PubMed:25446991 JSONTXT

{"project":"test-210614","denotations":[{"id":"25446991_0","span":{"begin":60,"end":66},"obj":"ProteinMutation"},{"id":"25446991_1","span":{"begin":794,"end":800},"obj":"ProteinMutation"},{"id":"25446991_2","span":{"begin":722,"end":728},"obj":"ProteinMutation"},{"id":"25446991_3","span":{"begin":591,"end":597},"obj":"ProteinMutation"},{"id":"25446991_4","span":{"begin":377,"end":383},"obj":"ProteinMutation"},{"id":"25446991_5","span":{"begin":288,"end":294},"obj":"ProteinMutation"},{"id":"25446991_6","span":{"begin":123,"end":129},"obj":"ProteinMutation"}],"attributes":[{"id":"25446991_0_ProteinMutation","pred":"proteinmutation","subj":"25446991_0","obj":"rs34637584"},{"id":"25446991_1_ProteinMutation","pred":"proteinmutation","subj":"25446991_1","obj":"rs34637584"},{"id":"25446991_2_ProteinMutation","pred":"proteinmutation","subj":"25446991_2","obj":"rs34637584"},{"id":"25446991_3_ProteinMutation","pred":"proteinmutation","subj":"25446991_3","obj":"rs34637584"},{"id":"25446991_4_ProteinMutation","pred":"proteinmutation","subj":"25446991_4","obj":"rs34637584"},{"id":"25446991_5_ProteinMutation","pred":"proteinmutation","subj":"25446991_5","obj":"rs34637584"},{"id":"25446991_6_ProteinMutation","pred":"proteinmutation","subj":"25446991_6","obj":"rs34637584"}],"text":"Threonine 56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy.\nThe G2019S leucine-rich repeat kinase 2 (LRRK2) mutation is the most common cause of genetic Parkinson's disease (PD). However, the molecular mechanism underlying LRRK2 G2019S-induced cellular pathology is poorly understood. Here, we demonstrated that LRRK2 G2019S bound to and phosphorylated Bcl-2, a mitochondrial anti-apoptotic protein, at Threonine 56. Either stable expression of Bcl-2 or transient expression of a Bcl-2 phosphor mutant (Bcl-2(T56A)) abolished LRRK2 G2019S-induced mitochondrial depolarization and autophagy. Together, our findings reveal a previously unidentified target of LRRK2 G2019S, showing that Bcl-2 serves as a point of crosstalk between LRRK2 G2019S-mediated mitochondrial disorder and dysregulation of autophagy."}

{"project":"PubTator4TogoVar","denotations":[{"id":"25446991_0","span":{"begin":60,"end":66},"obj":"ProteinMutation"},{"id":"25446991_1","span":{"begin":794,"end":800},"obj":"ProteinMutation"},{"id":"25446991_2","span":{"begin":722,"end":728},"obj":"ProteinMutation"},{"id":"25446991_3","span":{"begin":591,"end":597},"obj":"ProteinMutation"},{"id":"25446991_4","span":{"begin":377,"end":383},"obj":"ProteinMutation"},{"id":"25446991_5","span":{"begin":288,"end":294},"obj":"ProteinMutation"},{"id":"25446991_6","span":{"begin":123,"end":129},"obj":"ProteinMutation"}],"attributes":[{"id":"25446991_0_ProteinMutation","pred":"proteinmutation","subj":"25446991_0","obj":"rs34637584"},{"id":"25446991_1_ProteinMutation","pred":"proteinmutation","subj":"25446991_1","obj":"rs34637584"},{"id":"25446991_2_ProteinMutation","pred":"proteinmutation","subj":"25446991_2","obj":"rs34637584"},{"id":"25446991_3_ProteinMutation","pred":"proteinmutation","subj":"25446991_3","obj":"rs34637584"},{"id":"25446991_4_ProteinMutation","pred":"proteinmutation","subj":"25446991_4","obj":"rs34637584"},{"id":"25446991_5_ProteinMutation","pred":"proteinmutation","subj":"25446991_5","obj":"rs34637584"},{"id":"25446991_6_ProteinMutation","pred":"proteinmutation","subj":"25446991_6","obj":"rs34637584"}],"text":"Threonine 56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy.\nThe G2019S leucine-rich repeat kinase 2 (LRRK2) mutation is the most common cause of genetic Parkinson's disease (PD). However, the molecular mechanism underlying LRRK2 G2019S-induced cellular pathology is poorly understood. Here, we demonstrated that LRRK2 G2019S bound to and phosphorylated Bcl-2, a mitochondrial anti-apoptotic protein, at Threonine 56. Either stable expression of Bcl-2 or transient expression of a Bcl-2 phosphor mutant (Bcl-2(T56A)) abolished LRRK2 G2019S-induced mitochondrial depolarization and autophagy. Together, our findings reveal a previously unidentified target of LRRK2 G2019S, showing that Bcl-2 serves as a point of crosstalk between LRRK2 G2019S-mediated mitochondrial disorder and dysregulation of autophagy."}

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56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy.\nThe G2019S leucine-rich repeat kinase 2 (LRRK2) mutation is the most common cause of genetic Parkinson's disease (PD). However, the molecular mechanism underlying LRRK2 G2019S-induced cellular pathology is poorly understood. Here, we demonstrated that LRRK2 G2019S bound to and phosphorylated Bcl-2, a mitochondrial anti-apoptotic protein, at Threonine 56. Either stable expression of Bcl-2 or transient expression of a Bcl-2 phosphor mutant (Bcl-2(T56A)) abolished LRRK2 G2019S-induced mitochondrial depolarization and autophagy. Together, our findings reveal a previously unidentified target of LRRK2 G2019S, showing that Bcl-2 serves as a point of crosstalk between LRRK2 G2019S-mediated mitochondrial disorder and dysregulation of autophagy."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":212,"end":221},"obj":"HP_0001300"},{"id":"T2","span":{"begin":421,"end":434},"obj":"HP_0001427"},{"id":"T3","span":{"begin":606,"end":619},"obj":"HP_0001427"},{"id":"T4","span":{"begin":810,"end":823},"obj":"HP_0001427"}],"text":"Threonine 56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy.\nThe G2019S leucine-rich repeat kinase 2 (LRRK2) mutation is the most common cause of genetic Parkinson's disease (PD). However, the molecular mechanism underlying LRRK2 G2019S-induced cellular pathology is poorly understood. Here, we demonstrated that LRRK2 G2019S bound to and phosphorylated Bcl-2, a mitochondrial anti-apoptotic protein, at Threonine 56. Either stable expression of Bcl-2 or transient expression of a Bcl-2 phosphor mutant (Bcl-2(T56A)) abolished LRRK2 G2019S-induced mitochondrial depolarization and autophagy. Together, our findings reveal a previously unidentified target of LRRK2 G2019S, showing that Bcl-2 serves as a point of crosstalk between LRRK2 G2019S-mediated mitochondrial disorder and dysregulation of autophagy."}

{"project":"PubMed_ArguminSci","denotations":[{"id":"T1","span":{"begin":119,"end":237},"obj":"DRI_Approach"},{"id":"T2","span":{"begin":238,"end":281},"obj":"DRI_Background"},{"id":"T3","span":{"begin":303,"end":343},"obj":"DRI_Background"},{"id":"T4","span":{"begin":344,"end":370},"obj":"DRI_Outcome"},{"id":"T5","span":{"begin":384,"end":475},"obj":"DRI_Outcome"},{"id":"T6","span":{"begin":476,"end":584},"obj":"DRI_Background"},{"id":"T7","span":{"begin":606,"end":649},"obj":"DRI_Background"},{"id":"T8","span":{"begin":650,"end":715},"obj":"DRI_Outcome"},{"id":"T9","span":{"begin":728,"end":787},"obj":"DRI_Outcome"},{"id":"T10","span":{"begin":810,"end":864},"obj":"DRI_Outcome"}],"text":"Threonine 56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy.\nThe G2019S leucine-rich repeat kinase 2 (LRRK2) mutation is the most common cause of genetic Parkinson's disease (PD). However, the molecular mechanism underlying LRRK2 G2019S-induced cellular pathology is poorly understood. Here, we demonstrated that LRRK2 G2019S bound to and phosphorylated Bcl-2, a mitochondrial anti-apoptotic protein, at Threonine 56. Either stable expression of Bcl-2 or transient expression of a Bcl-2 phosphor mutant (Bcl-2(T56A)) abolished LRRK2 G2019S-induced mitochondrial depolarization and autophagy. Together, our findings reveal a previously unidentified target of LRRK2 G2019S, showing that Bcl-2 serves as a point of crosstalk between LRRK2 G2019S-mediated mitochondrial disorder and dysregulation of autophagy."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":212,"end":231},"obj":"Disease"},{"id":"T2","span":{"begin":233,"end":235},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0005180"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0005180"}],"text":"Threonine 56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy.\nThe G2019S leucine-rich repeat kinase 2 (LRRK2) mutation is the most common cause of genetic Parkinson's disease (PD). However, the molecular mechanism underlying LRRK2 G2019S-induced cellular pathology is poorly understood. Here, we demonstrated that LRRK2 G2019S bound to and phosphorylated Bcl-2, a mitochondrial anti-apoptotic protein, at Threonine 56. Either stable expression of Bcl-2 or transient expression of a Bcl-2 phosphor mutant (Bcl-2(T56A)) abolished LRRK2 G2019S-induced mitochondrial depolarization and autophagy. Together, our findings reveal a previously unidentified target of LRRK2 G2019S, showing that Bcl-2 serves as a point of crosstalk between LRRK2 G2019S-mediated mitochondrial disorder and dysregulation of autophagy."}