Evidence map›Paper›PMID 25281742›Full record

ArticleThe Journal of biological chemistry2014

The Eph tyrosine kinase receptors EphB2 and EphA2 are novel proteolytic substrates of tissue factor/coagulation factor VIIa.

Oskar Eriksson, Margareta Ramström, Katarina Hörnaeus, Jonas Bergquist, Dariush Mokhtari, Agneta Siegbahn

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.2field-weighted citation impact, top 25% 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

13 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
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  8. Review
  9. Therapeutic potential of targeting the Eph/ephrin signaling complex.The international journal of biochemistry & cell biology · 2018
    Review
  10. Review
  11. Article
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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

6 authors at 3 institutions in 1 country.

Oskar ErikssonFrom the Department of Medical Sciences, Clinical Chemistry, Uppsala University Hospital, SE-751 85 Uppsala, Science for Life Laboratory, Uppsala University, Sweden.
Margareta Ramströmthe Department of Chemistry, Analytical Chemistry, BMC, SE-751 24 Uppsala, and Science for Life Laboratory, Uppsala University, Sweden.
Katarina Hörnaeusthe Department of Chemistry, Analytical Chemistry, BMC, SE-751 24 Uppsala, and Science for Life Laboratory, Uppsala University, Sweden.
Jonas Bergquistthe Department of Chemistry, Analytical Chemistry, BMC, SE-751 24 Uppsala, and Science for Life Laboratory, Uppsala University, Sweden.
Dariush MokhtariFrom the Department of Medical Sciences, Clinical Chemistry, Uppsala University Hospital, SE-751 85 Uppsala, Science for Life Laboratory, Uppsala University, Sweden.
Agneta SiegbahnFrom the Department of Medical Sciences, Clinical Chemistry, Uppsala University Hospital, SE-751 85 Uppsala, Science for Life Laboratory, Uppsala University, Sweden agneta.siegbahn@medsci.uu.se.
Science for Life Laboratory · SEUppsala University · SEUppsala University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tissue factor (TF) binds the serine protease factor VIIa (FVIIa) to form a proteolytically active complex that can trigger coagulation or activate cell signaling. Here we addressed the involvement of tyrosine kinase receptors (RTKs) in TF/FVIIa signaling by antibody array analysis and subsequently found that EphB2 and EphA2 of the Eph RTK family were cleaved in their ectodomains by TF/FVIIa. We used N-terminal Edman sequencing and LC-MS/MS analysis to characterize the cleaved Eph isoforms and identified a key arginine residue at the cleavage site, in agreement with the tryptic serine protease activity of FVIIa. Protease-activated receptor 2 (PAR2) signaling and downstream coagulation activity was non-essential in this context, in further support of a direct cleavage by TF/FVIIa. EphB2 was cleaved by FVIIa concentrations in the subnanomolar range in a number of TF expressing cell types, indicating that the active cellular pool of TF was involved. FVIIa caused potentiation of cell repulsion by the EphB2 ligand ephrin-B1, demonstrating a novel proteolytical event to control Eph-mediated cell segregation. These results define Eph RTKs as novel proteolytical targets of TF/FVIIa and provide new insights into how TF/FVIIa regulates cellular functions independently of PAR2.

Indexed as

Amino Acid SequenceBinding SitesBlotting, WesternCell Line, TumorCell MovementCells, CulturedDisulfidesFactor VIIFactor VIIaHumansModels, MolecularMolecular Sequence DataOxidation-ReductionProtein BindingProtein Structure, TertiaryProteolysisDisulfidesFactor VIIFactor VIIaReceptor, EphA2Receptor, EphB2ThromboplastinCoagulation FactorMass Spectrometry (MS)Receptor Tyrosine KinaseSerine ProteaseTissue Factor

Identifiers

PMID25281742
PMCPMC4239594
OpenAlexW2012386252

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.