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

Akihiro Kimura, Tetsuji Naka, Shigekazu Nagata, Ichiro Kawase, Tadamitsu Kishimoto

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)991-999
Number of pages9
JournalInternational Immunology
Volume16
Issue number7
DOIs
Publication statusPublished - 2004 Jul

Fingerprint

Janus Kinases
Tumor Necrosis Factor-alpha
Apoptosis
Cytokines
Caspase 8
Tumor Necrosis Factor Receptors
DNA Fragmentation
Caspases
Transducers
Fibroblasts
Cell Line

Keywords

  • Caspase
  • Cell death
  • Negative feedback regulator
  • TNFR-1
  • Tyrosine kinase

ASJC Scopus subject areas

  • Immunology

Cite this

SOCS-1 suppresses TNF-α-induced apoptosis through the regulation of Jak activation. / Kimura, Akihiro; Naka, Tetsuji; Nagata, Shigekazu; Kawase, Ichiro; Kishimoto, Tadamitsu.

In: International Immunology, Vol. 16, No. 7, 07.2004, p. 991-999.

Research output: Contribution to journalArticle

Kimura, A, Naka, T, Nagata, S, Kawase, I & Kishimoto, T 2004, 'SOCS-1 suppresses TNF-α-induced apoptosis through the regulation of Jak activation', International Immunology, vol. 16, no. 7, pp. 991-999. https://doi.org/10.1093/intimm/dxh102
Kimura, Akihiro ; Naka, Tetsuji ; Nagata, Shigekazu ; Kawase, Ichiro ; Kishimoto, Tadamitsu. / SOCS-1 suppresses TNF-α-induced apoptosis through the regulation of Jak activation. In: International Immunology. 2004 ; Vol. 16, No. 7. pp. 991-999.
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