Two Mechanistically and Temporally Distinct NF-κB Activation Pathways in IL-1 Signaling
Kohsuke Yamazaki, Jin Gohda, Atsuhiro Kanayama, Yusei Miyamoto, Hiroaki Sakurai, Masahiro Yamamoto, Shizuo Akira, Hidetoshi Hayashi, Bing Su, Jun-ichiro Inoue*
*To whom correspondence should be addressed. E-mail:
This PDF file includes:
- Supplementary Text
- Fig. S1. Amino acid sequence alignment of TAK1 from various species.
- Fig. S2. IL-1 induces Lys63-linked polyubiquitination of TAK1 KR mutants.
- Fig. S3. The K209R mutation of TAK1 does not affect the interaction between TAK1 and TAB2.
- Fig. S4. Analysis of the association between TAK1, TRAF6, and MEKK3 in transiently transfected cells.
- Fig. S5. The activation of TAK1 by TAB1 does not require MEKK3 or the Lys63-linked polyubiquitination of TAK1.
- Fig. S6. The K209R mutation of TAK1 does not abolish the intrinsic kinase activity of TAK1.
- Fig. S7. Possible involvement of UbcH7 in TRAF6-induced activation of NF-κB.
- Fig. S8. Effect of a partial reduction in the abundance of Ubc13 on IL-1 signaling.
- Fig. S9. RING domain�independent and zinc finger�dependent activation of NF-κB by IL-1.
- Fig. S10. MEKK3, but not TAK1, is required for the Zinc pathway.
- Fig. S11. Severe reduction in the IL-1�induced activation of NF-κB in the absence of MEKK3.
- Fig. S12. The T6mZ5 mutant, in which the fifth zinc finger is inactivated, activates the RING pathway but not the Zinc pathway.
- Fig. S13. Time-dependent activation of NF-κB in Tak1–/– MEFs.
- Fig. S14. Time-dependent phosphorylation of IκBα induced by RING domain�defective mutants of TRAF6.
- Fig. S15. Cooperation of the RING and Zinc pathways results in the prolonged activation of NF-κB in the nucleus.
- Fig. S16. IL-1�induced polyubiquitination of MEKK3 depends on the RING domain of TRAF6 and Ubc13.
- Fig. S17. MEKK3 associates with p62 in a PB1 domain�dependent manner.
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Citation: K. Yamazaki, J. Gohda, A. Kanayama, Y. Miyamoto, H. Sakurai, M. Yamamoto, S. Akira, H. Hayashi, B. Su, J.-i. Inoue, Two mechanistically and temporally distinct NF-κB activation pathways in IL-1 signaling. Sci. Signal. 2, ra66 (2009).