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

被引：6
|
作者：
Athanasopoulos, Panagiotis S. [1 ,2 ]
Heumann, Rolf [2 ]
Kortholt, Arjan [1 ]
机构：
[1] Univ Groningen, Dept Cell Biochem, Nijenborgh 7, NL-9747 AG Groningen, Netherlands
[2] Ruhr Univ Bochum, Fac Chem & Biochem, Mol Neurobiochem, Univ Str 150, D-44780 Bochum, Germany
来源：
BIOLOGICAL CHEMISTRY | 2018年 / 399卷 / 07期
基金：
欧盟地平线“2020”;
关键词：
GTPase; kinase; neuronal degeneration; Parkinson's disease; phosphatases; DISEASE-ASSOCIATED MUTATIONS; SYNAPTIC VESICLE TRAFFICKING; PARKINSONS-DISEASE; KINASE-ACTIVITY; GTP-BINDING; PHOSPHORYLATION; PENETRANCE; PHENOTYPE; DISRUPTS;
D O I：
10.1515/hsz-2017-0332
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：643 / 647
页数：5
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