JAK2 is an important signal transducer in IL-33-induced NF-κB activation

Megumi Tago, Kenji Tago, Yoshinori Sato, Shin Ichi Tominaga, Tadashi Kasahara

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

IL-33, a member of the IL-1 family of cytokines, has been shown to activate NF-κB and MAP kinase family through the IL-1 receptor-related protein, ST2L. In this study, we found that IL-33 rapidly activated a tyrosine kinase, JAK2. Interestingly, we demonstrated the functional involvement of JAK2 in IL-33-induced IκBα degradation and NF-κB activation, since a JAK2 inhibitor, AG490, effectively inhibited this signaling pathway. Furthermore, IL-33 failed to induce IκBα degradation and NF-κB activation in JAK2-deficient MEFs expressing ST2L, compared with wild-type MEFs expressing ST2L. In addition, the introduction of wild-type JAK2 but not kinase dead JAK2 mutant (K882R) restored the IL-33-induced efficient activation of NF-κB in JAK2-deficient MEFs expressing ST2L, resulting in the induction of IL-6, CCL2/MCP-1 and CXCL1/KC expression. On the other hand, the activation of ERK, JNK and p38 was unaffected by JAK2 inhibition and JAK2 deficiency. Thus, these data demonstrate that JAK2 plays an important role in regulating IL-33-induced NF-κB activation.

Original languageEnglish
Pages (from-to)363-370
Number of pages8
JournalCellular Signalling
Volume23
Issue number2
DOIs
Publication statusPublished - 2011 Feb

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Transducers
Phosphotransferases
Interleukin-1 Receptors
Interleukin-1
Protein-Tyrosine Kinases
Interleukin-33
Interleukin-6
Cytokines
Proteins

Keywords

  • IL-33
  • JAK2
  • NF-κB
  • ST2L

ASJC Scopus subject areas

  • Cell Biology

Cite this

JAK2 is an important signal transducer in IL-33-induced NF-κB activation. / Tago, Megumi; Tago, Kenji; Sato, Yoshinori; Tominaga, Shin Ichi; Kasahara, Tadashi.

In: Cellular Signalling, Vol. 23, No. 2, 02.2011, p. 363-370.

Research output: Contribution to journalArticle

Tago, Megumi ; Tago, Kenji ; Sato, Yoshinori ; Tominaga, Shin Ichi ; Kasahara, Tadashi. / JAK2 is an important signal transducer in IL-33-induced NF-κB activation. In: Cellular Signalling. 2011 ; Vol. 23, No. 2. pp. 363-370.
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