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Silencing of TGF-β signalling by the pseudoreceptor BAMBI

Author

Listed:
  • Darya Onichtchouk

    (Divisions of Molecular Embryology)

  • Ye-Guang Chen

    (Memorial Sloan-Kettering Cancer Center and Howard Hughes Medical Institute)

  • Roland Dosch

    (Divisions of Molecular Embryology)

  • Volker Gawantka

    (Divisions of Molecular Embryology)

  • Hajo Delius

    (Applied Tumor Virology, Deutsches Krebsforschungszentrum)

  • Joan Massague´

    (Memorial Sloan-Kettering Cancer Center and Howard Hughes Medical Institute)

  • Christof Niehrs

    (Divisions of Molecular Embryology)

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.

Suggested Citation

  • Darya Onichtchouk & Ye-Guang Chen & Roland Dosch & Volker Gawantka & Hajo Delius & Joan Massague´ & Christof Niehrs, 1999. "Silencing of TGF-β signalling by the pseudoreceptor BAMBI," Nature, Nature, vol. 401(6752), pages 480-485, September.
    • Handle: RePEc:nat:nature:v:401:y:1999:i:6752:d:10.1038_46794
    DOI: 10.1038/46794
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