Differential effects of apolipoprotein E isoforms on phosphorylation at specific sites on tau by glycogen synthase kinase‐3β identified by nano‐electrospray mass spectrometry

FEBS Letters

Hoffmann, Michael M²  Maerz, Winfried²  Gibb, Graham M³  Betts, Joanna C¹  Pearce, Janice³  Blackstock, Walter P¹  Anderton, Brian H³  Lovestone, Simon³ 

[1] Biomolecular Structure Unit, GlaxoWellcome Research and Development, Stevenage SG1 2NY, UK;Klinicum der Albert-Ludwigs-Universität, Freiburg, Germany;Department of Neuroscience, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK

关键词: Tau;    Phosphorylation;    Apolipoprotein E;    Glycogen synthase kinase-3β;    Nano-electrospray mass spectrometry;    Two-dimensional phosphopeptide mapping;    AD;    Alzheimer's disease;    apoE;    apolipoprotein E;    BSA;    bovine serum albumin;    GSK-3β;    glycogen synthase kinase-3β;    MS;    mass spectrometry;    nano-ES;    nano-electrospray;    PHF;    paired helical filament;   

DOI  :  10.1016/S0014-5793(00)02196-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Previously published data have shown an allele-specific variation in the in vitro binding of apolipoprotein E (apoE) to tau, which prompted the hypothesis that apoE binding may protect tau from phosphorylation, apoE3 being more efficient than apoE4. We have, therefore, investigated the effects of apoE on tau phosphorylation in vitro by the proline-directed kinase, glycogen synthase kinase (GSK)-3β. The phosphopeptide maps of tau alone, of tau with apoE3 and of tau with apoE4 were very similar. When apoE2 was present a further four spots were evident. Additionally, of the 15 peptides phosphorylated in the presence or absence of apoE, subtle differences, some isoform-specific, in the relative amounts of phosphorylation were observed.

【 授权许可】

Unknown