ArticleNature communications2012
Sensitivity control through attenuation of signal transfer efficiency by negative regulation of cellular signalling.
Article in Nature communications, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
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- Understanding the mTOR signaling pathway via mathematical modeling.Wiley interdisciplinary reviews. Systems biology and medicine · 2017Review
- Robustness of MEK-ERK Dynamics and Origins of Cell-to-Cell Variability in MAPK Signaling.Cell reports · 2016Article
- Glucose Homeostatic Law: Insulin Clearance Predicts the Progression of Glucose Intolerance in Humans.PloS one · 2015Article
- Quantitative Analysis of Robustness of Dynamic Response and Signal Transfer in Insulin mediated PI3K/AKT Pathway.Computers & chemical engineering · 2014Article
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- Cellular compartments cause multistability and allow cells to process more information.Biophysical journal · 2013Article
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- Maximizing the information content of experiments in systems biology.PLoS computational biology · 2013Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sensitivity is one of the hallmarks of biological and pharmacological responses. However, the principle of controlling sensitivity remains unclear. Here we theoretically analyse a simple biochemical reaction and find that the signal transfer efficiency of the transient peak amplitude attenuates depending on the strength of negative regulation. We experimentally find that many signalling pathways in various cell lines, including the Akt and ERK pathways, can be approximated by simple biochemical reactions and that the same property of the attenuation of signal transfer efficiency was observed for such pathways. Because of this property, a downstream molecule should show higher sensitivity to an activator and lower sensitivity to an inhibitor than an upstream molecule. Indeed, we experimentally verify that S6, which lies downstream of Akt, shows lower sensitivity to an epidermal growth factor receptor inhibitor than Akt. Thus, cells can control downstream sensitivity through the attenuation of signal transfer efficiency by changing the expression level of negative regulators.
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