Phosphorylation of more than one site is required for tight interaction of human tau protein with 14-3-3zeta.
Serine residues phosphorylated by protein kinase A (PKA) in the shortest isoform of human tau protein (tau3) were sequentially replaced by alanine and interaction of phosphorylated tau3 and its mutants with 14-3-3 was investigated. Mutation S156A slightly decreased interaction of phosphorylated tau3 with 14-3-3. Double mutations S156A/S267A and especially S156A/S235A, strongly inhibited interaction of phosphorylated tau3 with 14-3-3. Thus, two sites located in the Pro-rich region and in the pseudo repeats of tau3 are involved in phosphorylation-dependent interaction of tau3 with 14-3-3. The state of tau3 phosphorylation affects the mode of 14-3-3 binding and by this means might modify tau filament formation.
Sluchanko
Nikolai N
NN
Department of Biochemistry, School of Biology, M.V. Lomonosov Moscow State University, Moscow, Russian Federation.
Seit-Nebi
Alim S
AS
Gusev
Nikolai B
NB
D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D017354:Point Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D048948:14-3-3 Proteins; C054369:MAPT protein, human; D020033:Protein Isoforms; D016875:tau Proteins; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases