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细胞因子诱导的信号网络优先考虑动态范围而不是信号强度
Kevin A Janes1, H Christian Reinhardt, Michael B Yaffe
1Koch Institute for Integrative Cancer Research, Center for Cell Decision Processes, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell
|October 30, 2008
概括
细胞信号通路通过动态范围传输信息,而不仅仅是信号强度. 了解这种动态范围对于预测细胞亡和避免信号网络响应发生灾难性故障至关重要.
科学领域:
- 蜂信号传输是如何进行的
- 系统生物学 系统生物学
- 细胞亡调节的调节
背景情况:
- 信号网络对刺激做出反应,但对下游细胞反应的传输仍然不清楚.
- 预测细胞命运需要了解信号状态是如何传递的.
研究的目的:
- 基于信号强度和动态范围,模拟信号分子的增量激活如何控制亡.
- 确定动态范围在信号传导中的作用及其对细胞反应的影响.
- 开发一种用于分析信号网络故障的计算技术.
主要方法:
- 信号网络激活和亡的计算建模.
- 分析信号输入-输出关系和动态范围.
- 开发和应用"模型断点分析"用于故障机制调查.
- 实验验证已识别的酶作用.
主要成果:
- 信号输入和响应输出之间的线性关系,具有统一的动态范围分布,最好的预测细胞亡.
- 非线性信号和压缩的动态范围导致了灾难性的,刺激特定的预测失败.
- 模型断点分析确定了Akt,ERK和MK2激酶活性在亡中的新型时间和刺激特异性作用.
- 动态范围成为细胞命运的潜在决定因素,比信号强度更大.
结论:
- 动态范围是一个关键的,经常被忽视的,信号传导和细胞命运决定的因素.
- 模型断点分析为剖析信号机制和识别关键监管点提供了强大的工具.
- 了解动态范围对于准确预测细胞对各种刺激的反应至关重要.
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