2005 Articles
Role of Gas6 Receptors in Platelet Signaling during Thrombus Stabilization and Implications for Antithrombotic Therapy
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 β3 integrin, thereby amplifying outside-in signaling via αIIbβ3. Blocking the Gas6-R–αIIbβ3 integrin cross-talk might be a novel approach to the reduction of thrombosis.
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Also Published In
- Title
- Journal for Clinical Investigation
- DOI
- https://doi.org/10.1172/JCI22079
More About This Work
- Academic Units
- Biochemistry and Molecular Biophysics
- Pathology and Cell Biology
- Publisher
- American Society for Clinical Investigation
- Published Here
- August 24, 2014