title: Chemical Reaction Network Theory elucidates sources of multistability in interferon signaling.
abstract: Bistability has important implications in signaling pathways, since it indicates a potential cell decision between alternative outcomes. We present two approaches developed in the framework of the Chemical Reaction Network Theory for easy and efficient search of multiple steady state behavior in signaling networks (both with and without mass conservation), and apply them to search for sources of bistability at different levels of the interferon signaling pathway. Different type I interferon subtypes and/or doses are known to elicit differential bioactivities (ranging from antiviral, antiproliferative to immunomodulatory activities). How different signaling outcomes can be generated through the same receptor and activating the same JAK/STAT pathway is still an open question. Here, we detect bistability at the level of early STAT signaling, showing how two different cell outcomes are achieved under or above a threshold in ligand dose or ligand-receptor affinity. This finding could contribute to explain the differential signaling (antiviral vs apoptotic) depending on interferon dose and subtype (α vs β) observed in type I interferons.
authors.affiliation: Department of Biosystems Science and Engineering and Swiss Institute of Bioinformatics, ETH Zurich, Zurich, Switzerland.
authors.forename: Irene
authors.identifier: 0000-0003-2895-997X
authors.initials: I
authors.lastname: Otero-Muras
authors.affiliation: Department of Biosystems Science and Engineering and Swiss Institute of Bioinformatics, ETH Zurich, Zurich, Switzerland.
authors.forename: Pencho
authors.initials: P
authors.lastname: Yordanov
authors.affiliation: Department of Biosystems Science and Engineering and Swiss Institute of Bioinformatics, ETH Zurich, Zurich, Switzerland.
authors.forename: Joerg
authors.initials: J
authors.lastname: Stelling
mesh_terms: D002450:Cell Communication / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D060066:Protein Interaction Maps / Q000502:physiology*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D049490:Systems Biology
chemical_list: D007370:Interferon Type I; D050791:STAT Transcription Factors; D053612:Janus Kinases