（自）磷酸化在 LRRK2 复杂激活机制中的作用。

The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2.

机构信息

Department of Cell Biochemistry, University of Groningen, Nijenborgh 7, NL-9747 AG Groningen, The Netherlands.

Faculty of Chemistry and Biochemistry, Molecular Neurobiochemistry, Ruhr University Bochum, Universitätstrasse 150, D-44780 Bochum, Germany.

出版信息

Biol Chem. 2018 Jun 27;399(7):643-647. doi: 10.1515/hsz-2017-0332.

DOI:10.1515/hsz-2017-0332

PMID:29537215

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.

摘要

人类富含亮氨酸重复激酶 2（LRRK2）的突变已被发现是导致晚发性帕金森病（PD）的最常见原因。LRRK2 是一种具有两个酶结构域的大型蛋白质，即 GTPase 和激酶结构域。研究表明，LRRK2 N 端的一簇（自身）磷酸化位点对于 LRRK2 的定位至关重要，并且对 PD 的发病机制很重要。此外，蛋白质 G 结构域内的磷酸化位点的磷酸化会影响 GTPase 活性。在这里，我们讨论这些 LRRK2 的（自身）磷酸化位点及其被磷酸酶和上游激酶调节的作用。