期刊
BLOOD
卷 116, 期 14, 页码 2570-2578出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-02-268136
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资金
- Pennsylvania Department of Health
- Southeastern Pennsylvania Affiliate of the American Heart Association
- National Institutes of Health [HL60683, HL80444, HL81322, CA 78499]
T-cell ubiquitin ligand-2 (TULA-2) is a recently discovered histidine tyrosine phosphatase thought to be ubiquitously expressed. In this work, we have investigated whether TULA-2 has a key role in platelet glycoprotein VI (GPVI) signaling. This study indicates that TULA-2 is expressed in human and murine platelets and is able to associate with Syk and dephosphorylate it. Ablation of TULA-2 resulted in hyperphosphorylation of Syk and its downstream effector phospholipase C-gamma 2 as well as enhanced GPVI-mediated platelet functional responses. In addition, shorter bleeding times and a prothrombotic phenotype were observed in mice lacking TULA-2. We therefore propose that TULA-2 is the primary tyrosine phosphatase mediating the dephosphorylation of Syk and thus functions as a negative regulator of GPVI signaling in platelets. (Blood. 2010;116(14):2570-2578)
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