PubMed:7629157 JSONTXT

{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":133},"obj":"Sentence"},{"id":"T2","span":{"begin":134,"end":328},"obj":"Sentence"},{"id":"T3","span":{"begin":329,"end":463},"obj":"Sentence"},{"id":"T4","span":{"begin":464,"end":768},"obj":"Sentence"},{"id":"T5","span":{"begin":769,"end":1021},"obj":"Sentence"},{"id":"T6","span":{"begin":1022,"end":1323},"obj":"Sentence"},{"id":"T7","span":{"begin":1324,"end":1492},"obj":"Sentence"},{"id":"T8","span":{"begin":1493,"end":1659},"obj":"Sentence"},{"id":"T9","span":{"begin":1660,"end":1883},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":133},"obj":"Sentence"},{"id":"T2","span":{"begin":134,"end":328},"obj":"Sentence"},{"id":"T3","span":{"begin":329,"end":463},"obj":"Sentence"},{"id":"T4","span":{"begin":464,"end":768},"obj":"Sentence"},{"id":"T5","span":{"begin":769,"end":1021},"obj":"Sentence"},{"id":"T6","span":{"begin":1022,"end":1323},"obj":"Sentence"},{"id":"T7","span":{"begin":1324,"end":1492},"obj":"Sentence"},{"id":"T8","span":{"begin":1493,"end":1659},"obj":"Sentence"},{"id":"T9","span":{"begin":1660,"end":1883},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites.\nActivation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor, I kappa B alpha, although the underlying mechanism remains unclear. In the present study, the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated. Our studies demonstrate that incubation of human T cells with low concentrations (approximately 1-5 nM) of calyculin A or okadaic acid, potent inhibitors of protein phosphatase type 1 (PP-1) and type 2A (PP-2A), induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus. This action of the phosphatase inhibitors, which is associated with the activation of the RelA.p50 NF-kappa B heterodimer, is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha (TNF-alpha). Furthermore, the phosphorylated I kappa B alpha from calyculin A-treated cells, but not that from TNF-alpha-stimulated cells, is sensitive to PP-2A in vitro, suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers. However, induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha. We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor. Together, these results suggest that phosphorylation of I kappa B alpha, mediated through both the TNF-alpha-inducible and the PP-2A-opposing kinases, may serve to target I kappa B alpha for proteasome-mediated degradation."}

{"project":"jnlpba-st-training","denotations":[{"id":"T1","span":{"begin":14,"end":24},"obj":"protein"},{"id":"T2","span":{"begin":28,"end":39},"obj":"protein"},{"id":"T3","span":{"begin":83,"end":98},"obj":"protein"},{"id":"T4","span":{"begin":102,"end":132},"obj":"protein"},{"id":"T5","span":{"begin":148,"end":158},"obj":"protein"},{"id":"T6","span":{"begin":261,"end":276},"obj":"protein"},{"id":"T7","span":{"begin":363,"end":392},"obj":"protein"},{"id":"T8","span":{"begin":414,"end":429},"obj":"protein"},{"id":"T9","span":{"begin":507,"end":520},"obj":"cell_type"},{"id":"T10","span":{"begin":621,"end":666},"obj":"protein"},{"id":"T11","span":{"begin":668,"end":673},"obj":"protein"},{"id":"T12","span":{"begin":707,"end":722},"obj":"protein"},{"id":"T13","span":{"begin":859,"end":890},"obj":"protein"},{"id":"T14","span":{"begin":946,"end":961},"obj":"protein"},{"id":"T15","span":{"begin":981,"end":1008},"obj":"protein"},{"id":"T16","span":{"begin":1010,"end":1019},"obj":"protein"},{"id":"T17","span":{"begin":1039,"end":1069},"obj":"protein"},{"id":"T18","span":{"begin":1075,"end":1100},"obj":"cell_line"},{"id":"T19","span":{"begin":1120,"end":1146},"obj":"cell_line"},{"id":"T20","span":{"begin":1164,"end":1169},"obj":"protein"},{"id":"T21","span":{"begin":1258,"end":1273},"obj":"protein"},{"id":"T22","span":{"begin":1303,"end":1313},"obj":"protein"},{"id":"T23","span":{"begin":1346,"end":1361},"obj":"protein"},{"id":"T24","span":{"begin":1386,"end":1395},"obj":"protein"},{"id":"T25","span":{"begin":1476,"end":1491},"obj":"protein"},{"id":"T26","span":{"begin":1716,"end":1731},"obj":"protein"},{"id":"T27","span":{"begin":1759,"end":1768},"obj":"protein"},{"id":"T28","span":{"begin":1787,"end":1809},"obj":"protein"},{"id":"T29","span":{"begin":1831,"end":1846},"obj":"protein"},{"id":"T30","span":{"begin":1851,"end":1861},"obj":"protein"}],"text":"Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites.\nActivation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor, I kappa B alpha, although the underlying mechanism remains unclear. In the present study, the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated. Our studies demonstrate that incubation of human T cells with low concentrations (approximately 1-5 nM) of calyculin A or okadaic acid, potent inhibitors of protein phosphatase type 1 (PP-1) and type 2A (PP-2A), induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus. This action of the phosphatase inhibitors, which is associated with the activation of the RelA.p50 NF-kappa B heterodimer, is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha (TNF-alpha). Furthermore, the phosphorylated I kappa B alpha from calyculin A-treated cells, but not that from TNF-alpha-stimulated cells, is sensitive to PP-2A in vitro, suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers. However, induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha. We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor. Together, these results suggest that phosphorylation of I kappa B alpha, mediated through both the TNF-alpha-inducible and the PP-2A-opposing kinases, may serve to target I kappa B alpha for proteasome-mediated degradation."}

{"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":133},"obj":"Sentence"},{"id":"S2","span":{"begin":134,"end":328},"obj":"Sentence"},{"id":"S3","span":{"begin":329,"end":463},"obj":"Sentence"},{"id":"S4","span":{"begin":464,"end":768},"obj":"Sentence"},{"id":"S5","span":{"begin":769,"end":1021},"obj":"Sentence"},{"id":"S6","span":{"begin":1022,"end":1323},"obj":"Sentence"},{"id":"S7","span":{"begin":1324,"end":1492},"obj":"Sentence"},{"id":"S8","span":{"begin":1493,"end":1659},"obj":"Sentence"},{"id":"S9","span":{"begin":1660,"end":1883},"obj":"Sentence"}],"text":"Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites.\nActivation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor, I kappa B alpha, although the underlying mechanism remains unclear. In the present study, the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated. Our studies demonstrate that incubation of human T cells with low concentrations (approximately 1-5 nM) of calyculin A or okadaic acid, potent inhibitors of protein phosphatase type 1 (PP-1) and type 2A (PP-2A), induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus. This action of the phosphatase inhibitors, which is associated with the activation of the RelA.p50 NF-kappa B heterodimer, is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha (TNF-alpha). Furthermore, the phosphorylated I kappa B alpha from calyculin A-treated cells, but not that from TNF-alpha-stimulated cells, is sensitive to PP-2A in vitro, suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers. However, induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha. We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor. Together, these results suggest that phosphorylation of I kappa B alpha, mediated through both the TNF-alpha-inducible and the PP-2A-opposing kinases, may serve to target I kappa B alpha for proteasome-mediated degradation."}

{"project":"genia-medco-coref","denotations":[{"id":"C1","span":{"begin":14,"end":24},"obj":"NP"},{"id":"C2","span":{"begin":28,"end":50},"obj":"NP"},{"id":"C4","span":{"begin":83,"end":98},"obj":"NP"},{"id":"C3","span":{"begin":60,"end":98},"obj":"NP"},{"id":"C5","span":{"begin":148,"end":158},"obj":"NP"},{"id":"C7","span":{"begin":246,"end":249},"obj":"NP"},{"id":"C6","span":{"begin":246,"end":259},"obj":"NP"},{"id":"C8","span":{"begin":261,"end":276},"obj":"NP"},{"id":"C9","span":{"begin":414,"end":445},"obj":"NP"},{"id":"C10","span":{"begin":571,"end":598},"obj":"NP"},{"id":"C11","span":{"begin":600,"end":674},"obj":"NP"},{"id":"C13","span":{"begin":707,"end":722},"obj":"NP"},{"id":"C12","span":{"begin":684,"end":722},"obj":"NP"},{"id":"C15","span":{"begin":784,"end":810},"obj":"NP"},{"id":"C14","span":{"begin":769,"end":810},"obj":"NP"},{"id":"C16","span":{"begin":812,"end":817},"obj":"NP"},{"id":"C17","span":{"begin":911,"end":917},"obj":"NP"},{"id":"C18","span":{"begin":918,"end":922},"obj":"NP"},{"id":"C19","span":{"begin":946,"end":977},"obj":"NP"},{"id":"C20","span":{"begin":981,"end":1020},"obj":"NP"},{"id":"C21","span":{"begin":1035,"end":1069},"obj":"NP"},{"id":"C22","span":{"begin":1110,"end":1114},"obj":"NP"},{"id":"C24","span":{"begin":1258,"end":1273},"obj":"NP"},{"id":"C23","span":{"begin":1235,"end":1273},"obj":"NP"},{"id":"C25","span":{"begin":1346,"end":1377},"obj":"NP"},{"id":"C26","span":{"begin":1386,"end":1395},"obj":"NP"},{"id":"C27","span":{"begin":1400,"end":1426},"obj":"NP"},{"id":"C28","span":{"begin":1476,"end":1491},"obj":"NP"},{"id":"C30","span":{"begin":1716,"end":1731},"obj":"NP"},{"id":"C29","span":{"begin":1697,"end":1731},"obj":"NP"},{"id":"C31","span":{"begin":1831,"end":1846},"obj":"NP"}],"relations":[{"id":"R1","pred":"coref-ident","subj":"C5","obj":"C1"},{"id":"R2","pred":"coref-pron","subj":"C7","obj":"C5"},{"id":"R3","pred":"coref-ident","subj":"C6","obj":"C4"},{"id":"R4","pred":"coref-appos","subj":"C8","obj":"C6"},{"id":"R5","pred":"coref-ident","subj":"C9","obj":"C3"},{"id":"R6","pred":"coref-appos","subj":"C11","obj":"C10"},{"id":"R7","pred":"coref-ident","subj":"C13","obj":"C8"},{"id":"R8","pred":"coref-ident","subj":"C12","obj":"C9"},{"id":"R9","pred":"coref-ident","subj":"C15","obj":"C2"},{"id":"R10","pred":"coref-relat","subj":"C16","obj":"C14"},{"id":"R11","pred":"coref-relat","subj":"C18","obj":"C17"},{"id":"R12","pred":"coref-ident","subj":"C19","obj":"C12"},{"id":"R13","pred":"coref-pron","subj":"C22","obj":"C21"},{"id":"R14","pred":"coref-ident","subj":"C24","obj":"C13"},{"id":"R15","pred":"coref-ident","subj":"C23","obj":"C19"},{"id":"R16","pred":"coref-ident","subj":"C25","obj":"C23"},{"id":"R17","pred":"coref-ident","subj":"C26","obj":"C20"},{"id":"R18","pred":"coref-ident","subj":"C27","obj":"C15"},{"id":"R19","pred":"coref-ident","subj":"C28","obj":"C24"},{"id":"R20","pred":"coref-ident","subj":"C30","obj":"C28"},{"id":"R21","pred":"coref-ident","subj":"C29","obj":"C25"},{"id":"R22","pred":"coref-ident","subj":"C31","obj":"C30"}],"text":"Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites.\nActivation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor, I kappa B alpha, although the underlying mechanism remains unclear. In the present study, the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated. Our studies demonstrate that incubation of human T cells with low concentrations (approximately 1-5 nM) of calyculin A or okadaic acid, potent inhibitors of protein phosphatase type 1 (PP-1) and type 2A (PP-2A), induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus. This action of the phosphatase inhibitors, which is associated with the activation of the RelA.p50 NF-kappa B heterodimer, is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha (TNF-alpha). Furthermore, the phosphorylated I kappa B alpha from calyculin A-treated cells, but not that from TNF-alpha-stimulated cells, is sensitive to PP-2A in vitro, suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers. However, induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha. We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor. Together, these results suggest that phosphorylation of I kappa B alpha, mediated through both the TNF-alpha-inducible and the PP-2A-opposing kinases, may serve to target I kappa B alpha for proteasome-mediated degradation."}

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{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":981,"end":986},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0002664"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites.\nActivation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor, I kappa B alpha, although the underlying mechanism remains unclear. In the present study, the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated. Our studies demonstrate that incubation of human T cells with low concentrations (approximately 1-5 nM) of calyculin A or okadaic acid, potent inhibitors of protein phosphatase type 1 (PP-1) and type 2A (PP-2A), induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus. This action of the phosphatase inhibitors, which is associated with the activation of the RelA.p50 NF-kappa B heterodimer, is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha (TNF-alpha). Furthermore, the phosphorylated I kappa B alpha from calyculin A-treated cells, but not that from TNF-alpha-stimulated cells, is sensitive to PP-2A in vitro, suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers. However, induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha. We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor. Together, these results suggest that phosphorylation of I kappa B alpha, mediated through both the TNF-alpha-inducible and the PP-2A-opposing kinases, may serve to target I kappa B alpha for proteasome-mediated degradation."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":981,"end":986},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"}],"text":"Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites.\nActivation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor, I kappa B alpha, although the underlying mechanism remains unclear. In the present study, the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated. Our studies demonstrate that incubation of human T cells with low concentrations (approximately 1-5 nM) of calyculin A or okadaic acid, potent inhibitors of protein phosphatase type 1 (PP-1) and type 2A (PP-2A), induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus. This action of the phosphatase inhibitors, which is associated with the activation of the RelA.p50 NF-kappa B heterodimer, is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha (TNF-alpha). Furthermore, the phosphorylated I kappa B alpha from calyculin A-treated cells, but not that from TNF-alpha-stimulated cells, is sensitive to PP-2A in vitro, suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers. However, induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha. We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor. Together, these results suggest that phosphorylation of I kappa B alpha, mediated through both the TNF-alpha-inducible and the PP-2A-opposing kinases, may serve to target I kappa B alpha for proteasome-mediated degradation."}

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":507,"end":512},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"}],"text":"Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites.\nActivation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor, I kappa B alpha, although the underlying mechanism remains unclear. In the present study, the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated. Our studies demonstrate that incubation of human T cells with low concentrations (approximately 1-5 nM) of calyculin A or okadaic acid, potent inhibitors of protein phosphatase type 1 (PP-1) and type 2A (PP-2A), induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus. This action of the phosphatase inhibitors, which is associated with the activation of the RelA.p50 NF-kappa B heterodimer, is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha (TNF-alpha). Furthermore, the phosphorylated I kappa B alpha from calyculin A-treated cells, but not that from TNF-alpha-stimulated cells, is sensitive to PP-2A in vitro, suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers. However, induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha. We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor. Together, these results suggest that phosphorylation of I kappa B alpha, mediated through both the TNF-alpha-inducible and the PP-2A-opposing kinases, may serve to target I kappa B alpha for proteasome-mediated degradation."}

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":513,"end":520},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000084"}],"text":"Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites.\nActivation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor, I kappa B alpha, although the underlying mechanism remains unclear. In the present study, the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated. Our studies demonstrate that incubation of human T cells with low concentrations (approximately 1-5 nM) of calyculin A or okadaic acid, potent inhibitors of protein phosphatase type 1 (PP-1) and type 2A (PP-2A), induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus. This action of the phosphatase inhibitors, which is associated with the activation of the RelA.p50 NF-kappa B heterodimer, is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha (TNF-alpha). Furthermore, the phosphorylated I kappa B alpha from calyculin A-treated cells, but not that from TNF-alpha-stimulated cells, is sensitive to PP-2A in vitro, suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers. However, induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha. We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor. Together, these results suggest that phosphorylation of I kappa B alpha, mediated through both the TNF-alpha-inducible and the PP-2A-opposing kinases, may serve to target I kappa B alpha for proteasome-mediated degradation."}