title: Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system.
abstract: Several neurological diseases, including Parkinson disease and dementia with Lewy bodies, are characterized by the accumulation of alpha-synuclein phosphorylated at Ser-129 (p-Ser-129). The kinase or kinases responsible for this phosphorylation have been the subject of intense investigation. Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons. PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay. Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo. Finally, specific knockdown of PLK2 expression by transduction with short hairpin RNA constructs or by knock-out of the plk2 gene reduced p-Ser-129 levels. These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system.
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Inglis
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: David
authors.initials: D
authors.lastname: Chereau
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Brigham
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: San-San
authors.initials: SS
authors.lastname: Chiou
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schöbel
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Normand L
authors.initials: NL
authors.lastname: Frigon
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Caccavello
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Seth
authors.initials: S
authors.lastname: Nelson
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Ruth
authors.initials: R
authors.lastname: Motter
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wright
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: David
authors.initials: D
authors.lastname: Chian
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Pamela
authors.initials: P
authors.lastname: Santiago
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Ferdie
authors.initials: F
authors.lastname: Soriano
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Carla
authors.initials: C
authors.lastname: Ramos
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Kyle
authors.initials: K
authors.lastname: Powell
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Goldstein
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Michael
authors.initials: M
authors.lastname: Babcock
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Ted
authors.initials: T
authors.lastname: Yednock
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Frederique
authors.initials: F
authors.lastname: Bard
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Guriqbal S
authors.initials: GS
authors.lastname: Basi
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Hing
authors.initials: H
authors.lastname: Sham
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Tamie J
authors.initials: TJ
authors.lastname: Chilcote
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Lisa
authors.initials: L
authors.lastname: McConlogue
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080.
authors.forename: Irene
authors.initials: I
authors.lastname: Griswold-Prenner
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080. Electronic address: john.p.anderson@elan.com.
authors.forename: John P
authors.initials: JP
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002490:Central Nervous System / Q000201:enzymology / Q000378:metabolism*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D034622:RNA Interference; D012694:Serine / Q000378:metabolism*; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D051844:alpha-Synuclein; D012694:Serine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C444640:serum-inducible kinase