Ligand-induced dimerization of the extracellular domain of the TGF-beta receptor type II.

Transforming growth factor-beta (TGF-beta) signals by mediating the association of two distinct transmembrane serine/threonine kinase receptors, the type I (T beta RI) and II (T beta RII). Here, we took advantage of recombinant human T beta RII extracellular domain (T beta RII-ED) to analyze TGF-beta/T beta RII complex formation which is the initial event in the construction of a signaling complex. We found that recombinant T beta RII-ED binds TGF-beta 3 more efficiently than TGF-beta 2 and therefore maintains the native T beta RII binding selectivity for the different TGF-beta isoforms. Biochemical analysis showed that free T beta RII-ED is expressed as a monomer. Upon ligand binding, both TGF-beta 3 and -beta 2 isoforms induce homodimerization of T beta RII-ED, each TGF-beta subunit being able to bind one T beta RII-ED molecule. These results suggested that ligand dependent receptor dimerization may be an important early step in the TGF-beta signaling complex formation.