Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy.
J Clin Invest
; 115(2): 237-46, 2005 Feb.
Article
en En
| MEDLINE
| ID: mdl-15650770
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trombosis
/
Transducción de Señal
/
Agregación Plaquetaria
/
Péptidos y Proteínas de Señalización Intercelular
Límite:
Animals
Idioma:
En
Revista:
J Clin Invest
Año:
2005
Tipo del documento:
Article
País de afiliación:
Suiza