Hepatitis C virus core protein differently regulates the JAK-STAT signaling pathway under interleukin-6 and interferon-γ stimuli

被引:55
作者
Hosui, A
Ohkawa, K
Ishida, H
Sato, A
Nakanishi, F
Ueda, K
Takehara, T
Kasahara, A
Sasaki, Y
Hori, M
Hayashi, N
机构
[1] Osaka Univ, Sch Med, Dept Mol Therapeut, Grad Sch Med, Osaka 5650871, Japan
[2] Osaka Univ, Sch Med, Dept Internal Med & Therapeut, Grad Sch Med, Osaka 5650871, Japan
[3] Osaka Univ, Sch Med, Dept Microbiol, Grad Sch Med, Osaka 5650871, Japan
[4] Osaka Univ, Sch Med, Dept Gen Med, Grad Sch Med, Osaka 5650871, Japan
关键词
D O I
10.1074/jbc.M210485200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:28562 / 28571
页数:10
相关论文
共 56 条
[51]   A PROTEIN TYROSINE KINASE IN THE INTERFERON-ALPHA/BETA SIGNALING PATHWAY [J].
VELAZQUEZ, L ;
FELLOUS, M ;
STARK, GR ;
PELLEGRINI, S .
CELL, 1992, 70 (02) :313-322
[52]   Hepatitis C virus core protein activates nuclear factor κB-dependent signaling through tumor necrosis factor receptor-associated factor [J].
Yoshida, H ;
Kato, N ;
Shiratori, Y ;
Otsuka, M ;
Maeda, S ;
Kato, J ;
Omata, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (19) :16399-16405
[53]   AMINO ACID-MEDIATED EPSPS AT PRIMARY AFFERENT SYNAPSES WITH SUBSTANTIA GELATINOSA NEURONS IN THE RAT SPINAL-CORD [J].
YOSHIMURA, M ;
JESSELL, T .
JOURNAL OF PHYSIOLOGY-LONDON, 1990, 430 :315-335
[54]   STAT3 participates in transcriptional activation of the C-reactive protein gene by interleukin-6 [J].
Zhang, DX ;
Sun, M ;
Samols, D ;
Kushner, I .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (16) :9503-9509
[55]   STAT3 - A STAT FAMILY MEMBER ACTIVATED BY TYROSINE PHOSPHORYLATION IN RESPONSE TO EPIDERMAL GROWTH-FACTOR AND INTERLEUKIN-6 [J].
ZHONG, Z ;
WEN, ZL ;
DARNELL, JE .
SCIENCE, 1994, 264 (5155) :95-98
[56]   Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor (TNF) receptor 1 and enhances TNF-induced apoptosis [J].
Zhu, NL ;
Khoshnan, A ;
Schneider, R ;
Matsumoto, M ;
Dennert, G ;
Ware, C ;
Lai, MMC .
JOURNAL OF VIROLOGY, 1998, 72 (05) :3691-3697