PubMed:8631809 JSONTXT

{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":87},"obj":"Sentence"},{"id":"T2","span":{"begin":88,"end":289},"obj":"Sentence"},{"id":"T3","span":{"begin":290,"end":461},"obj":"Sentence"},{"id":"T4","span":{"begin":462,"end":533},"obj":"Sentence"},{"id":"T5","span":{"begin":534,"end":683},"obj":"Sentence"},{"id":"T6","span":{"begin":684,"end":926},"obj":"Sentence"},{"id":"T7","span":{"begin":927,"end":1104},"obj":"Sentence"},{"id":"T8","span":{"begin":1105,"end":1197},"obj":"Sentence"},{"id":"T9","span":{"begin":1198,"end":1319},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":87},"obj":"Sentence"},{"id":"T2","span":{"begin":88,"end":289},"obj":"Sentence"},{"id":"T3","span":{"begin":290,"end":461},"obj":"Sentence"},{"id":"T4","span":{"begin":462,"end":533},"obj":"Sentence"},{"id":"T5","span":{"begin":534,"end":683},"obj":"Sentence"},{"id":"T6","span":{"begin":684,"end":926},"obj":"Sentence"},{"id":"T7","span":{"begin":927,"end":1104},"obj":"Sentence"},{"id":"T8","span":{"begin":1105,"end":1197},"obj":"Sentence"},{"id":"T9","span":{"begin":1198,"end":1319},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway.\nThe mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex. Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene. IL-2 production by CsA-treated cells is therefore dramatically reduced. We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway. In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha-CD28 stimulation, and this activation was resistant to CsA. Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28. Peripheral blood T cells stimulated with PMA/alphaCD28 produced IL-2 in the presence of CsA. Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner."}

{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":1055,"end":1060},"obj":"http://purl.obolibrary.org/obo/MAT_0000083"},{"id":"T2","span":{"begin":1055,"end":1060},"obj":"http://purl.obolibrary.org/obo/MAT_0000315"},{"id":"T3","span":{"begin":1116,"end":1121},"obj":"http://purl.obolibrary.org/obo/MAT_0000083"},{"id":"T4","span":{"begin":1116,"end":1121},"obj":"http://purl.obolibrary.org/obo/MAT_0000315"}],"text":"Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway.\nThe mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex. Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene. IL-2 production by CsA-treated cells is therefore dramatically reduced. We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway. In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha-CD28 stimulation, and this activation was resistant to CsA. Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28. Peripheral blood T cells stimulated with PMA/alphaCD28 produced IL-2 in the presence of CsA. Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner."}

{"project":"jnlpba-st-training","denotations":[{"id":"T1","span":{"begin":14,"end":49},"obj":"protein"},{"id":"T2","span":{"begin":189,"end":243},"obj":"protein"},{"id":"T3","span":{"begin":244,"end":255},"obj":"protein"},{"id":"T4","span":{"begin":263,"end":288},"obj":"protein"},{"id":"T5","span":{"begin":299,"end":310},"obj":"protein"},{"id":"T6","span":{"begin":337,"end":372},"obj":"protein"},{"id":"T7","span":{"begin":374,"end":378},"obj":"protein"},{"id":"T8","span":{"begin":383,"end":403},"obj":"protein"},{"id":"T9","span":{"begin":435,"end":460},"obj":"DNA"},{"id":"T10","span":{"begin":462,"end":466},"obj":"protein"},{"id":"T11","span":{"begin":481,"end":498},"obj":"cell_line"},{"id":"T12","span":{"begin":569,"end":573},"obj":"protein"},{"id":"T13","span":{"begin":618,"end":622},"obj":"protein"},{"id":"T14","span":{"begin":660,"end":664},"obj":"protein"},{"id":"T15","span":{"begin":733,"end":737},"obj":"protein"},{"id":"T16","span":{"begin":743,"end":800},"obj":"DNA"},{"id":"T17","span":{"begin":867,"end":871},"obj":"protein"},{"id":"T18","span":{"begin":990,"end":1016},"obj":"protein"},{"id":"T19","span":{"begin":1044,"end":1068},"obj":"cell_type"},{"id":"T20","span":{"begin":1094,"end":1103},"obj":"protein"},{"id":"T21","span":{"begin":1105,"end":1129},"obj":"cell_type"},{"id":"T22","span":{"begin":1149,"end":1159},"obj":"protein"},{"id":"T23","span":{"begin":1169,"end":1173},"obj":"protein"},{"id":"T24","span":{"begin":1236,"end":1240},"obj":"protein"},{"id":"T25","span":{"begin":1262,"end":1266},"obj":"protein"},{"id":"T26","span":{"begin":1288,"end":1299},"obj":"protein"}],"text":"Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway.\nThe mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex. Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene. IL-2 production by CsA-treated cells is therefore dramatically reduced. We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway. In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha-CD28 stimulation, and this activation was resistant to CsA. Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28. Peripheral blood T cells stimulated with PMA/alphaCD28 produced IL-2 in the presence of CsA. Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner."}

{"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":87},"obj":"Sentence"},{"id":"S2","span":{"begin":88,"end":289},"obj":"Sentence"},{"id":"S3","span":{"begin":290,"end":461},"obj":"Sentence"},{"id":"S4","span":{"begin":462,"end":533},"obj":"Sentence"},{"id":"S5","span":{"begin":534,"end":683},"obj":"Sentence"},{"id":"S6","span":{"begin":684,"end":926},"obj":"Sentence"},{"id":"S7","span":{"begin":927,"end":1104},"obj":"Sentence"},{"id":"S8","span":{"begin":1105,"end":1197},"obj":"Sentence"},{"id":"S9","span":{"begin":1198,"end":1319},"obj":"Sentence"}],"text":"Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway.\nThe mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex. Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene. IL-2 production by CsA-treated cells is therefore dramatically reduced. We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway. In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha-CD28 stimulation, and this activation was resistant to CsA. Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28. Peripheral blood T cells stimulated with PMA/alphaCD28 produced IL-2 in the presence of CsA. Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner."}

{"project":"genia-medco-coref","denotations":[{"id":"C1","span":{"begin":14,"end":49},"obj":"NP"},{"id":"C2","span":{"begin":55,"end":69},"obj":"NP"},{"id":"C3","span":{"begin":115,"end":161},"obj":"NP"},{"id":"C4","span":{"begin":333,"end":379},"obj":"NP"},{"id":"C5","span":{"begin":381,"end":460},"obj":"NP"},{"id":"C6","span":{"begin":481,"end":485},"obj":"NP"},{"id":"C7","span":{"begin":569,"end":573},"obj":"NP"},{"id":"C8","span":{"begin":618,"end":622},"obj":"NP"},{"id":"C9","span":{"begin":646,"end":650},"obj":"NP"},{"id":"C10","span":{"begin":733,"end":738},"obj":"NP"},{"id":"C11","span":{"begin":922,"end":925},"obj":"NP"},{"id":"C12","span":{"begin":990,"end":994},"obj":"NP"},{"id":"C14","span":{"begin":1085,"end":1103},"obj":"NP"},{"id":"C13","span":{"begin":1044,"end":1103},"obj":"NP"},{"id":"C16","span":{"begin":1146,"end":1159},"obj":"NP"},{"id":"C15","span":{"begin":1105,"end":1159},"obj":"NP"},{"id":"C17","span":{"begin":1169,"end":1173},"obj":"NP"},{"id":"C18","span":{"begin":1193,"end":1196},"obj":"NP"},{"id":"C19","span":{"begin":1236,"end":1240},"obj":"NP"},{"id":"C20","span":{"begin":1262,"end":1266},"obj":"NP"}],"relations":[{"id":"R1","pred":"coref-ident","subj":"C3","obj":"C2"},{"id":"R2","pred":"coref-ident","subj":"C4","obj":"C1"},{"id":"R3","pred":"coref-appos","subj":"C5","obj":"C4"},{"id":"R4","pred":"coref-ident","subj":"C6","obj":"C3"},{"id":"R5","pred":"coref-ident","subj":"C7","obj":"C4"},{"id":"R6","pred":"coref-ident","subj":"C9","obj":"C6"},{"id":"R7","pred":"coref-ident","subj":"C10","obj":"C7"},{"id":"R8","pred":"coref-ident","subj":"C11","obj":"C9"},{"id":"R9","pred":"coref-ident","subj":"C12","obj":"C11"},{"id":"R10","pred":"coref-ident","subj":"C16","obj":"C14"},{"id":"R11","pred":"coref-ident","subj":"C15","obj":"C13"},{"id":"R12","pred":"coref-ident","subj":"C17","obj":"C8"},{"id":"R13","pred":"coref-ident","subj":"C18","obj":"C12"},{"id":"R14","pred":"coref-ident","subj":"C19","obj":"C10"},{"id":"R15","pred":"coref-ident","subj":"C20","obj":"C17"}],"text":"Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway.\nThe mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex. Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene. IL-2 production by CsA-treated cells is therefore dramatically reduced. We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway. In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha-CD28 stimulation, and this activation was resistant to CsA. Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28. Peripheral blood T cells stimulated with PMA/alphaCD28 produced IL-2 in the presence of CsA. Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner."}

{"project":"GENIAcorpus","denotations":[{"id":"T1","span":{"begin":14,"end":41},"obj":"protein_family_or_group"},{"id":"T2","span":{"begin":42,"end":49},"obj":"cell_type"},{"id":"T3","span":{"begin":55,"end":68},"obj":"other_organic_compound"},{"id":"T4","span":{"begin":119,"end":141},"obj":"other_organic_compound"},{"id":"T5","span":{"begin":142,"end":155},"obj":"other_organic_compound"},{"id":"T6","span":{"begin":157,"end":160},"obj":"other_organic_compound"},{"id":"T7","span":{"begin":189,"end":193},"obj":"atom"},{"id":"T8","span":{"begin":244,"end":255},"obj":"protein_molecule"},{"id":"T9","span":{"begin":263,"end":288},"obj":"protein_complex"},{"id":"T10","span":{"begin":299,"end":310},"obj":"protein_molecule"},{"id":"T11","span":{"begin":337,"end":372},"obj":"protein_family_or_group"},{"id":"T12","span":{"begin":374,"end":378},"obj":"protein_family_or_group"},{"id":"T13","span":{"begin":383,"end":403},"obj":"protein_family_or_group"},{"id":"T14","span":{"begin":435,"end":450},"obj":"DNA_domain_or_region"},{"id":"T15","span":{"begin":450,"end":454},"obj":"protein_molecule"},{"id":"T16","span":{"begin":462,"end":466},"obj":"protein_molecule"},{"id":"T17","span":{"begin":481,"end":484},"obj":"other_organic_compound"},{"id":"T18","span":{"begin":569,"end":573},"obj":"protein_family_or_group"},{"id":"T19","span":{"begin":618,"end":622},"obj":"protein_molecule"},{"id":"T20","span":{"begin":646,"end":649},"obj":"other_organic_compound"},{"id":"T21","span":{"begin":660,"end":664},"obj":"protein_molecule"},{"id":"T22","span":{"begin":687,"end":716},"obj":"other_name"},{"id":"T23","span":{"begin":733,"end":737},"obj":"protein_family_or_group"},{"id":"T24","span":{"begin":743,"end":747},"obj":"protein_molecule"},{"id":"T25","span":{"begin":823,"end":856},"obj":"other_name"},{"id":"T26","span":{"begin":856,"end":859},"obj":"other_organic_compound"},{"id":"T27","span":{"begin":867,"end":871},"obj":"protein_molecule"},{"id":"T28","span":{"begin":922,"end":925},"obj":"other_organic_compound"},{"id":"T29","span":{"begin":927,"end":963},"obj":"other_name"},{"id":"T30","span":{"begin":990,"end":993},"obj":"other_organic_compound"},{"id":"T31","span":{"begin":1004,"end":1008},"obj":"protein_family_or_group"},{"id":"T32","span":{"begin":1024,"end":1040},"obj":"cell_component"},{"id":"T33","span":{"begin":1044,"end":1068},"obj":"cell_type"},{"id":"T34","span":{"begin":1085,"end":1088},"obj":"other_organic_compound"},{"id":"T35","span":{"begin":1094,"end":1103},"obj":"protein_molecule"},{"id":"T36","span":{"begin":1105,"end":1129},"obj":"cell_type"},{"id":"T37","span":{"begin":1146,"end":1149},"obj":"other_organic_compound"},{"id":"T38","span":{"begin":1149,"end":1159},"obj":"protein_molecule"},{"id":"T39","span":{"begin":1169,"end":1173},"obj":"protein_molecule"},{"id":"T40","span":{"begin":1193,"end":1196},"obj":"other_organic_compound"},{"id":"T41","span":{"begin":1236,"end":1240},"obj":"protein_family_or_group"},{"id":"T42","span":{"begin":1262,"end":1266},"obj":"protein_molecule"},{"id":"T43","span":{"begin":1288,"end":1299},"obj":"protein_molecule"}],"text":"Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway.\nThe mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex. Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene. IL-2 production by CsA-treated cells is therefore dramatically reduced. We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway. In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha-CD28 stimulation, and this activation was resistant to CsA. Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28. Peripheral blood T cells stimulated with PMA/alphaCD28 produced IL-2 in the presence of CsA. Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner."}

{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":1055,"end":1060},"obj":"Body_part"},{"id":"T3","span":{"begin":1116,"end":1121},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000083"},{"id":"A2","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000315"},{"id":"A3","pred":"mat_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MAT_0000083"},{"id":"A4","pred":"mat_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MAT_0000315"}],"text":"Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway.\nThe mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex. Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene. IL-2 production by CsA-treated cells is therefore dramatically reduced. We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway. In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha-CD28 stimulation, and this activation was resistant to CsA. Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28. Peripheral blood T cells stimulated with PMA/alphaCD28 produced IL-2 in the presence of CsA. Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":856,"end":859},"obj":"Disease"},{"id":"T3","span":{"begin":1085,"end":1088},"obj":"Disease"},{"id":"T5","span":{"begin":1146,"end":1149},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0016692"},{"id":"A2","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0018687"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0016692"},{"id":"A4","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0018687"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0016692"},{"id":"A6","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0018687"}],"text":"Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway.\nThe mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex. Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene. IL-2 production by CsA-treated cells is therefore dramatically reduced. We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway. In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha-CD28 stimulation, and this activation was resistant to CsA. Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28. Peripheral blood T cells stimulated with PMA/alphaCD28 produced IL-2 in the presence of CsA. Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":1055,"end":1060},"obj":"Body_part"},{"id":"T2","span":{"begin":1116,"end":1121},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"text":"Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway.\nThe mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex. Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene. IL-2 production by CsA-treated cells is therefore dramatically reduced. We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway. In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha-CD28 stimulation, and this activation was resistant to CsA. Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28. Peripheral blood T cells stimulated with PMA/alphaCD28 produced IL-2 in the presence of CsA. Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner."}

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":42,"end":49},"obj":"Cell"},{"id":"T2","span":{"begin":365,"end":372},"obj":"Cell"},{"id":"T3","span":{"begin":1061,"end":1068},"obj":"Cell"},{"id":"T4","span":{"begin":1122,"end":1129},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A4","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0000084"}],"text":"Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway.\nThe mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex. Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene. IL-2 production by CsA-treated cells is therefore dramatically reduced. We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway. In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha-CD28 stimulation, and this activation was resistant to CsA. Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28. Peripheral blood T cells stimulated with PMA/alphaCD28 produced IL-2 in the presence of CsA. Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner."}