Polo-like Kinase 2 (PLK2) Phosphorylates α-Synuclein at Serine 129 in Central Nervous System

被引：182

作者：

Inglis, Kelly J. ^{[1
]}

Chereau, David ^{[1
]}

Brigham, Elizabeth F. ^{[1
]}

Chiou, San-San ^{[1
]}

Schoebel, Susanne ^{[1
]}

Frigon, Normand L. ^{[1
]}

Yu, Mei ^{[1
]}

Caccavello, Russell J. ^{[1
]}

Nelson, Seth ^{[1
]}

Motter, Ruth ^{[1
]}

Wright, Sarah ^{[1
]}

Chian, David ^{[1
]}

Santiago, Pamela ^{[1
]}

Soriano, Ferdie ^{[1
]}

Ramos, Carla ^{[1
]}

Powell, Kyle ^{[1
]}

Goldstein, Jason M. ^{[1
]}

Babcock, Michael ^{[1
]}

Yednock, Ted ^{[1
]}

Bard, Frederique ^{[1
]}

Basi, Guriqbal S. ^{[1
]}

Sham, Hing ^{[1
]}

Chilcote, Tamie J. ^{[1
]}

McConlogue, Lisa ^{[1
]}

Griswold-Prenner, Irene ^{[1
]}

Anderson, John P. ^{[1
]}

机构：

[1] Elan Pharmaceut Inc, San Francisco, CA 94080 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 05期

关键词：

FAMILIAL PARKINSONS-DISEASE; LEWY BODIES; SYNAPTIC PLASTICITY; PROTEIN-KINASE; DEMENTIA; MUTATION; SER-129; IDENTIFICATION; NEUROTOXICITY; DUPLICATION;

D O I：

10.1074/jbc.C800206200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2598 / 2602

页数：5

共 33 条

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