en
Scientific article
Open access
English

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

Published inThe Journal of clinical investigation, vol. 115, no. 2, p. 237-246
Publication date2005
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
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)
accessLevelPublic
Identifiers
ISSN of the journal0021-9738
650views
561downloads

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