Evidence map›Paper›PMID 25212232›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2014

Disabled-2 is required for efficient hemostasis and platelet activation by thrombin in mice.

Hui-Ju Tsai, Chien-Ling Huang, Yao-Wen Chang, Ding-Yuan Huang, Chung-Ching Lin, Jonathan A Cooper, Ju-Chien Cheng, Ching-Ping Tseng

Abstract 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 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Human Disabled-2 regulates thromboxane ANature communications · 2024
    Article
  2. Review
  3. Article
  4. Article
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  7. CaJournal of thrombosis and haemostasis : JTH · 2022
    Article
  8. GαFrontiers in cell and developmental biology · 2022
    Review
  9. Article
  10. Function of Platelet Glycosphingolipid Microdomains/Lipid Rafts.International journal of molecular sciences · 2020
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Integrin αBlood · 2017
    Review
  16. Review
  17. Article
  18. Review
  19. 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

8 authors at 2 institutions in 2 countries.

Hui-Ju TsaiFrom the Graduate Institute of Biomedical Sciences (H.-J.T., Y.-W.C., C.-P.T.), and Department of Medical Biotechnology and Laboratory Science (C.-L.H., D.-Y.H., C.-C.L., C.-P.T.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (J.A.C.); Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan (J.-C.C.); Molecular Medicine Research Center, Chang Gung University (C.-P.T.) and Department of Family Medicine (C.-P.T.), Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Chien-Ling HuangFrom the Graduate Institute of Biomedical Sciences (H.-J.T., Y.-W.C., C.-P.T.), and Department of Medical Biotechnology and Laboratory Science (C.-L.H., D.-Y.H., C.-C.L., C.-P.T.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (J.A.C.); Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan (J.-C.C.); Molecular Medicine Research Center, Chang Gung University (C.-P.T.) and Department of Family Medicine (C.-P.T.), Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Yao-Wen ChangFrom the Graduate Institute of Biomedical Sciences (H.-J.T., Y.-W.C., C.-P.T.), and Department of Medical Biotechnology and Laboratory Science (C.-L.H., D.-Y.H., C.-C.L., C.-P.T.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (J.A.C.); Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan (J.-C.C.); Molecular Medicine Research Center, Chang Gung University (C.-P.T.) and Department of Family Medicine (C.-P.T.), Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Ding-Yuan HuangFrom the Graduate Institute of Biomedical Sciences (H.-J.T., Y.-W.C., C.-P.T.), and Department of Medical Biotechnology and Laboratory Science (C.-L.H., D.-Y.H., C.-C.L., C.-P.T.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (J.A.C.); Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan (J.-C.C.); Molecular Medicine Research Center, Chang Gung University (C.-P.T.) and Department of Family Medicine (C.-P.T.), Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Chung-Ching LinFrom the Graduate Institute of Biomedical Sciences (H.-J.T., Y.-W.C., C.-P.T.), and Department of Medical Biotechnology and Laboratory Science (C.-L.H., D.-Y.H., C.-C.L., C.-P.T.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (J.A.C.); Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan (J.-C.C.); Molecular Medicine Research Center, Chang Gung University (C.-P.T.) and Department of Family Medicine (C.-P.T.), Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Jonathan A CooperFrom the Graduate Institute of Biomedical Sciences (H.-J.T., Y.-W.C., C.-P.T.), and Department of Medical Biotechnology and Laboratory Science (C.-L.H., D.-Y.H., C.-C.L., C.-P.T.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (J.A.C.); Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan (J.-C.C.); Molecular Medicine Research Center, Chang Gung University (C.-P.T.) and Department of Family Medicine (C.-P.T.), Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Ju-Chien ChengFrom the Graduate Institute of Biomedical Sciences (H.-J.T., Y.-W.C., C.-P.T.), and Department of Medical Biotechnology and Laboratory Science (C.-L.H., D.-Y.H., C.-C.L., C.-P.T.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (J.A.C.); Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan (J.-C.C.); Molecular Medicine Research Center, Chang Gung University (C.-P.T.) and Department of Family Medicine (C.-P.T.), Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Ching-Ping TsengFrom the Graduate Institute of Biomedical Sciences (H.-J.T., Y.-W.C., C.-P.T.), and Department of Medical Biotechnology and Laboratory Science (C.-L.H., D.-Y.H., C.-C.L., C.-P.T.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (J.A.C.); Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan (J.-C.C.); Molecular Medicine Research Center, Chang Gung University (C.-P.T.) and Department of Family Medicine (C.-P.T.), Chang Gung Memorial Hospital, Taoyuan, Taiwan. ctseng@mail.cgu.edu.tw.
Fred Hutch Cancer Center · USChina Medical University · TW

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
In vivo functions of possible tumor suppressor Dab2R01GM066257 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI COOPER, JONATHAN A · 2003 to 2011
$3.3M
NCI NIH HHS P30 CA015704NIGMS NIH HHS GM066257NIGMS NIH HHS R01 GM066257
6 · The paper itself

Abstract

objectiveThe essential role of platelet activation in hemostasis and thrombotic diseases focuses attention on unveiling the underlying intracellular signals of platelet activation. Disabled-2 (Dab2) has been implicated in platelet aggregation and in the control of clotting responses. However, there is not yet any in vivo study to provide direct evidence for the role of Dab2 in hemostasis and platelet activation. APPROACH AND

resultsMegakaryocyte lineage-restricted Dab2 knockout (Dab2(-/-)) mice were generated to delineate in vivo functions of Dab2 in platelets. Dab2(-/-) mice appeared normal in size with prolonged bleeding time and impaired thrombus formation. Although normal in platelet production and granule biogenesis, Dab2(-/-) platelets elicited a selective defect in platelet aggregation and spreading on fibrinogen in response to low concentrations of thrombin, but not other soluble agonists. Investigation of the role of Dab2 in thrombin signaling revealed that Dab2 has no effect on the expression of thrombin receptors and the outside-in signaling. Dab2(-/-) platelets stimulated by low concentrations of thrombin were normal in Gαq-mediated calcium mobilization and protein kinase C activation, but were defective in Gα₁₂/₁₃-mediated RhoA-ROCKII activation. The attenuated Gα₁₂/₁₃ signaling led to impaired ADP release, Akt-mammalian target of rapamycin and integrin αIIbβ3 activation, fibrinogen binding, and clot retraction. The defective responses of Dab2(-/-) platelets to low concentrations of thrombin stimulation may contribute to the impaired hemostasis and thrombosis of Dab2(-/-) mice.

conclusionsThis study sheds new insight in platelet biology and represents the first report demonstrating that Dab2 is a key regulator of hemostasis and thrombosis by functional interplay with Gα₁₂/₁₃-mediated thrombin signaling.

Indexed as

Adaptor Proteins, Signal TransducingAdenosine DiphosphateAnimalsDisease Models, AnimalDNA-Binding ProteinsHemostasisMiceMice, KnockoutPlatelet ActivationPlatelet Glycoprotein GPIIb-IIIa ComplexProtein Kinase CrhoA GTP-Binding Proteinrho-Associated KinasesSignal TransductionThrombinThrombosisAdaptor Proteins, Signal TransducingAdenosine DiphosphateDNA-Binding ProteinsmTOR protein, mouseNostrin protein, mousePlatelet Glycoprotein GPIIb-IIIa ComplexProtein Kinase CrhoA GTP-Binding Proteinrho-Associated KinasesThrombinTOR Serine-Threonine KinasesDab2 protein, mouseplatelet activationthrombin

Identifiers

PMID25212232
PMCPMC4199904
OpenAlexW2120187775

What OpenQuestion holds

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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.