title: Identification of casein kinase-1 phosphorylation sites on TDP-43.
abstract: TAR DNA-binding protein of 43 kDa (TDP-43) is deposited as hyperphosphorylated cytoplasmic and intranuclear inclusions in brains of patients with frontotemporal lobar degeneration with ubiquitinated inclusions and amyotrophic lateral sclerosis. In this study, we identified 29 phosphorylation sites on recombinant TDP-43 that are phosphorylated by casein kinase-1 (CK1). Interestingly, 18 of them were located in the C-terminal glycine-rich region of TDP-43. Our results indicate that CK1-mediated phosphorylation may play a role in the pathogenesis of these diseases.
authors.affiliation: Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan. kametani@prit.go.jp
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Kametani
authors.forename: Takashi
authors.initials: T
authors.lastname: Nonaka
authors.forename: Takehiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Arai
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
mesh_terms: D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D047389:Casein Kinase I / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D010768:Phosphoserine; D012694:Serine; D047389:Casein Kinase I