PubMed:8995243 JSONTXT

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    sentences

    {"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":130},"obj":"Sentence"},{"id":"T2","span":{"begin":131,"end":296},"obj":"Sentence"},{"id":"T3","span":{"begin":297,"end":646},"obj":"Sentence"},{"id":"T4","span":{"begin":647,"end":820},"obj":"Sentence"},{"id":"T5","span":{"begin":821,"end":1142},"obj":"Sentence"},{"id":"T6","span":{"begin":1143,"end":1302},"obj":"Sentence"},{"id":"T7","span":{"begin":1303,"end":1431},"obj":"Sentence"},{"id":"T8","span":{"begin":1432,"end":1607},"obj":"Sentence"},{"id":"T9","span":{"begin":1608,"end":1702},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":130},"obj":"Sentence"},{"id":"T2","span":{"begin":131,"end":296},"obj":"Sentence"},{"id":"T3","span":{"begin":297,"end":646},"obj":"Sentence"},{"id":"T4","span":{"begin":647,"end":820},"obj":"Sentence"},{"id":"T5","span":{"begin":821,"end":1142},"obj":"Sentence"},{"id":"T6","span":{"begin":1143,"end":1302},"obj":"Sentence"},{"id":"T7","span":{"begin":1303,"end":1431},"obj":"Sentence"},{"id":"T8","span":{"begin":1432,"end":1607},"obj":"Sentence"},{"id":"T9","span":{"begin":1608,"end":1702},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Ras-dependent, Ca2+-stimulated activation of nuclear factor of activated T cells by a constitutively active Cbl mutant in T cells.\nT cell receptor (TCR) stimulation induces rapid tyrosine phosphorylation of cellular proteins, including Cbl, a protooncogene product whose function remains unclear. As a first step toward elucidating the function of Cbl in TCR-initiated signaling, we evaluated the ability of wild-type Cbl or a transforming Cbl mutant (70Z/3) to induce transcriptional activation of a nuclear factor of activated T cells (NFAT) element derived from the interleukin 2 (IL2) promoter in transiently cotransfected Jurkat-TAg T cells. 70Z/3, but not Cbl, caused NFAT activation which was significantly enhanced by stimulation with calcium ionophore, and was drastically reduced by cyclosporin A pretreatment. A point mutation of a potential phosphatidylinositol 3-kinase (PI3-K) binding site (Y731EAM to Y731EAC) in 70Z/3 disrupted the association of PI3-K with 70Z/3, but did not reduce the induction of NFAT activity, suggesting that the interaction between Cbl and PI3-K is not required in the 70Z/3-mediated induction of NFAT. Additional mapping studies indicated that defined deletions of C-terminal 70Z/3 sequences affected to a variable degree its ability to stimulate NFAT activity. Strikingly, deletion of 346 C-terminal residues augmented this activity, whereas removal of 20 additional residues abolished it. Coexpression of dominant negative Ras abrogated the basal or ionomycin-stimulated, 70Z/3-mediated NFAT activation, suggesting a functional Ras is required for this activation. These results implicate Cbl in Ras-dependent signaling pathways which lead to NFAT activation."}

    jnlpba-st-training

    {"project":"jnlpba-st-training","denotations":[{"id":"T1","span":{"begin":0,"end":3},"obj":"protein"},{"id":"T2","span":{"begin":45,"end":80},"obj":"protein"},{"id":"T3","span":{"begin":108,"end":118},"obj":"protein"},{"id":"T4","span":{"begin":122,"end":129},"obj":"cell_type"},{"id":"T5","span":{"begin":131,"end":146},"obj":"protein"},{"id":"T6","span":{"begin":148,"end":151},"obj":"protein"},{"id":"T7","span":{"begin":207,"end":224},"obj":"protein"},{"id":"T8","span":{"begin":236,"end":239},"obj":"protein"},{"id":"T9","span":{"begin":243,"end":264},"obj":"protein"},{"id":"T10","span":{"begin":348,"end":351},"obj":"protein"},{"id":"T11","span":{"begin":355,"end":358},"obj":"protein"},{"id":"T12","span":{"begin":408,"end":421},"obj":"protein"},{"id":"T13","span":{"begin":440,"end":450},"obj":"protein"},{"id":"T14","span":{"begin":501,"end":551},"obj":"DNA"},{"id":"T15","span":{"begin":569,"end":597},"obj":"DNA"},{"id":"T16","span":{"begin":627,"end":645},"obj":"cell_line"},{"id":"T17","span":{"begin":647,"end":652},"obj":"protein"},{"id":"T18","span":{"begin":662,"end":665},"obj":"protein"},{"id":"T19","span":{"begin":674,"end":678},"obj":"protein"},{"id":"T20","span":{"begin":853,"end":903},"obj":"DNA"},{"id":"T21","span":{"begin":905,"end":912},"obj":"DNA"},{"id":"T22","span":{"begin":916,"end":923},"obj":"DNA"},{"id":"T23","span":{"begin":928,"end":933},"obj":"protein"},{"id":"T24","span":{"begin":963,"end":968},"obj":"protein"},{"id":"T25","span":{"begin":974,"end":979},"obj":"protein"},{"id":"T26","span":{"begin":1017,"end":1021},"obj":"protein"},{"id":"T27","span":{"begin":1072,"end":1075},"obj":"protein"},{"id":"T28","span":{"begin":1080,"end":1085},"obj":"protein"},{"id":"T29","span":{"begin":1109,"end":1114},"obj":"protein"},{"id":"T30","span":{"begin":1137,"end":1141},"obj":"protein"},{"id":"T31","span":{"begin":1217,"end":1222},"obj":"protein"},{"id":"T32","span":{"begin":1288,"end":1292},"obj":"protein"},{"id":"T33","span":{"begin":1327,"end":1350},"obj":"protein"},{"id":"T34","span":{"begin":1448,"end":1469},"obj":"protein"},{"id":"T35","span":{"begin":1515,"end":1520},"obj":"protein"},{"id":"T36","span":{"begin":1530,"end":1534},"obj":"protein"},{"id":"T37","span":{"begin":1560,"end":1574},"obj":"protein"},{"id":"T38","span":{"begin":1632,"end":1635},"obj":"protein"},{"id":"T39","span":{"begin":1639,"end":1642},"obj":"protein"},{"id":"T40","span":{"begin":1686,"end":1690},"obj":"protein"}],"text":"Ras-dependent, Ca2+-stimulated activation of nuclear factor of activated T cells by a constitutively active Cbl mutant in T cells.\nT cell receptor (TCR) stimulation induces rapid tyrosine phosphorylation of cellular proteins, including Cbl, a protooncogene product whose function remains unclear. As a first step toward elucidating the function of Cbl in TCR-initiated signaling, we evaluated the ability of wild-type Cbl or a transforming Cbl mutant (70Z/3) to induce transcriptional activation of a nuclear factor of activated T cells (NFAT) element derived from the interleukin 2 (IL2) promoter in transiently cotransfected Jurkat-TAg T cells. 70Z/3, but not Cbl, caused NFAT activation which was significantly enhanced by stimulation with calcium ionophore, and was drastically reduced by cyclosporin A pretreatment. A point mutation of a potential phosphatidylinositol 3-kinase (PI3-K) binding site (Y731EAM to Y731EAC) in 70Z/3 disrupted the association of PI3-K with 70Z/3, but did not reduce the induction of NFAT activity, suggesting that the interaction between Cbl and PI3-K is not required in the 70Z/3-mediated induction of NFAT. Additional mapping studies indicated that defined deletions of C-terminal 70Z/3 sequences affected to a variable degree its ability to stimulate NFAT activity. Strikingly, deletion of 346 C-terminal residues augmented this activity, whereas removal of 20 additional residues abolished it. Coexpression of dominant negative Ras abrogated the basal or ionomycin-stimulated, 70Z/3-mediated NFAT activation, suggesting a functional Ras is required for this activation. These results implicate Cbl in Ras-dependent signaling pathways which lead to NFAT activation."}

    pubmed-sentences-benchmark

    {"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":130},"obj":"Sentence"},{"id":"S2","span":{"begin":131,"end":296},"obj":"Sentence"},{"id":"S3","span":{"begin":297,"end":646},"obj":"Sentence"},{"id":"S4","span":{"begin":647,"end":820},"obj":"Sentence"},{"id":"S5","span":{"begin":821,"end":1142},"obj":"Sentence"},{"id":"S6","span":{"begin":1143,"end":1302},"obj":"Sentence"},{"id":"S7","span":{"begin":1303,"end":1431},"obj":"Sentence"},{"id":"S8","span":{"begin":1432,"end":1607},"obj":"Sentence"},{"id":"S9","span":{"begin":1608,"end":1702},"obj":"Sentence"}],"text":"Ras-dependent, Ca2+-stimulated activation of nuclear factor of activated T cells by a constitutively active Cbl mutant in T cells.\nT cell receptor (TCR) stimulation induces rapid tyrosine phosphorylation of cellular proteins, including Cbl, a protooncogene product whose function remains unclear. As a first step toward elucidating the function of Cbl in TCR-initiated signaling, we evaluated the ability of wild-type Cbl or a transforming Cbl mutant (70Z/3) to induce transcriptional activation of a nuclear factor of activated T cells (NFAT) element derived from the interleukin 2 (IL2) promoter in transiently cotransfected Jurkat-TAg T cells. 70Z/3, but not Cbl, caused NFAT activation which was significantly enhanced by stimulation with calcium ionophore, and was drastically reduced by cyclosporin A pretreatment. A point mutation of a potential phosphatidylinositol 3-kinase (PI3-K) binding site (Y731EAM to Y731EAC) in 70Z/3 disrupted the association of PI3-K with 70Z/3, but did not reduce the induction of NFAT activity, suggesting that the interaction between Cbl and PI3-K is not required in the 70Z/3-mediated induction of NFAT. Additional mapping studies indicated that defined deletions of C-terminal 70Z/3 sequences affected to a variable degree its ability to stimulate NFAT activity. Strikingly, deletion of 346 C-terminal residues augmented this activity, whereas removal of 20 additional residues abolished it. Coexpression of dominant negative Ras abrogated the basal or ionomycin-stimulated, 70Z/3-mediated NFAT activation, suggesting a functional Ras is required for this activation. These results implicate Cbl in Ras-dependent signaling pathways which lead to NFAT activation."}

    genia-medco-coref

    {"project":"genia-medco-coref","denotations":[{"id":"C1","span":{"begin":45,"end":80},"obj":"NP"},{"id":"C2","span":{"begin":84,"end":118},"obj":"NP"},{"id":"C3","span":{"begin":236,"end":239},"obj":"NP"},{"id":"C5","span":{"begin":241,"end":264},"obj":"NP"},{"id":"C6","span":{"begin":265,"end":270},"obj":"NP"},{"id":"C4","span":{"begin":241,"end":295},"obj":"NP"},{"id":"C7","span":{"begin":348,"end":351},"obj":"NP"},{"id":"C8","span":{"begin":425,"end":458},"obj":"NP"},{"id":"C9","span":{"begin":647,"end":652},"obj":"NP"},{"id":"C10","span":{"begin":662,"end":665},"obj":"NP"},{"id":"C11","span":{"begin":674,"end":689},"obj":"NP"},{"id":"C12","span":{"begin":690,"end":695},"obj":"NP"},{"id":"C13","span":{"begin":928,"end":933},"obj":"NP"},{"id":"C14","span":{"begin":963,"end":968},"obj":"NP"},{"id":"C15","span":{"begin":974,"end":979},"obj":"NP"},{"id":"C16","span":{"begin":1017,"end":1030},"obj":"NP"},{"id":"C17","span":{"begin":1072,"end":1075},"obj":"NP"},{"id":"C18","span":{"begin":1080,"end":1085},"obj":"NP"},{"id":"C19","span":{"begin":1137,"end":1141},"obj":"NP"},{"id":"C20","span":{"begin":1263,"end":1266},"obj":"NP"},{"id":"C21","span":{"begin":1288,"end":1301},"obj":"NP"},{"id":"C22","span":{"begin":1361,"end":1374},"obj":"NP"},{"id":"C23","span":{"begin":1428,"end":1430},"obj":"NP"},{"id":"C24","span":{"begin":1480,"end":1545},"obj":"NP"},{"id":"C25","span":{"begin":1591,"end":1606},"obj":"NP"},{"id":"C26","span":{"begin":1632,"end":1635},"obj":"NP"},{"id":"C27","span":{"begin":1639,"end":1671},"obj":"NP"},{"id":"C28","span":{"begin":1672,"end":1677},"obj":"NP"}],"relations":[{"id":"R1","pred":"coref-relat","subj":"C6","obj":"C5"},{"id":"R2","pred":"coref-appos","subj":"C4","obj":"C3"},{"id":"R3","pred":"coref-ident","subj":"C7","obj":"C3"},{"id":"R4","pred":"coref-ident","subj":"C8","obj":"C2"},{"id":"R5","pred":"coref-ident","subj":"C9","obj":"C8"},{"id":"R6","pred":"coref-ident","subj":"C10","obj":"C7"},{"id":"R7","pred":"coref-relat","subj":"C12","obj":"C11"},{"id":"R8","pred":"coref-ident","subj":"C13","obj":"C9"},{"id":"R9","pred":"coref-ident","subj":"C15","obj":"C13"},{"id":"R10","pred":"coref-ident","subj":"C17","obj":"C10"},{"id":"R11","pred":"coref-ident","subj":"C18","obj":"C14"},{"id":"R12","pred":"coref-ident","subj":"C19","obj":"C1"},{"id":"R13","pred":"coref-pron","subj":"C20","obj":"C15"},{"id":"R14","pred":"coref-ident","subj":"C21","obj":"C16"},{"id":"R15","pred":"coref-ident","subj":"C22","obj":"C21"},{"id":"R16","pred":"coref-pron","subj":"C23","obj":"C22"},{"id":"R17","pred":"coref-ident","subj":"C25","obj":"C24"},{"id":"R18","pred":"coref-ident","subj":"C26","obj":"C17"},{"id":"R19","pred":"coref-relat","subj":"C28","obj":"C27"}],"text":"Ras-dependent, Ca2+-stimulated activation of nuclear factor of activated T cells by a constitutively active Cbl mutant in T cells.\nT cell receptor (TCR) stimulation induces rapid tyrosine phosphorylation of cellular proteins, including Cbl, a protooncogene product whose function remains unclear. As a first step toward elucidating the function of Cbl in TCR-initiated signaling, we evaluated the ability of wild-type Cbl or a transforming Cbl mutant (70Z/3) to induce transcriptional activation of a nuclear factor of activated T cells (NFAT) element derived from the interleukin 2 (IL2) promoter in transiently cotransfected Jurkat-TAg T cells. 70Z/3, but not Cbl, caused NFAT activation which was significantly enhanced by stimulation with calcium ionophore, and was drastically reduced by cyclosporin A pretreatment. A point mutation of a potential phosphatidylinositol 3-kinase (PI3-K) binding site (Y731EAM to Y731EAC) in 70Z/3 disrupted the association of PI3-K with 70Z/3, but did not reduce the induction of NFAT activity, suggesting that the interaction between Cbl and PI3-K is not required in the 70Z/3-mediated induction of NFAT. Additional mapping studies indicated that defined deletions of C-terminal 70Z/3 sequences affected to a variable degree its ability to stimulate NFAT activity. Strikingly, deletion of 346 C-terminal residues augmented this activity, whereas removal of 20 additional residues abolished it. Coexpression of dominant negative Ras abrogated the basal or ionomycin-stimulated, 70Z/3-mediated NFAT activation, suggesting a functional Ras is required for this activation. These results implicate Cbl in Ras-dependent signaling pathways which lead to NFAT activation."}

    GENIAcorpus

    {"project":"GENIAcorpus","denotations":[{"id":"T1","span":{"begin":0,"end":3},"obj":"protein_family_or_group"},{"id":"T2","span":{"begin":15,"end":19},"obj":"atom"},{"id":"T3","span":{"begin":45,"end":80},"obj":"protein_molecule"},{"id":"T4","span":{"begin":108,"end":118},"obj":"protein_molecule"},{"id":"T5","span":{"begin":122,"end":129},"obj":"cell_type"},{"id":"T6","span":{"begin":131,"end":146},"obj":"protein_family_or_group"},{"id":"T7","span":{"begin":148,"end":151},"obj":"protein_family_or_group"},{"id":"T8","span":{"begin":179,"end":187},"obj":"amino_acid_monomer"},{"id":"T9","span":{"begin":207,"end":224},"obj":"protein_family_or_group"},{"id":"T10","span":{"begin":236,"end":239},"obj":"protein_molecule"},{"id":"T11","span":{"begin":243,"end":264},"obj":"protein_molecule"},{"id":"T12","span":{"begin":348,"end":351},"obj":"protein_molecule"},{"id":"T13","span":{"begin":355,"end":358},"obj":"protein_family_or_group"},{"id":"T14","span":{"begin":408,"end":417},"obj":"protein_molecule"},{"id":"T15","span":{"begin":418,"end":421},"obj":"protein_molecule"},{"id":"T16","span":{"begin":440,"end":443},"obj":"protein_molecule"},{"id":"T17","span":{"begin":501,"end":528},"obj":"protein_family_or_group"},{"id":"T18","span":{"begin":529,"end":536},"obj":"cell_type"},{"id":"T19","span":{"begin":538,"end":542},"obj":"protein_family_or_group"},{"id":"T20","span":{"begin":569,"end":582},"obj":"protein_molecule"},{"id":"T21","span":{"begin":584,"end":587},"obj":"protein_molecule"},{"id":"T22","span":{"begin":627,"end":637},"obj":"cell_line"},{"id":"T23","span":{"begin":638,"end":645},"obj":"cell_type"},{"id":"T24","span":{"begin":647,"end":652},"obj":"protein_molecule"},{"id":"T25","span":{"begin":662,"end":665},"obj":"protein_molecule"},{"id":"T26","span":{"begin":674,"end":678},"obj":"protein_family_or_group"},{"id":"T27","span":{"begin":743,"end":760},"obj":"other_organic_compound"},{"id":"T28","span":{"begin":793,"end":806},"obj":"other_organic_compound"},{"id":"T29","span":{"begin":853,"end":882},"obj":"protein_molecule"},{"id":"T30","span":{"begin":884,"end":889},"obj":"protein_molecule"},{"id":"T31","span":{"begin":905,"end":912},"obj":"DNA_domain_or_region"},{"id":"T32","span":{"begin":916,"end":923},"obj":"DNA_domain_or_region"},{"id":"T33","span":{"begin":928,"end":933},"obj":"protein_molecule"},{"id":"T34","span":{"begin":963,"end":968},"obj":"protein_molecule"},{"id":"T35","span":{"begin":974,"end":979},"obj":"protein_molecule"},{"id":"T36","span":{"begin":1017,"end":1021},"obj":"protein_family_or_group"},{"id":"T37","span":{"begin":1072,"end":1075},"obj":"protein_molecule"},{"id":"T38","span":{"begin":1080,"end":1085},"obj":"protein_molecule"},{"id":"T39","span":{"begin":1109,"end":1114},"obj":"protein_molecule"},{"id":"T40","span":{"begin":1137,"end":1141},"obj":"protein_family_or_group"},{"id":"T41","span":{"begin":1217,"end":1222},"obj":"protein_molecule"},{"id":"T42","span":{"begin":1288,"end":1292},"obj":"protein_family_or_group"},{"id":"T43","span":{"begin":1327,"end":1350},"obj":"protein_domain_or_region"},{"id":"T44","span":{"begin":1448,"end":1469},"obj":"protein_molecule"},{"id":"T45","span":{"begin":1493,"end":1514},"obj":"other_name"},{"id":"T46","span":{"begin":1515,"end":1520},"obj":"protein_molecule"},{"id":"T47","span":{"begin":1530,"end":1534},"obj":"protein_family_or_group"},{"id":"T48","span":{"begin":1560,"end":1574},"obj":"protein_family_or_group"},{"id":"T49","span":{"begin":1632,"end":1635},"obj":"protein_molecule"},{"id":"T50","span":{"begin":1639,"end":1642},"obj":"protein_molecule"},{"id":"T51","span":{"begin":1686,"end":1690},"obj":"protein_family_or_group"}],"text":"Ras-dependent, Ca2+-stimulated activation of nuclear factor of activated T cells by a constitutively active Cbl mutant in T cells.\nT cell receptor (TCR) stimulation induces rapid tyrosine phosphorylation of cellular proteins, including Cbl, a protooncogene product whose function remains unclear. As a first step toward elucidating the function of Cbl in TCR-initiated signaling, we evaluated the ability of wild-type Cbl or a transforming Cbl mutant (70Z/3) to induce transcriptional activation of a nuclear factor of activated T cells (NFAT) element derived from the interleukin 2 (IL2) promoter in transiently cotransfected Jurkat-TAg T cells. 70Z/3, but not Cbl, caused NFAT activation which was significantly enhanced by stimulation with calcium ionophore, and was drastically reduced by cyclosporin A pretreatment. A point mutation of a potential phosphatidylinositol 3-kinase (PI3-K) binding site (Y731EAM to Y731EAC) in 70Z/3 disrupted the association of PI3-K with 70Z/3, but did not reduce the induction of NFAT activity, suggesting that the interaction between Cbl and PI3-K is not required in the 70Z/3-mediated induction of NFAT. Additional mapping studies indicated that defined deletions of C-terminal 70Z/3 sequences affected to a variable degree its ability to stimulate NFAT activity. Strikingly, deletion of 346 C-terminal residues augmented this activity, whereas removal of 20 additional residues abolished it. Coexpression of dominant negative Ras abrogated the basal or ionomycin-stimulated, 70Z/3-mediated NFAT activation, suggesting a functional Ras is required for this activation. These results implicate Cbl in Ras-dependent signaling pathways which lead to NFAT activation."}

    Anatomy-UBERON

    {"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":131,"end":137},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000084"}],"text":"Ras-dependent, Ca2+-stimulated activation of nuclear factor of activated T cells by a constitutively active Cbl mutant in T cells.\nT cell receptor (TCR) stimulation induces rapid tyrosine phosphorylation of cellular proteins, including Cbl, a protooncogene product whose function remains unclear. As a first step toward elucidating the function of Cbl in TCR-initiated signaling, we evaluated the ability of wild-type Cbl or a transforming Cbl mutant (70Z/3) to induce transcriptional activation of a nuclear factor of activated T cells (NFAT) element derived from the interleukin 2 (IL2) promoter in transiently cotransfected Jurkat-TAg T cells. 70Z/3, but not Cbl, caused NFAT activation which was significantly enhanced by stimulation with calcium ionophore, and was drastically reduced by cyclosporin A pretreatment. A point mutation of a potential phosphatidylinositol 3-kinase (PI3-K) binding site (Y731EAM to Y731EAC) in 70Z/3 disrupted the association of PI3-K with 70Z/3, but did not reduce the induction of NFAT activity, suggesting that the interaction between Cbl and PI3-K is not required in the 70Z/3-mediated induction of NFAT. Additional mapping studies indicated that defined deletions of C-terminal 70Z/3 sequences affected to a variable degree its ability to stimulate NFAT activity. Strikingly, deletion of 346 C-terminal residues augmented this activity, whereas removal of 20 additional residues abolished it. Coexpression of dominant negative Ras abrogated the basal or ionomycin-stimulated, 70Z/3-mediated NFAT activation, suggesting a functional Ras is required for this activation. These results implicate Cbl in Ras-dependent signaling pathways which lead to NFAT activation."}

    CL-cell

    {"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":73,"end":80},"obj":"Cell"},{"id":"T2","span":{"begin":122,"end":129},"obj":"Cell"},{"id":"T3","span":{"begin":131,"end":137},"obj":"Cell"},{"id":"T4","span":{"begin":529,"end":536},"obj":"Cell"},{"id":"T5","span":{"begin":638,"end":645},"obj":"Cell"},{"id":"T6","span":{"begin":1484,"end":1489},"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"},{"id":"A5","pred":"cl_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A6","pred":"cl_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL:0002324"}],"text":"Ras-dependent, Ca2+-stimulated activation of nuclear factor of activated T cells by a constitutively active Cbl mutant in T cells.\nT cell receptor (TCR) stimulation induces rapid tyrosine phosphorylation of cellular proteins, including Cbl, a protooncogene product whose function remains unclear. As a first step toward elucidating the function of Cbl in TCR-initiated signaling, we evaluated the ability of wild-type Cbl or a transforming Cbl mutant (70Z/3) to induce transcriptional activation of a nuclear factor of activated T cells (NFAT) element derived from the interleukin 2 (IL2) promoter in transiently cotransfected Jurkat-TAg T cells. 70Z/3, but not Cbl, caused NFAT activation which was significantly enhanced by stimulation with calcium ionophore, and was drastically reduced by cyclosporin A pretreatment. A point mutation of a potential phosphatidylinositol 3-kinase (PI3-K) binding site (Y731EAM to Y731EAC) in 70Z/3 disrupted the association of PI3-K with 70Z/3, but did not reduce the induction of NFAT activity, suggesting that the interaction between Cbl and PI3-K is not required in the 70Z/3-mediated induction of NFAT. Additional mapping studies indicated that defined deletions of C-terminal 70Z/3 sequences affected to a variable degree its ability to stimulate NFAT activity. Strikingly, deletion of 346 C-terminal residues augmented this activity, whereas removal of 20 additional residues abolished it. Coexpression of dominant negative Ras abrogated the basal or ionomycin-stimulated, 70Z/3-mediated NFAT activation, suggesting a functional Ras is required for this activation. These results implicate Cbl in Ras-dependent signaling pathways which lead to NFAT activation."}