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The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis.
- Source :
-
Blood [Blood] 2009 May 14; Vol. 113 (20), pp. 4942-54. Date of Electronic Publication: 2009 Feb 25. - Publication Year :
- 2009
-
Abstract
- Platelets play a fundamental role in hemostasis and thrombosis. They are also involved in pathologic conditions resulting from blocked blood vessels, including myocardial infarction and ischemic stroke. Platelet adhesion, activation, and aggregation at sites of vascular injury are regulated by a diverse repertoire of tyrosine kinase-linked and G protein-coupled receptors. Src family kinases (SFKs) play a central role in initiating and propagating signaling from several platelet surface receptors; however, the underlying mechanism of how SFK activity is regulated in platelets remains unclear. CD148 is the only receptor-like protein tyrosine phosphatase identified in platelets to date. In the present study, we show that mutant mice lacking CD148 exhibited a bleeding tendency and defective arterial thrombosis. Basal SFK activity was found to be markedly reduced in CD148-deficient platelets, resulting in a global hyporesponsiveness to agonists that signal through SFKs, including collagen and fibrinogen. G protein-coupled receptor responses to thrombin and other agonists were also marginally reduced. These results highlight CD148 as a global regulator of platelet activation and a novel antithrombotic drug target.
- Subjects :
- Animals
Antigens, Surface metabolism
Blood Platelets metabolism
Cell Adhesion drug effects
Cells, Cultured
Fibrinogen pharmacology
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Platelet Aggregation drug effects
Platelet Membrane Glycoproteins metabolism
Platelet Membrane Glycoproteins physiology
Protein Tyrosine Phosphatases genetics
Protein Tyrosine Phosphatases physiology
Receptor-Like Protein Tyrosine Phosphatases, Class 3 genetics
Receptor-Like Protein Tyrosine Phosphatases, Class 3 metabolism
Receptor-Like Protein Tyrosine Phosphatases, Class 3 physiology
Receptors, IgG genetics
Signal Transduction immunology
Platelet Activation genetics
Thrombosis genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 113
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 19246339
- Full Text :
- https://doi.org/10.1182/blood-2008-08-174318