title: Phosphorylation of tau by cyclic-AMP-dependent protein kinase.
abstract: Alzheimer's disease paired helical filaments contain abnormally phosphorylated tau (PHF-tau) which has reduced electrophoretic mobility on sodium dodecyl sulphate polyacrylamide electrophoresis. We have investigated the effects of cyclic-AMP-dependent protein kinase (PKA) on recombinant human tau isoforms and two recombinant tau fragments. PKA phosphorylated tau and reduced its electrophoretic mobility, phosphorylation towards the C-terminus of tau having a major influence on this property. Substitution of serine396 (phosphorylated in PHF-tau) or serine416 (phosphorylated by calcium/calmodulin kinase II) by alanine demonstrated that these are not major sites for PKA phosphorylation. Although the phosphorylated forms of tau generated by PKA are not identical to those of PHF-tau, PKA may be involved in the generation of PHF-tau in Alzheimer's disease via phosphorylation of additional, as yet unidentified, sites on tau.
authors.affiliation: Department of Neuroscience, Institute of Psychiatry, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Robertson
authors.forename: T L
authors.initials: TL
authors.lastname: Loviny
authors.forename: M
authors.initials: M
authors.lastname: Goedert
authors.forename: R
authors.initials: R
authors.lastname: Jakes
authors.forename: K J
authors.initials: KJ
authors.lastname: Murray
authors.forename: B H
authors.initials: BH
authors.lastname: Anderton
authors.forename: D P
authors.initials: DP
authors.lastname: Hanger
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007536:Isomerism; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D016875:tau Proteins; D017868:Cyclic AMP-Dependent Protein Kinases