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A G i ‐independent mechanism mediating Akt phosphorylation in platelets
Author(s) -
XIANG B.,
ZHANG G.,
LIU J.,
MORRIS A. J.,
SMYTH S. S.,
GARTNER T. K.,
LI Z.
Publication year - 2010
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2010.03969.x
Subject(s) - protein kinase b , phosphorylation , microbiology and biotechnology , pi3k/akt/mtor pathway , platelet , thrombin , chemistry , p2y12 , akt1 , signal transduction , biology , immunology , platelet aggregation
Summary. Background: The serine‐threonine kinase Akt plays an important role in regulating platelet activation. Stimulation of platelets with various agonists results in Akt activation as indicated by Akt phosphorylation. However, the mechanisms of Akt phosphorylation in platelets are not completely understood. Objectives and Methods: We used P2Y 12 knockout mice to address the role of P2Y 12 in Akt phosphorylation in response to thrombin receptors in platelets. Results: Thrombin or the PAR4 thrombin receptor peptide AYPGKF at high concentrations stimulated substantial phosphorylation of Akt residues Thr 308 and Ser 473 in P2Y 12 ‐deficient platelets. AYPGKF‐induced Akt phosphorylation is enhanced by expression of recombinant human PAR4 cDNA in Chinese hamster ovary (CHO) cells. P2Y 12 ‐independent Akt phosphorylation was not inhibited by integrin inhibitor peptide RGDS or integrin β 3 deficiency. Akt phosphorylation induced by thrombin or AYPGKF in P2Y 12 ‐deficient platelets was inhibited by the calcium chelator dimethyl‐BAPTA, the Src family kinase inhibitor PP2, and PI3K inhibitors, respectively. Conclusions: Our results reveal a novel P2Y 12 ‐independent signaling pathway mediating Akt phosphorylation in response to thrombin receptors.