Tau-tubulin kinase phosphorylates tau at Ser-208 and Ser-210, sites found in paired helical filament-tau

Hyperphosphorylated tau protein is known to be a major component of the pai red helical filaments (PHFs) that accumulate in the brain of Alzheimer's pa tients, The kinase that phosphorylated Ser-208 and Ser-210 in PHF-tau had r emained unknown, We used anti-pS208 and anti-pS210 antibodies and Western b lots to confirm that the tau-tubulin kinase (TTK) phosphorylates tau at Ser -208 and at Ser-210, Using partial amino acid sequences of purified bovine brain TTK, a mouse cDNA of TTK was isolated and the sequence was determined . Its 963 bp coding region is composed of 320 amino acids and encodes a 36 kDa protein indistinguishable in size from authentic bovine brain TTK, Our immunoblot analysis demonstrated that TTK is ubiquitously distributed in th e rat tissues, and that it is developmentally regulated in the rat brain. ( C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.