通过TGFbeta受体调节极性蛋白 Par6,控制上皮细胞的可塑性
Barish Ozdamar1, Rohit Bose, Miriam Barrios-Rodiles
1Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Canada.
Science (New York, N.Y.)
|March 12, 2005
概括
转化生长因子β (TGFbeta) 通过化Par6.6触发了上皮细胞转化为介质酶细胞转化 (EMT). 这调节了紧密结的损失,这对于细胞在发育和疾病中的迁移至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 发展生物学 发展生物学
背景情况:
- 皮质到介质细胞的过渡 (EMT) 对形态发生至关重要,并与转移性癌症有关.
- 转化生长因子β (TGFbeta) 是已知的EMT的调节者.
- 在EMT期间控制紧结溶解的机制尚未完全理解.
研究的目的:
- 阐明TGFbeta诱导EMT的分子机制,重点关注紧结调节.
- 确定参与TGFbeta信号传递的关键蛋白质及其在上皮细胞极性中的作用.
主要方法:
- 研究了极性调节器Par6和TGFbeta受体之间的相互作用.
- 通过II型TGFbeta受体 (TbetaRII) 分析了Par6的酸化.
- 研究了 Par6 酸化在调节 Smurf1 E3 酶活性和 RhoA 降解中的作用.
主要成果:
- 帕尔6直接与TGFbeta受体相互作用,并被TbetaRII酸化.
- 在乳腺上皮细胞中,TGFbeta诱导的EMT中,Par6的酸化是必不可少的.
- 化Par6促进了Smurf1介导的RhoA降解,导致紧密结的损失.
结论:
- 定义了一种新的信号通路,通过Par6酸化将TGFbeta与上皮质极性机制联系起来.
- 这条通路控制紧密的结合完整性和上皮细胞形态.
- 研究结果提供了关于EMT在癌症转移和发展中的分子基础的见解.
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