Evidence map›Paper›PMID 32191874›Full record

ArticleCell systems2020

A Live-Cell Screen for Altered Erk Dynamics Reveals Principles of Proliferative Control.

Alexander G Goglia, Maxwell Z Wilson, Siddhartha G Jena, Jillian Silbert, Lena P Basta, Danelle Devenport, Jared E Toettcher

Open access · bronzeAbstract read
In one paragraph

Article in Cell systems, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

59 citing papers in PubMed, 92 citations in OpenAlex.

  1. Article
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  6. Review
  7. Article
  8. Optogenetic Rescue Reveals Spatiotemporal Rules of Germ-Layer Patterning.bioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. Optogenetic enzymes: A deep dive into design and impact.Current opinion in structural biology · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Methods for Controlling Small GTPase Activity.Chembiochem : a European journal of chemical biology · 2025
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. 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

7 authors at 1 institution in 1 country.

Alexander G GogliaDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544.
Maxwell Z WilsonDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544.
Siddhartha G JenaDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544.
Jillian SilbertDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544.
Lena P BastaDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544.
Danelle DevenportDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544.
Jared E ToettcherDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544. Electronic address: toettcher@princeton.edu.
Princeton University · US

Funding

PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007388 · NIGMS · PRINCETON UNIVERSITY · PI CRISTEA, ILEANA M. · 1985 to 2022
$27.4M
Harnessing optogenetics to diagnose and therapeutically rewire cancer cell signalingDP2EB024247 · NIBIB · PRINCETON UNIVERSITY · PI TOETTCHER, JARED E · 2016 to 2016
$2.4M
Optogenetic profiling of functional signaling abnormalities in triple negative breast cancerF30CA206408 · NCI · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · PI GOGLIA, ALEXANDER · 2016 to 2021
$299k
NCI NIH HHS F30 CA206408NIBIB NIH HHS DP2 EB024247NIGMS NIH HHS T32 GM007388
6 · The paper itself

Abstract

Complex, time-varying responses have been observed widely in cell signaling, but how specific dynamics are generated or regulated is largely unknown. One major obstacle has been that high-throughput screens are typically incompatible with the live-cell assays used to monitor dynamics. Here, we address this challenge by screening a library of 429 kinase inhibitors and monitoring extracellular-regulated kinase (Erk) activity over 5 h in more than 80,000 single primary mouse keratinocytes. Our screen reveals both known and uncharacterized modulators of Erk dynamics, including inhibitors of non-epidermal growth factor receptor (EGFR) receptor tyrosine kinases (RTKs) that increase Erk pulse frequency and overall activity. Using drug treatment and direct optogenetic control, we demonstrate that drug-induced changes to Erk dynamics alter the conditions under which cells proliferate. Our work opens the door to high-throughput screens using live-cell biosensors and reveals that cell proliferation integrates information from Erk dynamics as well as additional permissive cues.

Indexed as

AnimalsCell ProliferationDrug Evaluation, PreclinicalErbB ReceptorsExtracellular Signal-Regulated MAP KinasesHigh-Throughput Screening AssaysKeratinocytesMAP Kinase Signaling SystemMiceOptogeneticsPhosphorylationProto-Oncogene Proteins c-aktras ProteinsSignal TransductionErbB ReceptorsExtracellular Signal-Regulated MAP KinasesProto-Oncogene Proteins c-aktras Proteinscell proliferationcell signalingcellular decision-makingErkoptogeneticsRasreceptor tyrosine kinasesignal processingsingle-cell dynamics

Identifiers

PMID32191874
PMCPMC7540725
OpenAlexW3012041042

What OpenQuestion 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 OpenQuestion graph.