Evidence map›Paper›PMID 24265393›Full record

ArticleCirculation research2014

Growth factor receptor-bound protein 2 contributes to (hem)immunoreceptor tyrosine-based activation motif-mediated signaling in platelets.

Sebastian Dütting, Timo Vögtle, Martina Morowski, Sarah Schiessl, Carmen M Schäfer, Stephanie K Watson, Craig E Hughes, Jochen A Ackermann, Daniel Radtke, Heike M Hermanns and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

14 citing papers in PubMed, 24 citations in OpenAlex.

  1. Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026
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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

13 authors at 1 institution in 1 country.

Sebastian Dütting *Department of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Timo Vögtle *Department of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Martina MorowskiDepartment of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Sarah SchiesslDepartment of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Carmen M SchäferDepartment of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Stephanie K WatsonDepartment of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Craig E HughesDepartment of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Jochen A AckermannDepartment of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Daniel RadtkeDepartment of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Heike M HermannsDepartment of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Steve P WatsonDepartment of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Lars NitschkeDepartment of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Bernhard NieswandtDepartment of Experimental Biomedicine, University Hospital Würzburg (S.D., T.V., M.M., S.S., B.N.) and Rudolf Virchow Center for Experimental Biomedicine (S.D., T.V., C.M.S., H.M.H., B.N.), University of Würzburg, Würzburg, Germany; Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.K.W., C.E.H., S.P.W.); and Department of Biology, Division of Genetics, University of Erlangen, Erlangen, Germany (J.A.A., D.R., L.N.).
Friedrich-Alexander-Universität Erlangen-Nürnberg · DE

Funding

Wellcome Trust 088410
6 · The paper itself

Abstract

rationalePlatelets are anuclear cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity but may also cause pathological vessel occlusion. One major pathway of platelet activation is triggered by 2 receptors that signal through an (hem)immunoreceptor tyrosine-based activation motif (ITAM), the activating collagen receptor glycoprotein (GP) VI and the C-type lectin-like receptor 2 (CLEC-2). Growth factor receptor-bound protein 2 (Grb2) is a ubiquitously expressed adapter molecule involved in signaling processes of numerous receptors in different cell types, but its function in platelets and MKs is unknown.

objectiveWe tested the hypothesis that Grb2 is a crucial adapter protein in (hem)immunoreceptor tyrosine-based activation motif signaling in platelets. METHODS AND

resultsHere, we show that genetic ablation of Grb2 in MKs and platelets did not interfere with MK differentiation or platelet production. However, Grb2-deficiency severely impaired glycoprotein VI-mediated platelet activation because of defective stabilization of the linker of activated T-cell (LAT) signalosome and activation of downstream signaling proteins that resulted in reduced adhesion, aggregation, and coagulant activity on collagen in vitro. Similarly, CLEC-2-mediated signaling was impaired in Grb2-deficient platelets, whereas the cells responded normally to stimulation of G protein-coupled receptors. In vivo, this selective (hem)immunoreceptor tyrosine-based activation motif signaling defect resulted in prolonged bleeding times but affected arterial thrombus formation only after concomitant treatment with acetylsalicylic acid, indicating that defective glycoprotein VI signaling in the absence of Grb2 can be compensated through thromboxane A2-induced G protein-coupled receptor signaling pathways.

conclusionsThese results reveal an important contribution of Grb2 in (hem)immunoreceptor tyrosine-based activation motif signaling in platelets in hemostasis and thrombosis by stabilizing the LAT signalosome.

Indexed as

Amino Acid MotifsAnimalsBlood PlateletsCells, CulturedGRB2 Adaptor ProteinHemostasisImmunoreceptor Tyrosine-Based Activation MotifImmunoreceptor Tyrosine-Based Inhibition MotifMiceMice, Inbred C57BLMice, KnockoutPlatelet ActivationSignal TransductionThrombosisGRB2 Adaptor ProteinGrb2 protein, mouseblood plateletshemostasismicesignal transductionthrombosis

Identifiers

PMID24265393
PMCPMC4405766
OpenAlexW2152125480

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.