TRAF6 and C-SRC induce synergistic AP-1 activation via PI3-kinase-AKT-JNK pathway

Megumi Tago, Kenji Tago, Yoshiko Sonoda, Shin Ichi Tominaga, Tadashi Kasahara

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Interleukin-1 (IL-1) induces multiple genes via activation of transcription factors that include NF-κB and activator protein-1 (AP-1). We found that IL-1-mediated c-Src activation was required for AP-1 activation, but not for NF-κB activation and also revealed that c-Src-induced AP-1 activation was enhanced synergistically by the coexpression of TNF receptor associated factor 6 (TRAF6). In addition, c-Src interacts with TRAF6 in response to IL-1 and this interaction is required for c-Src activity. However, neither dominant negative mutants of TRAF6 (TRAF6 DN) nor kinase-dead mutant of c-Src (c-Src KD) counteracted each-induced AP-1 activation, suggesting no hierarchy between these two molecules. During the TRAF6 and c-Src-induced AP-1 activation, phosphatidylinositol 3 (PI3)-kinase, its downstream signaling molecule, Akt and c-Jun N-terminal kinase (JNK) were significantly activated and inhibition of these kinase activities down-regulated AP-1 activation through the suppression of c-fos expression. Furthermore, TRAF6 and c-Src-induced JNK activation was significantly inhibited by PI3-kinase inhibitor or a dominant negative mutant of Akt (Akt DN). Taken together, our results demonstrate that c-Src and TRAF6 are key mediators of IL-1-induced AP-1 activation and provide evidence of cross talk between c-Src and TRAF6 molecules through PI3 kinase-Akt-JNK pathways.

Original languageEnglish
Pages (from-to)1257-1268
Number of pages12
JournalEuropean Journal of Biochemistry
Volume270
Issue number6
DOIs
Publication statusPublished - 2003 Mar

Fingerprint

TNF Receptor-Associated Factor 6
Phosphatidylinositol 3-Kinase
Transcription Factor AP-1
Phosphotransferases
Chemical activation
Interleukin-1
Molecules
JNK Mitogen-Activated Protein Kinases
Transcriptional Activation
Transcription Factors
Genes

Keywords

  • Activator protein-1 (AP-1)
  • c-Jun N-terminal kinase (JNK)
  • NF-κB activation
  • Src kinase
  • TRAF6

ASJC Scopus subject areas

  • Biochemistry

Cite this

TRAF6 and C-SRC induce synergistic AP-1 activation via PI3-kinase-AKT-JNK pathway. / Tago, Megumi; Tago, Kenji; Sonoda, Yoshiko; Tominaga, Shin Ichi; Kasahara, Tadashi.

In: European Journal of Biochemistry, Vol. 270, No. 6, 03.2003, p. 1257-1268.

Research output: Contribution to journalArticle

Tago, Megumi ; Tago, Kenji ; Sonoda, Yoshiko ; Tominaga, Shin Ichi ; Kasahara, Tadashi. / TRAF6 and C-SRC induce synergistic AP-1 activation via PI3-kinase-AKT-JNK pathway. In: European Journal of Biochemistry. 2003 ; Vol. 270, No. 6. pp. 1257-1268.
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