File(s) not publicly available

Polo-like kinase 2 (PLK2) phosphorylates α-synuclein at Serine 129 in central nervous system

journal contribution
posted on 06.12.2017, 00:00 by KJ Inglis, D Chereau, EF Brigham, S-S Chiou, S Schobel, NL Frigon, M Yu, RJ Caccavello, S Nelson, R Motter
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-likekinase 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.

History

Volume

284

Issue

5

Start Page

2598

End Page

2602

Number of Pages

5

eISSN

1083-351X

ISSN

0021-9258

Location

USA

Publisher

American Society for Biochemistry and Molecular Biology

Additional Rights

Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0)

Language

en-aus

Peer Reviewed

Yes

Open Access

Yes

External Author Affiliations

ActiveSite Pharmaceuticals, Inc; Elan Pharmaceuticals, Inc; National Center for Preparedness, Detection, and Control of Infectious Diseases (U.S.); TBA Research Institute;

Era Eligible

Yes

Journal

Journal of Biological Chemistry

Usage metrics

Exports