Morphology of ras-transformed cells becomes apparently normal again with tyrosine kinase inhibitors without a decrease in the ras-GTP complex.
Morphology of ras-transformed cells becomes apparently normal again with tyrosine kinase inhibitors without a decrease in the ras-GTP complex.
复制标题
使用酪氨酸激酶抑制剂，ras 转化细胞的形态明显再次变得正常，而 ras-GTP 复合物没有减少。
DOI：
10.1093/oxfordjournals.jbchem.a124882
复制
发表时间：
1995
影响因子：
2.7
通讯作者：
S. Horinouchi
中科院分区：
文献类型：
--
作者：
H. Kwon;M. Yoshida;K. Muroya;S. Hattori;E. Nishida;Y. Fukui;T. Beppu;S. Horinouchi
研究发现，蛋白酪氨酸激酶抑制剂自由基可引起v-Ha-ras转化的NIH3T3成纤维细胞和含有激活的ras突变的人膀胱癌细胞T24的形态逆转。在自由基治疗过程中，肌动蛋白应激纤维网络得到恢复。另一种蛋白酪氨酸激酶抑制剂--去甲自由基对p21ras活性GTP结合体的比例或其亚细胞定位也没有引起任何改变。这些结果排除了自由基的形态逆转是由于直接或间接抑制p21ras功能的可能性。放线菌素D和放线菌素D抑制自由基诱导的细胞形态改变，提示酪氨酸激酶抑制剂抑制ras转化细胞的转化表型需要一个基因(S)的诱导转录和从头蛋白的合成。
Radicicol, an inhibitor of protein-tyrosine kinase, was found to cause morphological reversion of v-Ha-ras-transformed NIH3T3 fibroblasts and T24 human urinary bladder carcinoma cells that contain an activated ras mutation. The network of actin stress fibers was restored during the treatment with radicicol. A similar morphological change was observed with another protein-tyrosine kinase inhibitor, herbimycin A. Radicicol did not cause any changes in the proportion of the active GTP binding form of p21ras or its subcellular localization. These results rule out the possibility that the morphological reversion by radicicol is due to direct or indirect inhibition of the p21ras function. Cycloheximide and actinomycin D inhibited the morphological change by radicicol, suggesting that the induced transcription of a gene(s) followed by de novo protein synthesis is required for suppression of the transformed phenotype in ras-transformed cells by tyrosine kinase inhibitors.