Membrane Research Group, Hungarian Academy of Sciences, Budapest, Hungary.
PLoS One. 2011;6(9):e25548. doi: 10.1371/journal.pone.0025548. Epub 2011 Sep 27.
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.
转化生长因子-β（TGF-β）主要通过 Smad 途径传递其效应，然而，越来越多的证据表明，这种多效细胞因子也采用替代信号途径。例如，最近我们已经证明，配体占据的 TGF-β受体可以直接触发 TRAF6-TAK1 信号模块，导致 MAP 激酶激活。在这里，我们报告了衔接蛋白 TTRAP 作为这个非经典 TGF-β途径的新组成部分的鉴定。我们表明，该蛋白与 TGF-β受体和 TRAF6-TAK1 信号模块的组成部分结合，导致 TGF-β 激活的 p38 和 NF-κB 反应的差异调节。细胞 TTRAP 水平的调节会影响 TGF-β存在时的细胞活力，这表明该蛋白是 TGF-β诱导的凋亡过程的重要组成部分。
