PTEN, a negative regulator of PI3 kinase signalling, alters tau phosphorylation in cells by mechanisms independent of GSK-3

Fiona Kerr, Annika Rickle, Naushaba Nayeem, Sebastian Brandner, Richard F. Cowburn, Simon Lovestone

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
JournalFEBS Letters
Volume580
Issue number13
DOIs
Publication statusPublished - 29 May 2006

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Glycogen Synthase Kinase 3
Phosphorylation
Phosphatidylinositol 3-Kinases
Phosphoric Monoester Hydrolases
Alzheimer Disease
Deregulation
Tauopathies
Lipids
CHO Cells
Pathology
Point Mutation

Keywords

  • Alzheimer’s disease
  • phosphatase
  • tau phosphorylation

Cite this

Kerr, Fiona ; Rickle, Annika ; Nayeem, Naushaba ; Brandner, Sebastian ; Cowburn, Richard F. ; Lovestone, Simon. / PTEN, a negative regulator of PI3 kinase signalling, alters tau phosphorylation in cells by mechanisms independent of GSK-3. In: FEBS Letters. 2006 ; Vol. 580, No. 13.
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PTEN, a negative regulator of PI3 kinase signalling, alters tau phosphorylation in cells by mechanisms independent of GSK-3. / Kerr, Fiona; Rickle, Annika; Nayeem, Naushaba; Brandner, Sebastian; Cowburn, Richard F.; Lovestone, Simon.

In: FEBS Letters, Vol. 580, No. 13, 29.05.2006.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PTEN, a negative regulator of PI3 kinase signalling, alters tau phosphorylation in cells by mechanisms independent of GSK-3

AU - Kerr, Fiona

AU - Rickle, Annika

AU - Nayeem, Naushaba

AU - Brandner, Sebastian

AU - Cowburn, Richard F.

AU - Lovestone, Simon

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AB - 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.

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