Evidence map›Paper›PMID 19996090›Full record

ArticleBlood2010

Role for ADAP in shear flow-induced platelet mechanotransduction.

Ana Kasirer-Friede, Zaverio M Ruggeri, Sanford J Shattil

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

20 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Integrin αBlood · 2017
    Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Shear Stress Enhances Chemokine Secretion fromCellular and molecular bioengineering · 2013
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Platelet receptor signaling in thrombus formation.Journal of molecular medicine (Berlin, Germany) · 2011
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Ana Kasirer-FriedeDepartment of Medicine, University of California San Diego, La Jolla, CA 92093-0726, USA. akasirer@ucsd.edu
Zaverio M Ruggeri
Sanford J Shattil
University of California, San Diego · USScripps Research Institute · US

Funding

THROMBUS FORMATION IN BABOONSP01HL031950 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI GRIFFIN, JOHN H · 1985 to 2015
$29.4M
The Interaction of TPO and Integrins in Hematopoiesis CellsP01HL078784 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2005 to 2019
$28.3M
Discoveries at the Crossroads of Integrin and Inflammatory Signaling in PlateletsR01HL056595 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHATTIL, SANFORD J · 1996 to 2020
$7.5M
STRUCTURE &FUNCTION OF PLATELET MEMBRANE GLYCOPROTEINSR01HL042846 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI RUGGERI, ZAVERIO M · 1989 to 2014
$2.4M
Role of von Willebrand Factor in Platelet Thrombus FormationR01HL098542 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI RUGGERI, ZAVERIO M · 2010 to 2010
$475k
NHLBI NIH HHS HL31950NHLBI NIH HHS HL56595NHLBI NIH HHS HL78784NHLBI NIH HHS P01 HL031950NHLBI NIH HHS P01 HL078784NHLBI NIH HHS R01 HL042846NHLBI NIH HHS R01 HL056595NHLBI NIH HHS R01 HL098542
6 · The paper itself

Abstract

Binding of platelets to fibrinogen via integrin alphaIIbbeta3 stimulates cytoskeletal reorganization and spreading. These responses depend on tyrosine phosphorylation of multiple proteins by Src family members and Syk. Among Src substrates in platelets is adhesion- and degranulation-promoting adapter protein (ADAP), an adapter with potential binding partners: SLP-76, VASP, and SKAP-HOM. During studies of platelet function under shear flow, we discovered that ADAP(-/-) mouse platelets, unlike ADAP+/+ platelets, formed unstable thrombi in response to carotid artery injury. Moreover, fibrinogen-adherent ADAP(-/-) platelets in shear flow ex vivo showed reduced spreading and smaller zones of contact with the matrix. These abnormalities were not observed under static conditions, and they could not be rescued by stimulating platelets with a PAR4 receptor agonist or by direct alphaIIbbeta3 activation with MnCl2, consistent with a defect in outside-in alphaIIbbeta3 signaling. ADAP+/+ platelets subjected to shear flow assembled F-actin-rich structures that colocalized with SLP-76 and the Rac1 exchange factor, phospho-Vav1. In contrast, platelets deficient in ADAP, but not those deficient in VASP or SKAP-HOM, failed to form these structures. These results establish that ADAP is an essential component of alphaIIbbeta3-mediated platelet mechanotransduction that promotes F-actin assembly and enables platelet spreading and thrombus stabilization under fluid shear stress.

Indexed as

HemorheologyMechanotransduction, CellularStress, MechanicalActinsAdaptor Proteins, Signal TransducingAnimalsBlood PlateletsCarotid ArteriesCell Adhesion MoleculesCell MovementCytoskeletonFibrinogenIntracellular SpaceMiceMicrofilament ProteinsPhosphoproteinsActinsAdaptor Proteins, Signal TransducingCell Adhesion MoleculesFibrinogenFyb protein, mouseMicrofilament ProteinsPhosphoproteinsPlatelet Glycoprotein GPIIb-IIIa ComplexProto-Oncogene Proteins c-vavSLP-76 signal Transducing adaptor proteinsVasodilator-Stimulated PhosphoproteinVav1 protein, mouse

Identifiers

PMID19996090
PMCPMC2844019
OpenAlexW1970522778

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.