PubMed:10029589
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/10029589","sourcedb":"PubMed","sourceid":"10029589","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/10029589","text":"The Megakaryocyte/Platelet-specific enhancer of the alpha2beta1 integrin gene: two tandem AP1 sites and the mitogen-activated protein kinase signaling cascade.\nThe alpha2beta1 integrin, a collagen receptor on platelets and megakaryocytes, is required for normal platelet function. Transcriptional regulation of the alpha2 integrin gene in cells undergoing megakaryocytic differentiation requires a core promoter between bp -30 and -92, a silencer between bp -92 and -351, and megakaryocytic enhancers in the distal 5' flank. We have now identified a 229-bp region of the distal 5' flank of the alpha2 integrin gene required for high-level enhancer activity in cells with megakaryocytic features. Two tandem AP1 binding sites with dyad symmetry are required for enhancer activity and for DNA-protein complex formation with members of the c-fos/c-jun family. The requirement for AP1 activation suggested a role for the mitogen-activated protein kinase (MAPK) signaling pathway in regulating alpha2 integrin gene expression. Inhibition of the MAP kinase cascade with PD98059, a specific inhibitor of MAPK kinase 1, prevented the expression of the alpha2 integrin subunit in cells induced to become megakaryocytic. We provide a model of megakaryocytic differentiation in which expression of the alpha2 integrin gene requires signaling via the MAP kinase pathway to activate two tandem AP1 binding sites in the alpha2 integrin enhancer.","tracks":[{"project":"genia-medco-coref","denotations":[{"id":"C1","span":{"begin":48,"end":77},"obj":"NP"},{"id":"C2","span":{"begin":160,"end":184},"obj":"NP"},{"id":"C3","span":{"begin":186,"end":237},"obj":"NP"},{"id":"C4","span":{"begin":311,"end":335},"obj":"NP"},{"id":"C5","span":{"begin":356,"end":386},"obj":"NP"},{"id":"C6","span":{"begin":590,"end":614},"obj":"NP"},{"id":"C7","span":{"begin":989,"end":1020},"obj":"NP"},{"id":"C8","span":{"begin":1064,"end":1071},"obj":"NP"},{"id":"C9","span":{"begin":1073,"end":1110},"obj":"NP"},{"id":"C11","span":{"begin":1233,"end":1263},"obj":"NP"},{"id":"C10","span":{"begin":1222,"end":1263},"obj":"NP"},{"id":"C12","span":{"begin":1267,"end":1272},"obj":"NP"},{"id":"C14","span":{"begin":1287,"end":1311},"obj":"NP"},{"id":"C13","span":{"begin":1273,"end":1311},"obj":"NP"}],"relations":[{"id":"R1","pred":"coref-appos","subj":"C3","obj":"C2"},{"id":"R2","pred":"coref-ident","subj":"C4","obj":"C1"},{"id":"R3","pred":"coref-ident","subj":"C6","obj":"C4"},{"id":"R4","pred":"coref-appos","subj":"C9","obj":"C8"},{"id":"R5","pred":"coref-ident","subj":"C11","obj":"C5"},{"id":"R6","pred":"coref-relat","subj":"C12","obj":"C10"},{"id":"R7","pred":"coref-ident","subj":"C14","obj":"C6"},{"id":"R8","pred":"coref-ident","subj":"C13","obj":"C7"}],"attributes":[{"subj":"C1","pred":"source","obj":"genia-medco-coref"},{"subj":"C2","pred":"source","obj":"genia-medco-coref"},{"subj":"C3","pred":"source","obj":"genia-medco-coref"},{"subj":"C4","pred":"source","obj":"genia-medco-coref"},{"subj":"C5","pred":"source","obj":"genia-medco-coref"},{"subj":"C6","pred":"source","obj":"genia-medco-coref"},{"subj":"C7","pred":"source","obj":"genia-medco-coref"},{"subj":"C8","pred":"source","obj":"genia-medco-coref"},{"subj":"C9","pred":"source","obj":"genia-medco-coref"},{"subj":"C11","pred":"source","obj":"genia-medco-coref"},{"subj":"C10","pred":"source","obj":"genia-medco-coref"},{"subj":"C12","pred":"source","obj":"genia-medco-coref"},{"subj":"C14","pred":"source","obj":"genia-medco-coref"},{"subj":"C13","pred":"source","obj":"genia-medco-coref"}]},{"project":"2015-BEL-Sample-2","denotations":[{"id":"BEL:20043624","span":{"begin":0,"end":1020},"obj":"p(HGNC:JUN) increases r(HGNC:ITGA2)"},{"id":"BEL:20043794","span":{"begin":0,"end":1422},"obj":"p(HGNC:MAP2K1) increases r(HGNC:ITGA2B)"},{"id":"BEL:20043800","span":{"begin":0,"end":1422},"obj":"p(HGNC:MAP2K2) increases r(HGNC:ITGA2B)"}],"attributes":[{"subj":"BEL:20043624","pred":"source","obj":"2015-BEL-Sample-2"},{"subj":"BEL:20043794","pred":"source","obj":"2015-BEL-Sample-2"},{"subj":"BEL:20043800","pred":"source","obj":"2015-BEL-Sample-2"}]},{"project":"jnlpba-st-training","denotations":[{"id":"T1","span":{"begin":4,"end":44},"obj":"DNA"},{"id":"T2","span":{"begin":52,"end":77},"obj":"DNA"},{"id":"T3","span":{"begin":90,"end":99},"obj":"DNA"},{"id":"T4","span":{"begin":108,"end":140},"obj":"protein"},{"id":"T5","span":{"begin":164,"end":184},"obj":"protein"},{"id":"T6","span":{"begin":209,"end":218},"obj":"cell_type"},{"id":"T7","span":{"begin":223,"end":237},"obj":"cell_type"},{"id":"T8","span":{"begin":315,"end":335},"obj":"DNA"},{"id":"T9","span":{"begin":398,"end":411},"obj":"DNA"},{"id":"T10","span":{"begin":438,"end":446},"obj":"DNA"},{"id":"T11","span":{"begin":476,"end":500},"obj":"DNA"},{"id":"T12","span":{"begin":508,"end":523},"obj":"DNA"},{"id":"T13","span":{"begin":550,"end":563},"obj":"DNA"},{"id":"T14","span":{"begin":571,"end":586},"obj":"DNA"},{"id":"T15","span":{"begin":594,"end":614},"obj":"DNA"},{"id":"T16","span":{"begin":628,"end":665},"obj":"cell_type"},{"id":"T17","span":{"begin":707,"end":724},"obj":"DNA"},{"id":"T18","span":{"begin":787,"end":806},"obj":"protein"},{"id":"T19","span":{"begin":837,"end":855},"obj":"protein"},{"id":"T20","span":{"begin":877,"end":880},"obj":"protein"},{"id":"T21","span":{"begin":917,"end":949},"obj":"protein"},{"id":"T22","span":{"begin":951,"end":955},"obj":"protein"},{"id":"T23","span":{"begin":989,"end":1009},"obj":"DNA"},{"id":"T24","span":{"begin":1040,"end":1050},"obj":"protein"},{"id":"T25","span":{"begin":1097,"end":1110},"obj":"protein"},{"id":"T26","span":{"begin":1144,"end":1167},"obj":"protein"},{"id":"T27","span":{"begin":1291,"end":1311},"obj":"DNA"},{"id":"T28","span":{"begin":1339,"end":1349},"obj":"protein"},{"id":"T29","span":{"begin":1381,"end":1398},"obj":"DNA"},{"id":"T30","span":{"begin":1406,"end":1430},"obj":"DNA"}],"attributes":[{"subj":"T1","pred":"source","obj":"jnlpba-st-training"},{"subj":"T2","pred":"source","obj":"jnlpba-st-training"},{"subj":"T3","pred":"source","obj":"jnlpba-st-training"},{"subj":"T4","pred":"source","obj":"jnlpba-st-training"},{"subj":"T5","pred":"source","obj":"jnlpba-st-training"},{"subj":"T6","pred":"source","obj":"jnlpba-st-training"},{"subj":"T7","pred":"source","obj":"jnlpba-st-training"},{"subj":"T8","pred":"source","obj":"jnlpba-st-training"},{"subj":"T9","pred":"source","obj":"jnlpba-st-training"},{"subj":"T10","pred":"source","obj":"jnlpba-st-training"},{"subj":"T11","pred":"source","obj":"jnlpba-st-training"},{"subj":"T12","pred":"source","obj":"jnlpba-st-training"},{"subj":"T13","pred":"source","obj":"jnlpba-st-training"},{"subj":"T14","pred":"source","obj":"jnlpba-st-training"},{"subj":"T15","pred":"source","obj":"jnlpba-st-training"},{"subj":"T16","pred":"source","obj":"jnlpba-st-training"},{"subj":"T17","pred":"source","obj":"jnlpba-st-training"},{"subj":"T18","pred":"source","obj":"jnlpba-st-training"},{"subj":"T19","pred":"source","obj":"jnlpba-st-training"},{"subj":"T20","pred":"source","obj":"jnlpba-st-training"},{"subj":"T21","pred":"source","obj":"jnlpba-st-training"},{"subj":"T22","pred":"source","obj":"jnlpba-st-training"},{"subj":"T23","pred":"source","obj":"jnlpba-st-training"},{"subj":"T24","pred":"source","obj":"jnlpba-st-training"},{"subj":"T25","pred":"source","obj":"jnlpba-st-training"},{"subj":"T26","pred":"source","obj":"jnlpba-st-training"},{"subj":"T27","pred":"source","obj":"jnlpba-st-training"},{"subj":"T28","pred":"source","obj":"jnlpba-st-training"},{"subj":"T29","pred":"source","obj":"jnlpba-st-training"},{"subj":"T30","pred":"source","obj":"jnlpba-st-training"}]},{"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":159},"obj":"Sentence"},{"id":"S2","span":{"begin":160,"end":280},"obj":"Sentence"},{"id":"S3","span":{"begin":281,"end":524},"obj":"Sentence"},{"id":"S4","span":{"begin":525,"end":695},"obj":"Sentence"},{"id":"S5","span":{"begin":696,"end":856},"obj":"Sentence"},{"id":"S6","span":{"begin":857,"end":1021},"obj":"Sentence"},{"id":"S7","span":{"begin":1022,"end":1210},"obj":"Sentence"},{"id":"S8","span":{"begin":1211,"end":1431},"obj":"Sentence"}],"attributes":[{"subj":"S1","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S2","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S3","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S4","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S5","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S6","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S7","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S8","pred":"source","obj":"pubmed-sentences-benchmark"}]},{"project":"GENIAcorpus","denotations":[{"id":"T1","span":{"begin":4,"end":44},"obj":"DNA_domain_or_region"},{"id":"T2","span":{"begin":52,"end":77},"obj":"DNA_domain_or_region"},{"id":"T3","span":{"begin":90,"end":99},"obj":"DNA_domain_or_region"},{"id":"T4","span":{"begin":108,"end":140},"obj":"protein_family_or_group"},{"id":"T5","span":{"begin":164,"end":184},"obj":"protein_family_or_group"},{"id":"T6","span":{"begin":209,"end":218},"obj":"cell_type"},{"id":"T7","span":{"begin":223,"end":237},"obj":"cell_type"},{"id":"T8","span":{"begin":255,"end":279},"obj":"other_name"},{"id":"T9","span":{"begin":315,"end":335},"obj":"DNA_domain_or_region"},{"id":"T10","span":{"begin":356,"end":386},"obj":"other_name"},{"id":"T11","span":{"begin":398,"end":411},"obj":"DNA_domain_or_region"},{"id":"T12","span":{"begin":438,"end":446},"obj":"DNA_family_or_group"},{"id":"T13","span":{"begin":476,"end":500},"obj":"DNA_domain_or_region"},{"id":"T14","span":{"begin":508,"end":523},"obj":"DNA_domain_or_region"},{"id":"T15","span":{"begin":550,"end":563},"obj":"DNA_domain_or_region"},{"id":"T16","span":{"begin":571,"end":586},"obj":"DNA_domain_or_region"},{"id":"T17","span":{"begin":594,"end":614},"obj":"DNA_domain_or_region"},{"id":"T18","span":{"begin":628,"end":665},"obj":"cell_type"},{"id":"T19","span":{"begin":671,"end":694},"obj":"other_name"},{"id":"T20","span":{"begin":707,"end":724},"obj":"DNA_domain_or_region"},{"id":"T21","span":{"begin":761,"end":778},"obj":"other_name"},{"id":"T22","span":{"begin":787,"end":806},"obj":"protein_complex"},{"id":"T23","span":{"begin":837,"end":855},"obj":"protein_domain_or_region"},{"id":"T24","span":{"begin":877,"end":880},"obj":"protein_molecule"},{"id":"T25","span":{"begin":917,"end":949},"obj":"protein_family_or_group"},{"id":"T26","span":{"begin":951,"end":955},"obj":"protein_family_or_group"},{"id":"T27","span":{"begin":989,"end":1009},"obj":"DNA_domain_or_region"},{"id":"T28","span":{"begin":1040,"end":1050},"obj":"protein_family_or_group"},{"id":"T29","span":{"begin":1064,"end":1071},"obj":"other_organic_compound"},{"id":"T30","span":{"begin":1097,"end":1110},"obj":"protein_molecule"},{"id":"T31","span":{"begin":1144,"end":1167},"obj":"protein_subunit"},{"id":"T32","span":{"begin":1233,"end":1263},"obj":"other_name"},{"id":"T33","span":{"begin":1291,"end":1311},"obj":"DNA_domain_or_region"},{"id":"T34","span":{"begin":1339,"end":1349},"obj":"protein_family_or_group"},{"id":"T35","span":{"begin":1381,"end":1398},"obj":"DNA_domain_or_region"},{"id":"T36","span":{"begin":1406,"end":1430},"obj":"DNA_domain_or_region"}],"attributes":[{"subj":"T1","pred":"source","obj":"GENIAcorpus"},{"subj":"T2","pred":"source","obj":"GENIAcorpus"},{"subj":"T3","pred":"source","obj":"GENIAcorpus"},{"subj":"T4","pred":"source","obj":"GENIAcorpus"},{"subj":"T5","pred":"source","obj":"GENIAcorpus"},{"subj":"T6","pred":"source","obj":"GENIAcorpus"},{"subj":"T7","pred":"source","obj":"GENIAcorpus"},{"subj":"T8","pred":"source","obj":"GENIAcorpus"},{"subj":"T9","pred":"source","obj":"GENIAcorpus"},{"subj":"T10","pred":"source","obj":"GENIAcorpus"},{"subj":"T11","pred":"source","obj":"GENIAcorpus"},{"subj":"T12","pred":"source","obj":"GENIAcorpus"},{"subj":"T13","pred":"source","obj":"GENIAcorpus"},{"subj":"T14","pred":"source","obj":"GENIAcorpus"},{"subj":"T15","pred":"source","obj":"GENIAcorpus"},{"subj":"T16","pred":"source","obj":"GENIAcorpus"},{"subj":"T17","pred":"source","obj":"GENIAcorpus"},{"subj":"T18","pred":"source","obj":"GENIAcorpus"},{"subj":"T19","pred":"source","obj":"GENIAcorpus"},{"subj":"T20","pred":"source","obj":"GENIAcorpus"},{"subj":"T21","pred":"source","obj":"GENIAcorpus"},{"subj":"T22","pred":"source","obj":"GENIAcorpus"},{"subj":"T23","pred":"source","obj":"GENIAcorpus"},{"subj":"T24","pred":"source","obj":"GENIAcorpus"},{"subj":"T25","pred":"source","obj":"GENIAcorpus"},{"subj":"T26","pred":"source","obj":"GENIAcorpus"},{"subj":"T27","pred":"source","obj":"GENIAcorpus"},{"subj":"T28","pred":"source","obj":"GENIAcorpus"},{"subj":"T29","pred":"source","obj":"GENIAcorpus"},{"subj":"T30","pred":"source","obj":"GENIAcorpus"},{"subj":"T31","pred":"source","obj":"GENIAcorpus"},{"subj":"T32","pred":"source","obj":"GENIAcorpus"},{"subj":"T33","pred":"source","obj":"GENIAcorpus"},{"subj":"T34","pred":"source","obj":"GENIAcorpus"},{"subj":"T35","pred":"source","obj":"GENIAcorpus"},{"subj":"T36","pred":"source","obj":"GENIAcorpus"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"genia-medco-coref","color":"#ecda93","default":true},{"id":"2015-BEL-Sample-2","color":"#c093ec"},{"id":"jnlpba-st-training","color":"#93eca6"},{"id":"pubmed-sentences-benchmark","color":"#ec9399"},{"id":"GENIAcorpus","color":"#93b3ec"}]}]}}