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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
31
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pubmed:dateCreated |
2003-7-28
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pubmed:abstractText |
We established hepatitis C virus (HCV) core-expressing cells and investigated whether HCV core would modify the Janus kinase (JAK)-signal transducer and activator transcription factor (STAT) pathway under interleukin-6 (IL-6) and interferon (IFN)-gamma stimuli. Phosphorylation of JAK1/2 and STAT3, and STAT3-mediated transcription, were prevented by HCV core under IL-6 stimulation. In contrast, HCV core increased phosphorylation of JAK1/2 and STAT1 and STAT1-mediated transcription under IFN-gamma stimulation. Immunoprecipitation/Western blot analysis showed that HCV core could bind to JAK1/2. The PGYPWP sequences at codons 79-84 within HCV core were important for interaction with JAKs by in vitro binding analysis. In the reporter gene assay, HCV core-mediated suppression of JAK-STAT pathway under IL-6 stimulation was not observed by abrogation of PGYPWP sequence, suggesting that HCV core/JAK interaction may directly affect the signal transduction. In contrast, augmentation of JAK-STAT pathway was still seen by HCV core without functional PGYPWP sequence under IFN-gamma stimulation. Flow cytometric analysis revealed that HCV core up-regulated of IFN-gamma receptor 2 expression, which may be responsible for HCV core-mediated enhancement of JAK-STAT pathway under IFN-gamma stimulation. In conclusion, HCV core has different effects on the JAK-STAT pathway under IL-6 and IFN-gamma stimuli. This may be exerted by these two independent mechanisms.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/JAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/JAK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Jak1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Jak2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interferon,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Stat1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Core Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/interferon gamma receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:HayashiNorioN,
pubmed-author:HoriMasatsuguM,
pubmed-author:HosuiAtsushiA,
pubmed-author:IshidaHisashiH,
pubmed-author:KasaharaAkinoriA,
pubmed-author:NakanishiFumihikoF,
pubmed-author:OhkawaKazuyoshiK,
pubmed-author:SasakiYutakaY,
pubmed-author:SatoAkiA,
pubmed-author:TakeharaTetsuoT,
pubmed-author:UedaKeijiK
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28562-71
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12764155-Animals,
pubmed-meshheading:12764155-Binding Sites,
pubmed-meshheading:12764155-Carcinoma, Hepatocellular,
pubmed-meshheading:12764155-Cell Line,
pubmed-meshheading:12764155-DNA-Binding Proteins,
pubmed-meshheading:12764155-Flow Cytometry,
pubmed-meshheading:12764155-Gene Expression,
pubmed-meshheading:12764155-Gene Expression Regulation,
pubmed-meshheading:12764155-Hepacivirus,
pubmed-meshheading:12764155-Humans,
pubmed-meshheading:12764155-Interferon-gamma,
pubmed-meshheading:12764155-Interleukin-6,
pubmed-meshheading:12764155-Janus Kinase 1,
pubmed-meshheading:12764155-Janus Kinase 2,
pubmed-meshheading:12764155-Liver,
pubmed-meshheading:12764155-Liver Neoplasms,
pubmed-meshheading:12764155-Mice,
pubmed-meshheading:12764155-Phosphorylation,
pubmed-meshheading:12764155-Protein-Tyrosine Kinases,
pubmed-meshheading:12764155-Proto-Oncogene Proteins,
pubmed-meshheading:12764155-Receptors, Interferon,
pubmed-meshheading:12764155-STAT1 Transcription Factor,
pubmed-meshheading:12764155-STAT3 Transcription Factor,
pubmed-meshheading:12764155-Signal Transduction,
pubmed-meshheading:12764155-Trans-Activators,
pubmed-meshheading:12764155-Transcription, Genetic,
pubmed-meshheading:12764155-Transfection,
pubmed-meshheading:12764155-Tumor Cells, Cultured,
pubmed-meshheading:12764155-Tyrosine,
pubmed-meshheading:12764155-Viral Core Proteins
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pubmed:year |
2003
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pubmed:articleTitle |
Hepatitis C virus core protein differently regulates the JAK-STAT signaling pathway under interleukin-6 and interferon-gamma stimuli.
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pubmed:affiliation |
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
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pubmed:publicationType |
Journal Article
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