title: Casein kinase 2 is the major enzyme in brain that phosphorylates Ser129 of human alpha-synuclein: Implication for alpha-synucleinopathies.
abstract: In Lewy body diseases and multiple system atrophy, alpha-synuclein is hyperphosphorylated at Ser129, suggesting a role in pathogenesis. Here, we report purification of the protein kinase in rat brain that phosphorylates Ser129 and its identification as casein kinase-2 (CK2). We show that most of the activity can be inhibited by heparin, an inhibitor of CK2. Phosphorylated Ser129 was detected in primary cultured neurons and inhibited by CK2 inhibitors. In some cases of Lewy body disease, CK2-like immunoreactivity was recovered in the sarkosyl-insoluble fraction, which was enriched in phosphorylated alpha-synuclein. Taken together, these findings suggest that CK2 may be involved in the hyperphosphorylation of alpha-synuclein in alpha-synucleinopathies.
authors.affiliation: Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
authors.forename: Aasami
authors.initials: A
authors.lastname: Ishii
authors.forename: Takashi
authors.initials: T
authors.lastname: Nonaka
authors.forename: Sayuri
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Taro
authors.initials: T
authors.lastname: Saito
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Arai
authors.forename: David
authors.initials: D
authors.lastname: Mann
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Hisanaga
authors.forename: Michel
authors.initials: M
authors.lastname: Goedert
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
mesh_terms: D000409:Alanine / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*; D010768:Phosphoserine / Q000378:metabolism*; D051381:Rats; D046509:Tissue Culture Techniques; D051844:alpha-Synuclein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000939:Epitopes; D051844:alpha-Synuclein; D010768:Phosphoserine; D006493:Heparin; D047390:Casein Kinase II; D000409:Alanine