Evidence map›Paper›PMID 37989743›Full record

ArticleNature communications2023

Quantification of ligand and mutation-induced bias in EGFR phosphorylation in direct response to ligand binding.

Daniel Wirth, Ece Özdemir, Kalina Hristova

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

10 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. The role of kinase domain dimerization in EGFR activation.Structure (London, England : 1993) · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Frontiers in pharmacology · 2024
    Article
  10. Review
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.

Daniel WirthDepartment of Materials Science and Engineering and Institute for NanoBioTechnology, Johns Hopkins University, 3400 Charles Street, Baltimore, MD, 21218, USA.ORCID 0000-0003-3712-7841
Ece ÖzdemirDepartment of Materials Science and Engineering and Institute for NanoBioTechnology, Johns Hopkins University, 3400 Charles Street, Baltimore, MD, 21218, USA.
Kalina HristovaDepartment of Materials Science and Engineering and Institute for NanoBioTechnology, Johns Hopkins University, 3400 Charles Street, Baltimore, MD, 21218, USA. kh@jhu.edu.ORCID 0000-0003-4274-4406
Johns Hopkins University · US

Funding

Seeking the Physical Basis of AchondroplasiaR01GM068619 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI HRISTOVA, KALINA · 2004 to 2022
$5.4M
NIGMS NIH HHS R01 GM068619Wellcome Trust 068619
6 · The paper itself

Abstract

Signaling bias is the ability of a receptor to differentially activate downstream signaling pathways in response to different ligands. Bias investigations have been hindered by inconsistent results in different cellular contexts. Here we introduce a methodology to identify and quantify bias in signal transduction across the plasma membrane without contributions from feedback loops and system bias. We apply the methodology to quantify phosphorylation efficiencies and determine absolute bias coefficients. We show that the signaling of epidermal growth factor receptor (EGFR) to EGF and TGFα is biased towards Y1068 and against Y1173 phosphorylation, but has no bias for epiregulin. We further show that the L834R mutation found in non-small-cell lung cancer induces signaling bias as it switches the preferences to Y1173 phosphorylation. The knowledge gained here challenges the current understanding of EGFR signaling in health and disease and opens avenues for the exploration of biased inhibitors as anti-cancer therapies.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsEpidermal Growth FactorErbB ReceptorsHumansLigandsMutationPhosphorylationEGFR protein, humanEpidermal Growth FactorErbB ReceptorsLigands

Identifiers

PMID37989743
PMCPMC10663608
OpenAlexW4388856818

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.