Open AccessTemporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling
Author(s) -
Blum Yannick,
Mikelson Jan,
Dobrzyński Maciej,
Ryu Hyunryul,
Jacques MarcAntoine,
Jeon Noo Li,
Khammash Mustafa,
Pertz Olivier
Publication year - 2019
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20198947
Subject(s) - library science , computer science
Stimulation of PC ‐12 cells with epidermal ( EGF ) versus nerve ( NGF ) growth factors ( GF s) 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 ( FGF 2) 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 FGF 2 binding to FGF receptors ( FGFR s) 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.