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

Details

Serval ID
serval:BIB_AC83C7DDBD47
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy.
Journal
Journal of Clinical Investigation
Author(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
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
115
Number
2
Pages
237-246
Language
english
Notes
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Feb
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.
Keywords
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
Yes
Create date
25/01/2008 15:22
Last modification date
20/08/2019 15:16
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