The integrin effector PINCH regulates JNK activity and epithelial migration in concert with Ras suppressor 1.
The integrin effector PINCH regulates JNK activity and epithelial migration in concert with Ras suppressor 1.
复制标题
整联蛋白效应子捏合与RAS抑制器1一起调节JNK活性和上皮迁移。
DOI：
10.1083/jcb.200408090
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发表时间：
2004-12-20
影响因子：
7.8
通讯作者：
Beckerle, Mary C
中科院分区：
文献类型：
--
作者：
Kadrmas, Julie L;Smith, Mark A;Clark, Kathleen A;Pronovost, Stephen M;Muster, Nemone;Yates, John R 3rd;Beckerle, Mary C
细胞黏附和迁移是动态的过程，需要多个信号通路的协调作用，但信号整合的机制仍然难以捉摸。果蝇胚胎背部闭合(DC)需要整合素功能和c-jun氨基末端激酶(JNK)信号来使相反的上皮片迁移、相遇和缝合。在这里，我们表明，PINCH，一种依赖整合素的细胞黏附和肌动蛋白-膜锚定所需的蛋白质，存在于这些迁移上皮的前沿，是DC所必需的。通过对天然蛋白质复合体的分析，我们确定RSU-1是哺乳动物细胞中RAS信号的调节者，是一种新的有助于Pinch稳定性的Pinch结合伙伴。编码RSU-1的基因突变导致果蝇翅膀起泡，证明了它在整合素依赖的细胞黏附中的作用。遗传互作分析表明，PINCH和RSU-1都能拮抗DC过程中的JNK信号。我们的结果表明，PINCH和RSU-1在果蝇发育过程中参与了JNK和整合素功能的整合。
Cell adhesion and migration are dynamic processes requiring the coordinated action of multiple signaling pathways, but the mechanisms underlying signal integration have remained elusive. Drosophila embryonic dorsal closure (DC) requires both integrin function and c-Jun amino-terminal kinase (JNK) signaling for opposed epithelial sheets to migrate, meet, and suture. Here, we show that PINCH, a protein required for integrin-dependent cell adhesion and actin–membrane anchorage, is present at the leading edge of these migrating epithelia and is required for DC. By analysis of native protein complexes, we identify RSU-1, a regulator of Ras signaling in mammalian cells, as a novel PINCH binding partner that contributes to PINCH stability. Mutation of the gene encoding RSU-1 results in wing blistering in Drosophila, demonstrating its role in integrin-dependent cell adhesion. Genetic interaction analyses reveal that both PINCH and RSU-1 antagonize JNK signaling during DC. Our results suggest that PINCH and RSU-1 contribute to the integration of JNK and integrin functions during Drosophila development.