Fetal-type phosphorylation of the tau in paired helical filaments.

To determine the phosphorylation sites of the tau in paired helical filaments (PHF), two types of PHF antisera with different specificities were used: One was a conventional anti-PHF, and the other was an antiserum to formic acid-denatured PHF (anti-HFoPHF). Phosphorylated tau-specific antibodies, anti-ptau 1 and anti-ptau 2, were prepared from anti-PHF and anti-HFoPHF, respectively. We found that both anti-ptau 1 and anti-ptau 2 labeled fetal or juvenile tau but not adult tau. The anti-ptau 1- and anti-ptau 2-recognition sites were immunochemically localized to the fragment Asp313 to Ile328 in the most COOH-terminal portion of tau. Furthermore, Ser315 was determined as the anti-ptau 2 recognition site. The sequence surrounding Ser315 was not found in the canonical sequences phosphorylated with known kinases.