| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-97 |
DRI_Background |
denotes |
Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. |
| T2 |
98-263 |
DRI_Outcome |
denotes |
Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) cause late-onset Parkinson's disease (PD) with a clinical appearance indistinguishable from idiopathic PD. |
| T3 |
264-435 |
DRI_Background |
denotes |
Initial studies suggest that LRRK2 mutations are the most common yet identified determinant of PD susceptibility, transmitted in an autosomal-dominant mode of inheritance. |
| T4 |
436-538 |
DRI_Approach |
denotes |
Herein, we characterize the LRRK2 gene and transcript in human brain and subclone the predominant ORF. |
| T5 |
539-707 |
DRI_Background |
denotes |
Exogenously expressed LRRK2 protein migrates at approximately 280 kDa and is present largely in the cytoplasm but also associates with the mitochondrial outer membrane. |
| T6 |
708-839 |
DRI_Approach |
denotes |
Familial-linked mutations G2019S or R1441C do not have an obvious effect on protein steady-state levels, turnover, or localization. |
| T7 |
840-1050 |
DRI_Background |
denotes |
However, in vitro kinase assays using full-length recombinant LRRK2 reveal an increase in activity caused by familial-linked mutations in both autophosphorylation and the phosphorylation of a generic substrate. |
| T8 |
1051-1192 |
DRI_Challenge |
denotes |
These results suggest a gain-of-function mechanism for LRRK2-linked disease with a central role for kinase activity in the development of PD. |
