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J Clin Invest. 2005 Feb;115(2):237-46.

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

Author information

1
Division of Angiology and Hemostasis, Department of Internal Medicine, Faculty of Medicine and University Hospitals of Geneva, Geneva, Switzerland. Anne.Angelillo@medecine.unige.ch

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.

PMID:
15650770
PMCID:
PMC544035
DOI:
10.1172/JCI22079
[Indexed for MEDLINE]
Free PMC Article
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