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Scientific article
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English

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

Contributors

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

Published in

The Journal of clinical investigation, vol. 115, no. 2, p. 237-246

Publication date

2005

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 beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3. Blocking the Gas6-R-alphaIIbbeta3 integrin cross-talk might be a novel approach to the reduction of thrombosis.

Keywords

  • Animals
  • Integrin beta3/metabolism
  • Intercellular Signaling Peptides and Proteins/genetics/metabolism
  • Mice
  • Mice, Knockout
  • Phosphatidylinositol 3-Kinases/metabolism
  • Platelet Aggregation/genetics/physiology
  • Platelet Glycoprotein GPIIb-IIIa Complex/metabolism
  • Protein-Serine-Threonine Kinases/metabolism
  • Proto-Oncogene Proteins/metabolism
  • Proto-Oncogene Proteins c-akt
  • Receptor Protein-Tyrosine Kinases/administration & dosage/genetics/metabolism
  • Signal Transduction/genetics/physiology
  • Thrombosis/drug therapy/genetics/metabolism/pathology

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

ANGELILLO, Anne et al. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. In: The Journal of clinical investigation, 2005, vol. 115, n° 2, p. 237–246. doi: 10.1172/JCI22079

Main files (1)

Article (Published version)

Identifiers

Journal ISSN

0021-9738
779views
698downloads

Technical informations

Creation

14/05/2014 13:22:00

First validation

14/05/2014 13:22:00

Update

14/03/2023 21:14:13

Status update

14/03/2023 21:14:12

Last indexation

12/11/2024 17:00:15
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