Suppr超能文献

Y-27632作用的分子特征

Molecular characterization of the effects of Y-27632.

作者信息

Darenfed Hassina, Dayanandan Bama, Zhang Tong, Hsieh Sidney H-K, Fournier Alyson E, Mandato Craig A

机构信息

Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.

出版信息

Cell Motil Cytoskeleton. 2007 Feb;64(2):97-109. doi: 10.1002/cm.20168.

Abstract

Many key cellular functions, such as cell motility and cellular differentiation are mediated by Rho-associated protein kinases (ROCKs). Numerous studies have been conducted to examine the ROCK signal transduction pathways involved in these motile and contractile events with the aid of pharmacological inhibitors such as Y-27632. However the molecular mechanism of action of Y-27632 has not been fully defined. To assess the relative contribution of these Rho effectors to the effects of Y-27632, we compared the cytoskeletal phenotype, wound healing and neurite outgrowth in cells treated with Y-27632 or subjected to knockdown with ROCK-I, ROCK-II or PRK-2- specific siRNAs. Reduction of ROCK-I enhances the formation of thin actin-rich membrane extensions, a phenotype that closely resembles the effect of Y-27632. Knockdown of ROCK II or PRK-2, leads to the formation of disc-like extensions and thick actin bundles, respectively. The effect of ROCK-I knockdown also mimicked the effect of Y-27632 on wound closer rates. ROCK-I knockdown and Y-27632 enhanced wound closure rates, while ROCK-II and PRK-2 were not appreciably different from control cells. In neurite outgrowth assays, knockdown of ROCK-I, ROCK-II or PRK-2 enhances neurite lengths, however no individual knockdown stimulated neurite outgrowth as robustly as Y-27632. We conclude that several kinases contribute to the global effect of Y-27632 on cellular responses.

摘要

许多关键的细胞功能,如细胞运动和细胞分化,均由Rho相关蛋白激酶(ROCKs)介导。借助Y-27632等药理学抑制剂,已经开展了大量研究来检测参与这些运动和收缩事件的ROCK信号转导途径。然而,Y-27632的分子作用机制尚未完全明确。为了评估这些Rho效应器对Y-27632作用的相对贡献,我们比较了用Y-27632处理或用ROCK-I、ROCK-II或PRK-2特异性小干扰RNA(siRNAs)敲低后的细胞的细胞骨架表型、伤口愈合和神经突生长情况。ROCK-I的减少增强了富含肌动蛋白的薄膜延伸的形成,这种表型与Y-27632的作用非常相似。敲低ROCK II或PRK-2分别导致盘状延伸和粗肌动蛋白束的形成。敲低ROCK-I的作用也模拟了Y-27632对伤口闭合率的影响。敲低ROCK-I和Y-27632提高了伤口闭合率,而ROCK-II和PRK-2与对照细胞没有明显差异。在神经突生长试验中,敲低ROCK-I、ROCK-II或PRK-2可增加神经突长度,然而,没有一种单独的敲低能像Y-27632那样强烈地刺激神经突生长。我们得出结论,几种激酶对Y-27632对细胞反应的整体作用有贡献。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验