Article: article from journal or magazin.
Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy.
Journal of Clinical Investigation
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Feb
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.
1-Phosphatidylinositol 3-Kinase, Animals, Integrin beta3, Intercellular Signaling Peptides and Proteins, Mice, Mice, Knockout, Platelet Aggregation, Platelet Glycoprotein GPIIb-IIIa Complex, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Receptor Protein-Tyrosine Kinases, Signal Transduction, Thrombosis
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