Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling.
Mol Syst Biol
; 15(11): e8947, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31777174
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator 2 de Crescimento de Fibroblastos
/
Sistema de Sinalização das MAP Quinases
/
MAP Quinases Reguladas por Sinal Extracelular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article