The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis
| Autor: | Jenson Lim, Steve G. Thomas, Tarvinder S. Dhanjal, Jocelyn M. Auger, Alexandra Mazharian, Arthur Weiss, Steve P. Watson, Stuart Ellison, Yotis A. Senis, Kristin N. Kornerup, Jing W. Zhu, Yan Zhao, Neena Kalia, Michael G. Tomlinson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Blood Platelets
medicine.medical_specialty Platelet Aggregation Immunology Platelet Membrane Glycoproteins Protein tyrosine phosphatase 030204 cardiovascular system & hematology Biology R Medicine (General) Platelet membrane glycoprotein Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Thrombin Internal medicine Cell Adhesion medicine Animals Humans Protease-activated receptor Platelet Platelet activation Tyrosine Cells Cultured 030304 developmental biology Mice Knockout 0303 health sciences Receptor-Like Protein Tyrosine Phosphatases Class 3 Receptors IgG Fibrinogen Thrombosis Cell Biology Hematology Platelet Activation Platelets and Thrombopoiesis Mice Inbred C57BL Endocrinology Antigens Surface Cancer research Protein Tyrosine Phosphatases Signal transduction Signal Transduction medicine.drug |
| Zdroj: | Blood |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|