Evidence map›Paper›PMID 19823572›Full record

ArticlePLoS biology2009

Cytoplasmic relaxation of active Eph controls ephrin shedding by ADAM10.

Peter W Janes, Sabine H Wimmer-Kleikamp, Achilleas S Frangakis, Kane Treble, Bettina Griesshaber, Ola Sabet, Markus Grabenbauer, Alice Y Ting, Paul Saftig, Philippe I Bastiaens and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2009. 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
3.3field-weighted citation impact, top 7% 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, 76 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Targeting the EphA2 pathway: could it be the way for bone sarcomas?Cell communication and signaling : CCS · 2024
    Review
  5. Article
  6. Review
  7. Fully human monoclonal antibody targeting activated ADAM10 on colorectal cancer cells.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. ADAM Proteases and Gastrointestinal Function.Annual review of physiology · 2016
    Review
  20. 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

11 authors at 5 institutions in 3 countries.

Peter W JanesDepartment of Biochemistry and Molecular Biology, Monash University, Victoria, Australia.
Sabine H Wimmer-Kleikamp
Achilleas S Frangakis
Kane Treble
Bettina Griesshaber
Ola Sabet
Markus Grabenbauer
Alice Y Ting
Paul Saftig
Philippe I Bastiaens
Martin Lackmann
Monash University · AUMax Planck Institute of Molecular Physiology · DEEuropean Molecular Biology Laboratory · DEKiel University · DEMassachusetts Institute of Technology · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Release of cell surface-bound ligands by A-Disintegrin-And-Metalloprotease (ADAM) transmembrane metalloproteases is essential for signalling by cytokine, cell adhesion, and tyrosine kinase receptors. For Eph receptor ligands, it provides the switch between cell-cell adhesion and repulsion. Ligand shedding is tightly controlled by intrinsic tyrosine kinase activity, which for Eph receptors relies on the release of an inhibitory interaction of the cytoplasmic juxtamembrane segment with the kinase domain. However, a mechanism linking kinase and sheddase activities had remained elusive. We demonstrate that it is a membrane-proximal localisation of the latent kinase domain that prevents ephrin ligand shedding in trans. Fluorescence lifetime imaging microscopy and electron tomography reveal that activation extends the Eph receptor tyrosine kinase intracellular domain away from the cell membrane into a conformation that facilitates productive association with ADAM10. Accordingly, EphA3 mutants with constitutively-released kinase domains efficiently support shedding, even when their kinase is disabled. Our data suggest that this phosphorylation-activated conformational switch of EphA3 directly controls ADAM-mediated shedding.

Indexed as

ADAM10 ProteinADAM ProteinsAmyloid Precursor Protein SecretasesCalmodulinCell LineEphrin-A3EphrinsHumansL-SelectinMembrane ProteinsQuantum DotsReceptors, Eph FamilyADAM10 ProteinADAM10 protein, humanADAM ProteinsAmyloid Precursor Protein SecretasesCalmodulinEphrin-A3EphrinsL-SelectinMembrane ProteinsReceptors, Eph Family

Identifiers

PMID19823572
PMCPMC2753297
OpenAlexW2126611497

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.