title: The Alzheimer-like phosphorylation of tau protein reduces microtubule binding and involves Ser-Pro and Thr-Pro motifs.
abstract: Tau protein can be transformed into an Alzheimer-like state by phosphorylation with a kinase activity from brain [Biernat et al. (1992) EMBO J. 11, 1593-1597]. Here we show that the phosphorylation at Ser-Pro motifs strongly decreases tau's affinity for microtubules. The major reduction occurs during the first of the three main stages of phosphorylation. The data explain the lower stability of microtubules resulting from the pathological tau phosphorylation.
authors.affiliation: Max-Planck-Unit for Structural Molecular Biology, c/o DESY, Hamburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Gustke
authors.forename: B
authors.initials: B
authors.lastname: Steiner
authors.forename: E M
authors.initials: EM
authors.lastname: Mandelkow
authors.forename: J
authors.initials: J
authors.lastname: Biernat
authors.forename: H E
authors.initials: HE
authors.lastname: Meyer
authors.forename: M
authors.initials: M
authors.lastname: Goedert
authors.forename: E
authors.initials: E
authors.lastname: Mandelkow
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011392:Proline / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D013912:Threonine; D012694:Serine; D011392:Proline; D011494:Protein Kinases