Title: Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy
Authors: Angelillo-Scherrer, Anne
Burnier, Laurent
Flores, 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
Plaisance, St├ęphane
Collen, Desire
Conway, Edward
Wehrle-Haller, Bernhard
Carmeliet, Peter # ×
Issue Date: Feb-2005
Publisher: American Society for Clinical Investigation
Series Title: Journal of Clinical Investigation vol:115 issue:2 pages:237-246
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.
ISSN: 0021-9738
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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