Evidence map›Paper›PMID 31964804›Full record

ArticleScience signaling2020

Spatial and temporal alterations in protein structure by EGF regulate cryptic cysteine oxidation.

Jessica B Behring, Sjoerd van der Post, Arshag D Mooradian, Matthew J Egan, Maxwell I Zimmerman, Jenna L Clements, Gregory R Bowman, Jason M Held

Open access · greenAbstract read
In one paragraph

Article in Science signaling, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

36 citing papers in PubMed, 65 citations in OpenAlex.

  1. A mathematical theory of redox biology.Royal Society open science · 2026
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  5. Redox Regulation of Cell Migration via Nischarin S-glutathionylation.bioRxiv : the preprint server for biology · 2025
    Article
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  7. Review
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  10. Article
  11. Article
  12. Targeting ROS in cancer: rationale and strategies.Nature reviews. Drug discovery · 2024
    Review
  13. Article
  14. Article
  15. Article
  16. Alexander disease: the road ahead.Neural regeneration research · 2023
    Review
  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

8 authors at 1 institution in 1 country.

Jessica B BehringDepartment of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.ORCID 0000-0003-0146-7086
Sjoerd van der PostDepartment of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.ORCID 0000-0002-7965-5311
Arshag D MooradianDepartment of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.ORCID 0000-0002-5000-8620
Matthew J EganDepartment of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.ORCID 0000-0002-7701-4772
Maxwell I ZimmermanDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Jenna L ClementsDepartment of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.ORCID 0000-0003-3401-1886
Gregory R BowmanDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.ORCID 0000-0002-2083-4892
Jason M HeldDepartment of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA. jheld@wustl.edu.ORCID 0000-0001-8024-2736
Washington University in St. Louis · US

Funding

WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1M
TRAINING PROGRAM IN CELLULAR AND MOLECULAR BIOLOGYT32GM007067 · NIGMS · WASHINGTON UNIVERSITY · PI TRUE-KROB, HEATHER L · 1985 to 2020
$20.4M
INVESTIGATING NAPDH OXIDASES AND REDOX SIGNALING IN LUNG CANCER TUMORIGENICITYR01CA200893 · NCI · WASHINGTON UNIVERSITY · PI HELD, JASON M. · 2016 to 2020
$2.1M
MSMs, adaptive sampling, and data sharing on the cloudR01GM124007 · NIGMS · WASHINGTON UNIVERSITY · PI BOWMAN, GREGORY · 2017 to 2021
$2.0M
OxMRM: A Technique to Quantify Oxidation of Endogenous Redox-Sensitive CysteinesR21CA138308 · NCI · BUCK INSTITUTE FOR RESEARCH ON AGING · PI HELD, JASON M. · 2009 to 2011
$845k
The role of p53 redox-modification in cell fate signalingR21CA179452 · NCI · WASHINGTON UNIVERSITY · PI HELD, JASON M. · 2013 to 2014
$373k
NCI NIH HHS R01 CA200893NCI NIH HHS R21 CA138308NCI NIH HHS R21 CA179452NIDDK NIH HHS P30 DK020579NIGMS NIH HHS R01 GM124007NIGMS NIH HHS T32 GM007067
6 · The paper itself

Abstract

Stimulation of plasma membrane receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR), locally increases the abundance of reactive oxygen species (ROS). These ROS then oxidize cysteine residues in proteins to potentiate downstream signaling. Spatial confinement of ROS is an important regulatory mechanism of redox signaling that enables the stimulation of different RTKs to oxidize distinct sets of downstream proteins. To uncover additional mechanisms that specify cysteines that are redox regulated by EGF stimulation, we performed time-resolved quantification of the EGF-dependent oxidation of 4200 cysteine sites in A431 cells. Fifty-one percent of cysteines were statistically significantly oxidized by EGF stimulation. Furthermore, EGF induced three distinct spatiotemporal patterns of cysteine oxidation in functionally organized protein networks, consistent with the spatial confinement model. Unexpectedly, protein crystal structure analysis and molecular dynamics simulations indicated widespread redox regulation of cryptic cysteine residues that are solvent exposed only upon changes in protein conformation. Phosphorylation and increased flux of nucleotide substrates served as two distinct modes by which EGF specified the cryptic cysteine residues that became solvent exposed and redox regulated. Because proteins that are structurally regulated by different RTKs or cellular perturbations are largely unique, these findings suggest that solvent exposure and redox regulation of cryptic cysteine residues contextually delineate redox signaling networks.

Indexed as

Cell Line, TumorCell MembraneCrystallography, X-RayCysteineEpidermal Growth FactorErbB ReceptorsHumansMolecular Dynamics SimulationOxidation-ReductionPhosphorylationProtein ConformationReactive Oxygen SpeciesSignal TransductionTime FactorsCysteineEpidermal Growth FactorErbB ReceptorsReactive Oxygen Species

Identifiers

PMID31964804
PMCPMC7263378
OpenAlexW3002327160

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.