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Mol Cell. 2008 Sep 26;31(6):918-24. doi: 10.1016/j.molcel.2008.09.002.

TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta.

Author information

1
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.

Abstract

In many physiological and disease processes, TGF-beta usurps branches of MAP kinase pathways in conjunction with Smads to induce apoptosis and epithelial-to-mesenchymal transition, but the detailed mechanism of how a MAP kinase cascade is activated by TGF-beta receptors is not clear. We report here that TRAF6 is specifically required for the Smad-independent activation of JNK and p38, and its carboxyl TRAF homology domain physically interacts with TGF-beta receptors. TGF-beta induces K63-linked ubiquitination of TRAF6 and promotes association between TRAF6 and TAK1. Our results indicate that TGF-beta activates JNK and p38 through a mechanism similar to that operating in the interleukin-1beta/Toll-like receptor pathway.

PMID:
18922473
PMCID:
PMC2621323
DOI:
10.1016/j.molcel.2008.09.002
[Indexed for MEDLINE]
Free PMC Article

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