Multiple RTK pathways downregulate groucho-mediated repression in Drosophila embryogenesis
Multiple RTK pathways downregulate groucho-mediated repression in Drosophila embryogenesis
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DOI：
10.1242/dev.015206
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发表时间：
2008-03-01
期刊：
影响因子：
4.6
通讯作者：
Paroush, Zeev
中科院分区：
文献类型：
--
作者：
Cinnamon, Einat;Helman, Aharon;Paroush, Zeev
RTK途径在广泛的发育过程中确定细胞命运。然而，通路效应物MAPK如何协调调节多个靶基因的表达还不完全清楚。我们以前已经表明，EGFR RTK途径导致磷酸化和下调Groucho，一个全球性的共阻遏物，广泛用于许多发育重要的阻遏物沉默他们的各种目标。在这里，我们使用特异性抗体，揭示了MAPK的Groucho磷酸化的动力学，并显示Groucho在果蝇胚胎发生过程中响应几个RTK途径被磷酸化。专注于通过躯干RTK途径的终端图案的调节，我们证明，通过磷酸化的格劳乔的阻遏物功能的衰减是必不可少的转录输出的途径和终端细胞规格。重要的是，Groucho通过一种有效的机制磷酸化，这种机制不会改变其亚细胞定位或降低其稳定性;相反，在MAPK激活终止后，修饰的Groucho持续很长时间。我们认为Groucho的磷酸化提供了一种广泛的、长期的机制，RTK信号通过这种机制控制靶基因的表达。
RTK pathways establish cell fates in a wide range of developmental processes. However, how the pathway effector MAPK coordinately regulates the expression of multiple target genes is not fully understood. We have previously shown that the EGFR RTK pathway causes phosphorylation and downregulation of Groucho, a global co-repressor that is widely used by many developmentally important repressors for silencing their various targets. Here, we use specific antibodies that reveal the dynamics of Groucho phosphorylation by MAPK, and show that Groucho is phosphorylated in response to several RTK pathways during Drosophila embryogenesis. Focusing on the regulation of terminal patterning by the Torso RTK pathway, we demonstrate that attenuation of Groucho's repressor function via phosphorylation is essential for the transcriptional output of the pathway and for terminal cell specification. Importantly, Groucho is phosphorylated by an efficient mechanism that does not alter its subcellular localisation or decrease its stability; rather, modified Groucho endures long after MAPK activation has terminated. We propose that phosphorylation of Groucho provides a widespread, long-term mechanism by which RTK signals control target gene expression.