Most cell types express three sizes of receptors for TGF-beta. These are designated type I (53 kDa), type II (70-85 kDa), and type III (250-350 kDa). The type III receptor, a proteoglycan that exists in membrane-bound and soluble forms, binds TGF-beta 1, TGF-beta 2, and TGF-beta 3 but does not appear to be involved in signal transduction. The type II receptor is a membrane-bound serine/threonine kinase that binds TGF-beta 1 and TGF-beta 3 with high affinity and TGF-beta 2 with a much lower affinity. The type I receptor is also a membrane-bound serine/threonine kinase that apparently requires the presence of the type II receptor to bind TGF-beta. Current evidence suggests that signal transduction requires the cytoplasmic domains of both the type I and type II receptors.
The recombinant soluble TGF-beta type II receptor is capable of binding TGF-beta 1, TGF-beta 3, and TGF-beta 5 with sufficient affinity to act as an inhibitor of these isoforms at high concentrations. The soluble receptor also binds TGF-beta 2, but with an affinity at least two orders of magnitude lower. Binding of TGF-beta 1, TGF-beta 3, and TGF-beta 5 to the soluble TGF-beta type II receptor can also be demonstrated by using the soluble receptor as a capture agent on ELISA plates and this observation has been used as the basis for the development of immunoassays for these isoforms of TGF-beta.