SOCS-1 suppresses TNF-α-induced apoptosis through the regulation of Jak activation

被引：44
作者：
Kimura, A
Naka, T
Nagata, S
Kawase, I
Kishimoto, T
机构：
[1] Osaka Univ, Grad Sch Frontier Biosci, Lab Immune Regulat, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Grad Sch Med, Dept Mol Med, Suita, Osaka 5650871, Japan
[3] Osaka Univ, Sch Med, Dept Genet, Suita, Osaka 5650871, Japan
来源：
INTERNATIONAL IMMUNOLOGY | 2004年 / 16卷 / 07期
关键词：
caspase; cell death; negative feedback regulator; TNFR-1; tyrosine kinase;
D O I：
10.1093/intimm/dxh102
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Suppressor of cytokine signaling-1 (SOCS-1) was identified as one of the negative feedback regulators of Janus kinase (Jak)-signal-transducer-and-activator-of-transcription (STAT) signaling. So far, it has been reported that SOCS-1 inhibits the action of multiple cytokines at least in vitro. We previously showed that SOCS-1 suppresses tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in murine embryonic fibroblast, but the mechanism of suppression was not fully clarified. In this study, we show that Jaks bind to TNF receptor-1 (TNFR-1) and are activated by TNF-alpha. We also show that the activations of Jaks and caspases by TNF-alpha are suppressed by SOCS-1. Furthermore, in Jak-deficient cell lines, DNA fragmentation and caspase-8 activation by TNF-alpha are suppressed, indicating that Jaks participate in TNF-alpha-induced apoptosis signaling. Taken together, these results suggest that SOCS-1 inhibits TNF-alpha-induced apoptosis through regulation of Jaks.
引用
收藏
页码：991 / 999
页数：9
相关论文
共 46 条
[1]   SOCS1 is a critical inhibitor of interferon γ signaling and prevents the potentially fatal neonatal actions of this cytokine [J].
Alexander, WS ;
Starr, R ;
Fenner, JE ;
Scott, GL ;
Handman, E ;
Sprigg, NS ;
Corbin, JE ;
Cornish, AL ;
Darwiche, R ;
Owczarek, CM ;
Kay, TWH ;
Nicola, NA ;
Hertzog, PJ ;
Metcalf, D ;
Hilton, DJ .
CELL, 1999, 98 (05) :597-608
[2]   Apoptotic molecular machinery: Vastly increased complexity in vertebrates revealed by genome comparisons [J].
Aravind, L ;
Dixit, VM ;
Koonin, EV .
SCIENCE, 2001, 291 (5507) :1279-+
[3]   Death receptors: Signaling and modulation [J].
Ashkenazi, A ;
Dixit, VM .
SCIENCE, 1998, 281 (5381) :1305-1308
[4]   Signal transduction by tumor necrosis factor and its relatives [J].
Baud, V ;
Karin, M .
TRENDS IN CELL BIOLOGY, 2001, 11 (09) :372-377
[5]   Activation-induced cell death [J].
Budd, RC .
CURRENT OPINION IN IMMUNOLOGY, 2001, 13 (03) :356-362
[6]   TNF-R1 signaling: A beautiful pathway [J].
Chen, GQ ;
Goeddel, DV .
SCIENCE, 2002, 296 (5573) :1634-1635
[7]   Suppressor of cytokine signaling-1 regulates the sensitivity of pancreatic β cells to tumor necrosis factor [J].
Chong, MMW ;
Thomas, HE ;
Kay, TWH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (31) :27945-27952
[8]   The α and β subunits of IκB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF [J].
Devin, A ;
Lin, Y ;
Yamaoka, S ;
Li, ZW ;
Karin, M ;
Liu, ZG .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (12) :3986-3994
[9]   A new protein containing an SH2 domain that inhibits JAK kinases [J].
Endo, TA ;
Masuhara, M ;
Yokouchi, M ;
Suzuki, R ;
Sakamoto, H ;
Mitsui, K ;
Matsumoto, A ;
Tanimura, S ;
Ohtsubo, M ;
Misawa, H ;
Miyazaki, T ;
Leonor, N ;
Taniguchi, T ;
Fujita, T ;
Kanakura, Y ;
Komiya, S ;
Yoshimura, A .
NATURE, 1997, 387 (6636) :921-924
[10]  
Fujishima A., 2000, J PHOTOCH PHOTOBIO C, V1, P1, DOI DOI 10.1016/S1389-5567(00)00002-2
12345