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Blood. 2009 May 14;113(20):4942-54. doi: 10.1182/blood-2008-08-174318. Epub 2009 Feb 25.

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

Author information

1
Centre for Cardiovascular Sciences, Institute of Biomedical Research, University of Birmingham, United Kingdom. y.senis@bham.ac.uk

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.

PMID:
19246339
PMCID:
PMC2686144
DOI:
10.1182/blood-2008-08-174318
[Indexed for MEDLINE]
Free PMC Article

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