Identification of TIFA as an adapter protein that links tumor necrosis factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling

Hiroshi Takatsuna, Hiroki Kato, Jin Gohda, Taishin Akiyama, Ayaka Moriya, Yoshinari Okamoto, Yuriko Yamagata, Masami Otsuka, Kazuo Umezawa, Kentaro Senba, Jun Ichiro Inoue

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Tumor necrosis factor receptor-associated factor 6 (TRAF6) transduces signals from members of the Toll/interleukin-1 (IL-1) receptor family by interacting with IL-1 receptor-associated kinase-1 (IRAK-1) after IRAK-1 is released from the receptor-MyD88 complex upon IL-1 stimulation. However, the molecular mechanisms underlying regulation of the IRAK-1/TRAF6 interaction are largely unknown. We have identified TIFA, a TRAF-interacting protein with a forkhead-associated (FHA) domain. The FHA domain is a motif known to bind directly to phosphothreonine and phosphoserine. In transient transfection assays, TIFA activates NFκB and c-Jun amino-terminal kinase. However, TIFA carrying a mutation that abolishes TRAF6 binding or mutations in the FHA domain that are known to abolish FHA domain binding to phosphopeptide fails to activate NFκB and c-Jun amino-terminal kinase. TIFA, when overexpressed, binds both TRAF6 and IRAK-1 and significantly enhances the IRAK-1/TRAF6 interaction. Furthermore, analysis of endogenous proteins indicates that TIFA associates with TRAF6 constitutively, whereas it associates with IRAK-1 in an IL-1 stimulation-dependent manner in vivo. Thus, TIFA is likely to mediate IRAK-1/TRAF6 interaction upon IL-1 stimulation.

Original languageEnglish
Pages (from-to)12144-12150
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number14
DOIs
Publication statusPublished - 2003 Apr 4
Externally publishedYes

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Interleukin-1 Receptor-Associated Kinases
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Interleukin-1 Receptors
Interleukin-1
JNK Mitogen-Activated Protein Kinases
Phosphothreonine
Phosphoserine
Phosphopeptides
Mutation
link protein
Transfection
Assays

ASJC Scopus subject areas

  • Biochemistry

Cite this

Identification of TIFA as an adapter protein that links tumor necrosis factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling. / Takatsuna, Hiroshi; Kato, Hiroki; Gohda, Jin; Akiyama, Taishin; Moriya, Ayaka; Okamoto, Yoshinari; Yamagata, Yuriko; Otsuka, Masami; Umezawa, Kazuo; Senba, Kentaro; Inoue, Jun Ichiro.

In: Journal of Biological Chemistry, Vol. 278, No. 14, 04.04.2003, p. 12144-12150.

Research output: Contribution to journalArticle

Takatsuna, Hiroshi ; Kato, Hiroki ; Gohda, Jin ; Akiyama, Taishin ; Moriya, Ayaka ; Okamoto, Yoshinari ; Yamagata, Yuriko ; Otsuka, Masami ; Umezawa, Kazuo ; Senba, Kentaro ; Inoue, Jun Ichiro. / Identification of TIFA as an adapter protein that links tumor necrosis factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 14. pp. 12144-12150.
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AU - Kato, Hiroki

AU - Gohda, Jin

AU - Akiyama, Taishin

AU - Moriya, Ayaka

AU - Okamoto, Yoshinari

AU - Yamagata, Yuriko

AU - Otsuka, Masami

AU - Umezawa, Kazuo

AU - Senba, Kentaro

AU - Inoue, Jun Ichiro

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