皮表皮肤生长因子受体的功能独立性从一个域所需的体诱导内部化和调节的域
W S Chen1, C S Lazar, K A Lund
1School of Medicine, University of California, San Diego, La Jolla 92093.
Cell
|October 6, 1989
概括
研究人员在表皮生长因子 (EGF) 受体C端中确定了一种特定的序列,该序列对受体内化,下调和降解至关重要. 这一发现澄清了EGF信号的监管和终止方式.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 接收器生物学 接收器生物学
背景情况:
- 表皮生长因子 (EGF) 受体是细胞生长和增殖的关键调节器.
- 了解EGF受体调节的机制,包括内化和降解,对于理解细胞反应至关重要.
- 这些过程所涉及的精确序列和域尚未完全阐明.
研究的目的:
- 为了确定在EGF受体C端内负责EGF依赖受体内部化的特定序列.
- 研究该序列在受体下调,降解和下游信号传输中的作用.
- 阐明酶活性,内化和线性基因信号传递之间的关系.
主要方法:
- 针对位点的突变发生,以确定EGF受体内的关键氨基酸序列.
- 基于细胞的测试以测量受体内部化,降解和信号.
- 基因转录和形态转换的分析,以回应EGF刺激.
主要成果:
- 氨酸激酶域的远端边界和明显的C'-终端序列对于EGF受体内部化至关重要.
- 一个18氨基酸,负电荷区域是需要高亲和内分细胞和连接体刺激的增加.
- 激酶活性但内化缺陷的受体仍然可以为基因转录和细胞生长发出信号.
结论:
- 通过特定的C'-终端序列介导的EGF受体的体诱导的内部化,用于终止基信号传递.
- EGF受体下调和降解对于防止持续信号传输至关重要.
- 线粒体反应主要是由内在的蛋白质氨酸激酶活性驱动的,内部化作为负反机制.
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