Evidence map›Paper›PMID 34515735›Full record

ArticleThe Journal of cell biology2021

EGFR-RAS-MAPK signaling is confined to the plasma membrane and associated endorecycling protrusions.

Sachin Surve, Simon C Watkins, Alexander Sorkin

Open access · greenAbstract read
In one paragraph

Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

20 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Subcellular Cartography of the Phosphoinositide Multiverse.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Multiplexed imaging for probing RAS-RAF interactions in living cells.Biochimica et biophysica acta. Biomembranes · 2023
    Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. TheScience signaling · 2022
    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

3 authors at 1 institution in 1 country.

Sachin SurveDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Simon C WatkinsDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA.ORCID 0000-0003-4092-1552
Alexander SorkinDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA.ORCID 0000-0002-4446-1920
University of Pittsburgh · US

Funding

PATHOGENESIS OF CANCER--ROLE OF EGF RECEPTOR ENDOCYTOSISR01CA089151 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SORKIN, ALEXANDER D · 2001 to 2023
$6.9M
Signaling by the EGF Receptor from EndosomesR01GM124186 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SORKIN, ALEXANDER D · 2017 to 2021
$1.6M
EGF Receptor Signaling in Time and Space in Tumor CellsR01CA112219 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SORKIN, ALEXANDER D · 2009 to 2012
$1.2M
NCI NIH HHS R01 CA089151NCI NIH HHS R01 CA112219NIGMS NIH HHS R01 GM124186NIH HHS CA089151
6 · The paper itself

Abstract

The subcellular localization of RAS GTPases defines the operational compartment of the EGFR-ERK1/2 signaling pathway within cells. Hence, we used live-cell imaging to demonstrate that endogenous KRAS and NRAS tagged with mNeonGreen are predominantly localized to the plasma membrane. NRAS was also present in the Golgi apparatus and a tubular, plasma-membrane derived endorecycling compartment, enriched in recycling endosome markers (TERC). In EGF-stimulated cells, there was essentially no colocalization of either mNeonGreen-KRAS or mNeonGreen-NRAS with endosomal EGFR, which, by contrast, remained associated with endogenous Grb2-mNeonGreen, a receptor adaptor upstream of RAS. ERK1/2 activity was diminished by blocking cell surface EGFR with cetuximab, even after most ligand-bound, Grb2-associated EGFRs were internalized. Endogenous mCherry-tagged RAF1, an effector of RAS, was recruited to the plasma membrane, with subsequent accumulation in mNG-NRAS-containing TERCs. We propose that a small pool of surface EGFRs sustain signaling within the RAS-ERK1/2 pathway and that RAS activation persists in TERCs, whereas endosomal EGFR does not significantly contribute to ERK1/2 activity.

Indexed as

Cell Line, TumorCell MembraneEndocytosisEndosomesEpidermal Growth FactorErbB ReceptorsGRB2 Adaptor ProteinHeLa CellsHumansLigandsMAP Kinase Signaling SystemMitogen-Activated Protein KinasesProtein Bindingras ProteinsSignal TransductionEGFR protein, humanEpidermal Growth FactorErbB ReceptorsGRB2 Adaptor ProteinLigandsMitogen-Activated Protein Kinasesras Proteins

Identifiers

PMID34515735
PMCPMC8563293
OpenAlexW3199769568

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.