期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 203, 期 11, 页码 2433-2440出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20061302
关键词
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资金
- NHLBI NIH HHS [HL-48872, HL-75507, R01 HL048872, HL-44525, R01 HL075507, HL-66277, R37 HL044525, R01 HL066277, R01 HL044525] Funding Source: Medline
Tissue factor (TF) is an essential cofactor for the activation of blood coagulation in vivo. We now report that quiescent human platelets express TF pre-mRNA and, in response to activation, splice this intronic-rich message into mature mRNA. Splicing of TF pre-mRNA is associated with increased TF protein expression, procoagulant activity, and accelerated formation of clots. Pre-mRNA splicing is controlled by Cdc2-like kinase (Clk)1, and interruption of Clk1 signaling prevents TF from accumulating in activated platelets. Elevated intravascular TF has been reported in a variety of prothrombotic diseases, but there is debate as to whether anucleate platelets-the key cellular effector of thrombosis-express TF. Our studies demonstrate that human platelets use Clk1-dependent splicing pathways to generate TF protein in response to cellular activation. We propose that platelet-derived TF contributes to the propagation and stabilization of a thrombus.
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