Forskning ved Københavns Universitet - Københavns Universitet

Forside

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Anne Angelillo-Scherrer
  • Laurent Pierre Burnier
  • Nathalie Flores
  • Pierre Savi
  • Maria DeMol
  • Paul Schaeffer
  • Jean-Marc Herbert
  • Greg Lemke
  • Stephen P Goff
  • Glenn K Matsushima
  • H Shelton Earp
  • Christian Vesin
  • Marc F Hoylaerts
  • Stéphane Plaisance
  • Désiré Collen
  • Edward M Conway
  • Bernhard Wehrle-Haller
  • Peter Carmeliet
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.
OriginalsprogEngelsk
TidsskriftThe Journal of Clinical Investigation
Vol/bind115
Udgave nummer2
Sider (fra-til)237-46
Antal sider10
ISSN0021-9738
DOI
StatusUdgivet - feb. 2005
Eksternt udgivetJa

ID: 100892334