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 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. 125I-TGF-beta 1 binds to and is chemically cross-linked to this protein. Unlabeled TGF-beta 1 inhibits the binding of 125I-TGF-beta 1 with an apparent dissociation constant (Kd) of approximately 200 pM, similar to the apparent Kd (approximately 50 pM) of the cell-surface type II receptor. TGF-beta 3 inhibits the binding of 125I-TGF-beta 1 to the soluble type II receptor with a similar dissociation constant, approximately 500 pM. In contrast, 125I-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 125I-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.
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
H Y
HY
Lin
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A
Moustakas
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P
Knaus
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Wells
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YI
Henis
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Lodish
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003432:Cross-Linking Reagents; D006031:Glycosylation; D006801:Humans; D007457:Iodine Radioisotopes; D008024:Ligands; D008969:Molecular Sequence Data; D011485:Protein Binding; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D003432:Cross-Linking Reagents; D007457:Iodine Radioisotopes; D008024:Ligands; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta