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Molecular and Cellular Biochemistry

, Volume 344, Issue 1–2, pp 211–215 | Cite as

Regulation of GSK3 isoforms by phosphatases PP1 and PP2A

  • Félix Hernández
  • Elena Langa
  • Raquel Cuadros
  • Jesús AvilaEmail author
  • Nieves Villanueva
Article

Abstract

Dephosphorylation of phospho GSK3 isoforms, from COS-7 cells, was determined in vitro and in cultured cells in the absence or the presence of okadaic acid and lithium. Our results indicate a preferential dephosphorylation of phospho GSK3α by PP2A phosphatase, whereas dephosphorylation of phospho GSK3β mainly takes place by PP1 phosphatase.

Keywords

GSK-3 PP1 PP2A Okadaic acid Lithium 

Notes

Acknowledgments

This study was supported by grants from the Comunidad de Madrid (NEURODEGMODELS-CM), the Spanish Comisión Interministerial de Ciencia y Tecnologia, Fundación Centro Investigación Enfermedades Neurológicas (Fundación CIEN), and the CIBER on Neurodegeneration and by institutional grants from the Fundación Ramón Areces.

References

  1. 1.
    Woodgett JR (1990) Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J 9:2431–2438PubMedGoogle Scholar
  2. 2.
    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 406:86–90CrossRefPubMedGoogle Scholar
  3. 3.
    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 6:329–337CrossRefPubMedGoogle Scholar
  4. 4.
    Doble BW, Woodgett JR (2003) GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci 116:1175–1186CrossRefPubMedGoogle Scholar
  5. 5.
    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):15–19PubMedGoogle Scholar
  6. 6.
    Grimes CA, Jope RS (2001) The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Prog Neurobiol 65:391–426CrossRefPubMedGoogle Scholar
  7. 7.
    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):701–704PubMedGoogle Scholar
  8. 8.
    Inestrosa NC, Arenas E (2010) Emerging roles of Wnts in the adult nervous system. Nat Rev Neurosci 11(2):77–86CrossRefPubMedGoogle Scholar
  9. 9.
    Greco SJ, Sarkar S, Casadesus G, Zhu X, Smith MA, Ashford JW, Johnston JM, Tezapsidis N (2009) Leptin inhibits glycogen synthase kinase-3beta to prevent tau phosphorylation in neuronal cells. Neurosci Lett 455:191–194CrossRefPubMedGoogle Scholar
  10. 10.
    Goni-Oliver P, Lucas JJ, Avila J, Hernandez F (2007) N-terminal cleavage of GSK-3 by calpain: a new form of GSK-3 regulation. J Biol Chem 282:22406–22413CrossRefPubMedGoogle Scholar
  11. 11.
    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 278:33067–33077CrossRefPubMedGoogle Scholar
  12. 12.
    Planel E, Yasutake K, Fujita SC, Ishiguro K (2001) Inhibition of protein phosphatase 2A overrides tau protein kinase I/glycogen synthase kinase 3 beta and cyclin-dependent kinase 5 inhibition and results in tau hyperphosphorylation in the hippocampus of starved mouse. J Biol Chem 276:34298–34306CrossRefPubMedGoogle Scholar
  13. 13.
    Tajes M, Yeste-Velasco M, Zhu X, Chou SP, Smith MA, Pallas M, Camins A, Casadesus G (2009) Activation of Akt by lithium: pro-survival pathways in aging. Mech Ageing Dev 130:253–261CrossRefPubMedGoogle Scholar
  14. 14.
    Tajes M, Gutierrez-Cuesta J, Folch J, Ferrer I, Caballero B, Smith MA, Casadesus G, Camins A, Pallas M (2008) Lithium treatment decreases activities of tau kinases in a murine model of senescence. J Neuropathol Exp Neurol 67:612–623CrossRefPubMedGoogle Scholar
  15. 15.
    Gluzman Y (1981) SV40-transformed simian cells support the replication of early SV40 mutants. Cell 23:175–182CrossRefPubMedGoogle Scholar
  16. 16.
    Asenjo A, Rodriguez L, Villanueva N (2005) Determination of phosphorylated residues from human respiratory syncytial virus P protein that are dynamically dephosphorylated by cellular phosphatases: a possible role for serine 54. J Gen Virol 86:1109–1120CrossRefPubMedGoogle Scholar
  17. 17.
    Banker GA, Cowan WM (1977) Rat hippocampal neurons in dispersed cell culture. Brain Res 126:397–425CrossRefPubMedGoogle Scholar
  18. 18.
    Cohen P (1991) Classification of protein-serine/threonine phosphatases: identification and quantitation in cell extracts. Methods Enzymol 201:389–398CrossRefPubMedGoogle Scholar
  19. 19.
    Munoz-Montano JR, Moreno FJ, Avila J, Diaz-Nido J (1997) Lithium inhibits Alzheimer’s disease-like tau protein phosphorylation in neurons. FEBS Lett 411:183–188CrossRefPubMedGoogle Scholar
  20. 20.
    Latif ML, Pillay TS (2008) Differential detection of phosphorylated glycogen synthase kinase 3 alpha and beta depending on blocking conditions. Anal Biochem 379:136–137CrossRefPubMedGoogle Scholar
  21. 21.
    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 320:667–670CrossRefPubMedGoogle Scholar
  22. 22.
    Cho J, Rameshwar P, Sadoshima J (2009) Distinct roles of glycogen synthase kinase (GSK)-3alpha and GSK-3beta in mediating cardiomyocyte differentiation in murine bone marrow-derived mesenchymal stem cells. J Biol Chem 284:36647–36658CrossRefPubMedGoogle Scholar
  23. 23.
    Hernandez F, Gomez-Ramos A, Goni-Oliver P, Avila J, Villanueva N (2008) Role of polyglycine repeats in the regulation of glycogen synthase kinase activity. Protein Pept Lett 15:586–589CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Félix Hernández
    • 1
  • Elena Langa
    • 1
  • Raquel Cuadros
    • 1
  • Jesús Avila
    • 1
    • 2
    Email author
  • Nieves Villanueva
    • 3
  1. 1.Centro de Biologia Molecular “Severo Ochoa” (CSIC-UAM)MadridSpain
  2. 2.CIBERNEDMadridSpain
  3. 3.Centro Nacional de Microbiología, Instituto de Salud Carlos IIIMadridSpain

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