EGF receptor/Rolled MAP kinase signalling protects cells against activated Armadillo in the Drosophila eye
EGF receptor/Rolled MAP kinase signalling protects cells against activated Armadillo in the Drosophila eye
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DOI：
10.1093/embo-reports/kve019
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发表时间：
2001-02-01
期刊：
影响因子：
7.7
通讯作者：
Bienz, M
中科院分区：
文献类型：
--
作者：
Freeman, M;Bienz, M
-catenin/Armadillo是在正常发育过程中介导Wnt信号传导的转录共激活因子。活化形式的-连环蛋白是致癌的。我们构建了与常见的人类致癌突变相对应的果蝇犰狳突变形式，并发现它们可以组成性地激活犰狳。当在果蝇眼中表达时，它们最终诱导所有细胞类型的凋亡。有趣的是，在蛹中期细胞死亡之前，眼睛中的细胞在很长一段时间内都对活化的犰狳的影响有抵抗力。这种潜伏期是由EGF受体(EGFR)/MAP激酶信号传导赋予的，这阻止了活化的犰狳诱导细胞凋亡；当EGFR信号自然停止时，细胞迅速死亡。小鼠NLK和秀丽隐隐线虫中lit1的果蝇同源物Nemo不能拮抗活化的Armadillo，这表明Nemo样MAP激酶可能通常不会与Armadillo/ β -catenin相互作用。因此，我们的研究结果表明，活化的Armadillo受到EGFR/Rolled MAP激酶信号的特异性阴性控制。
beta -catenin/Armadillo are transcriptional co-activators that mediate Wnt signalling in normal development. Activated forms of beta -catenin are oncogenic. We have constructed mutant forms of Drosophila Armadillo which correspond to common human oncogenic mutations, and find them to activate Armadillo constitutively. When expressed in the Drosophila eye, these eventually induce apoptosis in all cell types. Intriguingly, cells in the eye are resistant to the effects of activated Armadillo for a long period prior to the onset of cell death at the mid-pupal stage. This latency is conferred by EGF receptor (EGFR)/MAP kinase signalling, which prevents activated Armadillo from inducing apoptosis; when EGFR signalling naturally ceases, the cells rapidly die. Nemo, the Drosophila homologue of NLK in mice and LIT-1 in Caenorhabditis elegans, does not antagonize activated Armadillo, suggesting that the Nemo-like MAP kinases may not generally interact with Armadillo/beta -catenin Thus, our results show that activated Armadillo is subject to a specific negative control by EGFR/Rolled MAP kinase signalling.