Evidence map›Paper›PMID 32452765›Full record

ArticleeLife2020

Signaling diversity enabled by Rap1-regulated plasma membrane ERK with distinct temporal dynamics.

Jeremiah Keyes, Ambhighainath Ganesan, Olivia Molinar-Inglis, Archer Hamidzadeh, Jinfan Zhang, Megan Ling, JoAnn Trejo, Andre Levchenko, Jin Zhang

Open access · goldAbstract read
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

47 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
  2. Novel fenoterol derivatives as suppressors of ERK1/2 phosphorylation in melanoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026
    Article
  3. A Constellation of Fluorescent Biosensors to Illuminate the Galaxy of Protein Kinases.Chembiochem : a European journal of chemical biology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Sensitive and Selective Next-Generation FRET-based PKA Biosensors.bioRxiv : the preprint server for biology · 2026
    Article
  9. Histamine HPharmaceuticals (Basel, Switzerland) · 2026
    Article
  10. Article
  11. Two novel red-FRET ERK bosensors in the 670-720 nm range.Journal of biological engineering · 2025
    Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Lysosomal PIPProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Article
  19. Review
  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

9 authors at 3 institutions in 1 country.

Jeremiah KeyesDepartment of Pharmacology, University of California San Diego, La Jolla, United States.ORCID 0000-0003-4253-6834
Ambhighainath GanesanDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, United States.
Olivia Molinar-InglisDepartment of Pharmacology, University of California San Diego, La Jolla, United States.
Archer HamidzadehDepartment of Biomedical Engineering and Yale Systems Biology Institute, Yale University, New Haven, United States.
Jinfan ZhangDepartment of Pharmacology, University of California San Diego, La Jolla, United States.
Megan LingDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, United States.
JoAnn TrejoDepartment of Pharmacology, University of California San Diego, La Jolla, United States.
Andre LevchenkoDepartment of Biomedical Engineering and Yale Systems Biology Institute, Yale University, New Haven, United States.
Jin ZhangDepartment of Pharmacology, University of California San Diego, La Jolla, United States.ORCID 0000-0001-7145-7823
University of California San Diego · USYale University · USJohns Hopkins University · US

Funding

UCSD/SDSU IRACDAK12GM068524 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2003 to 2025
$24.4M
Live-cell Activity Architecture in CancerR35CA197622 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2015 to 2026
$11.2M
Mechanisms of Compartmentalized cAMP SignalingR01DK073368 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2006 to 2026
$7.6M
Cell Signaling by Protease-activated G Protein-coupled ReceptorsR35GM127121 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Joann Trejo · 2018 to 2026
$4.5M
NCI NIH HHS R35 CA197622NIDDK NIH HHS R01 DK073368NIGMS NIH HHS K12 GM068524NIGMS NIH HHS R35 GM127121
6 · The paper itself

Abstract

A variety of different signals induce specific responses through a common, extracellular-signal regulated kinase (ERK)-dependent cascade. It has been suggested that signaling specificity can be achieved through precise temporal regulation of ERK activity. Given the wide distrubtion of ERK susbtrates across different subcellular compartments, it is important to understand how ERK activity is temporally regulated at specific subcellular locations. To address this question, we have expanded the toolbox of Förster Resonance Energy Transfer (FRET)-based ERK biosensors by creating a series of improved biosensors targeted to various subcellular regions via sequence specific motifs to measure spatiotemporal changes in ERK activity. Using these sensors, we showed that EGF induces sustained ERK activity near the plasma membrane in sharp contrast to the transient activity observed in the cytoplasm and nucleus. Furthermore, EGF-induced plasma membrane ERK activity involves Rap1, a noncanonical activator, and controls cell morphology and EGF-induced membrane protrusion dynamics. Our work strongly supports that spatial and temporal regulation of ERK activity is integrated to control signaling specificity from a single extracellular signal to multiple cellular processes.

Indexed as

AnimalsEpidermal Growth FactorExtracellular Signal-Regulated MAP KinasesHEK293 CellsHumansPC12 Cellsrac1 GTP-Binding Proteinrap1 GTP-Binding ProteinsRatsEpidermal Growth FactorExtracellular Signal-Regulated MAP Kinasesrac1 GTP-Binding Proteinrap1 GTP-Binding Proteinsbiochemistrycell biologychemical biologyEGFERKnonePC12Rap1signal transductionspatiotemporal

Identifiers

PMID32452765
PMCPMC7289600
OpenAlexW3031732023

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.