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• W2046655645 abstract "The A2A adenosine receptor is prototypically coupled to stimulation of adenylyl cyclase by means of Gs. However, in human endothelial cells, adenosine stimulates proliferation and mitogen-activated protein kinase (MAP kinase) by means of the A2A receptor in a manner that is independent of cAMP. Here, we have investigated the regulation of p70S6-kinase, which relays signals from membrane-bound growth factor receptors to stimulation of translational efficiency in the G1 phase of the cell cycle. Our experiments show that adenosine analogues promote phosphorylation of p70S6 kinase in endothelial cells. The pharmacologic profile indicates that this effect is mediated by means of the A2A receptor. We have confirmed this pharmacologic classification by using a transfected Chinese hamster ovary- (CHO) A2A cell line (which stably expresses the human A2A adenosine receptor); all findings that were obtained in endothelial cells were faithfully reproduced in CHO-A2A. The signalling cascade that links the receptor to p70S6 kinase is independent of cAMP and MAP kinase activation but sensitive to rapamycin. Furthermore, the A2A-receptor–dependent activation of p70S6 kinase stimulation relies on a phosphatidylinositol-3 kinase isoform, because it is inhibited by wortmannin and the synthetic inhibitor LY294002. Conversely, MAP kinase stimulation by the A2A receptor was not affected by wortmannin. Taken together, our experiments show that the A2A adenosine receptor regulates cAMP levels, MAP kinase, and p70S6 kinase in human endothelial cells by means of three independent pathways. Drug Dev. Res. 45:140–150, 1998. © 1998 Wiley-Liss, Inc." @default.
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• W2046655645 date "1998-11-01" @default.
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• W2046655645 title "Stimulation of p70S6 kinase phosphorylation by the A2A adenosine receptor in primary human endothelial cells and in CHO cells heterologously expressing the receptor" @default.
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• W2046655645 doi "https://doi.org/10.1002/(sici)1098-2299(199811/12)45:3/4<140::aid-ddr9>3.0.co;2-m" @default.
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