Application of synthetic phospho‐ and unphospho‐ peptides to identify phosphorylation sites in a subregion of the tau molecule, which is modified in Alzheimer's disease

Abstract

Phospho- and unphospho- peptides were used to define the essential sequence for a tau epitope, which is recognized by Tau-1 antibody and phosphorylated in Alzheimer's disease (AD). The epitope was mapped within the amino acid residues 192–199 of tau and was phosphorylated by the p34^cdc2/p58^{cyclin A} proline directed kinase (PDPK), but not by purified mitogen activated protein kinase (p42^mapk). Addition of phosphate to the last serine of the epitope was the most effective in abolishing the reactivity of the epitope to Tau-1 antibody. Our results suggest that one and possibly more members of the PDPK family may play a role in the pathogenesis of AD.