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Silencing of TGF-β signalling by the pseudoreceptor BAMBI

机译：假受体BAMBI沉默TGF-β信号

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摘要

Members of the transforming growth factor-β (TGF-β) super-family, 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.
机译：转化生长因子-β（TGF-β）超家族的成员，包括TGF-β，骨形态发生蛋白（BMP），激活素和结节，对于调节生长和分化至关重要。这些生长因子通过成对的Ⅰ型和Ⅱ型受体激酶转导信号。在这里，我们克隆了跨膜蛋白BAMBI，它与TGF-β-家族Ⅰ型受体有关，但缺少细胞内激酶结构域。我们显示，非洲爪蟾胚胎发生过程中BAMBI与腹侧形态发生剂BMP4共表达（参考文献5、6），并且它需要BMP信号进行表达。该蛋白与TGF-β家族受体稳定结合，并抑制BMP和激活素以及TGF-β信号传导。最后，我们提供了证据，表明BAMBI的抑制作用是由其细胞内结构域介导的，该结构域类似于Ⅰ型受体的同型二聚体界面，并阻止了受体复合物的形成。结果表明，BAMBI通过涉及信号转导受体与假受体相互作用的调节机制负调节TGF-β-家族信号转导。

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