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适应蛋白Shc将一类整合素结合起来,以控制细胞周期进展
K K Wary1, F Mainiero, S J Isakoff
1Department of Pathology and Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
Cell
|November 15, 1996
概括
与Shc适应蛋白结合的特定整合素激活MAP激酶通路,促进细胞生存和生长. 不与Shc结合的整体素会导致细胞循环停止和细胞亡,突出显示Shcc.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 整合素是细胞表面受体,对细胞粘附和信号传递至关重要.
- Shc适配蛋白在信号传导途径中起着关键作用.
- 整合素结合启动细胞内信号级联,调节细胞行为.
研究的目的:
- 研究通过Shc适应蛋白传递整合素信号的分子机制.
- 确定Shc在MAP激酶通路的整合因介导激活中的作用.
- 阐明整合素-Shc关联如何影响细胞周期进展和存活.
主要方法:
- 同免疫沉测试检测蛋白质与蛋白质相互作用.
- 现场定向突变发生,以确定Shc招募的关键域.
- 主导负抑制研究,以评估Shc.的必要性和充分性.
- 记者基因测试测量Fos血清反应元素的转录激活.
主要成果:
- 整合素的一个子集直接与Shc适应蛋白结合,后者随后与Grb2.2结合.
- 对整合素的Shc招募由整合素α子单元的细胞外或膜外域介导,并涉及caveolin.
- 对于MAP激酶通路的整合素-配体诱导激活,Shc既必要又足够.
- 米托基因和Shc-激活整合素之间的合作促进G1过渡和Fos血清反应元素转录.
- 不与Shc结合的整体素会诱导细胞循环停止和细胞亡,即使有线原性刺激.
结论:
- 特定整合素与Shc适应蛋白的关联是细胞命运的关键决定因素.
- 集成蛋白-Shc信号通路调节细胞生存和细胞循环中的进展.
- 向整合素-Shc相互作用可能为控制细胞增殖和存活提供治疗策略.
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