TTRAP Is a Novel Component of the Non-Canonical TRAF6-TAK1 TGF-β Signaling Pathway

Transforming growth factor-beta (TGF-beta) principally relays its effects through the Smad pathway however, accumulating evidence indicate that alternative signaling routes are also employed by this pleiotropic cytokine. For instance recently, we have demonstrated that ligand occupied TGF-beta receptors can directly trigger the TRAF6-TAK1 signaling module, resulting in MAP kinase activation. Here we report identification of the adaptor molecule T TRAP as a novel component of this non-canonical TGF-beta pathway. We show that the protein associates with TGF-beta receptors and components of the TRAF6-TAK1 signaling module, resulting in differential regulation of TGF-beta activated p38 and NF-kappa B responses. Modulation of cellular TTRAP level affects cell viability in the presence of TGF-beta, suggesting that the protein is an important component of the TGF-beta induced apoptotic process.