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Frequency modulation of ERK activation dynamics rewires cell fate.
Journal article

Frequency modulation of ERK activation dynamics rewires cell fate.

  • Ryu H School of Mechanical and Aerospace Engineering Seoul National University, Seoul, Korea Institute of Advanced Machinery and Design Seoul National University, Seoul, Korea.
  • Chung M School of Mechanical and Aerospace Engineering Seoul National University, Seoul, Korea.
  • Dobrzyński M System Biology Ireland, University College Dublin, Belfield Dublin, Ireland.
  • Fey D System Biology Ireland, University College Dublin, Belfield Dublin, Ireland.
  • Blum Y Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Lee SS Institute of Biochemistry, Zurich, Switzerland.
  • Peter M Institute of Biochemistry, Zurich, Switzerland.
  • Kholodenko BN System Biology Ireland, University College Dublin, Belfield Dublin, Ireland boris.kholodenko@ucd.ie njeon@snu.ac.kr olivier.pertz@izb.unibe.ch.
  • Jeon NL School of Mechanical and Aerospace Engineering Seoul National University, Seoul, Korea Institute of Advanced Machinery and Design Seoul National University, Seoul, Korea boris.kholodenko@ucd.ie njeon@snu.ac.kr olivier.pertz@izb.unibe.ch.
  • Pertz O Department of Biomedicine, University of Basel, Basel, Switzerland boris.kholodenko@ucd.ie njeon@snu.ac.kr olivier.pertz@izb.unibe.ch.
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  • 2015-11-29
Published in:
  • Molecular systems biology. - 2015
ERK activity dynamics
FRET biosensor
cell fate decisions
signaling heterogeneity
single cell biology
Animals
Biosensing Techniques
Cell Differentiation
Extracellular Signal-Regulated MAP Kinases
Fluorescence Resonance Energy Transfer
Intercellular Signaling Peptides and Proteins
Microfluidic Analytical Techniques
Models, Biological
PC12 Cells
Rats
Signal Transduction
Systems Biology
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/93917
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