Cbl-CIN85-endophilin复合物调解了因联体诱导的EGF受体的下调
Philippe Soubeyran1, Katarzyna Kowanetz, Iwona Szymkiewicz
1Ludwig Institute for Cancer Research, Box 595, Husargatan 3, Uppsala, S-75124, Sweden.
Nature
|March 15, 2002
概括
Cbl蛋白调节表皮生长因子 (EGF) 受体内部化,通过与CIN85和内分泌蛋白结合. 这个过程与Cbl是独立的.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 信号传输 信号传输
背景情况:
- Cbl是一种多适应蛋白,对于降低受体氨酸激酶的调节至关重要.
- 通过Cbl介导的全方位化对于受体降解和信号传导停止至关重要.
研究的目的:
- 调查Cbl在表皮生长因子 (EGF) 受体内细胞结核中的作用.
- 阐明Cbl调节EGF受体内部化的机制.
主要方法:
- 研究了Cbl,CIN85和内分泌蛋白之间的相互作用.
- 使用EGF刺激来观察复杂的形成和受体贩运.
- 评估了抑制Cbl-CIN85相互作用对EGF受体内部化和降解的影响.
主要成果:
- Cbl招募CIN85和内分泌素来激活EGF受体,控制内部化.
- 在EGF刺激时,CIN85以构成性方式与内啡林结合,与Cbl的结合增加.
- 抑制这些相互作用阻断了EGF受体内部化和延迟降解,增强了基因转录.
结论:
- Cbl通过一种涉及CIN85和内分泌素的机制调节EGF受体内分泌.
- 这种内细胞调节在功能上与Cbl的泛素酶活性不同.
- Cbl的C终端区域通过一种新的途径调节依赖体的受体氨酸激酶下调.
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