PTEN Regulates Collagen-Induced Platelet Activation

Abstract 5126

PI3K has been shown to play an important role in collagen-induced platelet activation, but the role(s) of PTEN, a major regulator of the PI3K/Akt signaling pathway, has not been examined in platelets. Here, we report that PTEN−/− mouse blood contains 25% more platelets than PTEN+/+ blood, and that PTEN deficiency significantly shortened the bleeding time, increased the sensitivity of platelets to collagen-induced activation and aggregation, and enhanced phosphorylation of Akt at Ser473 in response to collagen. Furthermore, we found that PP2, and the combination of apyrase, indomethcin+1B5, respectively inhibited collagen-induced aggregation in both PTEN+/+ and PTEN−/− platelets. In contrast, LY294002 (a PI3K inhibitor) prevented the aggregation of PTEN+/+, but not PTEN−/− platelets. Therefore, PTEN apparently regulates collagen-induced platelet activation through PI3K/Akt dependent and independent signaling pathways.