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首页> 外文期刊>Cell motility and the cytoskeleton >Role of myosin II activity and the regulation of myosin light chain phosphorylation in astrocytomas.
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Role of myosin II activity and the regulation of myosin light chain phosphorylation in astrocytomas.

机译:星形细胞瘤中肌球蛋白II活性的作用和肌球蛋白轻链磷酸化的调节。

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The generation of contractile force mediated by actin-myosin interactions is essential for cell motility. Myosin activity is promoted by phosphorylation of myosin light chain (MLC). MLC phosphorylation in large part is controlled by kinases that are effectors of Rho family GTPases. Accordingly, in this study we examined the effects of ROCK and Rac1 inhibition on MLC phosphorylation in astrocytoma cells. We found that low concentrations of the ROCK inhibitor Y27632 increased the phosphorylation state of the Triton X-100 soluble fraction of MLC, whereas higher concentrations of Y27632 decreased soluble phospho-MLC. These effects of Y27632 were dependent on Rac1. The soluble form of phospho-MLC comprises about 10% of total phospho-MLC in control cells. Interestingly, ROCK inhibition led to a decrease in the phosphorylation state of total MLC, whereas Rac1 inhibition had little effect. Thus, the soluble form of MLC is differentially regulated by ROCK and Rac1 compared with MLC examined in a total cell extract. We also observed that astrocytoma migration is stimulated by low concentrations of the myosin II inhibitor blebbistatin. However, higher concentrations of blebbistatin inhibit migration leading us to believe that migration has a biphasic dependence on myosin II activity. Taken together, our data show that modulation of myosin II activity is important in determining optimal astrocytoma migration. In addition, these findings suggest that there are at least two populations of MLC that are differentially regulated.
机译:由肌动蛋白-肌球蛋白相互作用介导的收缩力的产生对于细胞运动至关重要。肌球蛋白轻链(MLC)的磷酸化促进了肌球蛋白的活性。 MLC磷酸化很大程度上受作为Rho家族GTPases效应子的激酶控制。因此,在这项研究中,我们检查了ROCK和Rac1抑制对星形细胞瘤细胞MLC磷酸化的影响。我们发现低浓度的ROCK抑制剂Y27632增加了MLC的Triton X-100可溶性级分的磷酸化状态,而较高浓度的Y27632降低了可溶性磷酸化MLC。 Y27632的这些作用取决于Rac1。磷酸-MLC的可溶形式占对照细胞中总磷酸-MLC的约10%。有趣的是,ROCK抑制导致总MLC的磷酸化状态降低,而Rac1抑制作用很小。因此,与总细胞提取物中检测到的MLC相比,ROCK和Rac1对MLC的可溶性形式有不同的调控。我们还观察到低浓度的肌球蛋白II抑制剂blebbistatin刺激星形细胞瘤迁移。然而,较高浓度的blebbistatin抑制迁移,使我们相信迁移对肌球蛋白II活性具有双相依赖性。两者合计,我们的数据表明,对肌球蛋白II活性的调节在确定最佳星形细胞瘤迁移中很重要。此外,这些发现表明至少有两个MLC群体受到不同的调控。

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