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Silencing of TGF-β signalling by the pseudoreceptor BAMBI

Nature volume 401, pages 480–485 (1999)Cite this article

Abstract

Members of the transforming growth factor-β (TGF-β) superfamily, including TGF-β, bone morphogenetic proteins (BMPs), activins and nodals, are vital for regulating growth and differentiation1. These growth factors transduce their signals through pairs of transmembrane type I and type II receptor kinases2,3,4. Here, we have cloned a transmembrane protein, BAMBI, which is related to TGF-β-family type I receptors but lacks an intracellular kinase domain. We show that BAMBI is co-expressed with the ventralizing morphogen BMP4 (refs 5, 6) during Xenopus embryogenesis and that it requires BMP signalling for its expression. The protein stably associates with TGF-β-family receptors and inhibits BMP and activin as well as TGF-β signalling. Finally, we provide evidence that BAMBI's inhibitory effects are mediated by its intracellular domain, which resembles the homodimerization interface of a type I receptor and prevents the formation of receptor complexes. The results indicate that BAMBI negatively regulates TGF-β-family signalling by a regulatory mechanism involving the interaction of signalling receptors with a pseudoreceptor.

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Figure 1: BAMBI is related to BMPR-I and is regulated by BMP4.
Figure 2: BAMBI inhibits BMP and activin signalling in Xenopus embryos.
Figure 3: BAMBI inhibits ligand-independent signalling by TGF-β family receptors.
Figure 4: BAMBI interacts with TGF-β receptors.
Figure 5: BAMBI inhibits formation of functional receptor complex.
Figure 6: The intracellular domain of BAMBI mediates inhibition of TGF-β family signalling in Xenopus.

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Acknowledgements

We thank U. Hebling and L. Swaby for assistance with sequencing work. Reagents were provided by M. Asashima, K. Cho, W. Knöchel, C.-H. Heldin, D. Melton, M. Ueno, M. Whitman and the Genetics Institute. This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft to C.N. and an NIH grant to J.M., who is a Howard Hughes Medical Institute Investigator.

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Author notes

  1. Darya Onichtchouk, Ye-Guang Chen and Hajo Delius: These authors contributed equally to this work.

Authors and Affiliations

  1. Divisions of Molecular Embryology,

    Darya Onichtchouk, Roland Dosch, Volker Gawantka & Christof Niehrs

  2. Applied Tumor Virology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, D-69120, Germany

    Hajo Delius

  3. Memorial Sloan-Kettering Cancer Center and Howard Hughes Medical Institute, New York, 10021, New York, USA

    Ye-Guang Chen & Joan Massague´

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  1. Darya Onichtchouk
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Correspondence to Joan Massague´ or Christof Niehrs.

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Onichtchouk, D., Chen, YG., Dosch, R. et al. Silencing of TGF-β signalling by the pseudoreceptor BAMBI. Nature 401, 480–485 (1999). https://doi.org/10.1038/46794

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