Sodium tungstate decreases the phosphorylation of tau through GSK3 inactivation

Authors

  • Alberto Gómez-Ramos,

    1. Centro de Biología Molecular, CSIC/UAM, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain
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  • Jorge Domínguez,

    1. Department of Biochemistry and Molecular Biology, and IRB-Barcelona Science Park, University of Barcelona, Barcelona, Spain
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  • Delia Zafra,

    1. Department of Biochemistry and Molecular Biology, and IRB-Barcelona Science Park, University of Barcelona, Barcelona, Spain
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  • Helena Corominola,

    1. Endocrinology and Diabetes Unit, Hospital Clínic de Barcelona, and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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  • Ramon Gomis,

    1. Endocrinology and Diabetes Unit, Hospital Clínic de Barcelona, and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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  • Joan J. Guinovart,

    1. Department of Biochemistry and Molecular Biology, and IRB-Barcelona Science Park, University of Barcelona, Barcelona, Spain
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  • Jesús Avila

    Corresponding author
    1. Centro de Biología Molecular, CSIC/UAM, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain
    • Centro de Biología Molecular (CSIC/UAM), Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain
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Abstract

Tungstate treatment increases the phosphorylation of glycogen synthase kinase-3β (GSK3β) at serine 9, which triggers its inactivation both in cultured neural cells and in vivo. GSK3 phosphorylation is dependent on the activation of extracellular signal-regulated kinases 1/2 (ERK1/2) induced by tungstate. As a consequence of GSK3 inactivation, the phosphorylation of several GSK3-dependent sites of the microtubule-associated protein tau decreases. Tungstate reduces tau phosphorylation only in primed sequences, namely, those prephosphorylated by other kinases before GSK3β modification, which are serines 198, 199, or 202 and threonine 231. The phosphorylation at these sites is involved in reduction of the interaction of tau with microtubules that occurs in Alzheimer's disease. © 2006 Wiley-Liss, Inc.

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