Frequency modulation of ERK activation dynamics rewires cell fate.

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

[img]
Preview
Text
838.full.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (1MB) | Preview

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:

03 May 2016 09:42

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

Actions (login required)

Edit item Edit item
Provide Feedback