title: Hyperphosphorylation of tau in PHF.
abstract: Tau in PHF is known to be highly phosphorylated and immunochemical study has indicated the similarity of the phosphorylation between PHF-tau and fetal tau. We have determined the exact phosphorylation sites in both PHF-tau and fetal rat tau by ion-spray mass spectrometry and sequencing of ethanethiol-modified peptides. In PHF-tau, 19 sites have been identified; all the phosphorylation sites except for Ser-262 are localized to the amino- and carboxyl-terminal flanking regions of the microtubule-binding domain. Half of them are shared by fetal tau. Thus, PHF-tau is much more phosphorylated. Whereas most of the sites in fetal tau are proline-directed, half of them in PHF-tau are nonproline-directed. Overall, the hyperphosphorylation of PHF-tau can be considered to consist of fetal-type phosphorylation and additional proline-directed and nonproline-directed phosphorylation. This extraphosphorylation may provide PHF-tau with the unusual characteristics including assembly incompetence.
authors.affiliation: Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Morishima-Kawashima
authors.forename: M
authors.initials: M
authors.lastname: Hasegawa
authors.forename: K
authors.initials: K
authors.lastname: Takio
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: A
authors.initials: A
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Titani
authors.forename: Y
authors.initials: Y
authors.lastname: Ihara
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D000939:Epitopes; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D009454:Neurofibrils / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D000939:Epitopes; D016875:tau Proteins