Phosphorylation of more than one site is required for tight interaction of human tau protein with 14-3-3ζ

Serine residues phosphorylated by protein kinase A (PKA) in the shortest isoform of human tau protein (tau 3) were sequentially replaced by alanine and interaction of phosphorylated tau 3 and its mutants with 14-3-3 was investigated. Mutation S156A slightly decreased interaction of phosphorylated tau 3 with 14-3-3. Double mutations S156A/S267A and especially S156A/S235A, strongly inhibited interaction of phosphorylated tau 3 with 14-3-3. Thus, two sites located in the Pro-rich region and in the pseudo repeats of tau 3 are involved in phosphorylation-dependent interaction of tau 3 with 14-3-3. The state of tau 3 phosphorylation affects the mode of 14-3-3 binding and by this means might modify tau filament formation. Structured summary: MINT-7233358, MINT-7233372, MINT-7233384: 14-3-3 zeta (uniprotkb: P63104) and Tau 3 ( uniprotkb: P10636-3) bind (MI: 0407) by molecular sieving ( MI: 0071) MINT-7233323, MINT-7233334, MINT-7233346: Tau 3 ( uniprotkb: P10636-3) and 14-3-3 zeta ( uniprotkb: P63104) bind ( MI: 0407) by crosslinking studies ( MI: 0030) MINT-7233285, MINT-7233297, MINT-7233310: 14-3-3 zeta ( uniprotkb: P63104) and Tau 3 ( uniprotkb: P10636-3) bind ( MI: 0407) by comigration in non-denaturing gel electrophoresis ( MI: 0404) (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.