Proline-directed and non-proline-directed phosphorylation of PHF-tau.
To gain insight into the abnormal phosphorylation of PHF-tau, we have determined the phosphorylation sites by identifying phosphopeptides by means of ion spray mass spectrometry followed by sequencing of ethane-thiol-modified peptides. Nineteen sites have been identified; all but Ser-262 are localized to the amino- and carboxyl-terminal flanking regions of the microtubule-binding domain. Eleven sites correspond to fetal type sites. Unexpectedly, 10 are non-proline-directed, whereas the others are proline-directed. Thus, the abnormal phosphorylation of PHF-tau can be considered to consist of fetal type phosphorylation and additional proline-directed and non-proline-directed phosphorylation. This non-fetal type phosphorylation may provide PHF-tau with the unusual characteristics.
Morishima-Kawashima
M
M
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
Hasegawa
M
M
Takio
K
K
Suzuki
M
M
Yoshida
H
H
Titani
K
K
Ihara
Y
Y
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D008969:Molecular Sequence Data; D009454:Neurofibrils / Q000378:metabolism*; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D011392:Proline / Q000378:metabolism*; D051381:Rats; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D010748:Phosphopeptides; D016875:tau Proteins; D011392:Proline