Cytoskeletal rearrangements and transcriptional activation of c-fos serum response element by Rho-kinase
Cytoskeletal rearrangements and transcriptional activation of c-fos serum response element by Rho-kinase
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DOI：
10.1074/jbc.272.40.25121
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发表时间：
1997-10-03
影响因子：
4.8
通讯作者：
Kaibuchi, K
中科院分区：
文献类型：
--
作者：
Chihara, K;Amano, M;Kaibuchi, K
小的GTP酶Rho参与细胞骨架重排，包括应力纤维和局部黏附的形成，以及c-fos血清反应元件的转录激活。在体外，被Rho激活的Rho-Kinase不仅能磷酸化肌球蛋白轻链(MLC)(从而激活肌球蛋白ATPase)，还能激活肌球蛋白磷酸酶，从而使肌球蛋白磷酸酶失活。Rho-Kinase参与成纤维细胞应力纤维和局灶性粘连的形成。在我们的研究中我们发现，结构性活性的Rho-Kinase的表达增加了MLC的磷酸化水平，Rho-Kinase的活性是维持含有纽蛋白的局灶性粘连所必需的，而组织化的肌动蛋白应激纤维不是必需的。在有组织的肌动蛋白应激纤维被破坏的情况下，向成纤维细胞微量注射结构性活性的Rho-Kinase在一定程度上诱导了局灶性粘连的形成，结构性活性的Rho-Kinase的表达也刺激了c-fos血清反应元件的转录活性。这些结果表明，Rho-Kinase在Rho下游的不同途径中具有不同的作用，这些途径包括MLC磷酸化导致应力纤维形成、焦点黏附形成和基因表达。
The small GTPase Rho is implicated in cytoskeletal rearrangements including stress fiber and focal adhesion formation and in the transcriptional activation of c-fos serum response element. In vitro, Rho-kinase, which is activated by Rho, phosphorylates not only myosin light chain (MLC) (thereby activating myosin ATPase) but also myosin phosphatase, thus inactivating myosin phosphatase. Rho-kinase is involved in the formation of stress fibers and focal adhesions in fibro blasts. Here we show that the expression of constitutively active Rho-kinase increased the level of MLC phosphorylation, The activity of Rho-kinase was necessary for maintaining the vinculin-containing focal adhesions, whereas organized actin stress fibers were not necessary for this, The microinjection of constitutively active Rho-kinase into fibroblasts induced the forma tion of focal adhesions to some extent under the conditions where organized actin stress fibers were disrupted, The expression of constitutively active Rho-kinase also stimulated the transcriptional activity of c-fos serum response element. These results suggest that Rho-kinase has distinct roles in divergent pathways downstream of Rho, which include MLC phosphorylation leading to stress fiber formation, focal adhesion formation, and gene expression.