| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
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. |
| T2 |
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. |
| T3 |
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. |
| T4 |
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. |
| T5 |
891-981 |
DRI_Outcome |
denotes |
LRRK2 was co-immunoprecipitated with tubulin-beta both from wild-type mouse brain and from |
| T6 |
1003-1051 |
DRI_Outcome |
denotes |
, non-neuronal human embryonic kidney 293 cells. |
| T7 |
1052-1163 |
DRI_Background |
denotes |
However, an effect of LRRK2 on tubulin phosphorylation and assembly was only detectable in mouse brain samples. |
| T8 |
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. |
| T9 |
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. |
