Repulsive axon guidance: Abelson and enabled play opposing roles downstream of the roundabout receptor
Repulsive axon guidance: Abelson and enabled play opposing roles downstream of the roundabout receptor
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DOI：
10.1016/s0092-8674(00)80883-1
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发表时间：
2000-06-23
期刊：
影响因子：
64.5
通讯作者：
Goodman, CS
中科院分区：
文献类型：
--
作者：
Bashaw, GJ;Kidd, T;Goodman, CS
果蝇 Roundabout (Robo) 是排斥性轴突导向受体保守家族的创始成员，该受体对分泌的 Slit 蛋白做出反应。人们对 Robe 下游介导排斥作用的信号机制知之甚少。在这里，我们提出了遗传和生化证据，表明 Abelson (Abl) 酪氨酸激酶及其底物 Enabled (Ena) 在 Robe 信号转导中发挥直接和相反的作用。遗传相互作用支持一个模型，其中 Abl 的作用是拮抗 Robe 信号传导，而 Ena 是 Robe 排斥性输出的部分需要。 Abl 和 Ena 都可以直接结合 Robo 的胞质结构域。干扰 Ena 结合的 Robe 突变形式在 Robe 功能中部分受损，而可被 Abl 磷酸化的保守细胞质酪氨酸的突变会产生高度活跃的 Robe 受体。
Drosophila Roundabout (Robo) is the founding member of a conserved family of repulsive axon guidance receptors that respond to secreted Slit proteins. Little is known about the signaling mechanisms which function downstream of Robe to mediate repulsion. Here, we present genetic and biochemical evidence that the Abelson (Abl) tyrosine kinase and its substrate Enabled (Ena) play direct and opposing roles in Robe signal transduction. Genetic interactions support a model in which Abl functions to antagonize Robe signaling, while Ena is required in part for Robe's repulsive output. Both Abl and Ena can directly bind to Robo's cytoplasmic domain. A mutant form of Robe that interferes with Ena binding is partially impaired in Robe function, while a mutation in a conserved cytoplasmic tyrosine that can be phosphorylated by Abl generates a hyperactive Robe receptor.