Monnier V, Dussillol F, Alves G, Lamour-Isnard C, Plessis A
Institut Jacques Monod CNRS, Université Paris VII, Paris, France.
Curr Biol. 1998 May 7;8(10):583-6. doi: 10.1016/s0960-9822(98)70227-1.
The Hedgehog (Hh) family of signalling proteins [1] mediate inductive interactions either directly or by controlling the transcription of other secreted proteins through the action of Gli transcription factors, such as Cubitus interruptus (Ci) [2]. In Drosophila, the transcription of Hh targets requires the activation of the protein kinase Fused (Fu) and the inactivation of both Suppressor of fused (Su(fu)) and Costal-2 (Cos-2) [3]. Fu is required for Hh signalling in the embryo and in the wing imaginal disc and acts also as an antitumorigen in ovaries [4]. All fu- phenotypes are suppressed by the loss of function of Su(fu) [5]. Fu, Cos-2 and Ci are co-associated in vivo in large complexes that are bound to microtubules in a Hh-dependent manner [6,7]. Here we investigate the role of Su(fu) in the intracellular part of the Hh signalling pathway. Using the yeast two-hybrid method and an in vitro binding assay, we show that Su(fu), Ci and Fu can interact directly to form a trimolecular complex, with Su(fu) binding to both its partners simultaneously. Su(fu) and Ci also co-immunoprecipitate from embryo extracts. We propose that, in the absence of Hh signalling, Su(fu) inhibits Ci by binding to it and that, upon reception of the Hh signal, Fu is activated and counteracts Su(fu), leading to the activation of Ci.
刺猬信号蛋白（Hh）家族[1]通过Gli转录因子（如截翅基因（Ci））的作用，直接或通过控制其他分泌蛋白的转录来介导诱导性相互作用[2]。在果蝇中，Hh靶标的转录需要蛋白激酶融合蛋白（Fu）的激活以及融合抑制因子（Su(fu)）和肋骨-2（Cos-2）的失活[3]。Fu在胚胎和翅成虫盘中的Hh信号传导中是必需的，并且在卵巢中还作为一种抗肿瘤因子发挥作用[4]。所有fu-表型都被Su(fu)功能缺失所抑制[5]。Fu、Cos-2和Ci在体内以与微管结合的大复合物形式共同存在，且这种结合依赖于Hh[6,7]。在这里，我们研究Su(fu)在Hh信号通路细胞内部分的作用。使用酵母双杂交方法和体外结合试验，我们表明Su(fu)、Ci和Fu可以直接相互作用形成三分子复合物，其中Su(fu)同时与它的两个伙伴结合。Su(fu)和Ci也能从胚胎提取物中共同免疫沉淀。我们提出，在没有Hh信号时，Su(fu)通过与Ci结合来抑制Ci，而在接收到Hh信号后，Fu被激活并抵消Su(fu)，从而导致Ci的激活。
