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

Savi, Pierre
DeMol, Maria
Schaeffer, Paul
Herbert, Jean-Marc
Lemke, Greg
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Published in Journal of Clinical Investigation. 2005, vol. 115, no. 2, p. 237-46
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 AnimalsIntegrin beta3/metabolismIntercellular Signaling Peptides and Proteins/genetics/metabolismMiceMice, KnockoutPhosphatidylinositol 3-Kinases/metabolismPlatelet Aggregation/genetics/physiologyPlatelet Glycoprotein GPIIb-IIIa Complex/metabolismProtein-Serine-Threonine Kinases/metabolismProto-Oncogene Proteins/metabolismProto-Oncogene Proteins c-aktReceptor Protein-Tyrosine Kinases/administration & dosage/genetics/metabolismSignal Transduction/genetics/physiologyThrombosis/drug therapy/genetics/metabolism/pathology
PMID: 15650770
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Research group Migration cellulaire (645)
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ANGELILLO, Anne et al. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. In: Journal of Clinical Investigation, 2005, vol. 115, n° 2, p. 237-46. doi: 10.1172/JCI22079 https://archive-ouverte.unige.ch/unige:36658

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Deposited on : 2014-05-16

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