title: Microtubule-associated protein tau, paired helical filaments, and phosphorylation.
abstract: This paper summarizes our recent studies on microtubule-associated protein tau and its pathological state resembling that of the paired helical filaments of Alzheimer's disease. The Alzheimer-like state of tau protein can be identified and analyzed in terms of certain phosphorylation sites and phosphorylation-dependent antibody epitopes. It can be induced by protein kinases which tend to phosphorylate serine or threonine residues followed by a proline; this includes mitogen-activated protein kinase (MAPK) and glycogen-synthase kinase 3 (GSK-3). Both of these are tightly associated with microtubules as well as with paired helical filaments. Structurally, tau appears as a rod-like molecule; it tends to self-associate into dimers whose monomers are antiparallel. Constructs of truncated tau made up of antiparallel dimers of the microtubule binding domain can be assembled into paired helical filaments in vitro.
authors.affiliation: Max-Planck-Unit for Structural Molecular Biology, Hamburg, Germany.
authors.forename: E M
authors.initials: EM
authors.lastname: Mandelkow
authors.forename: J
authors.initials: J
authors.lastname: Biernat
authors.forename: G
authors.initials: G
authors.lastname: Drewes
authors.forename: B
authors.initials: B
authors.lastname: Steiner
authors.forename: B
authors.initials: B
authors.lastname: Lichtenberg-Kraag
authors.forename: H
authors.initials: H
authors.lastname: Wille
authors.forename: N
authors.initials: N
authors.lastname: Gustke
authors.forename: E
authors.initials: E
authors.lastname: Mandelkow
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000939:Epitopes / Q000032:analysis; D006801:Humans; D008854:Microscopy, Electron; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000648:ultrastructure; D016875:tau Proteins / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000939:Epitopes; D011994:Recombinant Proteins; D016875:tau Proteins; D011494:Protein Kinases