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Arachidonic acid signaling to the cytoskeleton: The role of cyclooxygenase and cyclic AMP-dependent protein kinase in actin bundling.

机译:花生四烯酸向细胞骨架的信号转导:环氧合酶和环状AMP依赖性蛋白激酶在肌动蛋白束缚中的作用。

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摘要

Cell adhesion to the extracellular matrix via integrins is a primary regulatory mechanism for numerous aspects of normal cellular function. However, disruption of this interaction can result in pathology. For example, one characteristic of transformed cells is loss of adhesion dependence for viability. Adhesion also is a necessary step in tumor metastasis. It has been shown previously, in HeLa cells, that cell attachment to a gelatin-coated substrate results in the release of arachidonic acid, which is metabolized by lipoxygenase. A subsequent cascade of lipid second messengers activates protein kinase C, which triggers actin polymerization leading to cell spreading. We now demonstrate by inhibitor studies and biochemical analysis, a parallel branch of arachidonic acid signaling that reorganizes the actin cytoskeleton into small bundles. This branch of the pathway is initiated by cyclooxygenase, which generates prostaglandins and causes the downstream activation of cyclic AMP-dependent protein kinase. This work elucidates a system of interacting signals in which arachidonic acid functions at a branch point in cytoskeletal signaling. The lipoxygenase branch provides polymerized actin; these actin filaments act as a substrate for the cylooxygenase branch to generate actin bundles. Cell Motil. Cytoskeleton 53:239-250, 2002.
机译:通过整联蛋白将细胞粘附至细胞外基质是正常细胞功能的许多方面的主要调节机制。但是,这种相互作用的破坏会导致病理。例如,转化细胞的一个特征是丧失对生存力的粘附依赖性。粘附也是肿瘤转移的必要步骤。先前已经证明,在HeLa细胞中,细胞附着到明胶包被的底物上会导致花生四烯酸的释放,花生四烯酸被脂氧合酶代谢。随后的脂质第二信使级联反应激活蛋白激酶C,从而触发肌动蛋白聚合反应,导致细胞扩散。现在,我们通过抑制剂研究和生化分析证明,花生四烯酸信号的平行分支将肌动蛋白细胞骨架重组为小束。该途径的这一分支由环氧合酶起始,该环氧合酶产生前列腺素并引起环状AMP依赖性蛋白激酶的下游活化。这项工作阐明了一种相互作用的信号系统,其中花生四烯酸在细胞骨架信号传导的分支点起作用。脂氧合酶分支提供聚合的肌动蛋白;这些肌动蛋白丝充当环加氧酶分支的底物以生成肌动蛋白束。细胞动力。 Cytoskeleton 53:239-250,2002。

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