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J. Biol. Chem., Vol. 278, Issue 31, 28562-28571, August 1, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/31/28562    most recent M210485200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hosui, A. Articles by Hayashi, N. Search for Related Content PubMed PubMed Citation Articles by Hosui, A. Articles by Hayashi, N. Social Bookmarking                      What's this?

Hepatitis C Virus Core Protein Differently Regulates the JAK-STAT Signaling Pathway under Interleukin-6 and Interferon- Stimuli^*

Atsushi Hosui , Kazuyoshi Ohkawa , Hisashi Ishida , Aki Sato , Fumihiko Nakanishi , Keiji Ueda ¶, Tetsuo Takehara , Akinori Kasahara ||, Yutaka Sasaki , Masatsugu Hori  and Norio Hayashi  **

From the Department of Internal Medicine and Therapeutics, Department of Molecular Therapeutics, ^¶Department of Microbiology, and ^||Department of General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan

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)- 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- 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- stimulation. Flow cytometric analysis revealed that HCV core up-regulated of IFN- receptor 2 expression, which may be responsible for HCV core-mediated enhancement of JAK-STAT pathway under IFN- stimulation. In conclusion, HCV core has different effects on the JAK-STAT pathway under IL-6 and IFN- stimuli. This may be exerted by these two independent mechanisms.

Received for publication, October 13, 2002 , and in revised form, May 14, 2003.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** To whom correspondence should be addressed: Dept. of Molecular Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Tel.: 81-6-6879-3440; Fax: 81-6-6879-3449; E-mail: hayashin{at}moltx.med.osaka-u.ac.jp.

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