Glycogen synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localisation of the kinase.
Glycogen synthase kinase-3 (GSK-3) reduced the mobility of human tau on SDS-PAGE, prevented binding of the monoclonal antibody (mAb), Tau.1, and induced binding of the mAb 8D8. Recombinant tau phosphorylated by GSK-3 aligned on SDS-PAGE with the abnormally phosphorylated tau (PHF-tau) associated with the paired helical filaments in Alzheimer's disease brain. Phosphorylated serine396 (numbering of the largest human brain tau isoform) was identified as a binding site on tau for mAb 8D8. The localisation of GSK-3 within granular structures in pyramidal cells indicates that GSK-3 alpha and GSK-3 beta may have a role in the production of PHF-tau in Alzheimer's disease.
Hanger
D P
DP
Department of Neuroscience, Institute of Psychiatry, London, UK.
Hughes
K
K
Woodgett
J R
JR
Brion
J P
JP
Anderton
B H
BH
D000544:Alzheimer Disease / Q000378:metabolism*; D015153:Blotting, Western; D001923:Brain Chemistry; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004591:Electrophoresis, Polyacrylamide Gel; D038341:Glycogen Synthase Kinases; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007382:Intermediate Filaments / Q000201:enzymology*; D009474:Neurons / Q000201:enzymology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D011994:Recombinant Proteins; D016875:tau Proteins; D011494:Protein Kinases; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases