Protein Kinase C Isoform ε Negatively Regulates ADP-Induced Calcium Mobilization and Thromboxane Generation in Platelets

• DOI: 10.1161/atvbaha.111.242388
• Publication Date: 2012-02-24T06:27:08Z
• Authors: Yamini S. Bynagar...; Parth Lakhani; Jianguo Jin; Kamala Bhavaraju; Mario C. Rico; Soochong Kim; Donna Woulfe; Satya P. Kunapuli
• Keywords: Calcium in biology; Knockout mouse

Members of the protein kinase C (PKC) family are shown to positively and negatively regulate platelet activation. Although positive regulatory roles extensively studied, negative PKCs poorly understood. We investigated mechanism specific isoforms involved in PKC-mediated regulation ADP-induced functional responses.A pan-PKC inhibitor, GF109203X, potentiated cPLA(2) phosphorylation thromboxane generation as well ERK activation intracellular calcium (Ca(2+)(i)) mobilization, 2 signaling molecules, upstream Thus, inhibit by inhibiting Ca(2+)(i) mobilization. Because inhibitor classic PKC isoforms, GO-6976, did not affect ADP-mediated generation, we role novel class isoforms. were PKCε null murine platelets compared with from wild-type littermates. Interestingly, when release is blocked, aggregation knockout was similar, suggesting that does directly. mice exhibited shorter times occlusion an FeCl(3)-induced arterial injury model bleeding tail-bleeding experiments.We conclude regulates offers protection against thrombosis.