14-3-3 connects glycogen synthase kinase-3 beta to tau within a brain microtubule-associated tau phosphorylation complex.
In a recent study, we reported that in bovine brain extract, glycogen synthase kinase-3beta and tau are parts of an approximately 400-500 kDa microtubule-associated tau phosphorylation complex (Sun, W., Qureshi, H. Y., Cafferty, P. W., Sobue, K., Agarwal-Mawal, A., Neufield, K. D., and Paudel, H. K. (2002) J. Biol. Chem. ... 277, 11933-11940). In this study, we find that when purified brain microtubules are subjected to Superose 12 gel filtration column chromatography, the dimeric scaffold protein 14-3-3 zeta co-elutes with the tau phosphorylation complex components tau and GSK3 beta. From gel filtration fractions containing the tau phosphorylation complex, 14-3-3 zeta, GSK3 beta, and tau co-immunoprecipitate with each other. From extracts of bovine brain, COS-7 cells, and HEK-293 cells transfected with GSK3 beta, 14-3-3 zeta co-precipitates with GSK3 beta, indicating that GSK3 beta binds to 14-3-3 zeta. From HEK-293 cells transfected with tau, GSK3 beta, and 14-3-3 zeta in different combinations, tau co-immunoprecipitates with GSK3 beta only in the presence of 14-3-3 zeta. In vitro, approximately 10-fold more tau binds to GSK3 beta in the presence of than in the absence of 14-3-3 zeta. In transfected HEK-293 cells, 14-3-3 zeta stimulates GSK3 beta-catalyzed tau phosphorylation in a dose-dependent manner. These data indicate that in brain, the 14-3-3 zeta dimer simultaneously binds and bridges tau and GSK3 beta and stimulates GSK3 beta-catalyzed tau phosphorylation.
Mesh Terms:
14-3-3 Proteins, Animals, Base Sequence, Brain, COS Cells, Cattle, Cell Fractionation, Cell Line, Chlorocebus aethiops, Cloning, Molecular, DNA Primers, Glycogen Synthase Kinase 3, Glycogen Synthase Kinase 3 beta, Humans, Microtubules, Phosphorylation, Recombinant Fusion Proteins, Recombinant Proteins, Transfection, Tyrosine 3-Monooxygenase, tau Proteins
14-3-3 Proteins, Animals, Base Sequence, Brain, COS Cells, Cattle, Cell Fractionation, Cell Line, Chlorocebus aethiops, Cloning, Molecular, DNA Primers, Glycogen Synthase Kinase 3, Glycogen Synthase Kinase 3 beta, Humans, Microtubules, Phosphorylation, Recombinant Fusion Proteins, Recombinant Proteins, Transfection, Tyrosine 3-Monooxygenase, tau Proteins
J. Biol. Chem.
Date: Apr. 11, 2003
PubMed ID: 12551948
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