ArticleProceedings of the National Academy of Sciences of the United States of America2010
Pairwise network mechanisms in the host signaling response to coxsackievirus B3 infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed.
- Advances in cell death mechanisms involved in viral myocarditis.Frontiers in cardiovascular medicine · 2022Review
- MicroRNA-324-3p Plays A Protective Role Against Coxsackievirus B3-Induced Viral Myocarditis.Virologica Sinica · 2021Article
- Mechanistic Model of Signaling Dynamics Across an Epithelial Mesenchymal Transition.Frontiers in physiology · 2020Article
- An ultrasensitive fiveplex activity assay for cellular kinases.Scientific reports · 2019Article
- Connectivity problems on heterogeneous graphs.Algorithms for molecular biology : AMB · 2019Article
- An engineering design approach to systems biology.Integrative biology : quantitative biosciences from nano to macro · 2017Review
- Profiling Subcellular Protein Phosphatase Responses to Coxsackievirus B3 Infection of Cardiomyocytes.Molecular & cellular proteomics : MCP · 2017Article
- Cleavage of Grb2-Associated Binding Protein 2 by Viral Proteinase 2A duringFrontiers in cellular and infection microbiology · 2017Article
- An atlas of human kinase regulation.Molecular systems biology · 2016Article
- Systems Pharmacology and Rational Polypharmacy: Nitric Oxide-Cyclic GMP Signaling Pathway as an Illustrative Example and Derivation of the General Case.PLoS computational biology · 2016Article
- Fostering synergy between cell biology and systems biology.Trends in cell biology · 2015Review
- Analysis of single-cell cytokine secretion reveals a role for paracrine signaling in coordinating macrophage responses to TLR4 stimulation.Science signaling · 2015Article
- A new transcriptional role for matrix metalloproteinase-12 in antiviral immunity.Nature medicine · 2014Article
- Systems biology of cancer: a challenging expedition for clinical and quantitative biologists.Frontiers in bioengineering and biotechnology · 2014Article
- Models of signalling networks - what cell biologists can gain from them and give to them.Journal of cell science · 2013Review
- Circuit-level input integration in bacterial gene regulation.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Review
- Induction of a broad spectrum of inflammation-related genes by Coxsackievirus B3 requires Interleukin-1 signaling.Medical microbiology and immunology · 2013Article
- An ERK-p38 subnetwork coordinates host cell apoptosis and necrosis during coxsackievirus B3 infection.Cell host & microbe · 2013Article
- A systems biology starter kit for arenaviruses.Viruses · 2012Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Signal transduction networks can be perturbed biochemically, genetically, and pharmacologically to unravel their functions. But at the systems level, it is not clear how such perturbations are best implemented to extract molecular mechanisms that underlie network function. Here, we combined pairwise perturbations with multiparameter phosphorylation measurements to reveal causal mechanisms within the signaling network response of cardiomyocytes to coxsackievirus B3 (CVB3) infection. Using all possible pairs of six kinase inhibitors, we assembled a dynamic nine-protein phosphorylation signature of perturbed CVB3 infectivity. Cluster analysis of the resulting dataset showed repeatedly that paired inhibitor data were required for accurate data-driven predictions of kinase substrate links in the host network. With pairwise data, we also derived a high-confidence network based on partial correlations, which identified phospho-IκBα as a central "hub" in the measured phosphorylation signature. The reconstructed network helped to connect phospho-IκBα with an autocrine feedback circuit in host cells involving the proinflammatory cytokines, TNF and IL-1. Autocrine blockade substantially inhibited CVB3 progeny release and improved host cell viability, implicating TNF and IL-1 as cell autonomous components of CVB3-induced myocardial damage. We conclude that pairwise perturbations, when combined with network-level intracellular measurements, enrich for mechanisms that would be overlooked by single perturbants.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.