Chemical Reaction Network Theory elucidates sources of multistability in interferon signaling

Open access
Author
Otero-Muras, Irene
Yordanov, Pencho
Stelling, Joerg
Date
2017-04Type
- Journal Article
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 Show more
Permanent link
https://doi.org/10.3929/ethz-b-000190744Publication status
publishedJournal / series
PLoS Computational BiologyVolume
Pages
Publisher
Public Library of ScienceOrganisational unit
03699 - Stelling, Jörg03699 - Stelling, Jörg
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