Involvement of τ Protein Kinase I in Paired Helical Filament‐Like Phosphorylation of the Juvenile τ in Rat Brain

τ protein kinase 1 (TPK1) phosphorylates τ and forms paired helical filament epitopes in vitro. We studied temporal expression and histochemical distribution of τ phosphoserine epitopes at sites known to be phosphorylated by TPKI. Antibodies directed against phosphorylated Ser 199 (anti-PS 199) or phosphorylated Ser 396 (CS or anti-PS 396) were used. TPK1 is abundantly expressed in the young rat brain and the highly phosphorylated juvenile form of τ occurs in the same period. The activity peak of TPK1 coincided with the high level of phosphorylation of Ser 199 and Ser 396 in juvenile τ at around postnatal day 8. By immunohistochemistry on the hippocampus and neocortex of 3-11-day-old rats, phosphorylated Ser 396 was found in young axonal tracts and neuropil, where TPK1 immunoreactivity was also detected. TPK1 and phospho-Ser 199 immunoreactivities were also detected in the perikarya of pyramidal neurons. TPK1 immunoreactivity had declined to a low level and phosphorylated serine immunoreactivities were undetectable in the sections of adult brain. These findings implicate TPK1 in paired helical filament-like phosphorylation of juvenile form of τ in the developing brain