Transforming growth factor (TGF)-beta ligands signal through transmembrane type I and type 11 serine/threonine kinase receptors, which form heteromeric signalling complexes upon ligand binding. Type 11 TGF-beta receptors (T beta RII) are reported to exist as homodimers at the cell surface, but the oligomerization pattern and dynamics of T beta RII splice variants in live cells has not been demonstrated thus far. Using co-immunoprecipitation and bioluminescence resonance energy transfer (BRET), we demonstrate that the mouse T beta RII receptor splice variant T beta RII-B is capable of forming ligand-independent homodimers and heterodimers with T beta RII. The homomeric interaction of mouse (m)T beta RII-B isoforms, however, is less robust than the heteromeric interactions of mT beta RII-B with wild-type T beta RII, which indicates that these receptors may be more likely to heterodimerize when both receptors are expressed. Moreover, we demonstrate that mT beta RII-B is a signalling receptor with ubiquitous tissue expression. Our study thus demonstrates previously unappreciated complex formation of TGF-beta type 11 receptors, and suggests that mT beta RII-B can direct TGF-beta-induced signalling in vitro and in vivo. (c) 2006 Elsevier Inc. All rights reserved.