...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cellular Physiology >PKR activity is required for acute leukemic cell maintenance and growth: a role for PKR-mediated phosphatase activity to regulate GSK-3 phosphorylation.
【24h】

PKR activity is required for acute leukemic cell maintenance and growth: a role for PKR-mediated phosphatase activity to regulate GSK-3 phosphorylation.

机译：急性白血病细胞所需PKR活动维护和发展:PKR-mediated的角色调节GSK-3磷酸酶活动磷酸化。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Recent reports demonstrate that PKR is constitutively active in a variety of tumors and is required for tumor maintenance and growth. Here we report acute leukemia cell lines contain elevated levels of p-T451 PKR and PKR activity as compared to normal controls. Inhibition of PKR with a specific inhibitor, as well as overexpression of a dominant-negative PKR, inhibited cell proliferation and induced cell death. Interestingly, PKR inhibition using the specific inhibitor resulted in a time-dependent augmentation of AKT S473 and GSK-3alpha S21 phosphorylation, which was confirmed in patient samples. Increased phosphorylation of AKT and GSK-3alpha was not dependent on PI3K activity. PKR inhibition augmented levels of p-S473 AKT and p-S21/9 GSK-3alpha/beta in the presence of the PI3K inhibitor, LY294002, but was unable to augment GSK-3alpha or beta phosphorylation in the presence of the AKT inhibitor, A443654. Pre-treatment with the PKR inhibitor blocked the ability of A443654 and LY294002 to promote phosphorylation of eIF2alpha, indicating the mechanism leading to AKT phosphorylation and activation did not require eIF2alpha phosphorylation. The effects of PKR inhibition on AKT and GSK-3 phosphorylation were found to be, in part, PP2A-dependent. These data indicate that, in acute leukemia cell lines, constitutive basal activity of PKR is required for leukemic cell homeostasis and growth and functions as a negative regulator of AKT, thereby increasing the pool of potentially active GSK-3.
机译：最近的报告表明,PKR在各种肿瘤和持续活跃肿瘤需要维护和增长。这里我们报告急性白血病细胞系高浓度的p-T451 PKR和PKR活动与正常对照组相比。与一个特定的抑制剂,以及超表达的显性负PKR、抑制细胞增殖,诱导细胞死亡。特定抑制剂导致时间增加的一种蛋白激酶S473和GSK-3alpha S21磷酸化,确诊病人样本。GSK-3alpha并不依赖PI3K的活动。PKR抑制水平增强p-S473 AKT和p-S21/9 GSK-3alpha /β的存在LY294002 PI3K抑制剂,但不能增强GSK-3alpha或β磷酸化存在一种蛋白激酶抑制剂,A443654。预处理PKR抑制剂阻止了A443654和LY294002推广的能力的磷酸化eIF2alpha表示导致一种蛋白激酶磷酸化和机制不需要eIF2alpha激活磷酸化。一种蛋白激酶和GSK-3磷酸化被发现,在某种程度上,PP2A-dependent。在急性白血病细胞系,本构基底PKR白血病需要的活动细胞内稳态和增长和功能负监管机构的一种蛋白激酶,从而增加了池GSK-3潜在的活跃。

著录项

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号