期刊
FASEB JOURNAL
卷 15, 期 9, 页码 2019-+出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.00-0810fje
关键词
platelet aggregation; thrombosis; G protein-coupled receptors
Platelet aggregation and subsequent thrombosis are the major cause of ischemic diseases such as heart attack and stroke. ADP, acting via G protein-coupled receptors (GPCRs), is an important signal in thrombus formation and involves activation of phosphoinositide 3-kinases (PI3K). When platelets from mice lacking the G protein-activated PI3K gamma isoform were stimulated with ADP, aggregation was impaired. Collagen or thrombin, however, evoked a normal response. ADP stimulation of PI3K gamma -deficient platelets resulted in decreased PKB/Akt phosphorylation and alpha (IIb)beta (3) fibrinogen receptor activation. These effects did not influence bleeding time but protected PI3K gamma -null mice from death caused by ADP-induced platelet-dependent thromboembolic vascular occlusion. This result demonstrates an unsuspected, well-defined role for PI3K gamma downstream of ADP and suggests that pharmacological targeting of PI3K gamma has a potential use as antithrombotic therapy.
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