Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system.
Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system.
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DOI：
10.1074/jbc.c800206200
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发表时间：
2009-01-30
影响因子：
4.8
通讯作者：
Anderson, John P.
中科院分区：
文献类型：
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作者：
Inglis, Kelly J.;Chereau, David;Brigham, Elizabeth F.;Chiou, San-San;Schoebel, 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.
一些神经系统疾病，包括帕金森病和路易体痴呆，都是以α-突触核蛋白在Ser129(p-Ser129)处的磷酸化积累为特征的。负责这种磷酸化的一个或多个激酶一直是深入研究的对象。在这里，我们提出证据表明，Polo-like kinase2(PLK2，也被称为血清诱导的激酶或SNK)是神经元中α-突触核蛋白磷酸化的主要贡献者。在体外生化实验中，PLK2直接磷酸化α-突触核蛋白。在原代培养的大脑皮层细胞和体内的小鼠脑中，PLK激酶的抑制剂均抑制α-突触核蛋白的磷酸化。最后，通过短发夹状RNA结构的转导或通过敲除PLK2基因来特异性地抑制PLK2的表达，降低了p-Ser-129的水平。这些结果表明，PLK2在中枢神经系统α-突触核蛋白的磷酸化过程中起着关键作用。
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.