thromboxane-a2 and FR900359

Platelets play a key role in the physiological hemostasis or pathological process of thrombosis. Rhodocytin, an agonist of the C-type lectin-like receptor-2 (CLEC-2), elicits powerful platelet activation signals in conjunction with Src family kinases (SFKs), spleen tyrosine kinase (Syk), and phospholipase γ2 (PLCγ2). Previous reports have shown that rhodocytin-induced platelet aggregation depends on secondary mediators such as thromboxane A2 (TxA2) and ADP, which are agonists for G-protein-coupled receptors (GPCRs) on platelets. How the secondary mediators regulate CLEC-2-mediated platelet activation in terms of signaling is not clearly defined. In this study, we report that CLEC-2-induced Syk and PLCγ2 phosphorylation is potentiated by TxA2 and that TxA2 plays a critical role in the most proximal event of CLEC-2 signaling,

Topics: Animals; Blood Platelets; Coagulants; Depsipeptides; Enzyme Inhibitors; GTP-Binding Protein alpha Subunits, Gq-G11; Humans; Lectins, C-Type; Mice, Knockout; Models, Biological; Phospholipase C gamma; Phosphorylation; Platelet Aggregation; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-fyn; Signal Transduction; Specific Pathogen-Free Organisms; src-Family Kinases; Syk Kinase; Thromboxane A2; Viper Venoms