干特异性c-Fos表达源于ErbB网络动态的时空控制
Takashi Nakakuki1, Marc R Birtwistle, Yuko Saeki
1Computational Systems Biology Research Group, Advanced Computational Sciences Department, RIKEN Advanced Science Institute, 1-7-22 Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Cell
|May 25, 2010
概括
皮表皮生长因子 (EGF) 和黑雷古林 (HRG) 通过共享的途径触发不同的细胞命运. 数学建模揭示了这些连接体如何通过控制ERK信号动态来产生独特的c-Fos反应.
科学领域:
- 细胞信号传输和分子生物学
- 信号传导途径的信号传导途径.
- 基因调节 基因调节
背景情况:
- 皮表皮生长因子 (EGF) 和黑雷古林 (HRG) 激活ErbB受体,通过共享的信号通路导致不同的细胞命运决定.
- 了解这些连接体产生差异性细胞反应的机制,对于破译细胞命运决定至关重要.
研究的目的:
- 阐明表皮生长因子 (EGF) 和黑雷古林 (HRG) 如何产生酸化转录因子c-Fos的独特的全或无反应.
- 调查细胞外信号调节激酶 (ERK) 激活动态在调解联体特异性细胞结果中的作用.
主要方法:
- 利用数学建模和实验方法来分析信号通路.
- 执行双特异性酸酶的淘汰,以评估它们在调节核ERK活性和c-fos mRNA表达中的作用.
- 研究了HRG诱导的转录抑制中对新蛋白质合成的需求.
主要成果:
- EGF诱导了短暂的细胞质ERK激活,而HRG诱导了持续的激活.
- 核ERK活动和c-fos mRNA表达对于EGF和HRG都是暂时的.
- 确定了一种HRG诱导的抑制剂,需要新的蛋白质合成,该抑制剂限制了c-fos mRNA表达,独立于核ERK持续时间.
结论:
- 一个空间分布的信号转录级联在c-Fos系统层面强大地区分了短暂和持续的ERK活动.
- 识别的控制机制是一般的,适用于不同的细胞类型和连接体刺激.
- 这项研究揭示了一种新的转录抑制机制,有助于对联体特异性细胞反应.
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