PubMed:10380915 JSON TXT

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jnlpba-st-training

{"project":"jnlpba-st-training","denotations":[{"id":"T1","span":{"begin":45,"end":49},"obj":"protein"},{"id":"T2","span":{"begin":49,"end":58},"obj":"protein"},{"id":"T3","span":{"begin":133,"end":140},"obj":"cell_type"},{"id":"T4","span":{"begin":142,"end":163},"obj":"protein"},{"id":"T5","span":{"begin":169,"end":196},"obj":"protein"},{"id":"T6","span":{"begin":210,"end":216},"obj":"cell_type"},{"id":"T7","span":{"begin":246,"end":255},"obj":"protein"},{"id":"T8","span":{"begin":273,"end":332},"obj":"protein"},{"id":"T9","span":{"begin":358,"end":362},"obj":"protein"},{"id":"T10","span":{"begin":483,"end":487},"obj":"protein"},{"id":"T11","span":{"begin":658,"end":662},"obj":"protein"},{"id":"T12","span":{"begin":711,"end":780},"obj":"protein"},{"id":"T13","span":{"begin":834,"end":843},"obj":"protein"},{"id":"T14","span":{"begin":853,"end":861},"obj":"protein"},{"id":"T15","span":{"begin":885,"end":889},"obj":"protein"},{"id":"T16","span":{"begin":929,"end":936},"obj":"cell_type"},{"id":"T17","span":{"begin":1151,"end":1156},"obj":"protein"},{"id":"T18","span":{"begin":1160,"end":1166},"obj":"protein"},{"id":"T19","span":{"begin":1173,"end":1181},"obj":"protein"},{"id":"T20","span":{"begin":1203,"end":1210},"obj":"cell_type"},{"id":"T21","span":{"begin":1276,"end":1280},"obj":"protein"},{"id":"T22","span":{"begin":1328,"end":1334},"obj":"cell_type"},{"id":"T23","span":{"begin":1407,"end":1413},"obj":"cell_type"}],"text":"Tyrphostin AG-490 inhibits cytokine-mediated JAK3/STAT5a/b signal transduction and cellular proliferation of antigen-activated human T cells.\nJanus kinase 3 (JAK3) is a cytoplasmic tyrosine kinase required for T cell development and activated by cytokines that utilize the interleukin-2 (IL-2) receptor common gamma chain (gamma(c)). Genetic inactivation of JAK3 is manifested as severe combined immunodeficiency disease (SCID) in humans and mice. These findings have suggested that JAK3 represents a pharmacological target to control certain lymphoid-derived diseases. Here we provide novel evidence that AG-490 potently inhibits the autokinase activity of JAK3 and tyrosine phosphorylation and DNA binding of signal transducer and activator of transcription 5a and 5b (STAT5a/b). Similar inhibitory effects were observed with other cytokines that use gamma(c). AG-490 also inhibited IL-2-mediated proliferative growth in human T cells with an IC50) = 25 microM that was partially recoverable. Moreover, we demonstrate that this inhibitor prevented tetanus toxoid antigen-specific T cell proliferation and expansion but failed to block activation of Zap70 or p56Lck after anti-CD3 stimulation of human T cells. Taken together, these findings suggest that AG-490 inhibits the JAK3-mediated Type II signaling pathway but not the T cell receptor-derived Type I pathway and possesses therapeutic potential for T cell-derived pathologies such as graft-versus-host disease, allergy, and autoimmune disorders."}

pubmed-sentences-benchmark

{"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":141},"obj":"Sentence"},{"id":"S2","span":{"begin":142,"end":333},"obj":"Sentence"},{"id":"S3","span":{"begin":334,"end":447},"obj":"Sentence"},{"id":"S4","span":{"begin":448,"end":569},"obj":"Sentence"},{"id":"S5","span":{"begin":570,"end":781},"obj":"Sentence"},{"id":"S6","span":{"begin":782,"end":862},"obj":"Sentence"},{"id":"S7","span":{"begin":863,"end":994},"obj":"Sentence"},{"id":"S8","span":{"begin":995,"end":1211},"obj":"Sentence"},{"id":"S9","span":{"begin":1212,"end":1503},"obj":"Sentence"}],"text":"Tyrphostin AG-490 inhibits cytokine-mediated JAK3/STAT5a/b signal transduction and cellular proliferation of antigen-activated human T cells.\nJanus kinase 3 (JAK3) is a cytoplasmic tyrosine kinase required for T cell development and activated by cytokines that utilize the interleukin-2 (IL-2) receptor common gamma chain (gamma(c)). Genetic inactivation of JAK3 is manifested as severe combined immunodeficiency disease (SCID) in humans and mice. These findings have suggested that JAK3 represents a pharmacological target to control certain lymphoid-derived diseases. Here we provide novel evidence that AG-490 potently inhibits the autokinase activity of JAK3 and tyrosine phosphorylation and DNA binding of signal transducer and activator of transcription 5a and 5b (STAT5a/b). Similar inhibitory effects were observed with other cytokines that use gamma(c). AG-490 also inhibited IL-2-mediated proliferative growth in human T cells with an IC50) = 25 microM that was partially recoverable. Moreover, we demonstrate that this inhibitor prevented tetanus toxoid antigen-specific T cell proliferation and expansion but failed to block activation of Zap70 or p56Lck after anti-CD3 stimulation of human T cells. Taken together, these findings suggest that AG-490 inhibits the JAK3-mediated Type II signaling pathway but not the T cell receptor-derived Type I pathway and possesses therapeutic potential for T cell-derived pathologies such as graft-versus-host disease, allergy, and autoimmune disorders."}

genia-medco-coref

{"project":"genia-medco-coref","denotations":[{"id":"C1","span":{"begin":0,"end":17},"obj":"NP"},{"id":"C2","span":{"begin":142,"end":163},"obj":"NP"},{"id":"C3","span":{"begin":246,"end":255},"obj":"NP"},{"id":"C4","span":{"begin":256,"end":260},"obj":"NP"},{"id":"C5","span":{"begin":269,"end":332},"obj":"NP"},{"id":"C6","span":{"begin":358,"end":362},"obj":"NP"},{"id":"C7","span":{"begin":483,"end":487},"obj":"NP"},{"id":"C8","span":{"begin":586,"end":600},"obj":"NP"},{"id":"C9","span":{"begin":601,"end":605},"obj":"NP"},{"id":"C10","span":{"begin":606,"end":612},"obj":"NP"},{"id":"C11","span":{"begin":658,"end":662},"obj":"NP"},{"id":"C12","span":{"begin":828,"end":843},"obj":"NP"},{"id":"C13","span":{"begin":844,"end":848},"obj":"NP"},{"id":"C14","span":{"begin":853,"end":861},"obj":"NP"},{"id":"C15","span":{"begin":863,"end":869},"obj":"NP"},{"id":"C16","span":{"begin":923,"end":936},"obj":"NP"},{"id":"C17","span":{"begin":942,"end":962},"obj":"NP"},{"id":"C18","span":{"begin":963,"end":967},"obj":"NP"},{"id":"C19","span":{"begin":1025,"end":1039},"obj":"NP"},{"id":"C20","span":{"begin":1197,"end":1210},"obj":"NP"},{"id":"C21","span":{"begin":1256,"end":1262},"obj":"NP"}],"relations":[{"id":"R1","pred":"coref-relat","subj":"C4","obj":"C3"},{"id":"R2","pred":"coref-ident","subj":"C6","obj":"C2"},{"id":"R3","pred":"coref-ident","subj":"C7","obj":"C6"},{"id":"R4","pred":"coref-relat","subj":"C9","obj":"C8"},{"id":"R5","pred":"coref-ident","subj":"C10","obj":"C1"},{"id":"R6","pred":"coref-ident","subj":"C11","obj":"C7"},{"id":"R7","pred":"coref-relat","subj":"C13","obj":"C12"},{"id":"R8","pred":"coref-ident","subj":"C14","obj":"C5"},{"id":"R9","pred":"coref-ident","subj":"C15","obj":"C10"},{"id":"R10","pred":"coref-relat","subj":"C18","obj":"C17"},{"id":"R11","pred":"coref-ident","subj":"C19","obj":"C15"},{"id":"R12","pred":"coref-ident","subj":"C20","obj":"C16"},{"id":"R13","pred":"coref-ident","subj":"C21","obj":"C19"}],"text":"Tyrphostin AG-490 inhibits cytokine-mediated JAK3/STAT5a/b signal transduction and cellular proliferation of antigen-activated human T cells.\nJanus kinase 3 (JAK3) is a cytoplasmic tyrosine kinase required for T cell development and activated by cytokines that utilize the interleukin-2 (IL-2) receptor common gamma chain (gamma(c)). Genetic inactivation of JAK3 is manifested as severe combined immunodeficiency disease (SCID) in humans and mice. These findings have suggested that JAK3 represents a pharmacological target to control certain lymphoid-derived diseases. Here we provide novel evidence that AG-490 potently inhibits the autokinase activity of JAK3 and tyrosine phosphorylation and DNA binding of signal transducer and activator of transcription 5a and 5b (STAT5a/b). Similar inhibitory effects were observed with other cytokines that use gamma(c). AG-490 also inhibited IL-2-mediated proliferative growth in human T cells with an IC50) = 25 microM that was partially recoverable. Moreover, we demonstrate that this inhibitor prevented tetanus toxoid antigen-specific T cell proliferation and expansion but failed to block activation of Zap70 or p56Lck after anti-CD3 stimulation of human T cells. Taken together, these findings suggest that AG-490 inhibits the JAK3-mediated Type II signaling pathway but not the T cell receptor-derived Type I pathway and possesses therapeutic potential for T cell-derived pathologies such as graft-versus-host disease, allergy, and autoimmune disorders."}

GENIAcorpus

PubmedHPO

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":380,"end":412},"obj":"HP_0004430"},{"id":"T2","span":{"begin":387,"end":412},"obj":"HP_0005387"},{"id":"T3","span":{"begin":396,"end":412},"obj":"HP_0002721"},{"id":"T4","span":{"begin":1469,"end":1476},"obj":"HP_0012393"},{"id":"T5","span":{"begin":1482,"end":1492},"obj":"HP_0002960"},{"id":"T6","span":{"begin":1482,"end":1502},"obj":"HP_0002960"}],"text":"Tyrphostin AG-490 inhibits cytokine-mediated JAK3/STAT5a/b signal transduction and cellular proliferation of antigen-activated human T cells.\nJanus kinase 3 (JAK3) is a cytoplasmic tyrosine kinase required for T cell development and activated by cytokines that utilize the interleukin-2 (IL-2) receptor common gamma chain (gamma(c)). Genetic inactivation of JAK3 is manifested as severe combined immunodeficiency disease (SCID) in humans and mice. These findings have suggested that JAK3 represents a pharmacological target to control certain lymphoid-derived diseases. Here we provide novel evidence that AG-490 potently inhibits the autokinase activity of JAK3 and tyrosine phosphorylation and DNA binding of signal transducer and activator of transcription 5a and 5b (STAT5a/b). Similar inhibitory effects were observed with other cytokines that use gamma(c). AG-490 also inhibited IL-2-mediated proliferative growth in human T cells with an IC50) = 25 microM that was partially recoverable. Moreover, we demonstrate that this inhibitor prevented tetanus toxoid antigen-specific T cell proliferation and expansion but failed to block activation of Zap70 or p56Lck after anti-CD3 stimulation of human T cells. Taken together, these findings suggest that AG-490 inhibits the JAK3-mediated Type II signaling pathway but not the T cell receptor-derived Type I pathway and possesses therapeutic potential for T cell-derived pathologies such as graft-versus-host disease, allergy, and autoimmune disorders."}