河马和PI5P4K信号交叉来控制YAP的转录激活
Lavinia Palamiuc1, Jared L Johnson2,3, Zeinab Haratipour4,5
1Sanford Burnham Prebys, La Jolla, CA 92037, USA.
Science signaling
|May 28, 2024
概括
希波的通路酶MST1/2抑制酸酸酶 (PI5P4Ks),揭示了一个新的调节机制. 这种相互作用会影响细胞信号传递,影响Hippo-YAP通路活动和上皮细胞到介质细胞的过渡.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 包括PI5P和PI4,5P2在内的氨基酸是关键的信号分子.
- 氏酸酸酶的PI5P4K家族作为细胞内代谢和压力传感器.
- 河马通路调节细胞增殖,器官大小和组织平衡.
研究的目的:
- 为了确定PI5P4K信号的上游调节器.
- 为了研究PI5P4K信号传输与Hippo通路之间的相互作用.
- 阐明连接这些通路的分子机制.
主要方法:
- 无偏见的基因查,以确定信号调节器.
- 在体外激酶试验测试以评估PI5P4Ks的MST1/2酸化.
- 基于细胞的测试来评估Hippo-YAP表型和蛋白质相互作用.
- 生物化学试验以确定PI5P与MOB1.1的结合.
主要成果:
- 鉴定出Hippo通路激酶MST1/2是通过酸化来抑制PI5P4Ks的抑制剂.
- 表明PI5P4K活性调节与Hippo-YAP相关的表型,包括从上皮细胞转变为介质细胞的转变.
- 发现PI5P与MOB1相互作用,增强其与LATS的结合,从而将PI5P4K与Hippo通路联系起来.
结论:
- MST1/2激酶调节PI5P4K活动,将代谢和压力感知与Hippo通路信号结合起来.
- PI5P4K-MOB1-LATS相互作用为Hippo路径调节提供了一个新的机制.
- 类化物代谢与Hippo通路之间的这种交叉对话对metazoan发展和疾病至关重要.
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