title: PTEN regulates collagen-induced platelet activation.
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.
authors.affiliation: 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.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Weng
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Changgeng
authors.initials: C
authors.lastname: Ruan
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Chen
authors.forename: T Kent
authors.initials: TK
authors.lastname: Gartner
authors.forename: Junling
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015539:Platelet Activation
chemical_list: D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse