首页> 外文期刊>Genes to cells : >Activation of c-Jun amino-terminal kinase by GDNF induces G2/M cell cycle delay linked with actin reorganization.
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Activation of c-Jun amino-terminal kinase by GDNF induces G2/M cell cycle delay linked with actin reorganization.

机译:GDNF对c-Jun氨基末端激酶的激活诱导了与肌动蛋白重组有关的G2 / M细胞周期延迟。

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摘要

It is well known that the cell cycle is controlled by several cyclin/cyclin-dependent kinase (Cdk) complexes whose expression and phosphorylation states vary with orderly periodicity. During the cell cycle, activity of the cyclin/Cdk complexes can be regulated directly or indirectly by a number of molecules, including protein kinases and phosphatases, p53, and Cdk inhibitors. Here, we show that the addition of glial cell line-derived neurotrophic factor (GDNF) induced G2/M cell cycle delay in human SK-N-MC neuroectodermal tumor cells that express RET tyrosine kinase, accompanying actin reorganization. Cell cycle delay at G2/M was characterized by accelerated and prolonged Cdc2 phosphorylation and stabilization of cyclin B1 and Wee1 kinase expression. Interestingly, we found that phosphorylation and/or expression of Cdc2, cyclinB1, and Wee1 was controlled by the Rac1/c-Jun NH2-terminal kinase (JNK) pathway. Immunohistochemical analysis suggested that the G2/M cell cycle delay may be necessary to preventthe mitotic progression of SK-N-MC cells with perturbed actin cytoskeletons.
机译:众所周知,细胞周期受几种细胞周期蛋白/细胞周期蛋白依赖性激酶(Cdk)复合物控制,它们的表达和磷酸化状态按有规律的周期性变化。在细胞周期中,细胞周期蛋白/ Cdk复合物的活性可以直接或间接地受许多分子的调节,包括蛋白激酶和磷酸酶,p53和Cdk抑制剂。在这里,我们显示神经胶质细胞源性神经营养因子(GDNF)的添加诱导表达RET酪氨酸激酶的人SK-N-MC神经外胚层肿瘤细胞中的G2 / M细胞周期延迟,伴随肌动蛋白重组。 G2 / M的细胞周期延迟的特征是加速和延长的Cdc2磷酸化以及细胞周期蛋白B1和Wee1激酶表达的稳定。有趣的是,我们发现Cdc2,cyclinB1和Wee1的磷酸化和/或表达受Rac1 / c-Jun NH2-末端激酶(JNK)路径控制。免疫组织化学分析表明,G2 / M细胞周期延迟可能是必要的,以防止肌动蛋白细胞骨架受到干扰的SK-N-MC细胞的有丝分裂进程。

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