UseCases_ArguminSci_Discourse  

PubMed:19545277 JSONTXT 9 Projects

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Id Subject Object Predicate Lexical cue
T1 0-166 DRI_Outcome denotes Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoforms and modulates microtubule stability--a point of convergence in parkinsonian neurodegeneration?
T2 167-304 DRI_Background denotes Autosomal dominant mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of late-onset Parkinson's disease.
T3 305-504 DRI_Background denotes The most prevalent LRRK2(G2019S) mutation has repeatedly been shown to enhance kinase activity and neurotoxicity, however, the molecular mechanisms leading to neurodegeneration remain poorly defined.
T4 505-695 DRI_Outcome denotes Here we show that recombinant human LRRK2 preferentially phosphorylates tubulin-beta purified from bovine brain and that phosphorylation is three-fold enhanced by the LRRK2(G2019S) mutation.
T5 696-890 DRI_Background denotes By tandem mass spectrometry, Thr107 was identified as phosphorylation site which is highly conserved between tubulin-beta family members and also between tubulin-beta genes of different species.
T6 891-981 DRI_Outcome denotes LRRK2 was co-immunoprecipitated with tubulin-beta both from wild-type mouse brain and from
T7 982-1003 Token_Label.OUTSIDE denotes LRRK2 over-expressing
T8 1003-1051 DRI_Outcome denotes , non-neuronal human embryonic kidney 293 cells.
T9 1052-1163 DRI_Background denotes However, an effect of LRRK2 on tubulin phosphorylation and assembly was only detectable in mouse brain samples.
T10 1164-1394 DRI_Outcome denotes In vitro co-incubation of bovine brain tubulins with LRRK2 increased microtubule stability in the presence of microtubule-associated proteins which may explain the reduction in neurite length in LRRK2-deficient neurons in culture.
T11 1395-1595 DRI_Challenge denotes These findings suggest that LRRK2(G2019S)-induced neurodegeneration in Parkinsonian brains may be partly mediated by increased phosphorylation of tubulin-beta and constraining of microtubule dynamics.