Phosphorylation of JAK2 by serotonin 5-HT2A receptor activates both STAT3 and ERK1/2 pathways and increases growth of JEG-3 human placental choriocarcinoma cell

Serotonin 5-HT2A receptor activation improves viability, increases DNA synthesis and activates JAK2-STAT3 and MEK1/2-ERK1/2 signalling pathways in JEG-3 human trophoblast choriocarcinoma cells. The goal of this study was to characterize the signal transduction cascade involved in 5-HT2A receptor-induced growth of JEG-3 cells. Selective 5-HT2A receptor agonist. DOI, induced JEG-3 cell growth was inhibited by the inhibitor of JAK2 (AG490), MEK1/2 (U0126), phospholipase C-beta (PLC-beta; U73122) and protein kinase C-beta (PKC-beta; Go6976)), whereas the selective phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) had no effect. Specific inhibitors of PLC-beta, PKC-beta and Ras (farnesylthiosalicylic acid) inhibit activation of ERK1/2, whereas the PKC-zeta inhibitor GF109203X had no effect. Interestingly, inhibition of JAK2 prevented DOI-induced phosphorylation of ERK1/2 whereas inhibition of ERK1/2 pathway had no effect on DOI-induced activation of STAT3. Taken together, our results demonstrate that both the JAK2-STAT3 and PLC-beta-PKC-beta-Ras-ERK1/2 signalling pathways are involved in the stimulation of JEG-3 cell growth mediated by DOI. Moreover, this study shows that activation of JAK2 by the 5-HT2A receptor is essential to activate both STAT3 and ERK1/2 signalling pathways as well as to increase JEG-3 choriocarcinoma cell growth and survival. (C) 2011 Elsevier Ltd. All rights reserved.