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

Article Article scientifique Article Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy eng 2005 author Angelillo Anne 134421 author Burnier Laurent 559369 author Flores Ramirez-Fournier Nathalie 24521 author Savi Pierre author DeMol Maria author Schaeffer Paul author Herbert Jean-Marc author Lemke Greg author Goff Stephen P author Matsushima Glenn K author Earp H Shelton author Vesin Christian 22534 author Hoylaerts Marc F author Plaisance Stéphane author Collen Désiré author Conway Edward M author Wehrle-Haller Bernhard 0000-0002-1159-1147 116298 author Carmeliet Peter 237-246 10.1172/JCI22079 15650770 0021-9738 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. 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 Dewey 612 134 Département de physiologie cellulaire et métabolisme 21C false 379 Migration cellulaire 645 The Journal of clinical investigation 115 2 6e98b149-3031-4f1f-8c7d-600afc31053b Article (Published version) Public JCI22079-2.pdf 992883 application/pdf openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy	The Journal of clinical investigation			2005	770	675

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Flores Ramirez-Fournier, Nathalie