title: Phosphorylation of native and truncated isoforms of protein tau by the double-stranded DNA-dependent protein kinase (DNA-PK) shows that the primary phosphorylation sites are localized between amino acid residues 212-231 of the longest tau.
abstract: Alzheimer's disease (AD) is pathologically characterized by the appearance of neurofibrillary tangles (NFT), senile plaques, and loss of subpopulation of neuronal cells. The NFT is composed of paired helical filaments (PHT) with extensively modified protein T as its primary constituent. Previously we had reported on the hyperphosphorylation of T by a double-stranded-DNA-stimulated protein kinase (DNA-PK). In this communication, we have compared the DNA-PK mediated phosphorylation of native and truncated TS with that catalyzed by the cAMP-dependent protein kinase (PKA). In addition, we have attempted to map the primary site(s) of phosphorylation of T by DNA-PK. Our results suggest that DNA-PK phosphorylates T at sites substantially different from those targeted by PKA. Furthermore, we show that the primary phosphorylation sites lie between amino acid residues 212-231 (using numbering system for the longest T, which is the isoform with four "repeats" and a 58 amino acid "insert" at the carboxyl- and amino-termini, respectively, of the protein molecule).
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Wu
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: T C
authors.initials: TC
authors.lastname: Hsieh
authors.forename: R
authors.initials: R
authors.lastname: Brandt
authors.forename: G
authors.initials: G
authors.lastname: Lee
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D001665:Binding Sites; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D010748:Phosphopeptides / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D010748:Phosphopeptides; D016875:tau Proteins; D004247:DNA; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D014357:Trypsin