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

@article{citeulike:4809884, 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. 10.1182/blood-2008-08-174318}, author = {Senis, Yotis A. and Tomlinson, Michael G. and Ellison, Stuart and Mazharian, Alexandra and Lim, Jenson and Zhao, Yan and Kornerup, Kristin N. and Auger, Jocelyn M. and Thomas, Steve G. and Dhanjal, Tarvinder and Kalia, Neena and Zhu, Jing W. and Weiss, Arthur and Watson, Steve P.}, citeulike-article-id = {4809884}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2008-08-174318}, citeulike-linkout-1 = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/113/20/4942}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19246339}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19246339}, day = {14}, doi = {10.1182/blood-2008-08-174318}, journal = {Blood}, keywords = {cd148, gcoupledprotein, platelet, platelets, src, watson}, month = {May}, number = {20}, pages = {4942--4954}, posted-at = {2009-06-11 10:12:18}, priority = {2}, title = {The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis}, url = {http://dx.doi.org/10.1182/blood-2008-08-174318}, volume = {113}, year = {2009} }

TY - JOUR ID - citeulike:4809884 L3 - citeulike-article-id:4809884 N2 - 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. 10.1182/blood-2008-08-174318 IS - 20 JF - Blood EP - 4954 TI - The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis VL - 113 SP - 4942 KW - cd148 KW - gcoupledprotein KW - platelet KW - platelets KW - src KW - watson AU - Senis, Yotis AU - Tomlinson, Michael AU - Ellison, Stuart AU - Mazharian, Alexandra AU - Lim, Jenson AU - Zhao, Yan AU - Kornerup, Kristin AU - Auger, Jocelyn AU - Thomas, Steve AU - Dhanjal, Tarvinder AU - Kalia, Neena AU - Zhu, Jing AU - Weiss, Arthur AU - Watson, Steve PY - 2009/05/14/ UR - http://dx.doi.org/10.1182/blood-2008-08-174318 ER -