Evidence map›Paper›PMID 23896409›Full record

ArticleBlood2013

Kindlin-2 regulates hemostasis by controlling endothelial cell-surface expression of ADP/AMP catabolic enzymes via a clathrin-dependent mechanism.

Elzbieta Pluskota, Yi Ma, Kamila M Bledzka, Katarzyna Bialkowska, Dmitry A Soloviev, Dorota Szpak, Eugene A Podrez, Paul L Fox, Stanley L Hazen, James J Dowling and 2 more

Open access · greenAbstract read
In one paragraph

Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.4field-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

35 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Review
  3. Kindlin-2 Deletion in Mural Cells Leads to Vascular Instability.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  4. Article
  5. Article
  6. Role of Kindlin 2 in prostate cancer.Scientific reports · 2024
    Article
  7. Kindlin-2 controls angiogenesis through modulating Notch1 signaling.Cellular and molecular life sciences : CMLS · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Kindlins as modulators of breast cancer progression.Journal of breast cancer research · 2021
    Article
  13. Article
  14. Article
  15. Cell type- and tissue-specific functions of ecto-5'-nucleotidase (CD73).American journal of physiology. Cell physiology · 2019
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Elzbieta PluskotaJoseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, and.
Yi Ma
Kamila M Bledzka
Katarzyna Bialkowska
Dmitry A Soloviev
Dorota Szpak
Eugene A Podrez
Paul L Fox
Stanley L Hazen
James J Dowling
Yan-Qing Ma
Edward F Plow
Jacobs (United States) · USCleveland Clinic · USUniversity of Michigan–Ann Arbor · USVersiti Blood Center of Wisconsin · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Structure Basis for Talin-mediated Integrin ActivationP01HL073311 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BYZOVA, TATIANA V · 2004 to 2019
$27.4M
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
NCATS NIH HHS UL1 TR000439NCATS NIH HHS UL1TR000439NHLBI NIH HHS P01 HL 073311NHLBI NIH HHS P01 HL073311NHLBI NIH HHS R01 HL096062PHS HHS AIO 80596
6 · The paper itself

Abstract

Kindlin-2, a widely distributed cytoskeletal protein, has been implicated in integrin activation, and its absence is embryonically lethal in mice. In the present study, we tested whether hemostasis might be perturbed in kindlin-2(+/-) mice. Bleeding time and carotid artery occlusion time were significantly prolonged in kindlin-2(+/-) mice. Whereas plasma concentrations/activities of key coagulation/fibrinolytic proteins and platelet counts and aggregation were similar in wild-type and kindlin-2(+/-) mice, kindlin-2(+/-) endothelial cells (ECs) showed enhanced inhibition of platelet aggregation induced by adenosine 5'-diphosphate (ADP) or low concentrations of other agonists. Cell-surface expression of 2 enzymes involved in ADP/adenosine 5'-monophosphate (AMP) degradation, adenosine triphosphate (ATP) diphosphohydrolase (CD39) and ecto-5'-nucleotidase (CD73) were increased twofold to threefold on kindlin-2(+/-) ECs, leading to enhanced ATP/ADP catabolism and production of adenosine, an inhibitor of platelet aggregation. Trafficking of CD39 and CD73 at the EC surface was altered in kindlin-2(+/-) mice. Mechanistically, this was attributed to direct interaction of kindlin-2 with clathrin heavy chain, thereby controlling endocytosis and recycling of CD39 and CD73. The interaction of kindlin-2 with clathrin was independent of its integrin binding site but still dependent on a site within its F3 subdomain. Thus, kindlin-2 regulates trafficking of EC surface enzymes that control platelet responses and hemostasis.

Indexed as

5'-NucleotidaseAdenosine DiphosphateAdenosine MonophosphateAnimalsAntigens, CDApyraseBlood PlateletsCell MembraneClathrinCytoskeletal ProteinsEndothelial CellsFemaleFlow CytometryHemostasisImmunoprecipitationMale5'-NucleotidaseAdenosine DiphosphateAdenosine MonophosphateAntigens, CDApyraseCD39 antigenClathrinCytoskeletal Proteinskindlin-2 protein, mouseMuscle Proteins

Identifiers

PMID23896409
PMCPMC3790514
OpenAlexW2030360107

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.