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

Abstract 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 rec...

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Bibliographic Details
Published in:Placenta (Eastbourne) 2011-12, Vol.32 (12), p.1033-1040
Main Authors: Oufkir, T, Vaillancourt, C
Format: Article
Language:English
Subjects:
5-HT2A receptor
Biological and medical sciences
Cell signalling
Embryology: invertebrates and vertebrates. Teratology
Fundamental and applied biological sciences. Psychology
Internal Medicine
Janus kinase (JAK)
Mitogen-activated kinase (MAPK)
Obstetrics and Gynecology
phospholipase C (PLC)
Protein kinase C (PKC)
Serotonin
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Summary:Abstract 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-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-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.
ISSN:0143-4004
1532-3102
DOI:10.1016/j.placenta.2011.09.005