PTEN regulates collagen-induced platelet activation

Author:

Weng Zhen1,Li Ding1,Zhang Lin1,Chen Jian2,Ruan Changgeng3,Chen Guoqiang4,Gartner T. Kent5,Liu Junling1

Affiliation:

1. Department of Biochemistry and Molecular & Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai, China;

2. Intensive Care Unit, Xinjiang Traditional Chinese Medicine Hospital, Xinjiang Medical University, Xinjiang, China;

3. Jiangsu Institute of Hematology, China Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, China;

4. Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China; and

5. Department of Biology, University of Memphis, Memphis, TN

Abstract

Abstract Phosphatidylinositol 3-kinase (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, indomethacin + 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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