Analysis of inhibitory mechanism and antithrombotic effects of a novel anti-platelet function molecule, semaphorin 3A

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We analyzed the mechanism of inhibition of platelet function by semaphorin 3A. In addition to inhibition of actin polymerization via suppression of Rac-paxillin pathway, we found that semaphorin 3A inhibits downstream molecules of PI3 kinase, Rap1 and AKT. Interestingly, semaphorin 3A inhibited both thrombin-or convulxin-induced Rap1 and AKT activation, it inhibited mainly ADP-induced AKT phosphorylation. These results indicate that semaphorin 3A inhibits PI3 kinase pathway, and it may have direct inhibitory effects on ADP-induced AKT activation.