• Kelly J Inglis, David Chereau, Elizabeth F Brigham, San-San Chiou, Susanne Schöbel, Normand L Frigon, Mei Yu, Russell J Caccavello, Seth Nelson, Ruth Motter, Sarah Wright, David Chian, Pamela Santiago, Ferdie Soriano, Carla Ramos, Kyle Powell, Jason M Goldstein, Michael Babcock, Ted Yednock, Frederique Bard, Guriqbal S Basi, Hing Sham, Tamie J Chilcote, Lisa McConlogue, Irene Griswold-Prenner, and John P Anderson.
• Elan Pharmaceuticals Inc, South San Francisco, CA 94080, USA.
• J. Biol. Chem. 2009 Jan 30;284(5):2598-602.

AbstractSeveral 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.

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