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首页> 外文期刊>Journal of Cellular Physiology >The class II phosphoinositide 3-kinase PI3K-C2beta regulates cell migration by a PtdIns3P dependent mechanism.
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The class II phosphoinositide 3-kinase PI3K-C2beta regulates cell migration by a PtdIns3P dependent mechanism.

机译:类二磷酸肌醇3-kinase PI3K-C2beta调节细胞迁移PtdIns3P依赖机制。

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摘要

The biological and pathophysiological significance of class II phosphoinositide 3-kinase enzyme expression currently remains unclear. Using an in vitro scrape wound assay and time-lapse video microscopy, we demonstrate that cell motility is increased in cultures expressing recombinant PI3K-C2beta enzyme. In addition, overexpression of PI3K-C2beta transiently decreased cell adhesion, stimulated the formation of cytoplasmic processes, and decreased the rate of cell proliferation. Consistent with these observations, expression of PI3K-C2beta also decreased expression of alpha4 beta1 integrin subunits. Using asynchronous cultures, we show that endogenous PI3K-C2beta is present in lamellipodia of motile cells. When cells expressing recombinant PI3K-C2beta were plated onto fibronectin, cortical actin staining increased markedly and actin rich lamellipodia and filopodia became evident. Overexpression of a 2xFYVE(Hrs) domain fusion protein abolished this response demonstrating that the effect of PI3K-C2beta onthe reorganization of actin filaments is dependent upon PtdIns3P. Finally, overexpression of PI3K-C2beta increased GTP loading of Cdc42. Our data demonstrates for the first time, that PI3K-C2beta plays a regulatory role in cell motility and that the mechanism by which it reorganizes the actin cytoskeleton is dependent upon PtdIns3P production.
机译:生理和病理生理意义二磷酸肌醇类3-kinase酶目前尚不清楚表达。体外刮伤试验和延时视频显微镜,我们证明细胞运动性增加文化表达重组PI3K-C2beta酶。PI3K-C2beta瞬变的细胞减少附着力,刺激细胞质的形成流程,减少细胞的速度扩散。观察,PI3K-C2beta也的表情减少表达alpha4 beta1整合素子单元。内源性PI3K-C2beta存在板状伪足的能动的细胞。表达重组PI3K-C2beta镀纤连蛋白,皮质肌动蛋白染色明显增加,肌动蛋白丰富的板状伪足和丝状伪足变得明显。2 xfyve(小时)域融合蛋白废除反应,示范的效果PI3K-C2beta在肌动蛋白的重组细丝取决于PtdIns3P。过度的PI3K-C2beta三磷酸鸟苷增加Cdc42加载。第一次,PI3K-C2beta监管在细胞运动中作用的机制它进行肌动蛋白细胞骨架重组吗依赖于PtdIns3P生产。

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