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Science. 2014 Dec 12;346(6215):1370-3. doi: 10.1126/science.1254933.

Systems biology. Accurate information transmission through dynamic biochemical signaling networks.

Author information

1
Department of Bioengineering, University of California-San Diego, La Jolla, CA 92093, USA.
2
Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, CA 92093, USA.
3
Department of Molecular and Cellular Biology, University of California-Davis, Davis 95616, USA.
4
San Diego Center for Systems Biology, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences and Department of Microbiology, Immunology, and Molecular Genetics, University of California-Los Angeles, Los Angeles, CA 90025, USA.
5
San Diego Center for Systems Biology, La Jolla, CA 92093, USA. BioCircuits Institute, University of California-San Diego, La Jolla, CA 92093, USA.
6
Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, CA 92093, USA. San Diego Center for Systems Biology, La Jolla, CA 92093, USA. Cell and Developmental Biology Section, Division of Biological Sciences, University of California-San Diego, La Jolla, CA 92093, USA. rwollman@ucsd.edu.

Abstract

Stochasticity inherent to biochemical reactions (intrinsic noise) and variability in cellular states (extrinsic noise) degrade information transmitted through signaling networks. We analyzed the ability of temporal signal modulation--that is, dynamics--to reduce noise-induced information loss. In the extracellular signal-regulated kinase (ERK), calcium (Ca(2+)), and nuclear factor kappa-B (NF-κB) pathways, response dynamics resulted in significantly greater information transmission capacities compared to nondynamic responses. Theoretical analysis demonstrated that signaling dynamics has a key role in overcoming extrinsic noise. Experimental measurements of information transmission in the ERK network under varying signal-to-noise levels confirmed our predictions and showed that signaling dynamics mitigate, and can potentially eliminate, extrinsic noise-induced information loss. By curbing the information-degrading effects of cell-to-cell variability, dynamic responses substantially increase the accuracy of biochemical signaling networks.

PMID:
25504722
PMCID:
PMC4813785
DOI:
10.1126/science.1254933
[Indexed for MEDLINE]
Free PMC Article

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