TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta.
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.
Mesh Terms:
Animals, Apoptosis, Cell Line, Enzyme Activation, Epithelium, Humans, JNK Mitogen-Activated Protein Kinases, Lysine, MAP Kinase Kinase Kinases, Mesoderm, Mice, Protein Binding, Receptors, Transforming Growth Factor beta, Signal Transduction, Smad Proteins, TNF Receptor-Associated Factor 6, Transforming Growth Factor beta, Ubiquitination, p38 Mitogen-Activated Protein Kinases
Animals, Apoptosis, Cell Line, Enzyme Activation, Epithelium, Humans, JNK Mitogen-Activated Protein Kinases, Lysine, MAP Kinase Kinase Kinases, Mesoderm, Mice, Protein Binding, Receptors, Transforming Growth Factor beta, Signal Transduction, Smad Proteins, TNF Receptor-Associated Factor 6, Transforming Growth Factor beta, Ubiquitination, p38 Mitogen-Activated Protein Kinases
Mol. Cell
Date: Sep. 26, 2008
PubMed ID: 18922473
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