Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews...
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • Allergy (Apr 2019)
    • Biology of familial cancer predisposition syndromes (Feb 2019)
    • Mitochondrial dysfunction in disease (Aug 2018)
    • Lipid mediators of disease (Jul 2018)
    • Cellular senescence in human disease (Apr 2018)
    • View all review series...
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Scientific Show Stoppers
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Current issue
  • Past issues
  • By specialty
  • Subscribe
  • Alerts
  • Advertise
  • Contact
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • Brief Reports
  • Technical Advances
  • Commentaries
  • Editorials
  • Hindsight
  • Review series
  • Reviews
  • The Attending Physician
  • First Author Perspectives
  • Scientific Show Stoppers
  • Top read articles
  • Concise Communication
Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy
Anne Angelillo-Scherrer, … , Bernhard Wehrle-Haller, Peter Carmeliet
Anne Angelillo-Scherrer, … , Bernhard Wehrle-Haller, Peter Carmeliet
Published February 1, 2005
Citation Information: J Clin Invest. 2005;115(2):237-246. https://doi.org/10.1172/JCI22079.
View: Text | PDF
Categories: Article Hematology

Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy

  • Text
  • PDF
Abstract

Mechanisms regulating thrombus stabilization remain largely unknown. Here, we report that loss of any 1 of the Gas6 receptors (Gas6-Rs), i.e., Tyro3, Axl, or Mer, or delivery of a soluble extracellular domain of Axl that traps Gas6 protects mice against life-threatening thrombosis. Loss of a Gas6-R does not prevent initial platelet aggregation but impairs subsequent stabilization of platelet aggregates, at least in part by reducing “outside-in” signaling and platelet granule secretion. Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the β3 integrin, thereby amplifying outside-in signaling via αIIbβ3. Blocking the Gas6-R–αIIbβ3 integrin cross-talk might be a novel approach to the reduction of thrombosis.

Authors

Anne Angelillo-Scherrer, Laurent Burnier, Nathalie Flores, Pierre Savi, Maria DeMol, Paul Schaeffer, Jean-Marc Herbert, Greg Lemke, Stephen P. Goff, Glenn K. Matsushima, H. Shelton Earp, Christian Vesin, Marc F. Hoylaerts, Stéphane Plaisance, Désiré Collen, Edward M. Conway, Bernhard Wehrle-Haller, Peter Carmeliet

×

Figure 11

Options: View larger image (or click on image) Download as PowerPoint
Axl expression on the surface of WT, Tyro3–/–, Axl–/–, or Mer–/– platele...
Axl expression on the surface of WT, Tyro3–/–, Axl–/–, or Mer–/– platelets, activated by the PAR4-activating peptide AYPGKF (0.25 mM). Flow cytometry revealed that surface expression of Axl was dramatically reduced in platelets lacking any 1 of the Gas6-Rs as compared with WT platelets. Axl expression was not detected on the surface of activated Axl–/– platelets. Black lines denote isotype-matched control; red shading denotes Axl. A representative example of 3 independent experiments is shown.
Follow JCI:
Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts