Robustness and Information Transfer within IL-6-induced JAK/STAT Signalling
Ulrike Billing,Tomasz Jetka,Lukas Nortmann,Nicole Wundrack,Michał Komorowski,Steffen Waldherr,Fred Schaper,Anna Dittrich +7 more
- Vol. 2, Iss: 1, pp 27-27
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TLDR
Mechanisms preventing dysregulated signalling by enabling reliable JAK/STAT signalling despite cell-to-cell heterogeneity are elucidated.Abstract:
Cellular communication via intracellular signalling pathways is crucial. Expression and activation of signalling proteins is heterogenous between isogenic cells of the same cell-type. However, mechanisms evolved to enable sufficient communication and to ensure cellular functions. We use information theory to clarify mechanisms facilitating IL-6-induced JAK/STAT signalling despite cell-to-cell variability. We show that different mechanisms enabling robustness against variability complement each other. Early STAT3 activation is robust as long as cytokine concentrations are low. Robustness at high cytokine concentrations is ensured by high STAT3 expression or serine phosphorylation. Later the feedback-inhibitor SOCS3 increases robustness. Channel Capacity of JAK/STAT signalling is limited by cell-to-cell variability in STAT3 expression and is affected by the same mechanisms governing robustness. Increasing STAT3 amount increases Channel Capacity and robustness, whereas increasing STAT3 tyrosine phosphorylation reduces robustness but increases Channel Capacity. In summary, we elucidate mechanisms preventing dysregulated signalling by enabling reliable JAK/STAT signalling despite cell-to-cell heterogeneity.read more
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References
More filters
Journal ArticleDOI
A mathematical theory of communication
TL;DR: This final installment of the paper considers the case where the signals or the messages or both are continuously variable, in contrast with the discrete nature assumed until now.
Journal ArticleDOI
Systematic review and meta-analysis
TL;DR: In this review the usual methods applied in systematic reviews and meta-analyses are outlined, and the most common procedures for combining studies with binary outcomes are described, illustrating how they can be done using Stata commands.
BookDOI
Density estimation for statistics and data analysis
TL;DR: The Kernel Method for Multivariate Data: Three Important Methods and Density Estimation in Action.
Journal ArticleDOI
Principles of interleukin (IL)-6-type cytokine signalling and its regulation.
Peter C. Heinrich,Iris Behrmann,Serge Haan,Heike M. Hermanns,Gerhard Müller-Newen,Fred Schaper +5 more
TL;DR: This review focuses on recent progress in the understanding of the molecular mechanisms of IL-6-type cytokine signal transduction, with emphasis on the termination and modulation of the JAK/STAT signalling pathway mediated by tyrosine phosphatases, the SOCS (suppressor of cytokine signalling) feedback inhibitors and PIAS (protein inhibitor of activated STAT) proteins.
Journal ArticleDOI
The pro- and anti-inflammatory properties of the cytokine interleukin-6
TL;DR: It turns out that regenerative or anti-inflammatory activities of interleukin-6 are mediated by classic signaling whereas pro-inflammatory responses of interLEukin -6 are rather mediated by trans-signaling.