title: Differential expression of brain proteins in glycogen synthase kinase-3 transgenic mice: a proteomics point of view.
abstract: One of the landmarks of Alzheimer's disease are neurofibrillary tangles (NFT) in the brain. NFT mainly consist of a hyperphosphorylated form of the protein tau, which is responsible for stabilisation of the neuronal cytoskeleton by microtubule binding and is unable to function properly in its hyperphosphorylated form. Glycogen synthase kinase-3beta (GSK3beta) is able to phosphorylate tau in a cellular context which could play a role in the formation of these NFT. In order to learn more about the effect of GSK-3beta in the brain, two-dimensional electrophoresis patterns of cerebrum extracts of GSK3beta[S9A] transgenic mice and wild type mice were compared quantitatively. Fifty-one spots were identified as being different in integrated intensity by at least a factor 1.5. The spots were subsequently identified by mass spectrometry. Identification of several proteins linked to signal transduction pathways in which GSK3beta plays a role, indicates that our population of identified proteins includes some down stream proteins of GSK3beta. This study may contribute to filling the gaps between GSK3beta, its substrates and finally the phosphorylation of tau.
authors.affiliation: Department of Biochemistry, University of Antwerp, Antwerp, Belgium.
authors.forename: Kelly
authors.initials: K
authors.lastname: Tilleman
authors.forename: Ilse
authors.initials: I
authors.lastname: Stevens
authors.forename: Kurt
authors.initials: K
authors.lastname: Spittaels
authors.forename: Chris Van den
authors.initials: CV
authors.lastname: Haute
authors.forename: Stefan
authors.initials: S
authors.lastname: Clerens
authors.forename: Gert
authors.initials: G
authors.lastname: Van Den Bergh
authors.forename: Hugo
authors.initials: H
authors.lastname: Geerts
authors.forename: Fred
authors.initials: F
authors.lastname: Van Leuven
authors.forename: Frans
authors.initials: F
authors.lastname: Vandesande
authors.forename: Luc
authors.initials: L
authors.lastname: Moens
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010766:Phosphorylation; D020543:Proteome; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D020543:Proteome; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3