Polo-like Kinase 2 (PLK2) Phosphorylates α-Synuclein at Serine 129 in Central Nervous System
Year: 2008
Type: article
Abstract: 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.
Source: Journal of Biological Chemistry
Authors: 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, John P. Anderson
Institution: Elan Pharmaceuticals, Inc. (Ireland)
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1981172305