hen R, Avila J (2001) Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. EMBO J 20(1–2):27–39

    PubMed  CAS  Google Scholar 

  217. Jope RS (2003) Lithium and GSK-3: one inhibitor, two inhibitory actions, multiple outcomes. Trends Pharmacol Sci 24(9):441–443

    PubMed  CAS  Google Scholar 

  218. Chuang DM (2005) The antiapoptotic actions of mood stabilizers: molecular mechanisms and therapeutic potentials. Ann N Y Acad Sci 1053:195–204

    PubMed  CAS  Google Scholar 

  219. Koh SH, Kim Y, Kim HY, Hwang S, Lee CH, Kim SH (2007) Inhibition of glycogen synthase kinase-3 suppresses the onset of symptoms and disease progression of G93A-SOD1 mouse model of ALS. Exp Neurol 205(2):336–346

    PubMed  CAS  Google Scholar 

  220. Wang W, Yang Y, Ying C, Li W, Ruan H, Zhu X, You Y, Han Y, Chen R, Wang Y, Li M (2007) Inhibition of glycogen synthase kinase-3beta protects dopaminergic neurons from MPTP toxicity. Neuropharmacology 52(8):1678–1684

    PubMed  CAS  Google Scholar 

  221. 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

    PubMed  CAS  Google Scholar 

  222. Hernandez F, Borrell J, Guaza C, Avila J, Lucas JJ (2002) Spatial learning deficit in transgenic mice that conditionally over-express GSK-3beta in the brain but do not form tau filaments. J Neurochem 83(6):1529–1533

    PubMed  CAS  Google Scholar 

  223. Polter A, Beurel E, Yang S, Garner R, Song L, Miller CA, Sweatt JD, McMahon L, Bartolucci AA, Li X, Jope RS (2010) Deficiency in the inhibitory serine-phosphorylation of glycogen synthase kinase-3 increases sensitivity to mood disturbances. Neuropsychopharmacology 35(8):1761–1774

    PubMed  CAS  Google Scholar 

  224. Peineau S, Taghibiglou C, Bradley C, Wong TP, Liu L, Lu J, Lo E, Wu D, Saule E, Bouschet T, Matthews P, Isaac JT, Bortolotto ZA, Wang YT, Collingridge GL (2007) LTP inhibits LTD in the hippocampus via regulation of GSK3beta. Neuron 53(5):703–717

    PubMed  CAS  Google Scholar 

  225. Kimura T, Yamashita S, Nakao S, Park JM, Murayama M, Mizoroki T, Yoshiike Y, Sahara N, Takashima A (2008) GSK-3beta is required for memory reconsolidation in adult brain. PLoS One 3(10):e3540

    PubMed  Google Scholar 

  226. Li X, Jope RS (2010) Is glycogen synthase kinase-3 a central modulator in mood regulation? Neuropsychopharmacology 35(11):2143–2154

    PubMed  CAS  Google Scholar 

  227. Koros E, Dorner-Ciossek C (2007) The role of glycogen synthase kinase-3beta in schizophrenia. Drug News Perspect 20(7):437–445

    PubMed  CAS  Google Scholar 

  228. Lovestone S, Killick R, Di Forti M, Murray R (2007) Schizophrenia as a GSK-3 dysregulation disorder. Trends Neurosci 30(4):142–149

    PubMed  CAS  Google Scholar 

  229. Freyberg Z, Ferrando SJ, Javitch JA (2009) Roles of the Akt/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action. Am J Psychiatry 167(4):388–396

    PubMed  Google Scholar 

  230. Takashima A (2009) Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)-mediated signal transduction pathway: role of GSK-3beta in adult brain. J Pharmacol Sci 109(2):174–178

    PubMed  CAS  Google Scholar 

  231. Reitz C, Brayne C, Mayeux R (2011) Epidemiology of Alzheimer disease. Nat Rev Neurol 7(3):137–152

    PubMed  Google Scholar 

  232. Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256(5054):184–185

    PubMed  CAS  Google Scholar 

  233. Kosik KS (1992) Cellular aspects of Alzheimer neurofibrillary pathology. Prog Clin Biol Res 379:183–193

    PubMed  CAS  Google Scholar 

  234. Noble W, Planel E, Zehr C, Olm V, Meyerson J, Suleman F, Gaynor K, Wang L, LaFrancois J, Feinstein B, Burns M, Krishnamurthy P, Wen Y, Bhat R, Lewis J, Dickson D, Duff K (2005) Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo. Proc Natl Acad Sci U S A 102(19):6990–6995

    PubMed  CAS  Google Scholar 

  235. Caccamo A, Oddo S, Sugarman MC, Akbari Y, LaFerla FM (2005) Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders. Neurobiol Aging 26(5):645–654

    PubMed  CAS  Google Scholar 

  236. Su Y, Ryder J, Li B, Wu X, Fox N, Solenberg P, Brune K, Paul S, Zhou Y, Liu F, Ni B (2004) Lithium, a common drug for bipolar disorder treatment, regulates amyloid-beta precursor protein processing. Biochemistry 43(22):6899–6908

    PubMed  CAS  Google Scholar 

  237. Caccamo A, Oddo S, Tran LX, LaFerla FM (2007) Lithium reduces tau phosphorylation but not A beta or working memory deficits in a transgenic model with both plaques and tangles. Am J Pathol 170(5):1669–1675

    PubMed  CAS  Google Scholar 

  238. Sereno L, Coma M, Rodriguez M, Sanchez-Ferrer P, Sanchez MB, Gich I, Agullo JM, Perez M, Avila J, Guardia-Laguarta C, Clarimon J, Lleo A, Gomez-Isla T (2009) A novel GSK-3beta inhibitor reduces Alzheimer’s pathology and rescues neuronal loss in vivo. Neurobiol Dis 35(3):359–367

    PubMed  CAS  Google Scholar 

  239. Hu S, Begum AN, Jones MR, Oh MS, Beech WK, Beech BH, Yang F, Chen P, Ubeda OJ, Kim PC, Davies P, Ma Q, Cole GM, Frautschy SA (2009) GSK3 inhibitors show benefits in an Alzheimer’s disease (AD) model of neurodegeneration but adverse effects in control animals. Neurobiol Dis 33(2):193–206

    PubMed  CAS  Google Scholar 

  240. Zhong J, Lee WH (2007) Lithium: a novel treatment for Alzheimer’s disease? Expert Opin Drug Saf 6(4):375–383

    PubMed  CAS  Google Scholar 

  241. Perala J, Suvisaari J, Saarni SI, Kuoppasalmi K, Isometsa E, Pirkola S, Partonen T, Tuulio-Henriksson A, Hintikka J, Kieseppa T, Harkanen T, Koskinen S, Lonnqvist J (2007) Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry 64(1):19–28

    PubMed  Google Scholar 

  242. McGurk SR, Mueser KT (2004) Cognitive functioning, symptoms, and work in supported employment: a review and heuristic model. Schizophr Res 70(2–3):147–173

    PubMed  Google Scholar 

  243. Tamminga CA, Holcomb HH (2005) Phenotype of schizophrenia: a review and formulation. Mol Psychiatry 10(1):27–39

    PubMed  CAS  Google Scholar 

  244. Ross CA, Margolis RL, Reading SA, Pletnikov M, Coyle JT (2006) Neurobiology of schizophrenia. Neuron 52(1):139–153

    PubMed  CAS  Google Scholar 

  245. Harrison PJ, Weinberger DR (2005) Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 10(1):40–68, image 45

    PubMed  CAS  Google Scholar 

  246. Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, Grace AA (2008) Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci 31(5):234–242

    PubMed  CAS  Google Scholar 

  247. Kozlovsky N, Belmaker RH, Agam G (2001) Low GSK-3 activity in frontal cortex of schizophrenic patients. Schizophr Res 52(1–2):101–105

    PubMed  CAS  Google Scholar 

  248. Kozlovsky N, Regenold WT, Levine J, Rapoport A, Belmaker RH, Agam G (2004) GSK-3beta in cerebrospinal fluid of schizophrenia patients. J Neural Transm 111(8):1093–1098

    PubMed  CAS  Google Scholar 

  249. Kozlovsky N, Shanon-Weickert C, Tomaskovic-Crook E, Kleinman JE, Belmaker RH, Agam G (2004) Reduced GSK-3beta mRNA levels in postmortem dorsolateral prefrontal cortex of schizophrenic patients. J Neural Transm 111(12):1583–1592

    PubMed  CAS  Google Scholar 

  250. Yang SD, Yu JS, Lee TT, Yang CC, Ni MH, Yang YY (1995) Dysfunction of protein kinase FA/GSK-3 alpha in lymphocytes of patients with schizophrenic disorder. J Cell Biochem 59(1):108–116

    PubMed  CAS  Google Scholar 

  251. Souza RP, Romano-Silva MA, Lieberman JA, Meltzer HY, Wong AH, Kennedy JL (2008) Association study of GSK3 gene polymorphisms with schizophrenia and clozapine response. Psychopharmacology 200(2):177–186

    PubMed  CAS  Google Scholar 

  252. Prickaerts J, Moechars D, Cryns K, Lenaerts I, van Craenendonck H, Goris I, Daneels G, Bouwknecht JA, Steckler T (2006) Transgenic mice overexpressing glycogen synthase kinase 3beta: a putative model of hyperactivity and mania. J Neurosci 26(35):9022–9029

    PubMed  CAS  Google Scholar 

  253. Benedetti F, Poletti S, Radaelli D, Bernasconi A, Cavallaro R, Falini A, Lorenzi C, Pirovano A, Dallaspezia S, Locatelli C, Scotti G, Smeraldi E (2010) Temporal lobe grey matter volume in schizophrenia is associated with a genetic polymorphism influencing glycogen synthase kinase 3-beta activity. Genes Brain Behav 9(4):365–371

    PubMed  CAS  Google Scholar 

  254. Lipina TV, Kaidanovich-Beilin O, Patel S, Wang M, Clapcote SJ, Liu F, Woodgett JR, Roder JC (2010) Genetic and pharmacological evidence for schizophrenia-related Disc1 interaction with GSK-3. Synapse 65(3):234–248

    Google Scholar 

  255. Beaulieu JM, Gainetdinov RR, Caron MG (2009) Akt/GSK3 signaling in the action of psychotropic drugs. Annu Rev Pharmacol Toxicol 49:327–347

    PubMed  CAS  Google Scholar 

  256. Kang UG, Seo MS, Roh MS, Kim Y, Yoon SC, Kim YS (2004) The effects of clozapine on the GSK-3-mediated signaling pathway. FEBS Lett 560(1–3):115–119

    PubMed  CAS  Google Scholar 

  257. Gould TD (2006) Targeting glycogen synthase kinase-3 as an approach to develop novel mood-stabilising medications. Expert Opin Ther Targets 10(3):377–392

    PubMed  CAS  Google Scholar 

  258. Grimes CA, Jope RS (2001) The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Prog Neurobiol 65(4):391–426

    PubMed  CAS  Google Scholar 

  259. Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG (2005) An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell 122(2):261–273

    PubMed  CAS  Google Scholar 

  260. Miller JS, Tallarida RJ, Unterwald EM (2009) Cocaine-induced hyperactivity and sensitization are dependent on GSK3. Neuro­pharmacology 56(8):1116–1123

    PubMed  CAS  Google Scholar 

  261. Miller JS, Tallarida RJ, Unterwald EM (2010) Inhibition of GSK3 attenuates dopamine D1 receptor agonist-induced hyperactivity in mice. Brain Res Bull 82(3–4):184–187

    PubMed  CAS  Google Scholar 

  262. Xu CM, Wang J, Wu P, Zhu WL, Li QQ, Xue YX, Zhai HF, Shi J, Lu L (2009) Glycogen synthase kinase 3beta in the nucleus accumbens core mediates cocaine-induced behavioral sensitization. J Neurochem 111(6):1357–1368

    PubMed  CAS  Google Scholar 

  263. Brami-Cherrier K, Valjent E, Garcia M, Pages C, Hipskind RA, Caboche J (2002) Dopamine induces a PI3-kinase-independent activation of Akt in striatal neurons: a new route to cAMP response element-binding protein phosphorylation. J Neurosci 22(20):8911–8921

    PubMed  CAS  Google Scholar 

  264. McGinty JF, Shi XD, Schwendt M, Saylor A, Toda S (2008) Regulation of psychostimulant-induced signaling and gene expression in the striatum. J Neurochem 104(6):1440–1449

    PubMed  CAS  Google Scholar 

  265. Shi X, McGinty JF (2007) Repeated amphetamine treatment increases phosphorylation of extracellular signal-regulated kinase, protein kinase B, and cyclase response element-binding protein in the rat striatum. J Neurochem 103(2):706–713

    PubMed  CAS  Google Scholar 

  266. Nwaneshiudu CA, Unterwald EM (2010) NK-3 receptor antagonism prevents behavioral sensitization to cocaine: a role of glycogen synthase kinase-3 in the nucleus accumbens. J Neurochem 115(3):635–642

    PubMed  CAS  Google Scholar 

  267. Feder A, Alonso A, Tang M, Liriano W, Warner V, Pilowsky D, Barranco E, Wang Y, Verdeli H, Wickramaratne P, Weissman MM (2009) Children of low-income depressed mothers: psychiatric disorders and social adjustment. Depress Anxiety 26(6):513–520

    PubMed  Google Scholar 

  268. Martinowich K, Schloesser RJ, Manji HK (2009) Bipolar disorder: from genes to behavior pathways. J Clin Invest 119(4):726–736

    PubMed  CAS  Google Scholar 

  269. Gold PW, Chrousos GP (2002) Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry 7(3):254–275

    PubMed  CAS  Google Scholar 

  270. Pittenger C, Duman RS (2008) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33(1):88–109

    PubMed  CAS  Google Scholar 

  271. Zarate CA Jr, Singh J, Manji HK (2006) Cellular plasticity cascades: targets for the development of novel therapeutics for bipolar disorder. Biol Psychiatry 59(11):1006–1020

    PubMed  CAS  Google Scholar 

  272. Gould TD, Manji HK (2005) Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs. Neuropsycho­pharmacology 30(7):1223–1237

    PubMed  CAS  Google Scholar 

  273. O’Brien WT, Klein PS (2009) Validating GSK3 as an in vivo target of lithium action. Biochem Soc Trans 37(Pt 5):1133–1138

    PubMed  Google Scholar 

  274. De Sarno P, Li X, Jope RS (2002) Regulation of Akt and glycogen synthase kinase-3 beta phosphorylation by sodium valproate and lithium. Neuropharmacology 43(7):1158–1164

    PubMed  Google Scholar 

  275. Omata N, Chiu CT, Moya PR, Leng Y, Wang Z, Hunsberger JG, Leeds P, Chuang DM (2011) Lentivirally mediated GSK-3beta silencing in the hippocampal dentate gyrus induces antidepressant-like effects in stressed mice. Int J Neuropsychopharmacol 14(5):711–717

    PubMed  CAS  Google Scholar 

  276. O’Brien WT, Harper AD, Jove F, Woodgett JR, Maretto S, Piccolo S, Klein PS (2004) Glycogen synthase kinase-3beta haploinsufficiency mimics the behavioral and molecular effects of lithium. J Neurosci 24(30):6791–6798

    PubMed  Google Scholar 

  277. Gould TD, Einat H, Bhat R, Manji HK (2004) AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuro­psychopharmacol 7(4):387–390

    PubMed  CAS  Google Scholar 

  278. Kaidanovich-Beilin O, Milman A, Weizman A, Pick CG, Eldar-Finkelman H (2004) Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on beta-catenin in mouse hippocampus. Biol Psychiatry 55(8):781–784

    PubMed  CAS  Google Scholar 

  279. Rosa AO, Kaster MP, Binfare RW, Morales S, Martin-Aparicio E, Navarro-Rico ML, Martinez A, Medina M, Garcia AG, Lopez MG, Rodrigues AL (2008) Antidepressant-like effect of the novel thiadiazolidinone NP031115 in mice. Prog Neuropsychopharmacol Biol Psychiatry 32(6):1549–1556

    PubMed  CAS  Google Scholar 

  280. Li X, Liu M, Cai Z, Wang G, Li X (2010) Regulation of glycogen synthase kinase-3 during bipolar mania treatment. Bipolar Disord 12(7):741–752

    PubMed  Google Scholar 

  281. Raison CL, Capuron L, Miller AH (2006) Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 27(1):24–31

    PubMed  CAS  Google Scholar 

  282. Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65(9):732–741

    PubMed  CAS  Google Scholar 

  283. Adli M, Hollinde DL, Stamm T, Wiethoff K, Tsahuridu M, Kirchheiner J, Heinz A, Bauer M (2007) Response to lithium augmentation in depression is associated with the glycogen synthase kinase 3-beta-50T/C single nucleotide polymorphism. Biol Psychiatry 62(11):1295–1302

    PubMed  CAS  Google Scholar 

  284. Szczepankiewicz A, Rybakowski JK, Suwalska A, Skibinska M, Leszczynska-Rodziewicz A, Dmitrzak-Weglarz M, Czerski PM, Hauser J (2006) Association study of the glycogen synthase kinase-3beta gene polymorphism with prophylactic lithium response in bipolar patients. World J Biol Psychiatry 7(3):158–161

    PubMed  Google Scholar 

  285. Tsai SJ, Liou YJ, Hong CJ, Yu YW, Chen TJ (2008) Glycogen synthase kinase-3beta gene is associated with antidepressant treatment response in Chinese major depressive disorder. Pharmacogenomics J 8(6):384–390

    PubMed  CAS  Google Scholar 

  286. Inkster B, Nichols TE, Saemann PG, Auer DP, Holsboer F, Muglia P, Matthews PM (2009) Association of GSK3beta polymorphisms with brain structural changes in major depressive disorder. Arch Gen Psychiatry 66(7):721–728

    PubMed  CAS  Google Scholar 

  287. Beurel E, Jope RS (2009) Lipopolysaccharide-induced interleukin-6 production is controlled by glycogen synthase kinase-3 and STAT3 in the brain. J Neuroinflammation 6:9

    PubMed  Google Scholar 

  288. Martin M, Rehani K, Jope RS, Michalek SM (2005) Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol 6(8):777–784

    PubMed  CAS  Google Scholar 

  289. Hu X, Paik PK, Chen J, Yarilina A, Kockeritz L, Lu TT, Woodgett JR, Ivashkiv LB (2006) IFN-gamma suppresses IL-10 production and synergizes with TLR2 by regulating GSK3 and CREB/AP-1 proteins. Immunity 24(5):563–574

    PubMed  CAS  Google Scholar 

  290. Yuskaitis CJ, Jope RS (2009) Glycogen synthase kinase-3 regulates microglial migration, inflammation, and inflammation-induced neurotoxicity. Cell Signal 21(2):264–273

    PubMed  CAS  Google Scholar 

  291. Phukan S, Babu VS, Kannoji A, Hariharan R, Balaji VN (2010) GSK3beta: role in therapeutic landscape and development of modulators. Br J Pharmacol 160(1):1–19

    PubMed  CAS  Google Scholar 

  292. Eldar-Finkelman H, Licht-Murava A, Pietrokovski S, Eisenstein M (2009) Substrate competitive GSK-3 inhibitors – strategy and implications. Biochim Biophys Acta 1804(3):598–603

    PubMed  Google Scholar 

  293. Gurvich N, Klein PS (2002) Lithium and valproic acid: parallels and contrasts in diverse signaling contexts. Pharmacol Ther 96(1):45–66

    PubMed  CAS  Google Scholar 

  294. Huang HC, Klein PS (2006) Multiple roles for glycogen synthase kinase-3 as a drug target in Alzheimer’s disease. Curr Drug Targets 7(11):1389–1397

    PubMed  CAS  Google Scholar 

  295. Munoz-Montano JR, Moreno FJ, Avila J, Diaz-Nido J (1997) Lithium inhibits Alzheimer’s disease-like tau protein phosphorylation in neurons. FEBS Lett 411(2–3):183–188

    PubMed  CAS  Google Scholar 

  296. Chalecka-Franaszek E, Chuang DM (1999) Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proc Natl Acad Sci U S A 96(15):8745–8750

    PubMed  CAS  Google Scholar 

  297. Li X, Friedman AB, Zhu W, Wang L, Boswell S, May RS, Davis LL, Jope RS (2007) Lithium regulates glycogen synthase kinase-3beta in human peripheral blood mononuclear cells: implication in the treatment of bipolar disorder. Biol Psychiatry 61(2):216–222

    PubMed  CAS  Google Scholar 

  298. Ryves WJ, Harwood AJ (2001) Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochem Biophys Res Commun 280(3):720–725

    PubMed  CAS  Google Scholar 

  299. Engel T, Hernandez F, Avila J, Lucas JJ (2006) Full reversal of Alzheimer’s disease-like phenotype in a mouse model with conditional overexpression of glycogen synthase kinase-3. J Neurosci 26(19):5083–5090

    PubMed  CAS  Google Scholar 

  300. Murphy DL (1977) The behavioral toxicity of monoamine oxidase-inhibiting antidepressants. Adv Pharmacol Chemother 14:71–105

    PubMed  CAS  Google Scholar 

  301. Meijer L, Flajolet M, Greengard P (2004) Pharmacological inhibitors of glycogen synthase kinase 3. Trends Pharmacol Sci 25(9):471–480

    PubMed  CAS  Google Scholar 

  302. Bain J, McLauchlan H, Elliott M, Cohen P (2003) The specificities of protein kinase inhibitors: an update. Biochem J 371(Pt 1):199–204

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by CIHR grant MOP 74711 (to JW). We also thank our colleagues, John Roder, Albert Wong, Satish Patel and members of the Woodgett lab for their advice and input.

Author information

Authors and Affiliations

  1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada

    Oksana Kaidanovich-Beilin & James Robert Woodgett

  2. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

    James Robert Woodgett

Authors
  1. Oksana Kaidanovich-Beilin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James Robert Woodgett
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James Robert Woodgett .

Editor information

Editors and Affiliations

  1. Biosignal Research Center, Kobe University, Rokkodai 1-1, Kobe, 657-8501, Japan

    Hideyuki Mukai

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Kaidanovich-Beilin, O., Woodgett, J.R. (2012). Glycogen Synthase Kinase-3 in Neurological Diseases. In: Mukai, H. (eds) Protein Kinase Technologies. Neuromethods, vol 68. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-824-5_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-824-5_9

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-823-8

  • Online ISBN: 978-1-61779-824-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation