PubMed:22773119 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/22773119","sourcedb":"PubMed","sourceid":"22773119","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/22773119","text":"The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway.\nMutations in leucine-rich repeat kinase 2 (LRRK2) are a major cause of familial Parkinsonism, and the G2019S mutation of LRRK2 is one of the most prevalent mutations. The deregulation of autophagic processes in nerve cells is thought to be a possible cause of Parkinson's disease (PD). In this study, we observed that G2019S mutant fibroblasts exhibited higher autophagic activity levels than control fibroblasts. Elevated levels of autophagic activity can trigger cell death, and in our study, G2019S mutant cells exhibited increased apoptosis hallmarks compared to control cells. LRRK2 is able to induce the phosphorylation of MAPK/ERK kinases (MEK). The use of 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126), a highly selective inhibitor of MEK1/2, reduced the enhanced autophagy and sensibility observed in G2019S LRRK2 mutation cells. These data suggest that the G2019S mutation induces autophagy via MEK/ERK pathway and that the inhibition of this exacerbated autophagy reduces the sensitivity observed in G2019S mutant cells.","tracks":[{"project":"PubTator4TogoVar","denotations":[{"id":"22773119_0","span":{"begin":10,"end":16},"obj":"ProteinMutation"},{"id":"22773119_1","span":{"begin":197,"end":203},"obj":"ProteinMutation"},{"id":"22773119_2","span":{"begin":413,"end":419},"obj":"ProteinMutation"},{"id":"22773119_3","span":{"begin":590,"end":596},"obj":"ProteinMutation"},{"id":"22773119_4","span":{"begin":927,"end":933},"obj":"ProteinMutation"},{"id":"22773119_5","span":{"begin":984,"end":990},"obj":"ProteinMutation"},{"id":"22773119_6","span":{"begin":1128,"end":1134},"obj":"ProteinMutation"}],"attributes":[{"id":"22773119_0_ProteinMutation","pred":"proteinmutation","subj":"22773119_0","obj":"rs34637584"},{"id":"22773119_1_ProteinMutation","pred":"proteinmutation","subj":"22773119_1","obj":"rs34637584"},{"id":"22773119_2_ProteinMutation","pred":"proteinmutation","subj":"22773119_2","obj":"rs34637584"},{"id":"22773119_3_ProteinMutation","pred":"proteinmutation","subj":"22773119_3","obj":"rs34637584"},{"id":"22773119_4_ProteinMutation","pred":"proteinmutation","subj":"22773119_4","obj":"rs34637584"},{"id":"22773119_5_ProteinMutation","pred":"proteinmutation","subj":"22773119_5","obj":"rs34637584"},{"id":"22773119_6_ProteinMutation","pred":"proteinmutation","subj":"22773119_6","obj":"rs34637584"},{"subj":"22773119_0","pred":"source","obj":"PubTator4TogoVar"},{"subj":"22773119_1","pred":"source","obj":"PubTator4TogoVar"},{"subj":"22773119_2","pred":"source","obj":"PubTator4TogoVar"},{"subj":"22773119_3","pred":"source","obj":"PubTator4TogoVar"},{"subj":"22773119_4","pred":"source","obj":"PubTator4TogoVar"},{"subj":"22773119_5","pred":"source","obj":"PubTator4TogoVar"},{"subj":"22773119_6","pred":"source","obj":"PubTator4TogoVar"}]},{"project":"c_corpus","denotations":[{"id":"T1","span":{"begin":4,"end":9},"obj":"PR:Q5S006"},{"id":"T2","span":{"begin":4,"end":9},"obj":"PR:000003033"},{"id":"T3","span":{"begin":4,"end":9},"obj":"PR:Q5S007"},{"id":"T4","span":{"begin":42,"end":51},"obj":"GO:0016236"},{"id":"T5","span":{"begin":42,"end":51},"obj":"GO:0006914"},{"id":"T6","span":{"begin":78,"end":81},"obj":"CHEBI:28398"},{"id":"T7","span":{"begin":82,"end":85},"obj":"PR:P29323"},{"id":"T8","span":{"begin":82,"end":85},"obj":"PR:000007130"},{"id":"T9","span":{"begin":82,"end":85},"obj":"GO:0004707"},{"id":"T10","span":{"begin":86,"end":93},"obj":"CHEBI:34922"},{"id":"T12","span":{"begin":108,"end":115},"obj":"6308"},{"id":"T13","span":{"begin":108,"end":115},"obj":"SO:0001437"},{"id":"T11","span":{"begin":108,"end":115},"obj":"CHEBI:15603"},{"id":"T14","span":{"begin":108,"end":115},"obj":"D007930"},{"id":"T15","span":{"begin":108,"end":115},"obj":"CHEBI:25017"},{"id":"T16","span":{"begin":108,"end":115},"obj":"D007930"},{"id":"T17","span":{"begin":121,"end":127},"obj":"SO:0001068"},{"id":"T18","span":{"begin":138,"end":143},"obj":"PR:Q5S006"},{"id":"T19","span":{"begin":138,"end":143},"obj":"PR:000003033"},{"id":"T20","span":{"begin":138,"end":143},"obj":"PR:Q5S007"},{"id":"T21","span":{"begin":175,"end":187},"obj":"D020734"},{"id":"T22","span":{"begin":175,"end":187},"obj":"D020734"},{"id":"T23","span":{"begin":204,"end":212},"obj":"SO:0000109"},{"id":"T24","span":{"begin":216,"end":221},"obj":"PR:Q5S006"},{"id":"T25","span":{"begin":216,"end":221},"obj":"PR:000003033"},{"id":"T26","span":{"begin":216,"end":221},"obj":"PR:Q5S007"},{"id":"T27","span":{"begin":293,"end":302},"obj":"UBERON:0004529"},{"id":"T28","span":{"begin":306,"end":311},"obj":"UBERON:0001021"},{"id":"T33","span":{"begin":355,"end":374},"obj":"D010300"},{"id":"T34","span":{"begin":355,"end":374},"obj":"D010300"},{"id":"T37","span":{"begin":560,"end":570},"obj":"GO:0008219"},{"id":"T38","span":{"begin":630,"end":639},"obj":"GO:0097194"},{"id":"T39","span":{"begin":630,"end":639},"obj":"GO:0006915"},{"id":"T40","span":{"begin":677,"end":682},"obj":"PR:Q5S006"},{"id":"T41","span":{"begin":677,"end":682},"obj":"PR:000003033"},{"id":"T42","span":{"begin":677,"end":682},"obj":"PR:Q5S007"},{"id":"T43","span":{"begin":705,"end":720},"obj":"GO:0016310"},{"id":"T44","span":{"begin":724,"end":728},"obj":"PR:P63086"},{"id":"T45","span":{"begin":724,"end":728},"obj":"PR:P63085"},{"id":"T46","span":{"begin":724,"end":728},"obj":"P27638"},{"id":"T47","span":{"begin":724,"end":728},"obj":"PR:000000103"},{"id":"T49","span":{"begin":724,"end":728},"obj":"PR:P40417"},{"id":"T50","span":{"begin":724,"end":728},"obj":"PR:000000019"},{"id":"T48","span":{"begin":724,"end":728},"obj":"GO:0004707"},{"id":"T51","span":{"begin":724,"end":740},"obj":"D020929"},{"id":"T52","span":{"begin":729,"end":732},"obj":"PR:P29323"},{"id":"T53","span":{"begin":729,"end":732},"obj":"PR:000007130"},{"id":"T54","span":{"begin":729,"end":732},"obj":"GO:0004707"},{"id":"T55","span":{"begin":733,"end":745},"obj":"D020930"},{"id":"T58","span":{"begin":759,"end":818},"obj":"C113580"},{"id":"T59","span":{"begin":759,"end":818},"obj":"C113580"},{"id":"T60","span":{"begin":787,"end":790},"obj":"GO:0033815"},{"id":"T64","span":{"begin":787,"end":792},"obj":"PR:Q8S307"},{"id":"T65","span":{"begin":787,"end":792},"obj":"PR:000028348"},{"id":"T69","span":{"begin":820,"end":825},"obj":"C113580"},{"id":"T70","span":{"begin":820,"end":825},"obj":"C113580"},{"id":"T71","span":{"begin":820,"end":825},"obj":"CHEBI:90693"},{"id":"T72","span":{"begin":847,"end":856},"obj":"CHEBI:35222"},{"id":"T73","span":{"begin":860,"end":863},"obj":"CHEBI:28398"},{"id":"T74","span":{"begin":860,"end":864},"obj":"PR:Q02750"},{"id":"T75","span":{"begin":860,"end":864},"obj":"PR:Q21307"},{"id":"T76","span":{"begin":860,"end":864},"obj":"PR:Q55CL6"},{"id":"T77","span":{"begin":860,"end":864},"obj":"Q05116"},{"id":"T78","span":{"begin":860,"end":864},"obj":"Q63980"},{"id":"T80","span":{"begin":860,"end":864},"obj":"P31938"},{"id":"T81","span":{"begin":860,"end":864},"obj":"P29678"},{"id":"T82","span":{"begin":860,"end":864},"obj":"PR:000029222"},{"id":"T83","span":{"begin":860,"end":864},"obj":"PR:Q01986"},{"id":"T84","span":{"begin":860,"end":864},"obj":"PR:Q94A06"},{"id":"T85","span":{"begin":860,"end":864},"obj":"Q9XT09"},{"id":"T86","span":{"begin":860,"end":864},"obj":"Q02750"},{"id":"T87","span":{"begin":860,"end":864},"obj":"PR:P29678"},{"id":"T88","span":{"begin":860,"end":864},"obj":"Q91447"},{"id":"T89","span":{"begin":860,"end":864},"obj":"PR:Q10292"},{"id":"T90","span":{"begin":860,"end":864},"obj":"PR:P31938"},{"id":"T91","span":{"begin":860,"end":864},"obj":"Q01986"},{"id":"T92","span":{"begin":860,"end":864},"obj":"Q55CL6"},{"id":"T93","span":{"begin":860,"end":864},"obj":"PR:P24719"},{"id":"T94","span":{"begin":860,"end":864},"obj":"PR:000010125"},{"id":"T79","span":{"begin":860,"end":864},"obj":"GO:0004708"},{"id":"T95","span":{"begin":889,"end":898},"obj":"GO:0016236"},{"id":"T96","span":{"begin":889,"end":898},"obj":"GO:0006914"},{"id":"T97","span":{"begin":934,"end":939},"obj":"PR:Q5S006"},{"id":"T98","span":{"begin":934,"end":939},"obj":"PR:000003033"},{"id":"T99","span":{"begin":934,"end":939},"obj":"PR:Q5S007"},{"id":"T100","span":{"begin":940,"end":948},"obj":"SO:0000109"},{"id":"T101","span":{"begin":991,"end":999},"obj":"SO:0000109"},{"id":"T102","span":{"begin":1008,"end":1017},"obj":"GO:0016236"},{"id":"T103","span":{"begin":1008,"end":1017},"obj":"GO:0006914"},{"id":"T104","span":{"begin":1022,"end":1025},"obj":"CHEBI:28398"},{"id":"T105","span":{"begin":1026,"end":1029},"obj":"PR:P29323"},{"id":"T106","span":{"begin":1026,"end":1029},"obj":"PR:000007130"},{"id":"T107","span":{"begin":1026,"end":1029},"obj":"GO:0004707"},{"id":"T108","span":{"begin":1030,"end":1037},"obj":"CHEBI:34922"},{"id":"T109","span":{"begin":1082,"end":1091},"obj":"GO:0016236"},{"id":"T110","span":{"begin":1082,"end":1091},"obj":"GO:0006914"}],"attributes":[{"subj":"T1","pred":"source","obj":"c_corpus"},{"subj":"T2","pred":"source","obj":"c_corpus"},{"subj":"T3","pred":"source","obj":"c_corpus"},{"subj":"T4","pred":"source","obj":"c_corpus"},{"subj":"T5","pred":"source","obj":"c_corpus"},{"subj":"T6","pred":"source","obj":"c_corpus"},{"subj":"T7","pred":"source","obj":"c_corpus"},{"subj":"T8","pred":"source","obj":"c_corpus"},{"subj":"T9","pred":"source","obj":"c_corpus"},{"subj":"T10","pred":"source","obj":"c_corpus"},{"subj":"T12","pred":"source","obj":"c_corpus"},{"subj":"T13","pred":"source","obj":"c_corpus"},{"subj":"T11","pred":"source","obj":"c_corpus"},{"subj":"T14","pred":"source","obj":"c_corpus"},{"subj":"T15","pred":"source","obj":"c_corpus"},{"subj":"T16","pred":"source","obj":"c_corpus"},{"subj":"T17","pred":"source","obj":"c_corpus"},{"subj":"T18","pred":"source","obj":"c_corpus"},{"subj":"T19","pred":"source","obj":"c_corpus"},{"subj":"T20","pred":"source","obj":"c_corpus"},{"subj":"T21","pred":"source","obj":"c_corpus"},{"subj":"T22","pred":"source","obj":"c_corpus"},{"subj":"T23","pred":"source","obj":"c_corpus"},{"subj":"T24","pred":"source","obj":"c_corpus"},{"subj":"T25","pred":"source","obj":"c_corpus"},{"subj":"T26","pred":"source","obj":"c_corpus"},{"subj":"T27","pred":"source","obj":"c_corpus"},{"subj":"T28","pred":"source","obj":"c_corpus"},{"subj":"T33","pred":"source","obj":"c_corpus"},{"subj":"T34","pred":"source","obj":"c_corpus"},{"subj":"T37","pred":"source","obj":"c_corpus"},{"subj":"T38","pred":"source","obj":"c_corpus"},{"subj":"T39","pred":"source","obj":"c_corpus"},{"subj":"T40","pred":"source","obj":"c_corpus"},{"subj":"T41","pred":"source","obj":"c_corpus"},{"subj":"T42","pred":"source","obj":"c_corpus"},{"subj":"T43","pred":"source","obj":"c_corpus"},{"subj":"T44","pred":"source","obj":"c_corpus"},{"subj":"T45","pred":"source","obj":"c_corpus"},{"subj":"T46","pred":"source","obj":"c_corpus"},{"subj":"T47","pred":"source","obj":"c_corpus"},{"subj":"T49","pred":"source","obj":"c_corpus"},{"subj":"T50","pred":"source","obj":"c_corpus"},{"subj":"T48","pred":"source","obj":"c_corpus"},{"subj":"T51","pred":"source","obj":"c_corpus"},{"subj":"T52","pred":"source","obj":"c_corpus"},{"subj":"T53","pred":"source","obj":"c_corpus"},{"subj":"T54","pred":"source","obj":"c_corpus"},{"subj":"T55","pred":"source","obj":"c_corpus"},{"subj":"T58","pred":"source","obj":"c_corpus"},{"subj":"T59","pred":"source","obj":"c_corpus"},{"subj":"T60","pred":"source","obj":"c_corpus"},{"subj":"T64","pred":"source","obj":"c_corpus"},{"subj":"T65","pred":"source","obj":"c_corpus"},{"subj":"T69","pred":"source","obj":"c_corpus"},{"subj":"T70","pred":"source","obj":"c_corpus"},{"subj":"T71","pred":"source","obj":"c_corpus"},{"subj":"T72","pred":"source","obj":"c_corpus"},{"subj":"T73","pred":"source","obj":"c_corpus"},{"subj":"T74","pred":"source","obj":"c_corpus"},{"subj":"T75","pred":"source","obj":"c_corpus"},{"subj":"T76","pred":"source","obj":"c_corpus"},{"subj":"T77","pred":"source","obj":"c_corpus"},{"subj":"T78","pred":"source","obj":"c_corpus"},{"subj":"T80","pred":"source","obj":"c_corpus"},{"subj":"T81","pred":"source","obj":"c_corpus"},{"subj":"T82","pred":"source","obj":"c_corpus"},{"subj":"T83","pred":"source","obj":"c_corpus"},{"subj":"T84","pred":"source","obj":"c_corpus"},{"subj":"T85","pred":"source","obj":"c_corpus"},{"subj":"T86","pred":"source","obj":"c_corpus"},{"subj":"T87","pred":"source","obj":"c_corpus"},{"subj":"T88","pred":"source","obj":"c_corpus"},{"subj":"T89","pred":"source","obj":"c_corpus"},{"subj":"T90","pred":"source","obj":"c_corpus"},{"subj":"T91","pred":"source","obj":"c_corpus"},{"subj":"T92","pred":"source","obj":"c_corpus"},{"subj":"T93","pred":"source","obj":"c_corpus"},{"subj":"T94","pred":"source","obj":"c_corpus"},{"subj":"T79","pred":"source","obj":"c_corpus"},{"subj":"T95","pred":"source","obj":"c_corpus"},{"subj":"T96","pred":"source","obj":"c_corpus"},{"subj":"T97","pred":"source","obj":"c_corpus"},{"subj":"T98","pred":"source","obj":"c_corpus"},{"subj":"T99","pred":"source","obj":"c_corpus"},{"subj":"T100","pred":"source","obj":"c_corpus"},{"subj":"T101","pred":"source","obj":"c_corpus"},{"subj":"T102","pred":"source","obj":"c_corpus"},{"subj":"T103","pred":"source","obj":"c_corpus"},{"subj":"T104","pred":"source","obj":"c_corpus"},{"subj":"T105","pred":"source","obj":"c_corpus"},{"subj":"T106","pred":"source","obj":"c_corpus"},{"subj":"T107","pred":"source","obj":"c_corpus"},{"subj":"T108","pred":"source","obj":"c_corpus"},{"subj":"T109","pred":"source","obj":"c_corpus"},{"subj":"T110","pred":"source","obj":"c_corpus"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":175,"end":187},"obj":"HP_0001300"},{"id":"T2","span":{"begin":355,"end":364},"obj":"HP_0001300"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"}]},{"project":"Allie","denotations":[{"id":"SS1_22773119_1_0","span":{"begin":108,"end":136},"obj":"expanded"},{"id":"SS2_22773119_1_0","span":{"begin":138,"end":143},"obj":"abbr"},{"id":"SS1_22773119_2_0","span":{"begin":355,"end":374},"obj":"expanded"},{"id":"SS2_22773119_2_0","span":{"begin":376,"end":378},"obj":"abbr"},{"id":"SS1_22773119_5_0","span":{"begin":724,"end":740},"obj":"expanded"},{"id":"SS2_22773119_5_0","span":{"begin":742,"end":745},"obj":"abbr"}],"relations":[{"id":"AE1_22773119_1_0","pred":"abbreviatedTo","subj":"SS1_22773119_1_0","obj":"SS2_22773119_1_0"},{"id":"AE1_22773119_2_0","pred":"abbreviatedTo","subj":"SS1_22773119_2_0","obj":"SS2_22773119_2_0"},{"id":"AE1_22773119_5_0","pred":"abbreviatedTo","subj":"SS1_22773119_5_0","obj":"SS2_22773119_5_0"}],"attributes":[{"subj":"SS1_22773119_1_0","pred":"source","obj":"Allie"},{"subj":"SS2_22773119_1_0","pred":"source","obj":"Allie"},{"subj":"SS1_22773119_2_0","pred":"source","obj":"Allie"},{"subj":"SS2_22773119_2_0","pred":"source","obj":"Allie"},{"subj":"SS1_22773119_5_0","pred":"source","obj":"Allie"},{"subj":"SS2_22773119_5_0","pred":"source","obj":"Allie"}]},{"project":"UseCases_ArguminSci_Discourse","denotations":[{"id":"T1","span":{"begin":0,"end":3},"obj":"DRI_Outcome"},{"id":"T2","span":{"begin":4,"end":16},"obj":"Token_Label.OUTSIDE"},{"id":"T3","span":{"begin":17,"end":94},"obj":"DRI_Outcome"},{"id":"T4","span":{"begin":95,"end":261},"obj":"DRI_Approach"},{"id":"T5","span":{"begin":262,"end":380},"obj":"DRI_Challenge"},{"id":"T6","span":{"begin":381,"end":508},"obj":"DRI_Outcome"},{"id":"T7","span":{"begin":509,"end":676},"obj":"DRI_Background"},{"id":"T8","span":{"begin":677,"end":747},"obj":"DRI_Background"},{"id":"T9","span":{"begin":748,"end":926},"obj":"DRI_Background"},{"id":"T10","span":{"begin":927,"end":939},"obj":"Token_Label.OUTSIDE"},{"id":"T11","span":{"begin":940,"end":955},"obj":"DRI_Background"},{"id":"T12","span":{"begin":956,"end":1148},"obj":"DRI_Outcome"}],"attributes":[{"subj":"T1","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T2","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T3","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T4","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T5","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T6","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T7","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T8","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T9","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T10","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T11","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T12","pred":"source","obj":"UseCases_ArguminSci_Discourse"}]},{"project":"PubMed_ArguminSci","denotations":[{"id":"T1","span":{"begin":95,"end":261},"obj":"DRI_Approach"},{"id":"T2","span":{"begin":262,"end":380},"obj":"DRI_Challenge"},{"id":"T3","span":{"begin":381,"end":508},"obj":"DRI_Outcome"},{"id":"T4","span":{"begin":509,"end":676},"obj":"DRI_Background"},{"id":"T5","span":{"begin":677,"end":747},"obj":"DRI_Background"},{"id":"T6","span":{"begin":748,"end":926},"obj":"DRI_Background"},{"id":"T7","span":{"begin":940,"end":955},"obj":"DRI_Background"},{"id":"T8","span":{"begin":956,"end":1148},"obj":"DRI_Outcome"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T2","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T3","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T4","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T5","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T6","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T7","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T8","pred":"source","obj":"PubMed_ArguminSci"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubTator4TogoVar","color":"#93ecc9","default":true},{"id":"c_corpus","color":"#ecaf93"},{"id":"PubmedHPO","color":"#9593ec"},{"id":"Allie","color":"#aaec93"},{"id":"UseCases_ArguminSci_Discourse","color":"#ec93c4"},{"id":"PubMed_ArguminSci","color":"#93deec"}]}]}}