Robustness and Information Transfer within IL-6-induced JAK/STAT Signalling
- Author(s)
- Ulrike Billing, Tomasz Jetka, Lukas Nortmann, Nicole Wundrack, Michal Komorowski, Steffen Waldherr, Fred Schaper, Anna Dittrich
- 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.
- Organisation(s)
- Functional and Evolutionary Ecology
- External organisation(s)
- Otto-von-Guericke-Universität Magdeburg, Polish Academy of Sciences, Katholieke Universiteit Leuven
- Journal
- Communications Biology
- Volume
- 2
- ISSN
- 2399-3642
- DOI
- https://doi.org/10.1038/s42003-018-0259-4
- Publication date
- 12-2019
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106044 Systems biology
- ASJC Scopus subject areas
- Medicine (miscellaneous), General Biochemistry,Genetics and Molecular Biology, General Agricultural and Biological Sciences
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/96d91f14-e65c-4707-b3c6-4b62882f0038