title: Phosphorylation of JAK2 by serotonin 5-HT (2A) receptor activates both STAT3 and ERK1/2 pathways and increases growth of JEG-3 human placental choriocarcinoma cell.
abstract: Serotonin 5-HT(2A) 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-HT(2A) receptor-induced growth of JEG-3 cells. Selective 5-HT(2A) receptor agonist, DOI, induced JEG-3 cell growth was inhibited by the inhibitor of JAK2 (AG490), MEK1/2 (U0126), phospholipase C-β (PLC-β; U73122) and protein kinase C-β (PKC-β; Gö6976)), whereas the selective phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) had no effect. Specific inhibitors of PLC-β, PKC-β and Ras (farnesylthiosalicylic acid) inhibit activation of ERK1/2, whereas the PKC-ζ 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-β-PKC-β-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-HT(2A) receptor is essential to activate both STAT3 and ERK1/2 signalling pathways as well as to increase JEG-3 choriocarcinoma cell growth and survival.
authors: INRS-Institut Armand-Frappier, Université du Québec, 531 boul. des Prairies, Building 18, Laval, QC, Canada H7V 1B7.
authors: T
authors: T
authors: Oufkir
authors: C
authors: C
authors: Vaillancourt
mesh_terms: D000662:Amphetamines / Q000037:antagonists & inhibitors; D002070:Butadienes / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002822:Choriocarcinoma / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000187:drug effects / Q000378:metabolism; D054799:Phospholipase C beta / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011247:Pregnancy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D064546:Protein Kinase C beta; D011760:Pyrrolidinones / Q000494:pharmacology; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D002070:Butadienes; D002227:Carbazoles; D004963:Estrenes; D009570:Nitriles; D011760:Pyrrolidinones; D044402:Receptor, Serotonin, 5-HT2A; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C113580:U 0126; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C081021:Go 6976; D058539:Phosphatidylinositol 3-Kinase; D053614:Janus Kinase 2; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D054799:Phospholipase C beta; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine