TRAF6 is a critical signal transducer in IL-33 signaling pathway

Megumi Tago, Kenji Tago, Morisada Hayakawa, Shin ichi Tominaga, Tomoyuki Ohshio, Yoshiko Sonoda, Tadashi Kasahara

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

IL-33 has been shown to induce Th2 responses by signaling through the IL-1 receptor-related protein, ST2L. However, the signal transduction pathways activated by the ST2L have not been characterized. Here, we found that IL-33-induced monocyte chemoattractant protein (MCP)-1, MCP-3 and IL-6 expression was significantly inhibited in TNF receptor-associated Factor 6 (TRAF6)-deficient MEFs. IL-33 rapidly induced the formation of ST2L complex containing IL-1 receptor-associated kinase (IRAK), however, lack of TRAF6 abolished the recruitment of IRAK to ST2L. Consequently, p38, JNK and Nuclear factor-κB (NF-κB) activation induced by IL-33 was completely inhibited in TRAF6-deficient MEFs. On the other hand, IL-33-induced ERK activation was observed regardless of the presence of TRAF6. The introduction of TRAF6 restored the efficient activation of p38, JNK and NF-κB in TRAF6 deficient MEFs, resulting in the induction of MCP-1, MCP-3 and IL-6 expression. Moreover, IL-33 augmented autoubiquitination of TRAF6 and the reconstitution of TRAF6 mutant (C70A) that is defective in its ubiquitin ligase activity failed to restore IL-33-induced p38, JNK and NF-κB activation. Thus, these data demonstrate that TRAF6 plays a pivotal role in IL-33 signaling pathway through its ubiquitin ligase activity.

Original languageEnglish
Pages (from-to)1679-1686
Number of pages8
JournalCellular Signalling
Volume20
Issue number9
DOIs
Publication statusPublished - 2008 Sep

Fingerprint

TNF Receptor-Associated Factor 6
Transducers
Chemokine CCL7
Interleukin-1 Receptor-Associated Kinases
Chemokine CCL2
Ligases
Ubiquitin
Interleukin-6
Interleukin-33
Interleukin-1 Receptors
Signal Transduction

Keywords

  • IL-33
  • JNK
  • NF-κB
  • p38
  • ST2L
  • TRAF6

ASJC Scopus subject areas

  • Cell Biology

Cite this

Tago, M., Tago, K., Hayakawa, M., Tominaga, S. I., Ohshio, T., Sonoda, Y., & Kasahara, T. (2008). TRAF6 is a critical signal transducer in IL-33 signaling pathway. Cellular Signalling, 20(9), 1679-1686. https://doi.org/10.1016/j.cellsig.2008.05.013

TRAF6 is a critical signal transducer in IL-33 signaling pathway. / Tago, Megumi; Tago, Kenji; Hayakawa, Morisada; Tominaga, Shin ichi; Ohshio, Tomoyuki; Sonoda, Yoshiko; Kasahara, Tadashi.

In: Cellular Signalling, Vol. 20, No. 9, 09.2008, p. 1679-1686.

Research output: Contribution to journalArticle

Tago, M, Tago, K, Hayakawa, M, Tominaga, SI, Ohshio, T, Sonoda, Y & Kasahara, T 2008, 'TRAF6 is a critical signal transducer in IL-33 signaling pathway', Cellular Signalling, vol. 20, no. 9, pp. 1679-1686. https://doi.org/10.1016/j.cellsig.2008.05.013
Tago M, Tago K, Hayakawa M, Tominaga SI, Ohshio T, Sonoda Y et al. TRAF6 is a critical signal transducer in IL-33 signaling pathway. Cellular Signalling. 2008 Sep;20(9):1679-1686. https://doi.org/10.1016/j.cellsig.2008.05.013
Tago, Megumi ; Tago, Kenji ; Hayakawa, Morisada ; Tominaga, Shin ichi ; Ohshio, Tomoyuki ; Sonoda, Yoshiko ; Kasahara, Tadashi. / TRAF6 is a critical signal transducer in IL-33 signaling pathway. In: Cellular Signalling. 2008 ; Vol. 20, No. 9. pp. 1679-1686.
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