...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Elevated Phospholipase D Activity in H-Ras- but Not K-Ras-Transformed Cells by the Synergistic Action of RalA and ARF6
【24h】

Elevated Phospholipase D Activity in H-Ras- but Not K-Ras-Transformed Cells by the Synergistic Action of RalA and ARF6

机译：通过RalA和ARF6的协同作用，在H-Ras-但不是K-Ras转化的细胞中提高磷脂酶D的活性

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Phospholipase D (PLD) activity is elevated in response to the oncogenic stimulus of H-Ras but not K-Ras. H-Ras and K-Ras have been reported to localize to different membrane microdomains, with H-Ras localizing to caveolin-enriched light membrane fractions. We reported previously that PLD activity elevated in response to mitogenic stimulation is restricted to the caveolin-enriched light membrane fractions. PLD activity in H-Ras-transformed cells is dependent upon RalA, and consistent with a lack of elevated PLD activity in K-Ras-transformed cells, RalA was not activated in K-Ras-transformed cells. Although H-Ras-induced PLD activity is dependent upon RalA, an activated mutant of RalA is not sufficient to elevate PLD activity. We reported previously that RalA interacts with PLD activating ADP ribosylation factor (ARF) proteins. In cells transformed by H-Ras, we found increased coprecipitation of ARF6 with RalA. Moreover, ARF6 colocalized with RalA in light membrane fractions. Interestingly, ARF6 protein levels were elevated in H-Ras- but not K-Ras-transformed cells. A dominant-negative mutant of ARF6 inhibited PLD activity in H-Ras-transformed NIH 3T3 cells. Activated mutants of either ARF6 or RalA were not sufficient to elevate PLD activity in NIH 3T3 cells; however, expression of both activated RalA and activated ARF6 in NIH 3T3 cells led to increased PLD activity. These data suggest a model whereby H-Ras stimulates the activation of both RalA and ARF6, which together lead to the elevation of PLD activity.
机译：响应H-Ras而非K-Ras的致癌刺激，磷脂酶D（PLD）活性升高。据报道，H-Ras和K-Ras定位于不同的膜微区，而H-Ras定位于富含小孔蛋白的轻膜级分。我们以前曾报道过，响应有丝分裂刺激而升高的PLD活性仅限于富含小窝蛋白的轻膜部分。 H-Ras转化细胞中的PLD活性取决于RalA，并且与K-Ras转化细胞中缺乏升高的PLD活性一致，RalA在K-Ras转化细胞中未激活。尽管H-Ras诱导的PLD活性取决于RalA，但激活的RalA突变体不足以提高PLD活性。我们以前报道过RalA与PLD激活ADP核糖基化因子（ARF）蛋白质相互作用。在由H-Ras转化的细胞中，我们发现ARF6与RalA的共沉淀增加。此外，ARF6与RalA在轻膜部分共定位。有趣的是，在H-Ras转化的细胞中，ARF6蛋白水平升高了，但在K-Ras转化的细胞中没有升高。 ARF6的显性负突变体抑制H-Ras转化的NIH 3T3细胞中的PLD活性。活化的ARF6或RalA突变体不足以提高NIH 3T3细胞中的PLD活性。然而，在NIH 3T3细胞中激活RalA和激活ARF6的表达导致PLD活性增加。这些数据提示了一种模型，其中H-Ras刺激RalA和ARF6的激活，从而共同导致PLD活性的升高。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
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