A soluble transforming growth factor-beta (TGF-beta) type I receptor mimics TGF-beta responses

Transforming growth factor-beta (TGF-beta) signaling requires a ligand-depe ndent interaction of TGF-beta receptors T betaR-I and T betaR-II. It has be en previously demonstrated that a soluble TGF-beta type II receptor could b e used as a TGF-beta antagonist. Here we have generated and investigated th e biochemical and signaling properties of a soluble TGF-beta type I recepto r (T beta RIs-Fc). As reported for the wild-type receptor, the soluble T be taR-I does not bind TGF-beta1 on its own. Surprisingly, in the absence of T GF-beta1, the T beta RIs-Fc mimicked TGF-beta1-induced transcriptional and growth responses in mink lung epithelial cells (Mv1Lu). Signaling induced b y the soluble TGF-beta type I receptor is mediated via the obligatory prese nce 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 thr ee-dimensional model of the extracellular domain of T beta RI has shown tha t five residues of the supposed binding site of TGF-beta1 (Lys(31), His(34) , Glu(5), Tyr(91), and Lys(94)) were found with equivalent biochemical prop erties and similar spatial positions.