Evidence map›Paper›PMID 28320942›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

EGF and NRG induce phosphorylation of HER3/ERBB3 by EGFR using distinct oligomeric mechanisms.

Bettina van Lengerich, Christopher Agnew, Elias M Puchner, Bo Huang, Natalia Jura

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

63 citing papers in PubMed, 87 citations in OpenAlex.

  1. Review
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  10. HER4 is a high-affinity dimerization partner for all EGFR/HER/ErbB family proteins.Protein science : a publication of the Protein Society · 2024
    Article
  11. Article
  12. Review
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  17. HER4 and EGFR Activate Cell Signaling in NRG1 Fusion-Driven Cancers: Implications for HER2-HER3-specific Versus Pan-HER Targeting Strategies.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2024
    Article
  18. Article
  19. Review
  20. Review

3 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 1 country.

Bettina van LengerichCardiovascular Research Institute, University of California, San Francisco, CA 94158.
Christopher AgnewCardiovascular Research Institute, University of California, San Francisco, CA 94158.
Elias M PuchnerSchool of Physics and Astronomy, University of Minnesota, Twin Cities, Minneapolis, MN 55455.
Bo HuangDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158.
Natalia JuraCardiovascular Research Institute, University of California, San Francisco, CA 94158; natalia.jura@ucsf.edu.
University of California, San Francisco · USUniversity of Minnesota · US

Funding

Solving macromolecular complex architecture in situ by super-resolution microscopDP2OD008479 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, BO · 2011 to 2011
$2.3M
Structural and Functional Studies of HER Receptor Tyrosine KinasesR01GM109176 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JURA, NATALIA · 2014 to 2018
$1.8M
NIGMS NIH HHS R01 GM109176NIH HHS DP2 OD008479
6 · The paper itself

Abstract

Heteromeric interactions between the catalytically impaired human epidermal growth factor receptor (HER3/ERBB3) and its catalytically active homologs EGFR and HER2 are essential for their signaling. Different ligands can activate these receptor pairs but lead to divergent signaling outcomes through mechanisms that remain largely unknown. We used stochastic optical reconstruction microscopy (STORM) with pair-correlation analysis to show that EGF and neuregulin (NRG) can induce different extents of HER3 clustering that are dependent on the nature of the coexpressed HER receptor. We found that the presence of these clusters correlated with distinct patterns and mechanisms of receptor phosphorylation. NRG induction of HER3 phosphorylation depended on the formation of the asymmetric kinase dimer with EGFR in the absence of detectable higher-order oligomers. Upon EGF stimulation, HER3 paralleled previously observed EGFR behavior and formed large clusters within which HER3 was phosphorylated via a noncanonical mechanism. HER3 phosphorylation by HER2 in the presence of NRG proceeded through still another mechanism and involved the formation of clusters within which receptor phosphorylation depended on asymmetric kinase dimerization. Our results demonstrate that the higher-order organization of HER receptors is an essential feature of their ligand-induced behavior and plays an essential role in lateral cross-activation of the receptors. We also show that HER receptor ligands exert unique effects on signaling by modulating this behavior.

Indexed as

AnimalsCell LineEpidermal Growth FactorErb-b2 Receptor Tyrosine KinasesErbB ReceptorsHEK293 CellsHumansMiceMicroscopyMolecular ImagingNeuregulin-1PhosphorylationProtein MultimerizationReceptor, ErbB-3EGFR protein, humanEpidermal Growth FactorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesERBB3 protein, humanErbB ReceptorsNeuregulin-1Receptor, ErbB-3EGFR activationHER/ERBB receptorsreceptor clusteringreceptor tyrosine kinase signalingSTORM

Identifiers

PMID28320942
PMCPMC5389333
OpenAlexW2600590737

What OpenQuestion holds

Textmetadata
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.