THE SOLUBLE EXOPLASMIC DOMAIN OF THE TYPE-II TRANSFORMING GROWTH-FACTOR (TGF)-BETA RECEPTOR - A HETEROGENEOUSLY GLYCOSYLATED PROTEIN WITH HIGH-AFFINITY AND SELECTIVITY FOR TGF-BETA LIGANDS

The transforming growth factor (TGF)-beta type II receptor is a transmembrane serine/threonine kinase which is essential for all TGF-beta induced signals. In several cell types TGF-beta 2 is as potent as TGF-beta 1 or TGF-beta 3 in inducing cellular responses, yet TGF-beta 2 does not bind to the majority of expressed type II receptors. Here we characterized the properties of the soluble extracellular domain of the human TGF-beta type II receptor synthesized in COS-7 cells, Like the membrane-attached type II receptor, the soluble receptor contains complex N-linked oligosaccharides as well as additional sialic acid residues that cause it to migrate heterogenously upon SDS-polyacrylamide gel electrophoresis. I-125-TGF-beta 1 binds to and is chemically cross-linked to this protein. Unlabeled TGF-beta 1 inhibits the binding of I-125-TGF-beta 1 with an apparent dissociation constant (K-d) of similar to 200 pM, similar to the apparent K-d (similar to 50 pM) of the cell-surface type II receptor. TGF-beta 3 inhibits the binding of I-125-TGF-beta 1 to the soluble type II receptor with a similar dissociation constant, similar to 500 pM. In contrast, I-125-TGF-beta 2 cannot bind and be chemically cross-linked to the soluble type II receptor, nor does as much as a 125-fold excess of unlabeled TGF-beta 2 inhibit the binding of I-125-TGF-beta 1 to the soluble receptor. This is the first demonstration of the binding affinities of the type II receptor in the absence of the other cell-surface molecules known to bind TGF-beta. Expressed alone in COS-7 cells the type II receptor also cannot bind TGF-beta 2; co-expression of type III receptor enables the type II receptor to bind TGF-beta 2. Thus, the type III receptor or some other component is required for transmission of TGF-beta 2-induced signals by the type II receptor.