A Soluble Transforming Growth Factor-β (TGF-β) Type I Receptor Mimics TGF-β Responses

Abstract

Transforming growth factor-β (TGF-β) signaling requires a ligand-dependent interaction of TGF-β receptors TβR-1 and TβR-II. It has been previously demonstrated that a soluble TGF-β type II receptor could be used as a TGF-β antagonist. Here we have generated and investigated the biochemical and signaling properties of a soluble TGF-β type I receptor (TβRIs-Fc). As reported for the wild-type receptor, the soluble TβR-I does not bind TGF-β1 on its own. Surprisingly, in the absence of TGF-β1, the TβRIs-Fc mimicked TGF-β1-induced transcriptional and growth responses in mink lung epithelial cells (Mv1Lu). Signaling induced by the soluble TGF-β type I receptor is mediated via the obligatory presence of both TGF-β type I and type II receptors at the cell surface since no signal was observed in Mv1Lu-derivated mutants for TGF-β receptors R-1B and DR-26. The comparison between the structures of TGF-βs and a three-dimensional model of the extracellular domain of TβRI has shown that five residues of the supposed binding site of TGF-β1 (Lys 31, His34, Glu5, Tyr91, and Lys 94) were found with equivalent biochemical properties and similar spatial positions.