Evidence map›Paper›PMID 24501219›Full record

ArticleBlood2014

Quantitative phosphoproteomics unveils temporal dynamics of thrombin signaling in human endothelial cells.

Maartje van den Biggelaar, Juan Ramon Hernández-Fernaud, Bart L van den Eshof, Lisa J Neilson, Alexander B Meijer, Koen Mertens, Sara Zanivan

Abstract read
In one paragraph

Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Phosphoproteomics data-driven signalling network inference: Does it work?Computational and structural biotechnology journal · 2023
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Protease-Activated Receptor-1 Signaling: The Big Picture.Arteriosclerosis, thrombosis, and vascular biology · 2017
    Article
  16. Article
  17. Review
  18. Targeting PAR1: Now What?Trends in pharmacological sciences · 2017
    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

7 authors at 3 institutions in 2 countries.

Maartje van den BiggelaarDepartment of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands;
Juan Ramon Hernández-Fernaud
Bart L van den Eshof
Lisa J Neilson
Alexander B Meijer
Koen Mertens
Sara Zanivan
Cancer Research UK Scotland Institute · GBSanquin · NLUtrecht University · NL

Funding

Cancer Research UK 12935
6 · The paper itself

Abstract

Thrombin is the key serine protease of the coagulation cascade and a potent trigger of protease-activated receptor 1 (PAR1)-mediated platelet aggregation. In recent years, PAR1 has become an appealing target for anticoagulant therapies. However, the inhibitors that have been developed so far increase bleeding risk in patients, likely because they interfere with endogenous PAR1 signaling in the endothelium. Because of its complexity, thrombin-induced signaling in endothelial cells has remained incompletely understood. Here, we have combined stable isotope amino acids in cell culture, affinity-based phosphopeptide enrichment, and high-resolution mass spectrometry and performed a time-resolved analysis of the thrombin-induced signaling in human primary endothelial cells. We identified 2224 thrombin-regulated phosphorylation sites, the majority of which have not been previously related to thrombin. Those sites were localized on proteins that are novel to thrombin signaling, but also on well-known players such as PAR1, Rho-associated kinase 2, phospholipase C, and proteins related to actin cytoskeleton, cell-cell junctions, and Weibel-Palade body release. Our study provides a unique resource of phosphoproteins and phosphorylation sites that may generate novel insights into an intimate understanding of thrombin-mediated PAR signaling and the development of improved PAR1 antagonists that affect platelet but not endothelial cell function.

Indexed as

ActinsAdherens JunctionsCells, CulturedCytoskeletonEndothelial CellsHumansMass SpectrometryModels, BiologicalPhosphoproteinsProteomicsReceptor, PAR-1rhoA GTP-Binding ProteinSignal TransductionThrombinTight JunctionsWeibel-Palade BodiesActinsPhosphoproteinsReceptor, PAR-1rhoA GTP-Binding ProteinRHOA protein, humanThrombin

Identifiers

PMID24501219
PMCPMC3962174
OpenAlexW2057951190

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.