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

Détails

ID Serval
serval:BIB_AC83C7DDBD47
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy.
Périodique
Journal of Clinical Investigation
Auteur(s)
Angelillo-Scherrer A., Burnier L., Flores N., Savi P., DeMol M., Schaeffer P., Herbert J.M., Lemke G., Goff S.P., Matsushima G.K., Earp H.S., Vesin C., Hoylaerts M.F., Plaisance S., Collen D., Conway E.M., Wehrle-Haller B., Carmeliet P.
ISSN
0021-9738
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
115
Numéro
2
Pages
237-246
Langue
anglais
Notes
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Feb
Résumé
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.
Mots-clé
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
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 15:22
Dernière modification de la notice
20/08/2019 15:16
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