Growth factors belonging to the TGF-β superfamily, including activin, bone morphogenic protein (BMP), and TGF-β, exert their effects through transmembrane-type receptor serine-threonine kinases. Type I and type II TGF-β receptors form a heterotetrameric complex that, when bound to ligand, intiates receptor autophosphorylation and a signaling cascade. Onichtchouk et al. identified a transmembrane protein in Xenopus laevis that has an extracellular domain similar to that of the type I TGF-β receptor, but lacks the intracellular catalytic domain. The protein, called BAMBI, interfered with activin and BMP signaling in Xenopus embryos and in a mouse cell line. BAMBI inhibited constitutively activated forms of several type I receptors, and also coimmunoprecipitated with type I receptors. BAMBI was also found in receptor complexes containing type I and II receptors. The authors suggest that BAMBI negatively regulates TGF-β signaling by binding to type I receptors and disrupting the formation of receptor complexes.
Onichtchouk, D., Chen, Y-G., Dosch, R., Gawantka, V., Delius, H., Massague, J., and Niehrs, C. (1999) Silencing of TGF-β signalling by the pseudoreceptor BAMBI. Nature 401: 480-485. Online Journal