Evidence map›Paper›PMID 24969775›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2014

Direct interaction of kindlin-3 with integrin αIIbβ3 in platelets is required for supporting arterial thrombosis in mice.

Zhen Xu, Xue Chen, Huiying Zhi, Juan Gao, Katarzyna Bialkowska, Tatiana V Byzova, Elzbieta Pluskota, Gilbert C White, Junling Liu, Edward F Plow and 1 more

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

29 citing papers in PubMed, 46 citations in OpenAlex.

  1. Structural basis of kindlin-3 in leukocyte adhesion deficiency III.Journal of thrombosis and haemostasis : JTH · 2026
    Article
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  3. Kindlin-3 phosphorylation is crucial for thrombosis and hemostasisResearch and practice in thrombosis and haemostasis · 2025
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  17. A Short Half-Life αInternational journal of molecular sciences · 2018
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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

11 authors at 2 institutions in 2 countries.

Zhen XuFrom the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.).
Xue ChenFrom the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.).
Huiying ZhiFrom the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.).
Juan GaoFrom the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.).
Katarzyna BialkowskaFrom the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.).
Tatiana V ByzovaFrom the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.).
Elzbieta PluskotaFrom the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.).
Gilbert C WhiteFrom the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.).
Junling LiuFrom the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.).
Edward F PlowFrom the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.).
Yan-Qing MaFrom the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.). yanqing.ma@bcw.edu plowe@ccf.org.
Shanghai Jiao Tong University · CNVersiti Blood Center of Wisconsin · US

Funding

Structure Basis for Talin-mediated Integrin ActivationP01HL073311 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BYZOVA, TATIANA V · 2004 to 2019
$27.4M
Regulation of Integrins in Neovasculature DevelopmentR01HL071625 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BYZOVA, TATIANA V · 2003 to 2021
$7.3M
Activation of the beta-3 integrins: Role of the KindlinsR01HL096062 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI PLOW, EDWARD FRANKLIN · 2009 to 2022
$5.6M
NHLBI NIH HHS P01 HL073311NHLBI NIH HHS R01 HL071625NHLBI NIH HHS R01 HL096062
6 · The paper itself

Abstract

objectiveKindlin-3 is a critical supporter of integrin function in platelets. Lack of expression of kindlin-3 protein in patients impairs integrin αIIbβ3-mediated platelet aggregation. Although kindlin-3 has been categorized as an integrin-binding partner, the functional significance of the direct interaction of kindlin-3 with integrin αIIbβ3 in platelets has not been established. Here, we evaluated the significance of the binding of kindlin-3 to integrin αIIbβ3 in platelets in supporting integrin αIIbβ3-mediated platelet functions. APPROACH AND

resultsWe generated a strain of kindlin-3 knockin (K3KI) mice that express a kindlin-3 mutant that carries an integrin-interaction defective substitution. K3KI mice could survive normally and express integrin αIIbβ3 on platelets similar to their wild-type counterparts. Functional analysis revealed that K3KI mice exhibited defective platelet function, including impaired integrin αIIbβ3 activation, suppressed platelet spreading and platelet aggregation, prolonged tail bleeding time, and absence of platelet-mediated clot retraction. In addition, whole blood drawn from K3KI mice showed resistance to in vitro thrombus formation and, as a consequence, K3KI mice were protected from in vivo arterial thrombosis.

conclusionsThese observations demonstrate that the direct binding of kindlin-3 to integrin αIIbβ3 is involved in supporting integrin αIIbβ3 activation and integrin αIIbβ3-dependent responses of platelets and consequently contributes significantly to arterial thrombus formation.

Indexed as

Amino Acid SubstitutionAnimalsBleeding TimeBlood PlateletsCarotid Artery ThrombosisCell ShapeChloridesClot RetractionCytoskeletal ProteinsDisease Models, AnimalFemaleFerric CompoundsGene Knock-In TechniquesGenes, ReporterMaleMiceChloridesCytoskeletal Proteinsferric chlorideFerric Compoundskindlin-3 protein, mousePlatelet Glycoprotein GPIIb-IIIa ComplexRecombinant Fusion Proteinsblood plateletskindlin-3 proteinmousethrombosis

Identifiers

PMID24969775
PMCPMC4167429
OpenAlexW2168045254

What OpenQuestion holds

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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.