Docagne F, Colloc'h N, Bougueret V, Page M, Paput J, Tripier M, Dutartre P, MacKenzie E T, Buisson A, Komesli S, Vivien D
Université de Caen, UMR CNRS 6551, Centre Cyceron, IFR 47, Bd H. Becquerel, BP 5229, 14074 Caen Cedex, France.
J Biol Chem. 2001 Dec 7;276(49):46243-50. doi: 10.1074/jbc.M010915200.
Transforming growth factor-beta (TGF-beta) signaling requires a ligand-dependent interaction of TGF-beta receptors Tau beta R-I and Tau beta R-II. It has been previously demonstrated that a soluble TGF-beta type II receptor could be used as a TGF-beta antagonist. Here we have generated and investigated the biochemical and signaling properties of a soluble TGF-beta type I receptor (Tau beta RIs-Fc). As reported for the wild-type receptor, the soluble Tau beta R-I does not bind TGF-beta 1 on its own. Surprisingly, in the absence of TGF-beta1, the Tau beta RIs-Fc mimicked TGF-beta 1-induced transcriptional and growth responses in mink lung epithelial cells (Mv1Lu). Signaling induced by the soluble TGF-beta type I receptor is mediated via the obligatory presence of both TGF-beta type I and type II receptors at the cell surface since no signal was observed in Mv1Lu-derivated mutants for TGF-beta receptors R-1B and DR-26. The comparison between the structures of TGF-betas and a three-dimensional model of the extracellular domain of Tau beta RI has shown that five residues of the supposed binding site of TGF-beta 1 (Lys(31), His(34), Glu(5), Tyr(91), and Lys(94)) were found with equivalent biochemical properties and similar spatial positions.
转化生长因子-β（TGF-β）信号传导需要TGF-β受体TβR-I和TβR-II之间依赖配体的相互作用。先前已经证明，可溶性TGF-βII型受体可以用作TGF-β拮抗剂。在这里，我们生成并研究了可溶性TGF-βI型受体（TβRIs-Fc）的生化和信号特性。正如野生型受体的报道那样，可溶性TβR-I自身不结合TGF-β1。令人惊讶的是，在没有TGF-β1的情况下，TβRIs-Fc在貂肺上皮细胞（Mv1Lu）中模拟了TGF-β1诱导的转录和生长反应。可溶性TGF-βI型受体诱导的信号传导是通过细胞表面同时存在TGF-βI型和II型受体介导的，因为在Mv1Lu衍生的TGF-β受体R-1B和DR-26突变体中未观察到信号。TGF-β的结构与TβRI细胞外结构域的三维模型之间的比较表明，TGF-β1假定结合位点的五个残基（Lys(31)、His(34)、Glu(5)、Tyr(91)和Lys(94)）具有等效的生化特性和相似的空间位置。
