...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Activated Cdc42/Rac reconstitutes Fc_εRI-mediated Ca~2+ mobilization and degranulation in mutant RBL mast cells
【24h】

Activated Cdc42/Rac reconstitutes Fc_εRI-mediated Ca~2+ mobilization and degranulation in mutant RBL mast cells

机译：活化的Cdc42 / Rac在突变RBL肥大细胞中重建Fc_εRI介导的Ca〜2 +动员和脱粒

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

Antigen stimulation of mast cells via Fc_εRI, the high-affinity re- ceptor for IgE, triggers a signaling cascade that requires Ca~2+ mobilization for exocytosis of secretory granules during an allergic response. This study investigates critical signaling components by using mutant RBL mast cells that are defective in antigen-stimu- lated phospholipase Cγ (PLCγ) activation, as well as other signaling activities downstream of stimulated tyrosine phosphorylation. We show that the expression of activated versions of the Cdc42 or Rac1 GTPase restores antigen-stimulated Ca~2+ mobilization necessary for degranulation in these mutant cells. Wild-type Cdc42 and Rac1, as well as activated Cdc42 containing effector domain mutations, all fail to restore antigen-stimulated signaling leading to exocyto- sis. Expression of oncogenic DbI, a guanine nucleotide exchange factor for Cdc42 and Rac1, partially restores sustained Ca~2+ mobilization and degranulation, suggesting that activation of endogenous Cdc42 and/or Rac1 is impaired in the mutant cells. Overexpression of PLCγ1 with either activated Cdc42 or Rac1 synergistically stimulates degranulation, consistent with a criti- cal defect in PLCγ activation in these cells. Thus. our results point to activation of Cdc42 and/or Rac1 playing an essential role in antigen stimulation of early events that culminate in mast cell degranulation.
机译：通过Fc_εRI（IgE的高亲和力受体）对肥大细胞的抗原刺激，触发了信号级联反应，该信号级联反应在过敏反应期间需要Ca〜2 +动员以分泌颗粒的胞吐作用。本研究通过使用在抗原刺激的磷脂酶Cγ（PLCγ）活化以及刺激的酪氨酸磷酸化下游的其他信号传导活性方面存在缺陷的突变RBL肥大细胞研究关键的信号传导成分。我们表明，Cdc42或Rac1 GTPase的激活版本的表达恢复了这些突变细胞中脱颗粒所必需的抗原刺激的Ca〜2 +动员。野生型Cdc42和Rac1，以及含有效应子结构域突变的活化Cdc42，都无法恢复抗原刺激的信号，从而导致胞吐作用。致癌性DbI（Cdc42和Rac1的鸟嘌呤核苷酸交换因子）的表达部分恢复了持续的Ca〜2 +动员和脱粒，这表明突变细胞中内源性Cdc42和/或Rac1的激活受到损害。用激活的Cdc42或Rac1过度表达PLCγ1会协同刺激脱颗粒，这与这些细胞中PLCγ激活的严重缺陷相一致。从而。我们的研究结果表明，Cdc42和/或Rac1的激活在抗原刺激早期事件中起着至关重要的作用，最终导致肥大细胞脱粒。

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