14-3-3Zeta does not increase GSK3beta-mediated tau phosphorylation in cell culture models.
Tau is a neuronal microtubule-associated protein whose function is regulated by site-specific phosphorylation. One protein kinase that is likely to play an important role in regulating the phosphorylation state of tau in vivo is glycogen synthase kinase (GSK) 3beta. The activity of GSK3beta is regulated by specific protein-protein interactions and 14-3-3zeta, a member of a protein family that can act as scaffolds, was recently reported to co-purify with GSK3beta in a large protein complex that was isolated from bovine brain [A. Agarwal-Mawal, H.Y. Qureshi, P.W. Cafferty, Z. Yuan, D. Han, R. Lin, H.K. Paudel, 14-3-3 connects glycogen synthase kinase-3 beta to tau within a brain microtubule-associated tau phosphorylation complex, J. Biol. Chem. 278 (2003) 12722-12728]. The purpose of this study was to determine if 14-3-3zeta could act as a scaffolding protein to promote the interaction of GSK3beta with tau and subsequently, enhance GSK3beta-mediated tau hyperphosphorylation. We used cell culture models, immunoprecipitation, and Western blotting to examine the interaction of GSK3beta and 14-3-3zeta with both exogenously and endogenously expressed proteins. We found that GSK3beta, 14-3-3zeta and tau do not interact in these cellular models under our experimental conditions and that GSK3beta-mediated tau phosphorylation is not effected by the presence of 14-3-3zeta. These data indicate that 14-3-3zeta may not be directly interacting with GSK3beta and tau in the brain, but may indirectly facilitate the interactions by binding to other proteins.
Matthews
Tori A
TA
Department of Psychiatry, School of Medicine, 1720 7th Avenue South, SC1061, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA.
Johnson
Gail V W
GV
D048948:14-3-3 Proteins / Q000378:metabolism*; D002460:Cell Line; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
D048948:14-3-3 Proteins; D016875:tau Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3