title: Systems biology. Accurate information transmission through dynamic biochemical signaling networks.
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.
authors.affiliation: Department of Bioengineering, University of California-San Diego, La Jolla, CA 92093, USA.
authors.forename: Jangir
authors.initials: J
authors.lastname: Selimkhanov
authors.affiliation: Department of Bioengineering, University of California-San Diego, La Jolla, CA 92093, USA.
authors.forename: Brooks
authors.initials: B
authors.lastname: Taylor
authors.affiliation: Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, CA 92093, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, CA 92093, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Pilko
authors.affiliation: Department of Molecular and Cellular Biology, University of California-Davis, Davis 95616, USA.
authors.forename: John
authors.initials: J
authors.lastname: Albeck
authors.affiliation: 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.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoffmann
authors.affiliation: San Diego Center for Systems Biology, La Jolla, CA 92093, USA. BioCircuits Institute, University of California-San Diego, La Jolla, CA 92093, USA.
authors.forename: Lev
authors.initials: L
authors.lastname: Tsimring
authors.affiliation: 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.
authors.forename: Roy
authors.initials: R
authors.lastname: Wollman
mesh_terms: D020013:Calcium Signaling; D002460:Cell Line; D003198:Computer Simulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D059629:Signal-To-Noise Ratio; D059010:Single-Cell Analysis; D049490:Systems Biology
chemical_list: D016328:NF-kappa B; D048049:Extracellular Signal-Regulated MAP Kinases