title: TTRAP is a novel component of the non-canonical TRAF6-TAK1 TGF-β signaling pathway.
abstract: Transforming growth factor-β (TGF-β) 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-β receptors can directly trigger the TRAF6-TAK1 signaling module, resulting in MAP kinase activation. Here we report identification of the adaptor molecule TTRAP as a novel component of this non-canonical TGF-β pathway. We show that the protein associates with TGF-β receptors and components of the TRAF6-TAK1 signaling module, resulting in differential regulation of TGF-β activated p38 and NF-κB responses. Modulation of cellular TTRAP level affects cell viability in the presence of TGF-β, suggesting that the protein is an important component of the TGF-β induced apoptotic process.
authors: Membrane Research Group, Hungarian Academy of Sciences, Budapest, Hungary.
authors: György
authors: G
authors: Várady
authors: Balázs
authors: B
authors: Sarkadi
authors: Károly
authors: K
authors: Fátyol
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D055550:Protein Stability / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D048029:TNF Receptor-Associated Factor 6 / Q000737:chemistry / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D020930:MAP Kinase Kinase Kinases; D048029:TNF Receptor-Associated Factor 6; D053773:Transforming Growth Factor beta1; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D000099151:MAP Kinase Kinase Kinase 7