...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Ras Activation in Jurkat T cells following Low-Grade Stimulation of the T-Cell Receptor Is Specific to N-Ras and Occurs Only on the Golgi Apparatus
【24h】

Ras Activation in Jurkat T cells following Low-Grade Stimulation of the T-Cell Receptor Is Specific to N-Ras and Occurs Only on the Golgi Apparatus

机译：T细胞受体的低级刺激后Jurkat T细胞中的Ras激活是N-Ras特有的，仅在高尔基体上发生

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

摘要

Ras activation is critical for T-cell development and function, but the specific roles of the different Ras isoforms in T-lymphocyte function are poorly understood. We recently reported T-cell receptor (TCR) activation of ectopically expressed H-Ras on the the Golgi apparatus of T cells. Here we studied the isoform and subcellular compartment specificity of Ras signaling in Jurkat T cells. H-Ras was expressed at much lower levels than the other Ras isoforms in Jurkat and several other T-cell lines. Glutathione S-transferase-Ras-binding domain (RBD) pulldown assays revealed that, although high-grade TCR stimulation and phorbol ester activated both N-Ras and K-Ras, low-grade stimulation of the TCR resulted in specific activation of N-Ras. Surprisingly, whereas ectopically expressed H-Ras cocapped with the TCRs in lipid microdomains of the Jurkat plasma membrane, N-Ras did not. Live-cell imaging of Jurkat cells expressing green fluorescent protein-RBD, a fluorescent reporter of GTP-bound Ras, revealed that N-Ras activation occurs exclusively on the Golgi apparatus in a phospholipase Cγ- and RasGRP1-dependent fashion. The specificity of N-Ras signaling downstream of low-grade TCR stimulation was dependent on the monoacylation of the hypervariable membrane targeting sequence. Our data show that, in contrast to fibroblasts stimulated with growth factors in which all three Ras isoforms become activated and signaling occurs at both the plasma membrane and Golgi apparatus, Golgi-associated N-Ras is the critical Ras isoform and intracellular pool for low-grade TCR signaling in Jurkat T cells.
机译：Ras激活对于T细胞的发育和功能至关重要，但人们对不同Ras亚型在T淋巴细胞功能中的具体作用了解甚少。我们最近报道了在T细胞的高尔基体上异位表达的H-Ras的T细胞受体（TCR）激活。在这里，我们研究了Jurkat T细胞中Ras信号传导的亚型和亚细胞区室特异性。在Jurkat和其他一些T细胞系中，H-Ras的表达水平比其他Ras异构体低得多。谷胱甘肽 S -转移酶-Ras结合域（RBD）下拉测定法显示，尽管高级TCR刺激和佛波醇酯均激活N-Ras和K-Ras，但是低级刺激TCR导致N-Ras的特定激活。出人意料的是，尽管异位表达的H-Ras在Jurkat质膜的脂质微区中与TCRs结合，但N-Ras却没有。表达绿色荧光蛋白-RBD（GTP结合的Ras的荧光报告基因）的Jurkat细胞的活细胞成像显示，N-Ras活化仅在高尔基体上以磷脂酶Cγ和RasGRP1依赖性方式发生。低级TCR刺激下游的N-Ras信号传导的特异性取决于高变膜靶向序列的单酰化作用。我们的数据显示，与受生长因子刺激的成纤维细胞不同，成纤维细胞中的所有三种Ras亚型均被激活，并且在质膜和高尔基体均发生信号传导，而高尔基体相关的N-Ras是低Ras的关键Ras亚型和细胞内池。 Jurkat T细胞中的TCR级信号转导。

著录项

相似文献

  • 外文文献
  • 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