Identification of casein kinase-1 phosphorylation sites on TDP-43.
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.
Kametani
Fuyuki
F
Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan. kametani@prit.go.jp
Nonaka
Takashi
T
Suzuki
Takehiro
T
Arai
Tetsuaki
T
Dohmae
Naoshi
N
Akiyama
Haruhiko
H
Hasegawa
Masato
M
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
D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D010768:Phosphoserine; D012694:Serine; D047389:Casein Kinase I