Ryu, Hyunryul; Chung, Minhwan; Dobrzyński, Maciej; Fey, Dirk; Blum, Yannick; Lee, Sung Sik; Peter, Matthias; Kholodenko, Boris N; Jeon, Noo Li; Pertz, Olivier (2015). Frequency modulation of ERK activation dynamics rewires cell fate. Molecular systems biology, 11(11), p. 838. EMBO Press 10.15252/msb.20156458
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
08 Faculty of Science > Department of Biology > Institute of Cell Biology |
UniBE Contributor: |
Pertz, Olivier |
Subjects: |
500 Science > 570 Life sciences; biology |
ISSN: |
1744-4292 |
Publisher: |
EMBO Press |
Language: |
English |
Submitter: |
Olivier Pertz |
Date Deposited: |
03 May 2016 09:42 |
Last Modified: |
05 Dec 2022 14:55 |
Publisher DOI: |
10.15252/msb.20156458 |
PubMed ID: |
26613961 |
Uncontrolled Keywords: |
ERK activity dynamics; FRET biosensor; cell fate decisions; signaling heterogeneity; single cell biology |
BORIS DOI: |
10.7892/boris.81852 |
URI: |
https://boris.unibe.ch/id/eprint/81852 |
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