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PTEN, a negative regulator of PI3 kinase signalling, alters tau phosphorylation in cells by mechanisms independent of GSK‐3
Author(s) -
Kerr Fiona,
Rickle Annika,
Nayeem Naushaba,
Brandner Sebastian,
Cowburn Richard F.,
Lovestone Simon
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.04.064
Subject(s) - pten , phosphatase , phosphorylation , protein kinase b , tensin , tauopathy , cancer research , microbiology and biotechnology , protein phosphatase 2 , regulator , pi3k/akt/mtor pathway , biology , kinase , signal transduction , chemistry , neurodegeneration , biochemistry , medicine , disease , gene
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.