TY - JOUR
T1 - SOCS-1 suppresses TNF-α-induced apoptosis through the regulation of Jak activation
AU - Kimura, Akihiro
AU - Naka, Tetsuji
AU - Nagata, Shigekazu
AU - Kawase, Ichiro
AU - Kishimoto, Tadamitsu
N1 - Funding Information:
We gratefully acknowledge the provision of 2fTGH, U4A, U1A and U3A cell lines by Dr G. R. Stark at The Cleveland Clinic Foundation, Ohio, and TNFR-1 cDNA by Dr Y. Niitsu (Sapporo Medical University). We thank Dr T. Taga (Kumamoto University) for helpful discussion and Ms Ito for her secretarial assistance. This work was supported in part by grants, a grant-in-aid, and a Hitec Research Center grant from the Ministry of Education, Science, and Culture, Japan.
PY - 2004/7
Y1 - 2004/7
N2 - 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-α (TNF-α)-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-α. We also show that the activations of Jaks and caspases by TNF-α are suppressed by SOCS-1. Furthermore, in Jak-deficient cell lines, DNA fragmentation and caspase-8 activation by TNF-α are suppressed, indicating that Jaks participate in TNF-α-induced apoptosis signaling. Taken together, these results suggest that SOCS-1 inhibits TNF-α-induced apoptosis through regulation of Jaks.
AB - 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-α (TNF-α)-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-α. We also show that the activations of Jaks and caspases by TNF-α are suppressed by SOCS-1. Furthermore, in Jak-deficient cell lines, DNA fragmentation and caspase-8 activation by TNF-α are suppressed, indicating that Jaks participate in TNF-α-induced apoptosis signaling. Taken together, these results suggest that SOCS-1 inhibits TNF-α-induced apoptosis through regulation of Jaks.
KW - Caspase
KW - Cell death
KW - Negative feedback regulator
KW - TNFR-1
KW - Tyrosine kinase
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U2 - 10.1093/intimm/dxh102
DO - 10.1093/intimm/dxh102
M3 - Article
C2 - 15173123
AN - SCOPUS:3242661040
SN - 0953-8178
VL - 16
SP - 991
EP - 999
JO - International immunology
JF - International immunology
IS - 7
ER -