Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein
Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein
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DOI：
10.1038/17611
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发表时间：
1999-02-18
期刊：
影响因子：
64.8
通讯作者：
McMahon, AP
中科院分区：
文献类型：
--
作者：
Chuang, PT;McMahon, AP
Hedgehog信号通路对胚胎发生过程中多种组织的发育至关重要(1)。信号通过Hedgehog蛋白与多通道膜蛋白补丁（Ptc）结合而激活（2,3）。我们现在已经确定了脊椎动物信号通路中的一种新成分，我们将其命名为Hip（刺猬相互作用蛋白），因为它能够结合刺猬蛋白。Hip编码一种膜糖蛋白，它与所有三种哺乳动物的刺猬蛋白结合，其亲和力与Ptc-1相当。表达Hedgehog基因的细胞位于表达Hedgehog基因的细胞旁边。Hip表达是由异位Hedgehog信号诱导的，在Hedgehog突变体中缺失。因此，Hip和Ptc-1一样，是Hedgehog信号传导的一般转录靶点。在印度hedgehog基因（Ihh）控制生长的软骨中，髋关节过度表达(4)，导致缩短的骨骼，类似于Ihh功能丧失时所见的骨骼（B. St-Jacques， M. Hammerschmidt & a . p.m., in preparation）。我们的研究结果支持了一个模型，在这个模型中，由于与Hedgehog蛋白结合，Hip减弱了Hedgehog信号：以这种方式建立的负调节反馈回路因此可以调节对任何Hedgehog信号的反应。
The Hedgehog signalling pathway is essential for the development of diverse tissues during embryogenesis(1). Signalling is activated by binding: of Hedgehog protein to the multipass membrane protein Patched (Ptc)(2,3). We have now identified a novel component in the vertebrate signalling pathway, which we name Hip (for Hedgehog-interacting protein) because of its ability to bind Hedgehog proteins. Hip encodes a membrane glycoprotein that binds to all three mammalian Hedgehog proteins with an affinity comparable to that of Ptc-1. Hip-expressing cells are located next to cells that express each Hedgehog gene. Hip expression is induced by ectopic Hedgehog signalling and is lost in Hedgehog mutants. Thus, Hip, like Ptc-1, is a general transcriptional target of Hedgehog signalling. Overexpression of Hip in cartilage, where Indian hedgehog (Ihh) controls growth(4), leads to a shortened skeleton that resembles that seen when Ihh function is lost (B. St-Jacques, M. Hammerschmidt & A.P.M., in preparation). Our findings support a model in which Hip attenuates Hedgehog signalling as a result of binding to Hedgehog proteins: a negative regulatory feedback loop established in this way could thus modulate the responses to any Hedgehog signal.