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

36 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 1

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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