Polo-like Kinase 2 (PLK2) Phosphorylates α-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 α-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 sub...

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Bibliographic Details
Published in:The Journal of biological chemistry 2009-01, Vol.284 (5), p.2598-2602
Main Authors: Inglis, Kelly J., Chereau, David, Brigham, Elizabeth F., Chiou, San-San, Schöbel, Susanne, Frigon, Normand L., Yu, Mei, Caccavello, Russell J., Nelson, Seth, Motter, Ruth, Wright, Sarah, Chian, David, Santiago, Pamela, Soriano, Ferdie, Ramos, Carla, Powell, Kyle, Goldstein, Jason M., Babcock, Michael, Yednock, Ted, Bard, Frederique, Basi, Guriqbal S., Sham, Hing, Chilcote, Tamie J., McConlogue, Lisa, Griswold-Prenner, Irene, Anderson, John P.
Format: Article
Language:English
Subjects:
Accelerated Publication
alpha-Synuclein - chemistry
alpha-Synuclein - metabolism
Animals
Base Sequence
Cell Line
Central Nervous System - enzymology
Central Nervous System - metabolism
DNA Primers
Enzyme-Linked Immunosorbent Assay
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphorylation
Protein Kinases - metabolism
Protein-Serine-Threonine Kinases
RNA Interference
Serine - metabolism
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Summary:Several neurological diseases, including Parkinson disease and dementia with Lewy bodies, are characterized by the accumulation of α-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 α-synuclein phosphorylation at Ser-129 in neurons. PLK2 directly phosphorylates α-synuclein at Ser-129 in an in vitro biochemical assay. Inhibitors of PLK kinases inhibited α-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 α-synuclein phosphorylation in central nervous system.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.C800206200