PMC:3585731 / 31557-34067 JSON TXT

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testone

2_test

{"project":"2_test","denotations":[{"id":"23469174-8978681-90505450","span":{"begin":800,"end":802},"obj":"8978681"},{"id":"23469174-23030823-90505451","span":{"begin":1606,"end":1608},"obj":"23030823"}],"text":"Under serum free conditions all zVAD.fmk-induced downstream events (cell death, JNK activation, TNFα production) were dependent on the over expressed Myr-Akt. This allowed us to examine the effects of other Akt mutations on necroptosis. First, we found that membrane localization of Akt is required. Full length Akt or a mutant lacking both the PH domain and the Myr tag did not support the activation of cell death or increased Thr308 phosphorylation following zVAD.fmk addition under serum free conditions (Fig. S8A,B). Second, we found a specific and critical role for Thr308 phosphorylation in the regulation of the necroptotic functions of Akt. It has been reported that Ala mutations at Thr308 and Ser473 cause a reduction in the catalytic activity of Akt, while Asp mutants increase activity [38]. We examined the effect of Ala and Asp mutants at both sites during necroptosis. In our hands, both Asp mutants displayed activity comparable to wild type Akt, while both Ala mutants displayed comparable decreases in activity (Fig. S8C). Despite similar catalytic activities, Thr308 and Ser473 mutants displayed major differences in their ability to promote necroptotic changes (Fig. 7E,F,G). As expected, the S473D mutant, which was phosphorylated on Thr308 after the addition of zVAD, displayed only slightly reduced activity, while S473A was significantly less active in all aspects of necroptosis. S473A was unable to be efficiently phosphorylated on Thr308 possibly due to the inability of the Ala mutated 473 site to be phosphorylated and provide a docking site for PDK1 to phosphorylate Thr308 [39]. Strikingly, both Ala and Asp mutants of Thr308 were significantly less active in promoting cell death, phosphorylation of JNK and c-Jun, and TNFα mRNA. This suggests that T308D, in spite of being an active Akt construct, may not be a perfect mimic of phosphorylation and this mutant form of the kinase may not have sufficient activity to phosphorylate the entire repertoire of substrates in the cells. When tested, T308D did not support the downstream phosphorylation of several substrates that were phosphorylated by the Myr-Akt construct in the presence of zVAD including FoxO1, Foxo4, MDM2, and p70S6K (Fig. S8D). Our model, based on these results, is that necroptosis-specific Thr308 phosphorylation provides a critical link between necroptotic machinery and Akt kinase, allowing Akt to phosphorylate substrates during necroptosis, promote TNFα synthesis, JNK activation and eventual cell death."}

pmc-enju-pas

bionlp-st-ge-2016-coref

{"project":"bionlp-st-ge-2016-coref","denotations":[{"id":"T13834","span":{"begin":1214,"end":1226},"obj":"Antecedent"},{"id":"T13833","span":{"begin":1228,"end":1233},"obj":"Anaphor"},{"id":"T13832","span":{"begin":970,"end":974},"obj":"Anaphor"},{"id":"T13831","span":{"begin":854,"end":864},"obj":"Antecedent"},{"id":"T13830","span":{"begin":899,"end":903},"obj":"Anaphor"}],"relations":[{"id":"R9039","pred":"boundBy","subj":"T13830","obj":"T13831"},{"id":"R9040","pred":"boundBy","subj":"T13832","obj":"T13831"},{"id":"R9041","pred":"boundBy","subj":"T13833","obj":"T13834"}],"namespaces":[{"prefix":"_base","uri":"https://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"Under serum free conditions all zVAD.fmk-induced downstream events (cell death, JNK activation, TNFα production) were dependent on the over expressed Myr-Akt. This allowed us to examine the effects of other Akt mutations on necroptosis. First, we found that membrane localization of Akt is required. Full length Akt or a mutant lacking both the PH domain and the Myr tag did not support the activation of cell death or increased Thr308 phosphorylation following zVAD.fmk addition under serum free conditions (Fig. S8A,B). Second, we found a specific and critical role for Thr308 phosphorylation in the regulation of the necroptotic functions of Akt. It has been reported that Ala mutations at Thr308 and Ser473 cause a reduction in the catalytic activity of Akt, while Asp mutants increase activity [38]. We examined the effect of Ala and Asp mutants at both sites during necroptosis. In our hands, both Asp mutants displayed activity comparable to wild type Akt, while both Ala mutants displayed comparable decreases in activity (Fig. S8C). Despite similar catalytic activities, Thr308 and Ser473 mutants displayed major differences in their ability to promote necroptotic changes (Fig. 7E,F,G). As expected, the S473D mutant, which was phosphorylated on Thr308 after the addition of zVAD, displayed only slightly reduced activity, while S473A was significantly less active in all aspects of necroptosis. S473A was unable to be efficiently phosphorylated on Thr308 possibly due to the inability of the Ala mutated 473 site to be phosphorylated and provide a docking site for PDK1 to phosphorylate Thr308 [39]. Strikingly, both Ala and Asp mutants of Thr308 were significantly less active in promoting cell death, phosphorylation of JNK and c-Jun, and TNFα mRNA. This suggests that T308D, in spite of being an active Akt construct, may not be a perfect mimic of phosphorylation and this mutant form of the kinase may not have sufficient activity to phosphorylate the entire repertoire of substrates in the cells. When tested, T308D did not support the downstream phosphorylation of several substrates that were phosphorylated by the Myr-Akt construct in the presence of zVAD including FoxO1, Foxo4, MDM2, and p70S6K (Fig. S8D). Our model, based on these results, is that necroptosis-specific Thr308 phosphorylation provides a critical link between necroptotic machinery and Akt kinase, allowing Akt to phosphorylate substrates during necroptosis, promote TNFα synthesis, JNK activation and eventual cell death."}

bionlp-st-ge-2016-test-proteins

{"project":"bionlp-st-ge-2016-test-proteins","denotations":[{"id":"T13877","span":{"begin":2455,"end":2459},"obj":"Protein"},{"id":"T13876","span":{"begin":2209,"end":2215},"obj":"Protein"},{"id":"T13875","span":{"begin":2199,"end":2203},"obj":"Protein"},{"id":"T13874","span":{"begin":2192,"end":2197},"obj":"Protein"},{"id":"T13873","span":{"begin":2185,"end":2190},"obj":"Protein"},{"id":"T13872","span":{"begin":2133,"end":2140},"obj":"Protein"},{"id":"T13871","span":{"begin":2026,"end":2031},"obj":"Protein"},{"id":"T13870","span":{"begin":1782,"end":1787},"obj":"Protein"},{"id":"T13869","span":{"begin":1752,"end":1756},"obj":"Protein"},{"id":"T13868","span":{"begin":1741,"end":1746},"obj":"Protein"},{"id":"T13867","span":{"begin":1576,"end":1580},"obj":"Protein"},{"id":"T13866","span":{"begin":1406,"end":1411},"obj":"Protein"},{"id":"T13865","span":{"begin":1339,"end":1344},"obj":"Protein"},{"id":"T13864","span":{"begin":1214,"end":1226},"obj":"Protein"},{"id":"T13863","span":{"begin":758,"end":761},"obj":"Protein"},{"id":"T13862","span":{"begin":150,"end":157},"obj":"Protein"},{"id":"T13861","span":{"begin":96,"end":100},"obj":"Protein"}],"namespaces":[{"prefix":"_base","uri":"http://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"Under serum free conditions all zVAD.fmk-induced downstream events (cell death, JNK activation, TNFα production) were dependent on the over expressed Myr-Akt. This allowed us to examine the effects of other Akt mutations on necroptosis. First, we found that membrane localization of Akt is required. Full length Akt or a mutant lacking both the PH domain and the Myr tag did not support the activation of cell death or increased Thr308 phosphorylation following zVAD.fmk addition under serum free conditions (Fig. S8A,B). Second, we found a specific and critical role for Thr308 phosphorylation in the regulation of the necroptotic functions of Akt. It has been reported that Ala mutations at Thr308 and Ser473 cause a reduction in the catalytic activity of Akt, while Asp mutants increase activity [38]. We examined the effect of Ala and Asp mutants at both sites during necroptosis. In our hands, both Asp mutants displayed activity comparable to wild type Akt, while both Ala mutants displayed comparable decreases in activity (Fig. S8C). Despite similar catalytic activities, Thr308 and Ser473 mutants displayed major differences in their ability to promote necroptotic changes (Fig. 7E,F,G). As expected, the S473D mutant, which was phosphorylated on Thr308 after the addition of zVAD, displayed only slightly reduced activity, while S473A was significantly less active in all aspects of necroptosis. S473A was unable to be efficiently phosphorylated on Thr308 possibly due to the inability of the Ala mutated 473 site to be phosphorylated and provide a docking site for PDK1 to phosphorylate Thr308 [39]. Strikingly, both Ala and Asp mutants of Thr308 were significantly less active in promoting cell death, phosphorylation of JNK and c-Jun, and TNFα mRNA. This suggests that T308D, in spite of being an active Akt construct, may not be a perfect mimic of phosphorylation and this mutant form of the kinase may not have sufficient activity to phosphorylate the entire repertoire of substrates in the cells. When tested, T308D did not support the downstream phosphorylation of several substrates that were phosphorylated by the Myr-Akt construct in the presence of zVAD including FoxO1, Foxo4, MDM2, and p70S6K (Fig. S8D). Our model, based on these results, is that necroptosis-specific Thr308 phosphorylation provides a critical link between necroptotic machinery and Akt kinase, allowing Akt to phosphorylate substrates during necroptosis, promote TNFα synthesis, JNK activation and eventual cell death."}

bionlp-st-ge-2016-uniprot

UBERON-AE

{"project":"UBERON-AE","denotations":[{"id":"T13695","span":{"begin":486,"end":491},"obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"id":"T13694","span":{"begin":6,"end":11},"obj":"http://purl.obolibrary.org/obo/UBERON_0001977"}],"text":"Under serum free conditions all zVAD.fmk-induced downstream events (cell death, JNK activation, TNFα production) were dependent on the over expressed Myr-Akt. This allowed us to examine the effects of other Akt mutations on necroptosis. First, we found that membrane localization of Akt is required. Full length Akt or a mutant lacking both the PH domain and the Myr tag did not support the activation of cell death or increased Thr308 phosphorylation following zVAD.fmk addition under serum free conditions (Fig. S8A,B). Second, we found a specific and critical role for Thr308 phosphorylation in the regulation of the necroptotic functions of Akt. It has been reported that Ala mutations at Thr308 and Ser473 cause a reduction in the catalytic activity of Akt, while Asp mutants increase activity [38]. We examined the effect of Ala and Asp mutants at both sites during necroptosis. In our hands, both Asp mutants displayed activity comparable to wild type Akt, while both Ala mutants displayed comparable decreases in activity (Fig. S8C). Despite similar catalytic activities, Thr308 and Ser473 mutants displayed major differences in their ability to promote necroptotic changes (Fig. 7E,F,G). As expected, the S473D mutant, which was phosphorylated on Thr308 after the addition of zVAD, displayed only slightly reduced activity, while S473A was significantly less active in all aspects of necroptosis. S473A was unable to be efficiently phosphorylated on Thr308 possibly due to the inability of the Ala mutated 473 site to be phosphorylated and provide a docking site for PDK1 to phosphorylate Thr308 [39]. Strikingly, both Ala and Asp mutants of Thr308 were significantly less active in promoting cell death, phosphorylation of JNK and c-Jun, and TNFα mRNA. This suggests that T308D, in spite of being an active Akt construct, may not be a perfect mimic of phosphorylation and this mutant form of the kinase may not have sufficient activity to phosphorylate the entire repertoire of substrates in the cells. When tested, T308D did not support the downstream phosphorylation of several substrates that were phosphorylated by the Myr-Akt construct in the presence of zVAD including FoxO1, Foxo4, MDM2, and p70S6K (Fig. S8D). Our model, based on these results, is that necroptosis-specific Thr308 phosphorylation provides a critical link between necroptotic machinery and Akt kinase, allowing Akt to phosphorylate substrates during necroptosis, promote TNFα synthesis, JNK activation and eventual cell death."}

GO-BP

GO-MF

{"project":"GO-MF","denotations":[{"id":"T13963","span":{"begin":1576,"end":1580},"obj":"http://purl.obolibrary.org/obo/GO_0004740"},{"id":"T13962","span":{"begin":1058,"end":1078},"obj":"http://purl.obolibrary.org/obo/GO_0003824"},{"id":"T13961","span":{"begin":736,"end":754},"obj":"http://purl.obolibrary.org/obo/GO_0003824"},{"id":"T13959","span":{"begin":2471,"end":2474},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T13958","span":{"begin":1733,"end":1736},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T13957","span":{"begin":80,"end":83},"obj":"http://purl.obolibrary.org/obo/GO_0004705"}],"text":"Under serum free conditions all zVAD.fmk-induced downstream events (cell death, JNK activation, TNFα production) were dependent on the over expressed Myr-Akt. This allowed us to examine the effects of other Akt mutations on necroptosis. First, we found that membrane localization of Akt is required. Full length Akt or a mutant lacking both the PH domain and the Myr tag did not support the activation of cell death or increased Thr308 phosphorylation following zVAD.fmk addition under serum free conditions (Fig. S8A,B). Second, we found a specific and critical role for Thr308 phosphorylation in the regulation of the necroptotic functions of Akt. It has been reported that Ala mutations at Thr308 and Ser473 cause a reduction in the catalytic activity of Akt, while Asp mutants increase activity [38]. We examined the effect of Ala and Asp mutants at both sites during necroptosis. In our hands, both Asp mutants displayed activity comparable to wild type Akt, while both Ala mutants displayed comparable decreases in activity (Fig. S8C). Despite similar catalytic activities, Thr308 and Ser473 mutants displayed major differences in their ability to promote necroptotic changes (Fig. 7E,F,G). As expected, the S473D mutant, which was phosphorylated on Thr308 after the addition of zVAD, displayed only slightly reduced activity, while S473A was significantly less active in all aspects of necroptosis. S473A was unable to be efficiently phosphorylated on Thr308 possibly due to the inability of the Ala mutated 473 site to be phosphorylated and provide a docking site for PDK1 to phosphorylate Thr308 [39]. Strikingly, both Ala and Asp mutants of Thr308 were significantly less active in promoting cell death, phosphorylation of JNK and c-Jun, and TNFα mRNA. This suggests that T308D, in spite of being an active Akt construct, may not be a perfect mimic of phosphorylation and this mutant form of the kinase may not have sufficient activity to phosphorylate the entire repertoire of substrates in the cells. When tested, T308D did not support the downstream phosphorylation of several substrates that were phosphorylated by the Myr-Akt construct in the presence of zVAD including FoxO1, Foxo4, MDM2, and p70S6K (Fig. S8D). Our model, based on these results, is that necroptosis-specific Thr308 phosphorylation provides a critical link between necroptotic machinery and Akt kinase, allowing Akt to phosphorylate substrates during necroptosis, promote TNFα synthesis, JNK activation and eventual cell death."}

GO-CC

{"project":"GO-CC","denotations":[{"id":"T13973","span":{"begin":258,"end":266},"obj":"http://purl.obolibrary.org/obo/GO_0016020"},{"id":"T13969","span":{"begin":2499,"end":2503},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T13968","span":{"begin":2006,"end":2011},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"Under serum free conditions all zVAD.fmk-induced downstream events (cell death, JNK activation, TNFα production) were dependent on the over expressed Myr-Akt. This allowed us to examine the effects of other Akt mutations on necroptosis. First, we found that membrane localization of Akt is required. Full length Akt or a mutant lacking both the PH domain and the Myr tag did not support the activation of cell death or increased Thr308 phosphorylation following zVAD.fmk addition under serum free conditions (Fig. S8A,B). Second, we found a specific and critical role for Thr308 phosphorylation in the regulation of the necroptotic functions of Akt. It has been reported that Ala mutations at Thr308 and Ser473 cause a reduction in the catalytic activity of Akt, while Asp mutants increase activity [38]. We examined the effect of Ala and Asp mutants at both sites during necroptosis. In our hands, both Asp mutants displayed activity comparable to wild type Akt, while both Ala mutants displayed comparable decreases in activity (Fig. S8C). Despite similar catalytic activities, Thr308 and Ser473 mutants displayed major differences in their ability to promote necroptotic changes (Fig. 7E,F,G). As expected, the S473D mutant, which was phosphorylated on Thr308 after the addition of zVAD, displayed only slightly reduced activity, while S473A was significantly less active in all aspects of necroptosis. S473A was unable to be efficiently phosphorylated on Thr308 possibly due to the inability of the Ala mutated 473 site to be phosphorylated and provide a docking site for PDK1 to phosphorylate Thr308 [39]. Strikingly, both Ala and Asp mutants of Thr308 were significantly less active in promoting cell death, phosphorylation of JNK and c-Jun, and TNFα mRNA. This suggests that T308D, in spite of being an active Akt construct, may not be a perfect mimic of phosphorylation and this mutant form of the kinase may not have sufficient activity to phosphorylate the entire repertoire of substrates in the cells. When tested, T308D did not support the downstream phosphorylation of several substrates that were phosphorylated by the Myr-Akt construct in the presence of zVAD including FoxO1, Foxo4, MDM2, and p70S6K (Fig. S8D). Our model, based on these results, is that necroptosis-specific Thr308 phosphorylation provides a critical link between necroptotic machinery and Akt kinase, allowing Akt to phosphorylate substrates during necroptosis, promote TNFα synthesis, JNK activation and eventual cell death."}

sentences

simple1

{"project":"simple1","denotations":[{"id":"T14060","span":{"begin":2455,"end":2459},"obj":"Protein"},{"id":"T14059","span":{"begin":2209,"end":2215},"obj":"Protein"},{"id":"T14058","span":{"begin":2199,"end":2203},"obj":"Protein"},{"id":"T14057","span":{"begin":2192,"end":2197},"obj":"Protein"},{"id":"T14056","span":{"begin":2185,"end":2190},"obj":"Protein"},{"id":"T14055","span":{"begin":2133,"end":2140},"obj":"Protein"},{"id":"T14054","span":{"begin":2026,"end":2031},"obj":"Protein"},{"id":"T14053","span":{"begin":1782,"end":1787},"obj":"Protein"},{"id":"T14052","span":{"begin":1752,"end":1756},"obj":"Protein"},{"id":"T14051","span":{"begin":1741,"end":1746},"obj":"Protein"},{"id":"T14050","span":{"begin":1576,"end":1580},"obj":"Protein"},{"id":"T14049","span":{"begin":1406,"end":1411},"obj":"Protein"},{"id":"T14048","span":{"begin":1339,"end":1344},"obj":"Protein"},{"id":"T14047","span":{"begin":1214,"end":1226},"obj":"Protein"},{"id":"T14046","span":{"begin":758,"end":761},"obj":"Protein"},{"id":"T14045","span":{"begin":150,"end":157},"obj":"Protein"},{"id":"T14044","span":{"begin":96,"end":100},"obj":"Protein"}],"text":"Under serum free conditions all zVAD.fmk-induced downstream events (cell death, JNK activation, TNFα production) were dependent on the over expressed Myr-Akt. This allowed us to examine the effects of other Akt mutations on necroptosis. First, we found that membrane localization of Akt is required. Full length Akt or a mutant lacking both the PH domain and the Myr tag did not support the activation of cell death or increased Thr308 phosphorylation following zVAD.fmk addition under serum free conditions (Fig. S8A,B). Second, we found a specific and critical role for Thr308 phosphorylation in the regulation of the necroptotic functions of Akt. It has been reported that Ala mutations at Thr308 and Ser473 cause a reduction in the catalytic activity of Akt, while Asp mutants increase activity [38]. We examined the effect of Ala and Asp mutants at both sites during necroptosis. In our hands, both Asp mutants displayed activity comparable to wild type Akt, while both Ala mutants displayed comparable decreases in activity (Fig. S8C). Despite similar catalytic activities, Thr308 and Ser473 mutants displayed major differences in their ability to promote necroptotic changes (Fig. 7E,F,G). As expected, the S473D mutant, which was phosphorylated on Thr308 after the addition of zVAD, displayed only slightly reduced activity, while S473A was significantly less active in all aspects of necroptosis. S473A was unable to be efficiently phosphorylated on Thr308 possibly due to the inability of the Ala mutated 473 site to be phosphorylated and provide a docking site for PDK1 to phosphorylate Thr308 [39]. Strikingly, both Ala and Asp mutants of Thr308 were significantly less active in promoting cell death, phosphorylation of JNK and c-Jun, and TNFα mRNA. This suggests that T308D, in spite of being an active Akt construct, may not be a perfect mimic of phosphorylation and this mutant form of the kinase may not have sufficient activity to phosphorylate the entire repertoire of substrates in the cells. When tested, T308D did not support the downstream phosphorylation of several substrates that were phosphorylated by the Myr-Akt construct in the presence of zVAD including FoxO1, Foxo4, MDM2, and p70S6K (Fig. S8D). Our model, based on these results, is that necroptosis-specific Thr308 phosphorylation provides a critical link between necroptotic machinery and Akt kinase, allowing Akt to phosphorylate substrates during necroptosis, promote TNFα synthesis, JNK activation and eventual cell death."}

BioNLP16_DUT

BioNLP16_Messiy

DLUT931

bionlp-st-ge-2016-test-ihmc

bionlp-st-ge-2016-spacy-parsed

bionlp-st-ge-2016-test-tees

test3

PMC:3585731 / 31557-34067 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:3585731 / 31557-34067 JSON TXT