Research Output
PTEN, a negative regulator of PI3 kinase signalling, alters tau phosphorylation in cells by mechanisms independent of GSK-3
  Deregulation of PTEN/Akt signalling has been recently implicated in the pathogenesis of Alzheimer's disease (AD), but the effects on the molecular processes underlying AD pathology have not yet been fully described. Here we report that overexpression of PTEN reduces tau phosphorylation in CHO cells. This effect was abrogated by mutant PTEN constructs with either a catalytically inactive point mutation (C124S) or with only inactive lipid phosphatase activity (G129E), suggesting an indirect, lipid phosphatase-dependent process. The predominant effects of PTEN on tau appeared to be mediated by reducing ERK1/2 activity, but were independent of Akt, GSK-3, JNK and the tau phosphatases PP1 and PP2A. Our studies provide evidence for an effect of PTEN on the phosphorylation of tau in AD pathogenesis, and provide some insight into the mechanisms through which deregulation of PTEN may contribute towards the progression of tauopathy.

  • Type:

    Article

  • Date:

    02 May 2006

  • Publication Status:

    Published

  • Publisher

    Wiley-Blackwell

  • DOI:

    10.1016/j.febslet.2006.04.064

  • ISSN:

    0014-5793

  • Library of Congress:

    RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry

  • Dewey Decimal Classification:

    660 Chemical engineering

Citation

Kerr, F., Rickle, A., Nayeem, N., Brandner, S., Cowburn, R. F., & Lovestone, S. (2006). PTEN, a negative regulator of PI3 kinase signalling, alters tau phosphorylation in cells by mechanisms independent of GSK-3. FEBS Letters, 580(13), 3121-3128. https://doi.org/10.1016/j.febslet.2006.04.064

Authors

Keywords

PTEN; phosphatase and tensin homolog deleted on chromosome 1; GSK-3; glycogen synthase kinase 3; AD; Alzheimer's disease; MAP kinase; mitogen activated protein kinase; ERK; extracellular regulated MAP kinase; JNK; c-jun N-terminal kinase; PP1; protein phosphatase 1; PP2A; protein phosphatase 2A; PIP3 ; phosphatidylinositol (3,4,5)-triphosphate; Aβ; amyloid beta; CHO; Chinese hamster ovary; Akt; protein kinase B; Phosphatase and tensin homolog deleted on chromosome 1; Akt; glycogen synthase kinase 3; Alzheimer's disease; Tau phosphorylation

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