Back to Search Start Over

The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis.

Authors :
Senis YA
Tomlinson MG
Ellison S
Mazharian A
Lim J
Zhao Y
Kornerup KN
Auger JM
Thomas SG
Dhanjal T
Kalia N
Zhu JW
Weiss A
Watson SP
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.

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