Evidence map›Paper›PMID 31436532›Full record

ArticleeLife2019

Heparan sulfates are critical regulators of the inhibitory megakaryocyte-platelet receptor G6b-B.

Timo Vögtle, Sumana Sharma, Jun Mori, Zoltan Nagy, Daniela Semeniak, Cyril Scandola, Mitchell J Geer, Christopher W Smith, Jordan Lane, Scott Pollack and 18 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.4field-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

30 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Article
  3. Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026
    Review
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  19. Inside-to-outside and back to the future of megakaryopoiesis.Research and practice in thrombosis and haemostasis · 2023
    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

28 authors at 8 institutions in 4 countries.

Timo VögtleInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.ORCID 0000-0002-9400-4701
Sumana SharmaCell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.ORCID 0000-0003-0598-2181
Jun MoriInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.ORCID 0000-0002-6212-1604
Zoltan NagyInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.ORCID 0000-0001-6517-2071
Daniela SemeniakInstitute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany.
Cyril ScandolaUniversité de Strasbourg, Institut National de la Santé et de la Recherche Médicale, Etablissement Français du Sang Grand Est, Unité Mixte de Recherche-S 1255, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France.
Mitchell J GeerInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.ORCID 0000-0003-1457-987X
Christopher W SmithInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Jordan LaneSygnature Discovery Limited, Nottingham, United Kingdom.
Scott PollackSygnature Discovery Limited, Nottingham, United Kingdom.ORCID 0000-0002-8176-0997
Riitta LassilaCoagulation Disorders Unit, Department of Hematology, Comprehensive Cancer Center, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.ORCID 0000-0002-1911-3094
Annukka JouppilaCoagulation Disorders Unit, Helsinki University Hospital Research Institute, Helsinki, Finland.
Alastair J BarrDepartment of Biomedical Science, Faculty of Science & Technology, University of Westminster, London, United Kingdom.ORCID 0000-0001-7738-8419
Derek J OggPeak Proteins Limited, Alderley Park, Cheshire, United Kingdom.ORCID 0000-0002-7751-5913
Tina D HowardPeak Proteins Limited, Alderley Park, Cheshire, United Kingdom.
Helen J McMikenPeak Proteins Limited, Alderley Park, Cheshire, United Kingdom.
Juli WarwickerPeak Proteins Limited, Alderley Park, Cheshire, United Kingdom.
Catherine GehPeak Proteins Limited, Alderley Park, Cheshire, United Kingdom.
Rachel RowlinsonPeak Proteins Limited, Alderley Park, Cheshire, United Kingdom.
W Mark AbbottPeak Proteins Limited, Alderley Park, Cheshire, United Kingdom.
Anita EcklyUniversité de Strasbourg, Institut National de la Santé et de la Recherche Médicale, Etablissement Français du Sang Grand Est, Unité Mixte de Recherche-S 1255, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France.
Harald SchulzeInstitute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany.ORCID 0000-0003-1285-6407
Gavin J WrightCell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.ORCID 0000-0003-0537-0863
Alexandra MazharianInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.ORCID 0000-0002-0204-3325
Klaus FüttererSchool of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United Kingdom.ORCID 0000-0001-7445-5372
Sundaresan RajeshInstitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Michael R DouglasInstitute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Yotis A SenisInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.ORCID 0000-0002-0947-9957
University of Birmingham · GBÉtablissement Français du Sang · FRUniversitätsklinikum Würzburg · DEWellcome Sanger Institute · GBAston University · GBHelsinki University Hospital · FIUniversity of Helsinki · FIUniversity of Westminster · GB

Funding

British Heart Foundation FS/13/1/29894British Heart Foundation FS/15/58/31784British Heart Foundation RG/15/13/31673Medical Research Council Confidence in Concept 2018Medical Research Council MC_PC_17169Wellcome TrustWellcome Trust 206194
6 · The paper itself

Abstract

The immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptor G6b-B is critical for platelet production and activation. Loss of G6b-B results in severe macrothrombocytopenia, myelofibrosis and aberrant platelet function in mice and humans. Using a combination of immunohistochemistry, affinity chromatography and proteomics, we identified the extracellular matrix heparan sulfate (HS) proteoglycan perlecan as a G6b-B binding partner. Subsequent in vitro biochemical studies and a cell-based genetic screen demonstrated that the interaction is specifically mediated by the HS chains of perlecan. Biophysical analysis revealed that heparin forms a high-affinity complex with G6b-B and mediates dimerization. Using platelets from humans and genetically modified mice, we demonstrate that binding of G6b-B to HS and multivalent heparin inhibits platelet and megakaryocyte function by inducing downstream signaling via the tyrosine phosphatases Shp1 and Shp2. Our findings provide novel insights into how G6b-B is regulated and contribute to our understanding of the interaction of megakaryocytes and platelets with glycans.

Indexed as

AnimalsBlood PlateletsHeparan SulfateHumansMegakaryocytesMice, Inbred C57BLMice, KnockoutProtein BindingProtein MultimerizationProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6Receptors, ImmunologicSignal TransductionG6b-B receptor, mouseHeparan SulfateMPIG6B protein, humanProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6Receptors, Immunologicbiochemistrycell biologychemical biologyG6b-Bheparan sulfateheparinhumanITIM-receptormouseperlecanplatelets

Identifiers

PMID31436532
PMCPMC6742478
OpenAlexW2969611248

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.