Evidence map›Paper›PMID 35694820›Full record

ArticleMolecular systems biology2022

Optogenetic actuator - ERK biosensor circuits identify MAPK network nodes that shape ERK dynamics.

Coralie Dessauges, Jan Mikelson, Maciej Dobrzyński, Marc-Antoine Jacques, Agne Frismantiene, Paolo Armando Gagliardi, Mustafa Khammash, Olivier Pertz

Open access · goldAbstract read
In one paragraph

Article in Molecular systems biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Article
  3. Methods for Controlling Small GTPase Activity.Chembiochem : a European journal of chemical biology · 2025
    Review
  4. Review
  5. Article
  6. Article
  7. Optogenetic Regulation of EphA1 RTK Activation and Signaling.bioRxiv : the preprint server for biology · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Rapid optogenetic clustering of a cytoplasmic BcLOV4 variant.bioRxiv : the preprint server for biology · 2023
    Article
  14. The MAPK/ERK channel capacity exceeds 6 bit/hour.PLoS computational biology · 2023
    Article
  15. Dynamic regulation of RAS and RAS signaling.The Biochemical journal · 2023
    Article
  16. Article
  17. Article
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Coralie DessaugesInstitute of Cell Biology, University of Bern, Bern, Switzerland.ORCID 0000-0002-0817-6874
Jan MikelsonDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.ORCID 0000-0001-5233-4756
Maciej DobrzyńskiInstitute of Cell Biology, University of Bern, Bern, Switzerland.ORCID 0000-0002-0208-7758
Marc-Antoine JacquesInstitute of Cell Biology, University of Bern, Bern, Switzerland.ORCID 0000-0002-8224-9285
Agne FrismantieneInstitute of Cell Biology, University of Bern, Bern, Switzerland.ORCID 0000-0002-2018-2986
Paolo Armando GagliardiInstitute of Cell Biology, University of Bern, Bern, Switzerland.ORCID 0000-0002-4818-035X
Mustafa KhammashDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.ORCID 0000-0002-4855-9220
Olivier PertzInstitute of Cell Biology, University of Bern, Bern, Switzerland.ORCID 0000-0001-8579-4919
University of Bern · CHETH Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Combining single-cell measurements of ERK activity dynamics with perturbations provides insights into the MAPK network topology. We built circuits consisting of an optogenetic actuator to activate MAPK signaling and an ERK biosensor to measure single-cell ERK dynamics. This allowed us to conduct RNAi screens to investigate the role of 50 MAPK proteins in ERK dynamics. We found that the MAPK network is robust against most node perturbations. We observed that the ERK-RAF and the ERK-RSK2-SOS negative feedback operate simultaneously to regulate ERK dynamics. Bypassing the RSK2-mediated feedback, either by direct optogenetic activation of RAS, or by RSK2 perturbation, sensitized ERK dynamics to further perturbations. Similarly, targeting this feedback in a human ErbB2-dependent oncogenic signaling model increased the efficiency of a MEK inhibitor. The RSK2-mediated feedback is thus important for the ability of the MAPK network to produce consistent ERK outputs, and its perturbation can enhance the efficiency of MAPK inhibitors.

Indexed as

Biosensing TechniquesOptogeneticsHumansMAP Kinase Signaling SystemPhosphorylationProtein Kinase InhibitorsSignal TransductionProtein Kinase InhibitorsERK dynamicsMAPK networkoptogeneticssignaling robustnesssingle-cell biology

Identifiers

PMID35694820
PMCPMC9189677
OpenAlexW4282549436

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.