Frequency modulation of ERK activation dynamics rewires cell fate

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Erratum Frequency modulation of ERK activation dynamics.pdfErratum for article published in Mol Syst Biol. 2016 Apr 22;12(4):866. doi: 10.15252/msb.20166982.1.85 MBAdobe PDFDownload
Title: Frequency modulation of ERK activation dynamics rewires cell fate
Authors: Ryu, Hyunryul
Chung, Minhwan
Dobrzynsk, Maciej
Fey, Dirk
Kholodenko, Boris N.
et al.
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Date: 27-Nov-2015
Online since: 2019-04-03T08:27:19Z
Abstract: Transient versus sustained ERK MAP kinase (MAPK) activation dynamics induce proliferation versus differentiation in response to epidermal (EGF) or nerve (NGF) growth factors in PC-12 cells. Duration of ERK activation has therefore been proposed to specify cell fate decisions. Using a biosensor to measure ERK activation dynamics in single living cells reveals that sustained EGF/NGF application leads to a heterogeneous mix of transient and sustained ERK activation dynamics in distinct cells of the population, different than the population average. EGF biases toward transient, while NGF biases toward sustained ERK activation responses. In contrast, pulsed growth factor application can repeatedly and homogeneously trigger ERK activity transients across the cell population. These datasets enable mathematical modeling to reveal salient features inherent to the MAPK network. Ultimately, this predicts pulsed growth factor stimulation regimes that can bypass the typical feedback activation to rewire the system toward cell differentiation irrespective of growth factor identity.
Funding Details: European Commission - Seventh Framework Programme (FP7)
European Research Council
Science Foundation Ireland
University College Dublin
Type of material: Journal Article
Publisher: EMBO Press
Journal: Molecular Systems Biology
Volume: 11
Issue: 838
Copyright (published version): 2015 the Authors
Keywords: Cell fate decisionsERK activity dynamicsFRET biosensorSingle cell biologySignaling heterogeneity
DOI: 10.15252/msb.20156458
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
SBI Research Collection
Medicine Research Collection

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