细胞素是细胞质ErbB受体的激活剂
Anke Bill1, Anton Schmitz, Barbara Albertoni
1LIMES Institute, Program Unit Chemical Biology & Medicinal Chemistry, Laboratory of Chemical Biology, Rheinische Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany.
Cell
|October 16, 2010
概括
细胞素被确定为关键的细胞质因子,激活ErbB受体,对于细胞信号传递至关重要. 它们的抑制减少了癌细胞的增殖,突出了它们在EGFR驱动的肺癌中的治疗潜力.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- ErbB受体信号传递对于细胞功能至关重要.
- 连接物结合激活受体ectodomains,启动信号传输.
- 控制ErbB受体激活的细胞质因子在很大程度上是未知的.
研究的目的:
- 确定调节ErbB受体激活的细胞质因子.
- 调查细胞素在ErbB受体信号传递中的作用.
- 在EGFR依赖癌症中探索向cytohesins的治疗潜力.
主要方法:
- 蛋白质家族鉴定和功能测定.
- 无异型显微镜用于监测受体构成.
- 受体自酸化的无细胞复制.
- 对人类肺腺癌样本的分析.
- 在体外和体内生殖增殖试验.
主要成果:
- 细胞素被确定为ErbB受体的新型细胞质激活剂.
- 细胞酶抑制降低了ErbB受体自和信号传递.
- 细胞素过度表达增强了受体激活和EGF信号通路.
- 赛托赫辛促进了二元化受体的细胞内域的结构变化.
- 细胞素抑制降低了依赖EGFR的肺癌细胞的增殖.
结论:
- 细胞素作为ErbB受体的细胞质 conformational 激活剂.
- 细胞素在ErbB受体介导的信号传递中发挥着重要作用.
- 向cytohesins为EGFR驱动的肺癌提供了一个潜在的治疗策略.
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