@article{75e7e792c3924d88a763c2a1ac03c674,
title = "A Gi-independent mechanism mediating Akt phosphorylation in platelets",
abstract = "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 P2Y12 knockout mice to address the role of P2Y12 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 Thr308 and Ser473 in P2Y12-deficient platelets. AYPGKF-induced Akt phosphorylation is enhanced by expression of recombinant human PAR4 cDNA in Chinese hamster ovary (CHO) cells. P2Y12-independent Akt phosphorylation was not inhibited by integrin inhibitor peptide RGDS or integrin β3 deficiency. Akt phosphorylation induced by thrombin or AYPGKF in P2Y12-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 P2Y12-independent signaling pathway mediating Akt phosphorylation in response to thrombin receptors.",
keywords = "Akt, Gi, P2Y12, Phosphorylation, Platelets, Thrombin",
author = "B. Xiang and G. Zhang and J. Liu and Morris, {A. J.} and Smyth, {S. S.} and Gartner, {T. K.} and Z. Li",
year = "2010",
month = sep,
doi = "10.1111/j.1538-7836.2010.03969.x",
language = "English",
volume = "8",
pages = "2032--2041",
number = "9",
}