Silencing of TGF-beta signalling by the pseudoreceptor BAMBI

Nature. 1999 Sep 30;401(6752):480-5. doi: 10.1038/46794.

Abstract

Members of the transforming growth factor-beta (TGF-beta) superfamily, including TGF-beta, bone morphogenetic proteins (BMPs), activins and nodals, are vital for regulating growth and differentiation. These growth factors transduce their signals through pairs of transmembrane type I and type II receptor kinases. Here, we have cloned a transmembrane protein, BAMBI, which is related to TGF-beta-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-beta-family receptors and inhibits BMP and activin as well as TGF-beta 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-beta-family signalling by a regulatory mechanism involving the interaction of signalling receptors with a pseudoreceptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activins
  • Amino Acid Sequence
  • Animals
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein Receptors, Type I
  • Bone Morphogenetic Proteins / antagonists & inhibitors
  • Bone Morphogenetic Proteins / metabolism
  • COS Cells
  • Culture Techniques
  • Embryo, Nonmammalian / metabolism
  • Gene Expression
  • Humans
  • Inhibins / antagonists & inhibitors
  • Inhibins / metabolism
  • Ligands
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Protein-Serine-Threonine Kinases / chemistry
  • Receptors, Growth Factor / chemistry
  • Receptors, Transforming Growth Factor beta / metabolism
  • Sequence Homology
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism*
  • Tumor Cells, Cultured
  • Xenopus
  • Xenopus Proteins*

Substances

  • BAMBI protein, human
  • BMP4 protein, human
  • Bambi protein, mouse
  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Ligands
  • Membrane Proteins
  • Receptors, Growth Factor
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Xenopus Proteins
  • bambi-A protein, Xenopus
  • bmp4 protein, Xenopus
  • Activins
  • Inhibins
  • Protein-Serine-Threonine Kinases
  • Bone Morphogenetic Protein Receptors, Type I

Associated data

  • GENBANK/AJ243576