• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Spatial control of EGF receptor activation by reversible dimerization on living cells
【24h】

Spatial control of EGF receptor activation by reversible dimerization on living cells

机译：通过对活细胞的可逆二聚化来控制EGF受体激活的空间

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

Epidermal growth factor receptor (EGFR) is a type I receptor tyrosine kinase, the deregulation of which has been implicated in a variety of human carcinomas. EGFR signalling is preceded by receptor dimerization, typically thought to result from a ligand-induced conformational change in the ectodomain that exposes a loop (dimerization arm) required for receptor association. Ligand binding may also trigger allosteric changes in the cytoplasmic domain of the receptor that is crucial for signalling. Despite these insights, ensemble-averaging approaches have not determined the precise mechanism of receptor activation in situ. Using quantum-dot-based optical tracking of single molecules combined with a novel time-dependent diffusivity analysis, here we present the dimerization dynamics of individual EGFRs on living cells. Before ligand addition, EGFRs spontaneously formed finite-lifetime dimers kinetically stabilized by their dimerization arms. The dimers were primed both for ligand binding and for signalling, such that after EGF addition they rapidly showed a very slow diffusivity state that correlated with activation. Although the kinetic stability of unliganded dimers was in principle sufficient for EGF-independent activation, ligand binding was still required for signalling. Interestingly, dimers were enriched in the cell periphery in an actin- and receptor-expression-dependent fashion, resulting in a peripheral enhancement of EGF-induced signalling that may enable polarized responses to growth factors.
机译：表皮生长因子受体（EGFR）是一种I型受体酪氨酸激酶，其失调与多种人类癌症有关。 EGFR信号转导之前是受体二聚化，通常被认为是由配体诱导的胞外域构象变化所致，该构象变化暴露了受体缔合所需的环（二聚臂）。配体结合也可能触发受体细胞质结构域的变构变化，这对于信号传递至关重要。尽管有这些见解，但总体平均方法尚未确定受体激活的确切机制。使用基于量子点的单分子光学跟踪与新颖的时间依赖性扩散分析相结合，在这里我们展示了单个EGFR在活细胞上的二聚化动力学。在添加配体之前，EGFR通过其二聚化臂自发形成动力学稳定的有限寿命二聚体。这些二聚体既可用于配体结合也可用于信号传导，因此在添加EGF之后，它们迅速显示出与激活相关的非常缓慢的扩散状态。尽管未配体二聚体的动力学稳定性原则上足以实现EGF依赖性激活，但信号传递仍需要配体结合。有趣的是，二聚体以肌动蛋白和受体表达依赖性的方式富集在细胞外围，从而导致EGF诱导的信号传导在外围增强，从而可能对生长因子产生极化反应。

著录项

  • 来源
    《Nature》 |2010年第7289期|783-787|共5页
  • 作者

    Inhee Chung; Robert Akita; Richard Vandlen; Derek Toomre; Joseph Schlessinger; Ira Mellman;

  • 作者单位

    Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA;

    Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA;

    Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA;

    Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA;

    Deparment of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510, USA;

    Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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