A MAPK docking site is critical for downregulation of Capicua by Torso and EGFR RTK signaling
A MAPK docking site is critical for downregulation of Capicua by Torso and EGFR RTK signaling
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DOI：
10.1038/sj.emboj.7601532
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发表时间：
2007-02-07
期刊：
影响因子：
11.4
通讯作者：
Jimenez, Gerardo
中科院分区：
文献类型：
--
作者：
Astigarraga, Sergio;Grossman, Rona;Jimenez, Gerardo
果蝇的早期发育需要两个受体酪氨酸激酶（RTK）途径：躯干和表皮生长因子受体（EGFR）途径，分别调节终端和背腹图案。以前的研究表明，这些途径，直接或间接地，导致转录后下调的Capicua阻遏物在早期胚胎和卵巢。在这里，我们表明，这两个监管的影响是直接的，并依赖于在Capicua的MAPK停靠站点，物理上与MAPK卷相互作用。缺乏该对接位点的Capicua衍生物导致与躯干和EGFR活性丧失所导致的表型相似的显性表型。这种表型是由于对正常表达的响应于躯干和EGFR信号传导的基因的不适当抑制引起的。我们的研究结果与模型一致，其中Capicua是躯干通路的主要核效应子，但仅是响应EGFR信号传导的不同效应子之一。最后，我们描述了由躯干和EGFR信号传导的Capicua下调模式的差异，提出了这种差异有助于两种信号的组织特异性的可能性。
Early Drosophila development requires two receptor tyrosine kinase (RTK) pathways: the Torso and the Epidermal growth factor receptor (EGFR) pathways, which regulate terminal and dorsal-ventral patterning, respectively. Previous studies have shown that these pathways, either directly or indirectly, lead to post-transcriptional downregulation of the Capicua repressor in the early embryo and in the ovary. Here, we show that both regulatory effects are direct and depend on a MAPK docking site in Capicua that physically interacts with the MAPK Rolled. Capicua derivatives lacking this docking site cause dominant phenotypes similar to those resulting from loss of Torso and EGFR activities. Such phenotypes arise from inappropriate repression of genes normally expressed in response to Torso and EGFR signaling. Our results are consistent with a model whereby Capicua is the main nuclear effector of the Torso pathway, but only one of different effectors responding to EGFR signaling. Finally, we describe differences in the modes of Capicua downregulation by Torso and EGFR signaling, raising the possibility that such differences contribute to the tissue specificity of both signals.