Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling
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44320_2019_Article_BFMSB198947.pdf
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Author(s)
Blum, Yannick
Mikelson, Jan
Dobrzyński, Maciej
Ryu, Hyunryul
Jacques, Marc‐Antoine
Jeon, Noo L.
Khammash, Mustafa
Pertz, Olivier
Date Issued
November 19, 2019
Journal
Molecular Systems Biology
Publisher
Nature Publishing Group UK
Citation
Molecular Systems Biology. 2019 Nov 19;15(11):MSB198947
Version
Final published version
Abstract
Stimulation of PC‐12 cells with epidermal (EGF) versus nerve (NGF) growth factors (GFs) biases the distribution between transient and sustained single‐cell ERK activity states, and between proliferation and differentiation fates within a cell population. We report that fibroblast GF (FGF2) evokes a distinct behavior that consists of a gradually changing population distribution of transient/sustained ERK signaling states in response to increasing inputs in a dose response. Temporally controlled GF perturbations of MAPK signaling dynamics applied using microfluidics reveal that this wider mix of ERK states emerges through the combination of an intracellular feedback, and competition of FGF2 binding to FGF receptors (FGFRs) and heparan sulfate proteoglycan (HSPG) co‐receptors. We show that the latter experimental modality is instructive for model selection using a Bayesian parameter inference. Our results provide novel insights into how different receptor tyrosine kinase (RTK) systems differentially wire the MAPK network to fine‐tune fate decisions at the cell population level.
MIT Department
Massachusetts Institute of Technology. Research Laboratory of Electronics
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.15252/msb.20198947
