Lewis Patrick A, Greggio Elisa, Beilina Alexandra, Jain Shushant, Baker Acacia, Cookson Mark R
Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda, MD 20892-3707, USA.
Biochem Biophys Res Commun. 2007 Jun 8;357(3):668-71. doi: 10.1016/j.bbrc.2007.04.006. Epub 2007 Apr 10.
Mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are the leading genetic cause of Parkinson's disease (PD). LRRK2 is predicted to contain kinase and GTPase enzymatic domains, with recent evidence suggesting that the kinase activity of LRRK2 is central to the pathogenic process associated with this protein. The GTPase domain of LRRK2 plays an important role in the regulation of kinase activity. To investigate how the GTPase domain might be related to disease, we examined the GTP binding and hydrolysis properties of wild type and a mutant form of LRRK2. We show that LRRK2 immunoprecipitated from cells has a detectable GTPase activity that is disrupted by a familial mutation associated with PD located within the GTPase domain, R1441C.
富含亮氨酸重复激酶2（LRRK2）的突变是帕金森病（PD）的主要遗传病因。预计LRRK2含有激酶和GTP酶结构域，最近有证据表明LRRK2的激酶活性是与该蛋白相关的致病过程的核心。LRRK2的GTP酶结构域在激酶活性调节中起重要作用。为了研究GTP酶结构域可能与疾病的关系，我们检测了野生型和突变型LRRK2的GTP结合和水解特性。我们发现，从细胞中免疫沉淀的LRRK2具有可检测到的GTP酶活性，该活性被位于GTP酶结构域内的与PD相关的家族性突变R1441C破坏。
