Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/21101
Appears in Collections:Biological and Environmental Sciences Journal Articles
Peer Review Status: Refereed
Title: The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis
Authors: Senis, Yotis A
Tomlinson, Michael G
Ellison, Stuart
Mazharian, Alexandra
Lim, Jenson
Zhao, Yan
Kornerup, Kristin N
Auger, Jocelyn M
Thomas, Steve G
Dhanjal, Tarvinder
Kalia, Neena
Zhu, Jing W
Weiss, Arthur
Watson, Steve P
Contact Email: jenson.lim@stir.ac.uk
Issue Date: May-2009
Publisher: American Society of Hematology
Citation: 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 (2009) The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis, Blood, 113 (20), pp. 4942-4954.
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.
Type: Journal Article
URI: http://hdl.handle.net/1893/21101
DOI Link: http://dx.doi.org/10.1182/blood-2008-08-174318
Rights: The publisher does not allow this work to be made publicly available in this Repository. Please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study.
Affiliation: University of Birmingham
University of Birmingham
University of Birmingham
University of Birmingham
Biological and Environmental Sciences
University of Birmingham
University of Birmingham
University of Birmingham
University of Birmingham
University of Birmingham
University of Birmingham
University of California, San Francisco
University of California, San Francisco
University of Birmingham

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