Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system.
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.
Inglis
Kelly J
KJ
Elan Pharmaceuticals, South San Francisco, California 94080.
Chereau
David
D
Elan Pharmaceuticals, South San Francisco, California 94080.
Brigham
Elizabeth F
EF
Elan Pharmaceuticals, South San Francisco, California 94080.
Chiou
San-San
SS
Elan Pharmaceuticals, South San Francisco, California 94080.
Schöbel
Susanne
S
Elan Pharmaceuticals, South San Francisco, California 94080.
Frigon
Normand L
NL
Elan Pharmaceuticals, South San Francisco, California 94080.
Yu
Mei
M
Elan Pharmaceuticals, South San Francisco, California 94080.
Caccavello
Russell J
RJ
Elan Pharmaceuticals, South San Francisco, California 94080.
Nelson
Seth
S
Elan Pharmaceuticals, South San Francisco, California 94080.
Motter
Ruth
R
Elan Pharmaceuticals, South San Francisco, California 94080.
Wright
Sarah
S
Elan Pharmaceuticals, South San Francisco, California 94080.
Chian
David
D
Elan Pharmaceuticals, South San Francisco, California 94080.
Santiago
Pamela
P
Elan Pharmaceuticals, South San Francisco, California 94080.
Soriano
Ferdie
F
Elan Pharmaceuticals, South San Francisco, California 94080.
Ramos
Carla
C
Elan Pharmaceuticals, South San Francisco, California 94080.
Powell
Kyle
K
Elan Pharmaceuticals, South San Francisco, California 94080.
Goldstein
Jason M
JM
Elan Pharmaceuticals, South San Francisco, California 94080.
Babcock
Michael
M
Elan Pharmaceuticals, South San Francisco, California 94080.
Yednock
Ted
T
Elan Pharmaceuticals, South San Francisco, California 94080.
Bard
Frederique
F
Elan Pharmaceuticals, South San Francisco, California 94080.
Basi
Guriqbal S
GS
Elan Pharmaceuticals, South San Francisco, California 94080.
Sham
Hing
H
Elan Pharmaceuticals, South San Francisco, California 94080.
Chilcote
Tamie J
TJ
Elan Pharmaceuticals, South San Francisco, California 94080.
McConlogue
Lisa
L
Elan Pharmaceuticals, South San Francisco, California 94080.
Griswold-Prenner
Irene
I
Elan Pharmaceuticals, South San Francisco, California 94080.
Anderson
John P
JP
Elan Pharmaceuticals, South San Francisco, California 94080. Electronic address: john.p.anderson@elan.com.
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*
D017931:DNA Primers; D051844:alpha-Synuclein; D012694:Serine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C444640:serum-inducible kinase