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Activation of P2Y2 receptor induces c-FOS protein through a pathway involving mitogen-activated protein kinases and phosphoinositide 3-kinases in HeLa cells.
J Cell Physiol. 2003 May; 195(2):234-40.JC

Abstract

The effects of P2Y2 purinoceptor activation on c-Fos expression and the signaling pathways evoked by extracellular ATP/UTP in HeLa cells were investigated. We found that P2Y2 activation induced c-Fos protein and phosphorylated the extracellular signal-regulated kinases 1 and 2 (ERK1/2). The P2Y2-stimulated c-Fos induction was partly blocked (a) by U73122, a phospholipase C inhibitor, (b) by Gö6976, a conventional PKC inhibitor, (c) by PD098059, a mitogen-activated protein kinase kinase inhibitor, and, moreover, (d) by the inhibitors of phosphoinositide 3-kinases (PI3K), LY294002 and wortmannin. When Gö6976 and PD098059, or Gö6976 and wortmannin, were combined there was a totally inhibition of P2Y2-induced c-Fos increase. Either U73122 or Gö6976 did not inhibit ERK1/2 phosphorylation induced by ATP/UTP, while it was inhibited by LY294002 (or wortmannin) and by staurosporine. Additionally, wortmannin inhibited the cytosol-to-membrane translocation of PKC- epsilon induced by ATP/UTP. These data indicated that agonist-induced PI3K and downstream PKC- epsilon activation mediated the effect of ATP/UTP on ERK1/2 activation. To test the biological consequences of ERK1/2 activation, the effect of P2Y2 on cell functions were examined. P2Y2 stimulation increased cell proliferation and this effect was attenuated by PD098059 in a dose-dependent manner, thereby indicating that the ERK pathway mediates mitogenic signaling by P2Y2. In conclusion, the activation of conventional PKCs through P2Y2 receptor acts in concert with ERK and PI3K/PKC- epsilon pathways to induce c-Fos protein and HeLa cell proliferation.

Authors+Show Affiliations

Laboratory Physiology, Dipartimento di Scienze e Tecnologie Biologiche e Ambientali, University of Lecce, Ecotekne, Lecce, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12652650

Citation

Muscella, Antonella, et al. "Activation of P2Y2 Receptor Induces c-FOS Protein Through a Pathway Involving Mitogen-activated Protein Kinases and Phosphoinositide 3-kinases in HeLa Cells." Journal of Cellular Physiology, vol. 195, no. 2, 2003, pp. 234-40.
Muscella A, Elia MG, Greco S, et al. Activation of P2Y2 receptor induces c-FOS protein through a pathway involving mitogen-activated protein kinases and phosphoinositide 3-kinases in HeLa cells. J Cell Physiol. 2003;195(2):234-40.
Muscella, A., Elia, M. G., Greco, S., Storelli, C., & Marsigliante, S. (2003). Activation of P2Y2 receptor induces c-FOS protein through a pathway involving mitogen-activated protein kinases and phosphoinositide 3-kinases in HeLa cells. Journal of Cellular Physiology, 195(2), 234-40.
Muscella A, et al. Activation of P2Y2 Receptor Induces c-FOS Protein Through a Pathway Involving Mitogen-activated Protein Kinases and Phosphoinositide 3-kinases in HeLa Cells. J Cell Physiol. 2003;195(2):234-40. PubMed PMID: 12652650.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of P2Y2 receptor induces c-FOS protein through a pathway involving mitogen-activated protein kinases and phosphoinositide 3-kinases in HeLa cells. AU - Muscella,Antonella, AU - Elia,Maria Giovanna, AU - Greco,Simona, AU - Storelli,Carlo, AU - Marsigliante,Santo, PY - 2003/3/26/pubmed PY - 2003/5/31/medline PY - 2003/3/26/entrez SP - 234 EP - 40 JF - Journal of cellular physiology JO - J. Cell. Physiol. VL - 195 IS - 2 N2 - The effects of P2Y2 purinoceptor activation on c-Fos expression and the signaling pathways evoked by extracellular ATP/UTP in HeLa cells were investigated. We found that P2Y2 activation induced c-Fos protein and phosphorylated the extracellular signal-regulated kinases 1 and 2 (ERK1/2). The P2Y2-stimulated c-Fos induction was partly blocked (a) by U73122, a phospholipase C inhibitor, (b) by Gö6976, a conventional PKC inhibitor, (c) by PD098059, a mitogen-activated protein kinase kinase inhibitor, and, moreover, (d) by the inhibitors of phosphoinositide 3-kinases (PI3K), LY294002 and wortmannin. When Gö6976 and PD098059, or Gö6976 and wortmannin, were combined there was a totally inhibition of P2Y2-induced c-Fos increase. Either U73122 or Gö6976 did not inhibit ERK1/2 phosphorylation induced by ATP/UTP, while it was inhibited by LY294002 (or wortmannin) and by staurosporine. Additionally, wortmannin inhibited the cytosol-to-membrane translocation of PKC- epsilon induced by ATP/UTP. These data indicated that agonist-induced PI3K and downstream PKC- epsilon activation mediated the effect of ATP/UTP on ERK1/2 activation. To test the biological consequences of ERK1/2 activation, the effect of P2Y2 on cell functions were examined. P2Y2 stimulation increased cell proliferation and this effect was attenuated by PD098059 in a dose-dependent manner, thereby indicating that the ERK pathway mediates mitogenic signaling by P2Y2. In conclusion, the activation of conventional PKCs through P2Y2 receptor acts in concert with ERK and PI3K/PKC- epsilon pathways to induce c-Fos protein and HeLa cell proliferation. SN - 0021-9541 UR - https://www.unboundmedicine.com/medline/citation/12652650/Activation_of_P2Y2_receptor_induces_c_FOS_protein_through_a_pathway_involving_mitogen_activated_protein_kinases_and_phosphoinositide_3_kinases_in_HeLa_cells_ L2 - https://doi.org/10.1002/jcp.10242 DB - PRIME DP - Unbound Medicine ER -