Oufkir, Talal et Vaillancourt, Cathy 
ORCID: https://orcid.org/0000-0003-0543-6244
(2011).
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
Placenta
, vol. 32
, nº 12.
pp. 1033-1040.
DOI: 10.1016/j.placenta.2011.09.005.
Résumé
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; Go6976)), 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.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | 5-HT2A receptor; Serotonin; Cell signalling; Mitogen-activated kinase (MAPK); phospholipase C (PLC); Protein kinase C (PKC); Janus kinase (JAK) |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 27 mars 2024 15:23 |
| Dernière modification: | 27 mars 2024 15:23 |
| URI: | https://espace.inrs.ca/id/eprint/15011 |
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