PubMed_ArguminSci  

PubMed:17623048 JSONTXT 11 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 135-282 DRI_Background denotes Mutations in Leucine-rich repeat kinase 2 (LRRK2) are linked to the most common familial forms and some sporadic forms of Parkinson's disease (PD).
T2 283-392 DRI_Background denotes The LRRK2 protein contains two well-known functional domains, MAPKKK-like kinase and Rab-like GTPase domains.
T3 393-513 DRI_Background denotes Emerging evidence shows that LRRK2 contains kinase activity which is enhanced in several PD-associated mutants of LRRK2.
T4 514-588 DRI_Outcome denotes However, the GTPase activity of LRRK2 has yet to be formally demonstrated.
T5 589-623 DRI_Outcome denotes Here, we produced and purified the
T6 645-802 DRI_Outcome denotes protein from transgenic mouse brain, and showed that purified brain LRRK2 possesses both kinase and GTPase activity as assayed by GTP binding and hydrolysis.
T7 803-936 DRI_Background denotes The brain LRRK2 is associated with elevated kinase activity in comparison to that from transgenic lung or transfected cultured cells.
T8 937-1055 DRI_Outcome denotes In transfected cell cultures, we detected GTP hydrolysis activity in full-length as well as in GTPase domain of LRRK2.
T9 1056-1235 DRI_Outcome denotes This result indicates that LRRK2 GTPase can be active independent of LRRK2 kinase activity (while LRRK2 kinase activity requires the presence of LRRK2 GTPase as previously shown).
T10 1236-1438 DRI_Outcome denotes We further found that PD mutation R1441C/G in the GTPase domain causes reduced GTP hydrolysis activity, consistent with the altered enzymatic activity in the mutant LRRK2 carrying PD familial mutations.
T11 1439-1500 DRI_Outcome denotes Therefore, our study shows the biochemical characteristics of
T12 1522-1581 DRI_Outcome denotes which is associated with robust kinase and GTPase activity.
T13 1582-1741 DRI_Background denotes The distinctive levels of kinase/GTPase activity in brain LRRK2 may help explain LRRK2-associated neuronal functions or dysfunctions in the pathogenesis of PD.