PubMed:21708247 JSONTXT

{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":131},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":132,"end":343},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":344,"end":504},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":505,"end":754},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":755,"end":891},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":892,"end":1040},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":1041,"end":1267},"obj":"Sentence"},{"id":"TextSentencer_T8","span":{"begin":1268,"end":1357},"obj":"Sentence"},{"id":"TextSentencer_T9","span":{"begin":1358,"end":1572},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":131},"obj":"Sentence"},{"id":"T2","span":{"begin":132,"end":343},"obj":"Sentence"},{"id":"T3","span":{"begin":344,"end":504},"obj":"Sentence"},{"id":"T4","span":{"begin":505,"end":754},"obj":"Sentence"},{"id":"T5","span":{"begin":755,"end":891},"obj":"Sentence"},{"id":"T6","span":{"begin":892,"end":1040},"obj":"Sentence"},{"id":"T7","span":{"begin":1041,"end":1267},"obj":"Sentence"},{"id":"T8","span":{"begin":1268,"end":1357},"obj":"Sentence"},{"id":"T9","span":{"begin":1358,"end":1572},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"NADPH-oxidase-dependent reactive oxygen species mediate EGFR transactivation by FPRL1 in WKYMVm-stimulated human lung cancer cells.\nCross talk between unrelated cell surface receptors, such as G-protein-coupled receptors (GPCR) and receptor tyrosine kinases (RTK), is a crucial signaling mechanism to expand the cellular communication network. We investigated the ability of the GPCR formyl peptide receptor-like 1 (FPRL1) to transactivate the RTK epidermal growth factor receptor (EGFR) in CaLu-6 cells. We observed that stimulation with WKYMVm, an FPRL1 agonist isolated by screening synthetic peptide libraries, induces EGFR tyrosine phosphorylation, p47(phox) phosphorylation, NADPH-oxidase-dependent superoxide generation, and c-Src kinase activity. As a result of EGFR transactivation, phosphotyrosine residues provide docking sites for recruitment and triggering of the STAT3 pathway. WKYMVm-induced EGFR transactivation is prevented by the FPRL1-selective antagonist WRWWWW, by pertussis toxin (PTX), and by the c-Src inhibitor PP2. The critical role of NADPH-oxidase-dependent superoxide generation in this cross-talk mechanism is corroborated by the finding that apocynin or a siRNA against p22(phox) prevents EGFR transactivation and c-Src kinase activity. In addition, WKYMVm promotes CaLu-6 cell growth, which is prevented by PTX and by WRWWWW. These results highlight the role of FPRL1 as a potential target of new drugs and suggest that targeting both FPRL1 and EGFR may yield superior therapeutic effects compared with targeting either receptor separately."}

{"project":"Allie","denotations":[{"id":"SS1_21708247_1_0","span":{"begin":193,"end":220},"obj":"expanded"},{"id":"SS2_21708247_1_0","span":{"begin":222,"end":226},"obj":"abbr"},{"id":"SS1_21708247_1_1","span":{"begin":232,"end":257},"obj":"expanded"},{"id":"SS2_21708247_1_1","span":{"begin":259,"end":262},"obj":"abbr"},{"id":"SS1_21708247_2_0","span":{"begin":384,"end":414},"obj":"expanded"},{"id":"SS2_21708247_2_0","span":{"begin":416,"end":421},"obj":"abbr"},{"id":"SS1_21708247_2_1","span":{"begin":448,"end":480},"obj":"expanded"},{"id":"SS2_21708247_2_1","span":{"begin":482,"end":486},"obj":"abbr"},{"id":"SS1_21708247_5_0","span":{"begin":986,"end":1001},"obj":"expanded"},{"id":"SS2_21708247_5_0","span":{"begin":1003,"end":1006},"obj":"abbr"}],"relations":[{"id":"AE1_21708247_1_0","pred":"abbreviatedTo","subj":"SS1_21708247_1_0","obj":"SS2_21708247_1_0"},{"id":"AE1_21708247_1_1","pred":"abbreviatedTo","subj":"SS1_21708247_1_1","obj":"SS2_21708247_1_1"},{"id":"AE1_21708247_2_0","pred":"abbreviatedTo","subj":"SS1_21708247_2_0","obj":"SS2_21708247_2_0"},{"id":"AE1_21708247_2_1","pred":"abbreviatedTo","subj":"SS1_21708247_2_1","obj":"SS2_21708247_2_1"},{"id":"AE1_21708247_5_0","pred":"abbreviatedTo","subj":"SS1_21708247_5_0","obj":"SS2_21708247_5_0"}],"text":"NADPH-oxidase-dependent reactive oxygen species mediate EGFR transactivation by FPRL1 in WKYMVm-stimulated human lung cancer cells.\nCross talk between unrelated cell surface receptors, such as G-protein-coupled receptors (GPCR) and receptor tyrosine kinases (RTK), is a crucial signaling mechanism to expand the cellular communication network. We investigated the ability of the GPCR formyl peptide receptor-like 1 (FPRL1) to transactivate the RTK epidermal growth factor receptor (EGFR) in CaLu-6 cells. We observed that stimulation with WKYMVm, an FPRL1 agonist isolated by screening synthetic peptide libraries, induces EGFR tyrosine phosphorylation, p47(phox) phosphorylation, NADPH-oxidase-dependent superoxide generation, and c-Src kinase activity. As a result of EGFR transactivation, phosphotyrosine residues provide docking sites for recruitment and triggering of the STAT3 pathway. WKYMVm-induced EGFR transactivation is prevented by the FPRL1-selective antagonist WRWWWW, by pertussis toxin (PTX), and by the c-Src inhibitor PP2. The critical role of NADPH-oxidase-dependent superoxide generation in this cross-talk mechanism is corroborated by the finding that apocynin or a siRNA against p22(phox) prevents EGFR transactivation and c-Src kinase activity. In addition, WKYMVm promotes CaLu-6 cell growth, which is prevented by PTX and by WRWWWW. These results highlight the role of FPRL1 as a potential target of new drugs and suggest that targeting both FPRL1 and EGFR may yield superior therapeutic effects compared with targeting either receptor separately."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"21708247-0#80#85#gene2358","span":{"begin":80,"end":85},"obj":"gene2358"},{"id":"21708247-0#113#124#diseaseC0242379","span":{"begin":113,"end":124},"obj":"diseaseC0242379"},{"id":"21708247-0#113#124#diseaseC0684249","span":{"begin":113,"end":124},"obj":"diseaseC0684249"},{"id":"21708247-0#113#124#diseaseC1306460","span":{"begin":113,"end":124},"obj":"diseaseC1306460"}],"relations":[{"id":"80#85#gene2358113#124#diseaseC0242379","pred":"associated_with","subj":"21708247-0#80#85#gene2358","obj":"21708247-0#113#124#diseaseC0242379"},{"id":"80#85#gene2358113#124#diseaseC0684249","pred":"associated_with","subj":"21708247-0#80#85#gene2358","obj":"21708247-0#113#124#diseaseC0684249"},{"id":"80#85#gene2358113#124#diseaseC1306460","pred":"associated_with","subj":"21708247-0#80#85#gene2358","obj":"21708247-0#113#124#diseaseC1306460"}],"text":"NADPH-oxidase-dependent reactive oxygen species mediate EGFR transactivation by FPRL1 in WKYMVm-stimulated human lung cancer cells.\nCross talk between unrelated cell surface receptors, such as G-protein-coupled receptors (GPCR) and receptor tyrosine kinases (RTK), is a crucial signaling mechanism to expand the cellular communication network. We investigated the ability of the GPCR formyl peptide receptor-like 1 (FPRL1) to transactivate the RTK epidermal growth factor receptor (EGFR) in CaLu-6 cells. We observed that stimulation with WKYMVm, an FPRL1 agonist isolated by screening synthetic peptide libraries, induces EGFR tyrosine phosphorylation, p47(phox) phosphorylation, NADPH-oxidase-dependent superoxide generation, and c-Src kinase activity. As a result of EGFR transactivation, phosphotyrosine residues provide docking sites for recruitment and triggering of the STAT3 pathway. WKYMVm-induced EGFR transactivation is prevented by the FPRL1-selective antagonist WRWWWW, by pertussis toxin (PTX), and by the c-Src inhibitor PP2. The critical role of NADPH-oxidase-dependent superoxide generation in this cross-talk mechanism is corroborated by the finding that apocynin or a siRNA against p22(phox) prevents EGFR transactivation and c-Src kinase activity. In addition, WKYMVm promotes CaLu-6 cell growth, which is prevented by PTX and by WRWWWW. These results highlight the role of FPRL1 as a potential target of new drugs and suggest that targeting both FPRL1 and EGFR may yield superior therapeutic effects compared with targeting either receptor separately."}

{"project":"DisGeNet-2017-sample","denotations":[{"id":"T2047","span":{"begin":80,"end":85},"obj":"gene:2358"},{"id":"T2048","span":{"begin":113,"end":124},"obj":"disease:C0242379"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T2047","obj":"T2048"},{"id":"R2","pred":"associated_with","subj":"T2047","obj":"T2048"},{"id":"R3","pred":"associated_with","subj":"T2047","obj":"T2048"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"NADPH-oxidase-dependent reactive oxygen species mediate EGFR transactivation by FPRL1 in WKYMVm-stimulated human lung cancer cells.\nCross talk between unrelated cell surface receptors, such as G-protein-coupled receptors (GPCR) and receptor tyrosine kinases (RTK), is a crucial signaling mechanism to expand the cellular communication network. We investigated the ability of the GPCR formyl peptide receptor-like 1 (FPRL1) to transactivate the RTK epidermal growth factor receptor (EGFR) in CaLu-6 cells. We observed that stimulation with WKYMVm, an FPRL1 agonist isolated by screening synthetic peptide libraries, induces EGFR tyrosine phosphorylation, p47(phox) phosphorylation, NADPH-oxidase-dependent superoxide generation, and c-Src kinase activity. As a result of EGFR transactivation, phosphotyrosine residues provide docking sites for recruitment and triggering of the STAT3 pathway. WKYMVm-induced EGFR transactivation is prevented by the FPRL1-selective antagonist WRWWWW, by pertussis toxin (PTX), and by the c-Src inhibitor PP2. The critical role of NADPH-oxidase-dependent superoxide generation in this cross-talk mechanism is corroborated by the finding that apocynin or a siRNA against p22(phox) prevents EGFR transactivation and c-Src kinase activity. In addition, WKYMVm promotes CaLu-6 cell growth, which is prevented by PTX and by WRWWWW. These results highlight the role of FPRL1 as a potential target of new drugs and suggest that targeting both FPRL1 and EGFR may yield superior therapeutic effects compared with targeting either receptor separately."}

{"project":"UBERON-AE","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":113,"end":117},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"NADPH-oxidase-dependent reactive oxygen species mediate EGFR transactivation by FPRL1 in WKYMVm-stimulated human lung cancer cells.\nCross talk between unrelated cell surface receptors, such as G-protein-coupled receptors (GPCR) and receptor tyrosine kinases (RTK), is a crucial signaling mechanism to expand the cellular communication network. We investigated the ability of the GPCR formyl peptide receptor-like 1 (FPRL1) to transactivate the RTK epidermal growth factor receptor (EGFR) in CaLu-6 cells. We observed that stimulation with WKYMVm, an FPRL1 agonist isolated by screening synthetic peptide libraries, induces EGFR tyrosine phosphorylation, p47(phox) phosphorylation, NADPH-oxidase-dependent superoxide generation, and c-Src kinase activity. As a result of EGFR transactivation, phosphotyrosine residues provide docking sites for recruitment and triggering of the STAT3 pathway. WKYMVm-induced EGFR transactivation is prevented by the FPRL1-selective antagonist WRWWWW, by pertussis toxin (PTX), and by the c-Src inhibitor PP2. The critical role of NADPH-oxidase-dependent superoxide generation in this cross-talk mechanism is corroborated by the finding that apocynin or a siRNA against p22(phox) prevents EGFR transactivation and c-Src kinase activity. In addition, WKYMVm promotes CaLu-6 cell growth, which is prevented by PTX and by WRWWWW. These results highlight the role of FPRL1 as a potential target of new drugs and suggest that targeting both FPRL1 and EGFR may yield superior therapeutic effects compared with targeting either receptor separately."}

{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":113,"end":117},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"NADPH-oxidase-dependent reactive oxygen species mediate EGFR transactivation by FPRL1 in WKYMVm-stimulated human lung cancer cells.\nCross talk between unrelated cell surface receptors, such as G-protein-coupled receptors (GPCR) and receptor tyrosine kinases (RTK), is a crucial signaling mechanism to expand the cellular communication network. We investigated the ability of the GPCR formyl peptide receptor-like 1 (FPRL1) to transactivate the RTK epidermal growth factor receptor (EGFR) in CaLu-6 cells. We observed that stimulation with WKYMVm, an FPRL1 agonist isolated by screening synthetic peptide libraries, induces EGFR tyrosine phosphorylation, p47(phox) phosphorylation, NADPH-oxidase-dependent superoxide generation, and c-Src kinase activity. As a result of EGFR transactivation, phosphotyrosine residues provide docking sites for recruitment and triggering of the STAT3 pathway. WKYMVm-induced EGFR transactivation is prevented by the FPRL1-selective antagonist WRWWWW, by pertussis toxin (PTX), and by the c-Src inhibitor PP2. The critical role of NADPH-oxidase-dependent superoxide generation in this cross-talk mechanism is corroborated by the finding that apocynin or a siRNA against p22(phox) prevents EGFR transactivation and c-Src kinase activity. In addition, WKYMVm promotes CaLu-6 cell growth, which is prevented by PTX and by WRWWWW. These results highlight the role of FPRL1 as a potential target of new drugs and suggest that targeting both FPRL1 and EGFR may yield superior therapeutic effects compared with targeting either receptor separately."}