S1P activates translational regulators in ML-1 cells.

<p>(<b>A–D</b>) S1P induces phosphorylation of mTOR, eIF-4E and 4E-BP1 via PI3K and MEK and phosphorylation of p70S6K via PI3K. Cells were preincubated with wortmannin (W, 10 µM, 30 min) or U0126 (U0, 10 µM, 1 h) and stimulated with S1P (100 nM) for 30 min. (<b>E–G</b>) S1P induces phosphorylation of eIF-4E, 4E-BP1 and p70S6K via mTOR. Cells were preincubated with rapamycin (Rapa, 100 ng/ml, 1 h) and stimulated with S1P (100 nM) for 30 min. (<b>H</b>) Inhibition of p70S6K prevents S1P-induced HIF-1α expression. Cells were preincubated with p70S6K inhibitor (p70i, 10 µM, 1 h) and stimulated with S1P (100 nM) for 6 h. Results are mean ± SEM, n ≥ 3. *P < 0.05, **P < 0.01 and ***P < 0.001 indicate statistically significant difference between S1P treatment and respective vehicle control, ^ooP < 0.01 and ^oooP < 0.001 indicate statistically significant difference between inhibitor treatment and vehicle control.