Role of the growth arrest-specific gene 6 (gas6) product in thrombus stabilization.

Détails

ID Serval
serval:BIB_3EAD1A6A6B98
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
Role of the growth arrest-specific gene 6 (gas6) product in thrombus stabilization.
Périodique
Blood Cells, Molecules & Diseases
Auteur(s)
Saller F., Burnier L., Schapira M., Angelillo-Scherrer A.
ISSN
1079-9796
Statut éditorial
Publié
Date de publication
2006
Peer-reviewed
Oui
Volume
36
Numéro
3
Pages
373-378
Langue
anglais
Notes
Journal Article Research Support, Non-U.S. Gov't Review --- Old month value: May-Jun
Résumé
Growth arrest-specific gene 6 (gas6) product enhances the formation of stable platelet macroaggregates in response to various agonists. To determine whether Gas6 amplifies the response to known platelet agonists through one or more of its receptor tyrosine kinases of the Tyro3 family, mice deficient in any one of the Gas6 receptors (Gas6-Rs: Tyro3, Axl, or Mer) were submitted to thrombosis challenge and their platelet function. The loss of any one of the Gas6-Rs protects mice against thromboembolism induced by collagen-epinephrine and stasis-induced thrombosis. Importantly, these mice do not suffer spontaneous bleeding and have a normal bleeding time but a tendency to repetitively re-bleed after transient hemostasis. Re-bleeding in mice lacking any one of the Gas6-Rs is not due to thrombocytopenia or coagulopathy but to a platelet dysfunction characterized by a lack of the second wave of platelet aggregation and an impaired clot retraction, at least in part by reducing outside-in alpha(IIb)beta(3) signaling and platelet granule secretion. The early release of Gas6 by agonists perpetuates platelet activation through its three receptors, reinforcing outside-in alpha(IIb)beta(3) signaling by activation of PI3K and Akt signaling and stimulation of tyrosine phosphorylation of the beta(3) integrin. Furthermore, "trapping" Gas6 prevents pathological thrombosis, which indicates that blocking this novel cross-talk between the Gas6-Rs and alpha(IIb)beta(3) integrin may constitute a novel target for antithrombotic therapy.
Mots-clé
Animals, Blood Platelets, Humans, Intercellular Signaling Peptides and Proteins, Mice, Platelet Activation, Protein-Serine-Threonine Kinases, Signal Transduction, Thrombosis
Pubmed
Web of science
Création de la notice
25/01/2008 16:22
Dernière modification de la notice
20/08/2019 14:35
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