The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2
Author:
Athanasopoulos Panagiotis S.12, Heumann Rolf2, Kortholt Arjan1
Affiliation:
1. Department of Cell Biochemistry , University of Groningen , Nijenborgh 7 , NL-9747 AG Groningen , The Netherlands 2. Faculty of Chemistry and Biochemistry , Molecular Neurobiochemistry, Ruhr University Bochum , Universitätstrasse 150 , D-44780 Bochum , Germany
Abstract
Abstract
Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson’s Disease (PD). LRRK2 is a large protein with two enzymatic domains, a GTPase and a kinase domain. A cluster of (auto)-phosphorylation sites within the N-terminus of LRRK2 have been shown to be crucial for the localization of LRRK2 and is important for PD pathogenesis. In addition, phosphorylation of sites within the G-domain of the protein affect GTPase activity. Here we discuss the role of these (auto)-phosphorylation sites of LRRK2 and their regulation by phosphatases and upstream kinases.
Publisher
Walter de Gruyter GmbH
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
Reference30 articles.
1. Alcalay, R.N., Mirelman, A., Saunders-Pullman, R., Tang, M.-X., Mejia Santana, H., Raymond, D., Roos, E., Orbe-Reilly, M., Gurevich, T., Bar Shira, A., et al. (2013). Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations. Mov. Disord. 28, 1966–1971. 2. Anand, V.S., Reichling, L.J., Lipinski, K., Stochaj, W., Duan, W., Kelleher, K., Pungaliya, P., Brown, E.L., Reinhart, P.H., Somberg, R., et al. (2009). Investigation of leucine-rich repeat kinase 2: enzymological properties and novel assays. FEBS J. 276, 466–478. 3. Athanasopoulos, P.S., Wright, J., Neumann, S., Kutsch, M., Wolters, D., Tan, E.K., Bichler, Z., Herrmann, C., and Heumann, R. (2016). Identification of protein phosphatase 2A as an interacting protein of leucine-rich repeat kinase 2. Biol. Chem. 397, 541–554. 4. Carrion, M.D.P., Marsicano, S., Daniele, F., Marte, A., Pischedda, F., Di Cairano, E., Piovesana, E., von Zweydorf, F., Kremmer, E., Gloeckner, C.J., et al. (2017). The LRRK2 G2385R variant is a partial loss-of-function mutation that affects synaptic vesicle trafficking through altered protein interactions. Sci. Rep. 7, 5377. 5. Cookson, M. and Bandmann, O. (2010). Parkinson’s disease: insights from pathways. Hum. Mol. Genet. 19, R21–R27.
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