Frequency modulation of ERK activation dynamics rewires cell fate
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|Erratum Frequency modulation of ERK activation dynamics.pdf||Erratum for article published in Mol Syst Biol. 2016 Apr 22;12(4):866. doi: 10.15252/msb.20166982.||1.85 MB||Adobe PDF||Download|
|Title:||Frequency modulation of ERK activation dynamics rewires cell fate||Authors:||Ryu, Hyunryul
Kholodenko, Boris N.
|Permanent link:||http://hdl.handle.net/10197/9781||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 decisions; ERK activity dynamics; FRET biosensor; Single cell biology; Signaling 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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