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testone

2_test

{"project":"2_test","denotations":[{"id":"23469174-8702995-90505449","span":{"begin":323,"end":325},"obj":"8702995"}],"text":"We used L929 cells stably expressing constitutively active wild type Akt1 (Myr-Akt) or the catalytically inactive mutant K179M in order to further understand the contribution of growth factors and RIP1 kinase to Akt activation during necroptosis. Constitutively active Akt1 (Myr-Akt) was generated as previously described [37] by the addition of a myristoylation signal which provides constitutive localization to the plasma membrane and by the deletion of the auto-inhibitory PH domain (Fig. 7A) resulting in an Akt that is active under serum free. It is important to note that the cells expressing Myr-Akt were viable, grew in a manner indistinguishable from the empty vector control cells, and were not triggered to induce necroptosis by serum starvation (Fig. 7B). This indicates that active Akt alone is not sufficient to induce necroptotic cell death. Under serum free conditions Myr-Akt, but not the K179M mutant, fully restored zVAD.fmk-induced necroptosis (Fig. 7A,B). Nec-1 prevented both Myr-Akt dependent cell death and the necroptosis-specific delayed increase in Akt Thr308 phosphorylation (Fig. 7B,C). Myr-Akt also allowed other zVAD.fmk-dependent events, including activation of JNK and c-Jun phosphorylation (Fig. 7C) and upregulation of TNFα mRNA (Fig. 7D) to occur under serum free conditions, confirming an important role for Akt at the apex of necroptotic signaling. These data demonstrated that the presence of active and membrane localized Akt is sufficient to uncouple Akt activation during necroptosis from growth factor signaling. RIP1 kinase was still able to regulate Akt activation during necroptosis, suggesting that growth factors and RIP1 kinase provide two independent inputs required for Akt changes during necroptosis."}

pmc-enju-pas

bionlp-st-ge-2016-test-proteins

{"project":"bionlp-st-ge-2016-test-proteins","denotations":[{"id":"T13848","span":{"begin":1666,"end":1670},"obj":"Protein"},{"id":"T13847","span":{"begin":1557,"end":1561},"obj":"Protein"},{"id":"T13846","span":{"begin":1255,"end":1259},"obj":"Protein"},{"id":"T13845","span":{"begin":1203,"end":1208},"obj":"Protein"},{"id":"T13844","span":{"begin":999,"end":1006},"obj":"Protein"},{"id":"T13843","span":{"begin":907,"end":912},"obj":"Protein"},{"id":"T13842","span":{"begin":886,"end":893},"obj":"Protein"},{"id":"T13841","span":{"begin":600,"end":607},"obj":"Protein"},{"id":"T13840","span":{"begin":275,"end":282},"obj":"Protein"},{"id":"T13839","span":{"begin":269,"end":273},"obj":"Protein"},{"id":"T13838","span":{"begin":197,"end":201},"obj":"Protein"},{"id":"T13837","span":{"begin":121,"end":126},"obj":"Protein"},{"id":"T13836","span":{"begin":75,"end":82},"obj":"Protein"},{"id":"T13835","span":{"begin":69,"end":73},"obj":"Protein"}],"namespaces":[{"prefix":"_base","uri":"http://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"We used L929 cells stably expressing constitutively active wild type Akt1 (Myr-Akt) or the catalytically inactive mutant K179M in order to further understand the contribution of growth factors and RIP1 kinase to Akt activation during necroptosis. Constitutively active Akt1 (Myr-Akt) was generated as previously described [37] by the addition of a myristoylation signal which provides constitutive localization to the plasma membrane and by the deletion of the auto-inhibitory PH domain (Fig. 7A) resulting in an Akt that is active under serum free. It is important to note that the cells expressing Myr-Akt were viable, grew in a manner indistinguishable from the empty vector control cells, and were not triggered to induce necroptosis by serum starvation (Fig. 7B). This indicates that active Akt alone is not sufficient to induce necroptotic cell death. Under serum free conditions Myr-Akt, but not the K179M mutant, fully restored zVAD.fmk-induced necroptosis (Fig. 7A,B). Nec-1 prevented both Myr-Akt dependent cell death and the necroptosis-specific delayed increase in Akt Thr308 phosphorylation (Fig. 7B,C). Myr-Akt also allowed other zVAD.fmk-dependent events, including activation of JNK and c-Jun phosphorylation (Fig. 7C) and upregulation of TNFα mRNA (Fig. 7D) to occur under serum free conditions, confirming an important role for Akt at the apex of necroptotic signaling. These data demonstrated that the presence of active and membrane localized Akt is sufficient to uncouple Akt activation during necroptosis from growth factor signaling. RIP1 kinase was still able to regulate Akt activation during necroptosis, suggesting that growth factors and RIP1 kinase provide two independent inputs required for Akt changes during necroptosis."}

bionlp-st-ge-2016-uniprot

UBERON-AE

{"project":"UBERON-AE","denotations":[{"id":"T13693","span":{"begin":1290,"end":1295},"obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"id":"T13692","span":{"begin":864,"end":869},"obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"id":"T13691","span":{"begin":741,"end":746},"obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"id":"T13690","span":{"begin":538,"end":543},"obj":"http://purl.obolibrary.org/obo/UBERON_0001977"}],"text":"We used L929 cells stably expressing constitutively active wild type Akt1 (Myr-Akt) or the catalytically inactive mutant K179M in order to further understand the contribution of growth factors and RIP1 kinase to Akt activation during necroptosis. Constitutively active Akt1 (Myr-Akt) was generated as previously described [37] by the addition of a myristoylation signal which provides constitutive localization to the plasma membrane and by the deletion of the auto-inhibitory PH domain (Fig. 7A) resulting in an Akt that is active under serum free. It is important to note that the cells expressing Myr-Akt were viable, grew in a manner indistinguishable from the empty vector control cells, and were not triggered to induce necroptosis by serum starvation (Fig. 7B). This indicates that active Akt alone is not sufficient to induce necroptotic cell death. Under serum free conditions Myr-Akt, but not the K179M mutant, fully restored zVAD.fmk-induced necroptosis (Fig. 7A,B). Nec-1 prevented both Myr-Akt dependent cell death and the necroptosis-specific delayed increase in Akt Thr308 phosphorylation (Fig. 7B,C). Myr-Akt also allowed other zVAD.fmk-dependent events, including activation of JNK and c-Jun phosphorylation (Fig. 7C) and upregulation of TNFα mRNA (Fig. 7D) to occur under serum free conditions, confirming an important role for Akt at the apex of necroptotic signaling. These data demonstrated that the presence of active and membrane localized Akt is sufficient to uncouple Akt activation during necroptosis from growth factor signaling. RIP1 kinase was still able to regulate Akt activation during necroptosis, suggesting that growth factors and RIP1 kinase provide two independent inputs required for Akt changes during necroptosis."}

GO-BP

GO-MF

{"project":"GO-MF","denotations":[{"id":"T13956","span":{"begin":1195,"end":1198},"obj":"http://purl.obolibrary.org/obo/GO_0004705"}],"text":"We used L929 cells stably expressing constitutively active wild type Akt1 (Myr-Akt) or the catalytically inactive mutant K179M in order to further understand the contribution of growth factors and RIP1 kinase to Akt activation during necroptosis. Constitutively active Akt1 (Myr-Akt) was generated as previously described [37] by the addition of a myristoylation signal which provides constitutive localization to the plasma membrane and by the deletion of the auto-inhibitory PH domain (Fig. 7A) resulting in an Akt that is active under serum free. It is important to note that the cells expressing Myr-Akt were viable, grew in a manner indistinguishable from the empty vector control cells, and were not triggered to induce necroptosis by serum starvation (Fig. 7B). This indicates that active Akt alone is not sufficient to induce necroptotic cell death. Under serum free conditions Myr-Akt, but not the K179M mutant, fully restored zVAD.fmk-induced necroptosis (Fig. 7A,B). Nec-1 prevented both Myr-Akt dependent cell death and the necroptosis-specific delayed increase in Akt Thr308 phosphorylation (Fig. 7B,C). Myr-Akt also allowed other zVAD.fmk-dependent events, including activation of JNK and c-Jun phosphorylation (Fig. 7C) and upregulation of TNFα mRNA (Fig. 7D) to occur under serum free conditions, confirming an important role for Akt at the apex of necroptotic signaling. These data demonstrated that the presence of active and membrane localized Akt is sufficient to uncouple Akt activation during necroptosis from growth factor signaling. RIP1 kinase was still able to regulate Akt activation during necroptosis, suggesting that growth factors and RIP1 kinase provide two independent inputs required for Akt changes during necroptosis."}

GO-CC

{"project":"GO-CC","denotations":[{"id":"T13974","span":{"begin":1357,"end":1361},"obj":"http://purl.obolibrary.org/obo/GO_0097683"},{"id":"T13972","span":{"begin":1444,"end":1452},"obj":"http://purl.obolibrary.org/obo/GO_0016020"},{"id":"T13971","span":{"begin":425,"end":433},"obj":"http://purl.obolibrary.org/obo/GO_0016020"},{"id":"T13970","span":{"begin":418,"end":433},"obj":"http://purl.obolibrary.org/obo/GO_0005886"},{"id":"T13966","span":{"begin":686,"end":691},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T13965","span":{"begin":583,"end":588},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T13964","span":{"begin":13,"end":18},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"We used L929 cells stably expressing constitutively active wild type Akt1 (Myr-Akt) or the catalytically inactive mutant K179M in order to further understand the contribution of growth factors and RIP1 kinase to Akt activation during necroptosis. Constitutively active Akt1 (Myr-Akt) was generated as previously described [37] by the addition of a myristoylation signal which provides constitutive localization to the plasma membrane and by the deletion of the auto-inhibitory PH domain (Fig. 7A) resulting in an Akt that is active under serum free. It is important to note that the cells expressing Myr-Akt were viable, grew in a manner indistinguishable from the empty vector control cells, and were not triggered to induce necroptosis by serum starvation (Fig. 7B). This indicates that active Akt alone is not sufficient to induce necroptotic cell death. Under serum free conditions Myr-Akt, but not the K179M mutant, fully restored zVAD.fmk-induced necroptosis (Fig. 7A,B). Nec-1 prevented both Myr-Akt dependent cell death and the necroptosis-specific delayed increase in Akt Thr308 phosphorylation (Fig. 7B,C). Myr-Akt also allowed other zVAD.fmk-dependent events, including activation of JNK and c-Jun phosphorylation (Fig. 7C) and upregulation of TNFα mRNA (Fig. 7D) to occur under serum free conditions, confirming an important role for Akt at the apex of necroptotic signaling. These data demonstrated that the presence of active and membrane localized Akt is sufficient to uncouple Akt activation during necroptosis from growth factor signaling. RIP1 kinase was still able to regulate Akt activation during necroptosis, suggesting that growth factors and RIP1 kinase provide two independent inputs required for Akt changes during necroptosis."}

sentences

{"project":"sentences","denotations":[{"id":"T13705","span":{"begin":1557,"end":1753},"obj":"Sentence"},{"id":"T13704","span":{"begin":1388,"end":1556},"obj":"Sentence"},{"id":"T13703","span":{"begin":1117,"end":1387},"obj":"Sentence"},{"id":"T13702","span":{"begin":978,"end":1116},"obj":"Sentence"},{"id":"T13701","span":{"begin":858,"end":977},"obj":"Sentence"},{"id":"T13700","span":{"begin":769,"end":857},"obj":"Sentence"},{"id":"T13699","span":{"begin":550,"end":768},"obj":"Sentence"},{"id":"T13698","span":{"begin":247,"end":549},"obj":"Sentence"},{"id":"T13697","span":{"begin":0,"end":246},"obj":"Sentence"},{"id":"T177","span":{"begin":0,"end":246},"obj":"Sentence"},{"id":"T178","span":{"begin":247,"end":549},"obj":"Sentence"},{"id":"T179","span":{"begin":550,"end":768},"obj":"Sentence"},{"id":"T180","span":{"begin":769,"end":857},"obj":"Sentence"},{"id":"T181","span":{"begin":858,"end":977},"obj":"Sentence"},{"id":"T182","span":{"begin":978,"end":1116},"obj":"Sentence"},{"id":"T183","span":{"begin":1117,"end":1387},"obj":"Sentence"},{"id":"T184","span":{"begin":1388,"end":1556},"obj":"Sentence"},{"id":"T185","span":{"begin":1557,"end":1753},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"We used L929 cells stably expressing constitutively active wild type Akt1 (Myr-Akt) or the catalytically inactive mutant K179M in order to further understand the contribution of growth factors and RIP1 kinase to Akt activation during necroptosis. Constitutively active Akt1 (Myr-Akt) was generated as previously described [37] by the addition of a myristoylation signal which provides constitutive localization to the plasma membrane and by the deletion of the auto-inhibitory PH domain (Fig. 7A) resulting in an Akt that is active under serum free. It is important to note that the cells expressing Myr-Akt were viable, grew in a manner indistinguishable from the empty vector control cells, and were not triggered to induce necroptosis by serum starvation (Fig. 7B). This indicates that active Akt alone is not sufficient to induce necroptotic cell death. Under serum free conditions Myr-Akt, but not the K179M mutant, fully restored zVAD.fmk-induced necroptosis (Fig. 7A,B). Nec-1 prevented both Myr-Akt dependent cell death and the necroptosis-specific delayed increase in Akt Thr308 phosphorylation (Fig. 7B,C). Myr-Akt also allowed other zVAD.fmk-dependent events, including activation of JNK and c-Jun phosphorylation (Fig. 7C) and upregulation of TNFα mRNA (Fig. 7D) to occur under serum free conditions, confirming an important role for Akt at the apex of necroptotic signaling. These data demonstrated that the presence of active and membrane localized Akt is sufficient to uncouple Akt activation during necroptosis from growth factor signaling. RIP1 kinase was still able to regulate Akt activation during necroptosis, suggesting that growth factors and RIP1 kinase provide two independent inputs required for Akt changes during necroptosis."}

simple1

{"project":"simple1","denotations":[{"id":"T14031","span":{"begin":1666,"end":1670},"obj":"Protein"},{"id":"T14030","span":{"begin":1557,"end":1561},"obj":"Protein"},{"id":"T14029","span":{"begin":1255,"end":1259},"obj":"Protein"},{"id":"T14028","span":{"begin":1203,"end":1208},"obj":"Protein"},{"id":"T14027","span":{"begin":999,"end":1006},"obj":"Protein"},{"id":"T14026","span":{"begin":907,"end":912},"obj":"Protein"},{"id":"T14025","span":{"begin":886,"end":893},"obj":"Protein"},{"id":"T14024","span":{"begin":600,"end":607},"obj":"Protein"},{"id":"T14023","span":{"begin":275,"end":282},"obj":"Protein"},{"id":"T14022","span":{"begin":269,"end":273},"obj":"Protein"},{"id":"T14021","span":{"begin":197,"end":201},"obj":"Protein"},{"id":"T14020","span":{"begin":121,"end":126},"obj":"Protein"},{"id":"T14019","span":{"begin":75,"end":82},"obj":"Protein"},{"id":"T14018","span":{"begin":69,"end":73},"obj":"Protein"}],"text":"We used L929 cells stably expressing constitutively active wild type Akt1 (Myr-Akt) or the catalytically inactive mutant K179M in order to further understand the contribution of growth factors and RIP1 kinase to Akt activation during necroptosis. Constitutively active Akt1 (Myr-Akt) was generated as previously described [37] by the addition of a myristoylation signal which provides constitutive localization to the plasma membrane and by the deletion of the auto-inhibitory PH domain (Fig. 7A) resulting in an Akt that is active under serum free. It is important to note that the cells expressing Myr-Akt were viable, grew in a manner indistinguishable from the empty vector control cells, and were not triggered to induce necroptosis by serum starvation (Fig. 7B). This indicates that active Akt alone is not sufficient to induce necroptotic cell death. Under serum free conditions Myr-Akt, but not the K179M mutant, fully restored zVAD.fmk-induced necroptosis (Fig. 7A,B). Nec-1 prevented both Myr-Akt dependent cell death and the necroptosis-specific delayed increase in Akt Thr308 phosphorylation (Fig. 7B,C). Myr-Akt also allowed other zVAD.fmk-dependent events, including activation of JNK and c-Jun phosphorylation (Fig. 7C) and upregulation of TNFα mRNA (Fig. 7D) to occur under serum free conditions, confirming an important role for Akt at the apex of necroptotic signaling. These data demonstrated that the presence of active and membrane localized Akt is sufficient to uncouple Akt activation during necroptosis from growth factor signaling. RIP1 kinase was still able to regulate Akt activation during necroptosis, suggesting that growth factors and RIP1 kinase provide two independent inputs required for Akt changes during necroptosis."}

BioNLP16_DUT

{"project":"BioNLP16_DUT","denotations":[{"id":"T14960","span":{"begin":1239,"end":1251},"obj":"Positive_regulation"},{"id":"T14959","span":{"begin":1209,"end":1224},"obj":"Phosphorylation"},{"id":"T14958","span":{"begin":589,"end":599},"obj":"Gene_expression"},{"id":"T14957","span":{"begin":26,"end":36},"obj":"Gene_expression"},{"id":"T14927","span":{"begin":1666,"end":1670},"obj":"Protein"},{"id":"T14926","span":{"begin":1557,"end":1561},"obj":"Protein"},{"id":"T14925","span":{"begin":1255,"end":1259},"obj":"Protein"},{"id":"T14924","span":{"begin":1203,"end":1208},"obj":"Protein"},{"id":"T14923","span":{"begin":999,"end":1006},"obj":"Protein"},{"id":"T14922","span":{"begin":907,"end":912},"obj":"Protein"},{"id":"T14921","span":{"begin":886,"end":893},"obj":"Protein"},{"id":"T14920","span":{"begin":600,"end":607},"obj":"Protein"},{"id":"T14919","span":{"begin":275,"end":282},"obj":"Protein"},{"id":"T14918","span":{"begin":269,"end":273},"obj":"Protein"},{"id":"T14917","span":{"begin":197,"end":201},"obj":"Protein"},{"id":"T14916","span":{"begin":121,"end":126},"obj":"Protein"},{"id":"T14915","span":{"begin":75,"end":82},"obj":"Protein"},{"id":"T14914","span":{"begin":69,"end":73},"obj":"Protein"}],"relations":[{"id":"R9911","pred":"themeOf","subj":"T14914","obj":"T14957"},{"id":"R9912","pred":"themeOf","subj":"T14915","obj":"T14957"},{"id":"R9913","pred":"themeOf","subj":"T14916","obj":"T14957"},{"id":"R9914","pred":"themeOf","subj":"T14920","obj":"T14958"},{"id":"R9915","pred":"themeOf","subj":"T14924","obj":"T14959"},{"id":"R9916","pred":"themeOf","subj":"T14925","obj":"T14960"}],"text":"We used L929 cells stably expressing constitutively active wild type Akt1 (Myr-Akt) or the catalytically inactive mutant K179M in order to further understand the contribution of growth factors and RIP1 kinase to Akt activation during necroptosis. Constitutively active Akt1 (Myr-Akt) was generated as previously described [37] by the addition of a myristoylation signal which provides constitutive localization to the plasma membrane and by the deletion of the auto-inhibitory PH domain (Fig. 7A) resulting in an Akt that is active under serum free. It is important to note that the cells expressing Myr-Akt were viable, grew in a manner indistinguishable from the empty vector control cells, and were not triggered to induce necroptosis by serum starvation (Fig. 7B). This indicates that active Akt alone is not sufficient to induce necroptotic cell death. Under serum free conditions Myr-Akt, but not the K179M mutant, fully restored zVAD.fmk-induced necroptosis (Fig. 7A,B). Nec-1 prevented both Myr-Akt dependent cell death and the necroptosis-specific delayed increase in Akt Thr308 phosphorylation (Fig. 7B,C). Myr-Akt also allowed other zVAD.fmk-dependent events, including activation of JNK and c-Jun phosphorylation (Fig. 7C) and upregulation of TNFα mRNA (Fig. 7D) to occur under serum free conditions, confirming an important role for Akt at the apex of necroptotic signaling. These data demonstrated that the presence of active and membrane localized Akt is sufficient to uncouple Akt activation during necroptosis from growth factor signaling. RIP1 kinase was still able to regulate Akt activation during necroptosis, suggesting that growth factors and RIP1 kinase provide two independent inputs required for Akt changes during necroptosis."}

BioNLP16_Messiy

{"project":"BioNLP16_Messiy","denotations":[{"id":"T15274","span":{"begin":1239,"end":1251},"obj":"Positive_regulation"},{"id":"T15273","span":{"begin":1209,"end":1224},"obj":"Phosphorylation"},{"id":"T15272","span":{"begin":589,"end":599},"obj":"Gene_expression"},{"id":"T15241","span":{"begin":1666,"end":1670},"obj":"Protein"},{"id":"T15240","span":{"begin":1557,"end":1561},"obj":"Protein"},{"id":"T15239","span":{"begin":1255,"end":1259},"obj":"Protein"},{"id":"T15238","span":{"begin":1203,"end":1208},"obj":"Protein"},{"id":"T15237","span":{"begin":999,"end":1006},"obj":"Protein"},{"id":"T15236","span":{"begin":907,"end":912},"obj":"Protein"},{"id":"T15235","span":{"begin":886,"end":893},"obj":"Protein"},{"id":"T15234","span":{"begin":600,"end":607},"obj":"Protein"},{"id":"T15233","span":{"begin":275,"end":282},"obj":"Protein"},{"id":"T15232","span":{"begin":269,"end":273},"obj":"Protein"},{"id":"T15231","span":{"begin":197,"end":201},"obj":"Protein"},{"id":"T15230","span":{"begin":121,"end":126},"obj":"Protein"},{"id":"T15229","span":{"begin":75,"end":82},"obj":"Protein"},{"id":"T15228","span":{"begin":69,"end":73},"obj":"Protein"},{"id":"T15271","span":{"begin":26,"end":36},"obj":"Gene_expression"}],"relations":[{"id":"R10009","pred":"themeOf","subj":"T15228","obj":"T15271"},{"id":"R10010","pred":"themeOf","subj":"T15229","obj":"T15271"},{"id":"R10011","pred":"themeOf","subj":"T15230","obj":"T15271"},{"id":"R10012","pred":"themeOf","subj":"T15234","obj":"T15272"},{"id":"R10013","pred":"themeOf","subj":"T15238","obj":"T15273"},{"id":"R10014","pred":"themeOf","subj":"T15239","obj":"T15274"}],"text":"We used L929 cells stably expressing constitutively active wild type Akt1 (Myr-Akt) or the catalytically inactive mutant K179M in order to further understand the contribution of growth factors and RIP1 kinase to Akt activation during necroptosis. Constitutively active Akt1 (Myr-Akt) was generated as previously described [37] by the addition of a myristoylation signal which provides constitutive localization to the plasma membrane and by the deletion of the auto-inhibitory PH domain (Fig. 7A) resulting in an Akt that is active under serum free. It is important to note that the cells expressing Myr-Akt were viable, grew in a manner indistinguishable from the empty vector control cells, and were not triggered to induce necroptosis by serum starvation (Fig. 7B). This indicates that active Akt alone is not sufficient to induce necroptotic cell death. Under serum free conditions Myr-Akt, but not the K179M mutant, fully restored zVAD.fmk-induced necroptosis (Fig. 7A,B). Nec-1 prevented both Myr-Akt dependent cell death and the necroptosis-specific delayed increase in Akt Thr308 phosphorylation (Fig. 7B,C). Myr-Akt also allowed other zVAD.fmk-dependent events, including activation of JNK and c-Jun phosphorylation (Fig. 7C) and upregulation of TNFα mRNA (Fig. 7D) to occur under serum free conditions, confirming an important role for Akt at the apex of necroptotic signaling. These data demonstrated that the presence of active and membrane localized Akt is sufficient to uncouple Akt activation during necroptosis from growth factor signaling. RIP1 kinase was still able to regulate Akt activation during necroptosis, suggesting that growth factors and RIP1 kinase provide two independent inputs required for Akt changes during necroptosis."}

DLUT931

{"project":"DLUT931","denotations":[{"id":"T15148","span":{"begin":1181,"end":1191},"obj":"Positive_regulation"},{"id":"T15147","span":{"begin":1239,"end":1251},"obj":"Positive_regulation"},{"id":"T15146","span":{"begin":1209,"end":1224},"obj":"Phosphorylation"},{"id":"T15145","span":{"begin":589,"end":599},"obj":"Gene_expression"},{"id":"T15144","span":{"begin":26,"end":36},"obj":"Gene_expression"},{"id":"T15114","span":{"begin":1666,"end":1670},"obj":"Protein"},{"id":"T15113","span":{"begin":1557,"end":1561},"obj":"Protein"},{"id":"T15112","span":{"begin":1255,"end":1259},"obj":"Protein"},{"id":"T15111","span":{"begin":1203,"end":1208},"obj":"Protein"},{"id":"T15110","span":{"begin":999,"end":1006},"obj":"Protein"},{"id":"T15109","span":{"begin":907,"end":912},"obj":"Protein"},{"id":"T15108","span":{"begin":886,"end":893},"obj":"Protein"},{"id":"T15107","span":{"begin":600,"end":607},"obj":"Protein"},{"id":"T15106","span":{"begin":275,"end":282},"obj":"Protein"},{"id":"T15105","span":{"begin":269,"end":273},"obj":"Protein"},{"id":"T15104","span":{"begin":197,"end":201},"obj":"Protein"},{"id":"T15103","span":{"begin":121,"end":126},"obj":"Protein"},{"id":"T15102","span":{"begin":75,"end":82},"obj":"Protein"},{"id":"T15101","span":{"begin":69,"end":73},"obj":"Protein"}],"relations":[{"id":"R9949","pred":"themeOf","subj":"T15101","obj":"T15144"},{"id":"R9950","pred":"themeOf","subj":"T15102","obj":"T15144"},{"id":"R9951","pred":"themeOf","subj":"T15103","obj":"T15144"},{"id":"R9952","pred":"themeOf","subj":"T15107","obj":"T15145"},{"id":"R9953","pred":"themeOf","subj":"T15111","obj":"T15146"},{"id":"R9954","pred":"themeOf","subj":"T15112","obj":"T15147"},{"id":"R9981","pred":"themeOf","subj":"T15146","obj":"T15148"},{"id":"R9982","pred":"themeOf","subj":"T15146","obj":"T15147"},{"id":"R9983","pred":"themeOf","subj":"T15147","obj":"T15148"},{"id":"R9984","pred":"themeOf","subj":"T15147","obj":"T15148"}],"text":"We used L929 cells stably expressing constitutively active wild type Akt1 (Myr-Akt) or the catalytically inactive mutant K179M in order to further understand the contribution of growth factors and RIP1 kinase to Akt activation during necroptosis. Constitutively active Akt1 (Myr-Akt) was generated as previously described [37] by the addition of a myristoylation signal which provides constitutive localization to the plasma membrane and by the deletion of the auto-inhibitory PH domain (Fig. 7A) resulting in an Akt that is active under serum free. It is important to note that the cells expressing Myr-Akt were viable, grew in a manner indistinguishable from the empty vector control cells, and were not triggered to induce necroptosis by serum starvation (Fig. 7B). This indicates that active Akt alone is not sufficient to induce necroptotic cell death. Under serum free conditions Myr-Akt, but not the K179M mutant, fully restored zVAD.fmk-induced necroptosis (Fig. 7A,B). Nec-1 prevented both Myr-Akt dependent cell death and the necroptosis-specific delayed increase in Akt Thr308 phosphorylation (Fig. 7B,C). Myr-Akt also allowed other zVAD.fmk-dependent events, including activation of JNK and c-Jun phosphorylation (Fig. 7C) and upregulation of TNFα mRNA (Fig. 7D) to occur under serum free conditions, confirming an important role for Akt at the apex of necroptotic signaling. These data demonstrated that the presence of active and membrane localized Akt is sufficient to uncouple Akt activation during necroptosis from growth factor signaling. RIP1 kinase was still able to regulate Akt activation during necroptosis, suggesting that growth factors and RIP1 kinase provide two independent inputs required for Akt changes during necroptosis."}

bionlp-st-ge-2016-test-ihmc

bionlp-st-ge-2016-spacy-parsed

bionlp-st-ge-2016-test-tees

test3

PMC:3585731 / 27827-29580 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:3585731 / 27827-29580 JSON TXT