Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling.

Blum, Yannick; Mikelson, Jan; Dobrzynski, Maciej; Ryu, Hyunryul; Jacques, Marc-Antoine; Jeon, Noo Li; Khammash, Mustafa; Pertz, Olivier (2019). Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling. Molecular systems biology, 15(11), e8947. EMBO Press 10.15252/msb.20198947

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

09 Interdisciplinary Units > Microscopy Imaging Center (MIC)
08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Dobrzynski, Maciej; Jacques, Marc-Antoine and Pertz, Olivier

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1744-4292

Publisher:

EMBO Press

Language:

English

Submitter:

Olivier Pertz

Date Deposited:

20 Feb 2020 16:18

Last Modified:

27 Feb 2020 18:09

Publisher DOI:

10.15252/msb.20198947

PubMed ID:

31777174

Uncontrolled Keywords:

ERK signaling dynamics cell fate determination mechanistic modeling microfluidics parameter estimation

BORIS DOI:

10.7892/boris.139846

URI:

https://boris.unibe.ch/id/eprint/139846

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