使用蛋白质微阵列为ErbB受体的定量蛋白质相互作用网络
Richard B Jones1, Andrew Gordus, Jordan A Krall
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature
|November 8, 2005
概括
这项研究绘制了与ErbB受体的蛋白质相互作用图,揭示了新的连接,以及癌症中的受体乱交如何与蛋白质度有关. 它提供了对信号网络的定量观点.
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:
- 皮表皮生长因子受体 (EGFR) 信号传递至关重要,但其最初的蛋白质招募步骤尚未完全理解.
- 缺少ErbB通路中早期信号事件的全基因组视图.
研究的目的:
- 为四个ErbB受体创建一个定量蛋白相互作用网络.
- 调查ErbB信号传递的最早步骤:对激活受体的蛋白质招募.
主要方法:
- 使用的蛋白质微阵列含有人类Src同质性2 (SH2) 和铁结合 (PTB) 域.
- 在ErbB受体上测量了61种甲酸的平衡分离常数,进行了77,592次生物化学测试.
主要成果:
- 产生了定量蛋白相互作用网络,揭示了超出当前域选择性理解范围的新型相互作用.
- 在ErbB受体中观察到差异性乱交;EGFR和ErbB2在较低的亲和度值时变得更加乱交,与ErbB3不同.
结论:
- 受体杂交的度依赖变化可能有助于像EGFR和ErbB2这样的受体氨酸激酶的致癌潜力,这些受体在癌症中过度表达.
- 这项工作为信号网络动态和潜在的癌症机制提供了新的视角.
相关概念视频
Protein-protein Interfaces
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...
Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...


