Silencing of TGF-β signalling by the pseudoreceptor BAMBI Journal Article
| Authors: | Onichtchouk, D.; Chen, Y. G.; Dosch, R.; Gawantka, V.; Delius, H.; Massagué, J.; Niehrs, C. |
| Article Title: | Silencing of TGF-β signalling by the pseudoreceptor BAMBI |
| 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 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-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. |
| Keywords: | signal transduction; nonhuman; animal cell; animals; mice; reverse transcription polymerase chain reaction; gene expression; bone morphogenetic protein; transforming growth factor beta; embryo; membrane proteins; embryo development; genetic transcription; tumor cells, cultured; cos cells; animalia; embryo, nonmammalian; amino acid sequence; molecular sequence data; iodine 125; protein-serine-threonine kinases; transforming growth factor beta receptor; receptors, transforming growth factor beta; ligands; sequence homology; ligand binding; receptor binding; complementary dna; xenopus; bone morphogenetic proteins; receptors, growth factor; xenopus proteins; bone morphogenetic protein receptors, type i; activins; humans; priority journal; article; culture techniques; inhibins |
| Journal Title: | Nature |
| Volume: | 401 |
| Issue: | 6752 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1999-09-30 |
| Start Page: | 480 |
| End Page: | 485 |
| Language: | English |
| DOI: | 10.1038/46794 |
| PUBMED: | 10519551 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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