Frequency modulation of ERK activation dynamics rewires cell fate
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 biosen...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2015-11-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20156458 |
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| _version_ | 1849388846887731200 |
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| author | Hyunryul Ryu Minhwan Chung Maciej Dobrzyński Dirk Fey Yannick Blum Sung Sik Lee Matthias Peter Boris N Kholodenko Noo Li Jeon Olivier Pertz |
| author_facet | Hyunryul Ryu Minhwan Chung Maciej Dobrzyński Dirk Fey Yannick Blum Sung Sik Lee Matthias Peter Boris N Kholodenko Noo Li Jeon Olivier Pertz |
| author_sort | Hyunryul Ryu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2cf411f28d784c11ad6cd201b6d7880e |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2015-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-2cf411f28d784c11ad6cd201b6d7880e2025-08-20T03:42:09ZengSpringer NatureMolecular Systems Biology1744-42922015-11-01111111410.15252/msb.20156458Frequency modulation of ERK activation dynamics rewires cell fateHyunryul Ryu0Minhwan Chung1Maciej Dobrzyński2Dirk Fey3Yannick Blum4Sung Sik Lee5Matthias Peter6Boris N Kholodenko7Noo Li Jeon8Olivier Pertz9School of Mechanical and Aerospace Engineering, Seoul National UniversitySchool of Mechanical and Aerospace Engineering, Seoul National UniversitySystem Biology Ireland, University College DublinSystem Biology Ireland, University College DublinDepartment of Biomedicine, University of BaselInstitute of BiochemistryInstitute of BiochemistrySystem Biology Ireland, University College DublinSchool of Mechanical and Aerospace Engineering, Seoul National UniversityDepartment of Biomedicine, University of BaselAbstract 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.https://doi.org/10.15252/msb.20156458cell fate decisionsERK activity dynamicsFRET biosensorsingle cell biologysignaling heterogeneity |
| spellingShingle | Hyunryul Ryu Minhwan Chung Maciej Dobrzyński Dirk Fey Yannick Blum Sung Sik Lee Matthias Peter Boris N Kholodenko Noo Li Jeon Olivier Pertz Frequency modulation of ERK activation dynamics rewires cell fate Molecular Systems Biology cell fate decisions ERK activity dynamics FRET biosensor single cell biology signaling heterogeneity |
| title | Frequency modulation of ERK activation dynamics rewires cell fate |
| title_full | Frequency modulation of ERK activation dynamics rewires cell fate |
| title_fullStr | Frequency modulation of ERK activation dynamics rewires cell fate |
| title_full_unstemmed | Frequency modulation of ERK activation dynamics rewires cell fate |
| title_short | Frequency modulation of ERK activation dynamics rewires cell fate |
| title_sort | frequency modulation of erk activation dynamics rewires cell fate |
| topic | cell fate decisions ERK activity dynamics FRET biosensor single cell biology signaling heterogeneity |
| url | https://doi.org/10.15252/msb.20156458 |
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