UseCases_ArguminSci_Discourse  

PubMed:23241745 JSONTXT 11 Projects

Annnotations TAB TSV DIC JSON TextAE Lectin_function

Id Subject Object Predicate Lexical cue
T1 0-125 DRI_Background denotes Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations.
T2 126-248 DRI_Approach denotes Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson's disease (PD).
T3 249-447 DRI_Background denotes Although biochemical studies have shown that certain PD mutations confer elevated kinase activity in vitro on LRRK2, there are no methods available to directly monitor LRRK2 kinase activity in vivo.
T4 448-618 DRI_Outcome denotes We demonstrate that LRRK2 autophosphorylation on Ser(1292) occurs in vivo and is enhanced by several familial PD mutations including N1437H, R1441G/C, G2019S, and I2020T.
T5 619-703 DRI_Approach denotes Combining two PD mutations together further increases Ser(1292) autophosphorylation.
T6 704-855 DRI_Background denotes Mutation of Ser(1292) to alanine (S1292A) ameliorates the effects of LRRK2 PD mutations on neurite outgrowth in cultured rat embryonic primary neurons.
T7 856-960 DRI_Outcome denotes Using cell-based and pharmacodynamic assays with phosphorylated Ser(1292) as the readout, we developed a
T8 961-984 Token_Label.OUTSIDE denotes brain-penetrating LRRK2
T9 985-1124 DRI_Outcome denotes kinase inhibitor that blocks Ser(1292) autophosphorylation in vivo and attenuates the cellular consequences of LRRK2 PD mutations in vitro.
T10 1125-1305 DRI_Outcome denotes These data suggest that Ser(1292) autophosphorylation may be a useful indicator of LRRK2 kinase activity in vivo and may contribute to the cellular effects of certain PD mutations.