Strong negative feedback from Erk to Raf confers robustness to MAPK signalling.
Strong negative feedback from Erk to Raf confers robustness to MAPK signalling.
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DOI：
10.1038/msb.2011.27
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发表时间：
2011-05-24
影响因子：
9.9
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中科院分区：
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这项研究表明，由于Erk到Raf的强烈负反馈，MAPK信号传导对蛋白质水平变化具有鲁棒性。令人惊讶的是，通过快速翻译后机制提供了稳健性，尽管Erk水平的变化发生在几天的时间尺度上。信号转导途径中的蛋白质水平在细胞与细胞之间变化很大。在这里，我们分析了信号通路如何仍然可以处理信息定量尽管蛋白质水平的强烈异质性。我们系统地干扰了Erk的蛋白水平，Erk是一组人类细胞系中MAPK信号通路的末端激酶。我们发现，稳态磷酸化的Erk是非常强大的Erk蛋白水平的扰动。虽然存在多种机制可以提供对波动的蛋白质水平的鲁棒性，但我们发现从Erk到Raf-1的一个单一反馈解释了所观察到的鲁棒性。令人惊讶的是，通过快速翻译后机制提供了稳健性，尽管Erk水平的变化发生在几天的时间尺度上。
This study shows that MAPK signalling is robust against protein level changes due to a strong negative feedback from Erk to Raf. Surprisingly, robustness is provided through a fast post-translational mechanism although variation of Erk levels occurs on a timescale of days. Protein levels within signal transduction pathways vary strongly from cell to cell. Here, we analysed how signalling pathways can still process information quantitatively despite strong heterogeneity in protein levels. We systematically perturbed the protein levels of Erk, the terminal kinase in the MAPK signalling pathway in a panel of human cell lines. We found that the steady-state phosphorylation of Erk is very robust against perturbations of Erk protein level. Although a multitude of mechanisms exist that may provide robustness against fluctuating protein levels, we found that one single feedback from Erk to Raf-1 accounts for the observed robustness. Surprisingly, robustness is provided through a fast post-translational mechanism although variation of Erk levels occurs on a timescale of days.