Effects of extracellular nucleotides in the thyroid: P2Y2 receptor-mediated ERK1/2 activation and c-Fos induction in PC Cl3 cells

Maria Giovanna Elia, Antonella Muscella, Simona Romano, Simona Greco, Bruno Di Jeso, Tiziano Verri, Carlo Storelli, Santo Marsigliante

Research output: Contribution to journalArticlepeer-review

Abstract

Aim of the present paper was to investigate the signaling pathways of P2Y2 in rat thyroid PC Cl3 cell line and its effects on proliferation. This study demonstrates that P2Y2 activation provoked: (a) a cytosol-to-membrane translocation of PKC-α, -βI and -ε; (b) the phosphorylation of the extra cellular signal-regulated kinases 1 and 2 (ERK1/2); (c) the expression of c-Fos protein; (d) no effects on the G1/S progression and overall cell proliferation. The P2Y2-stimulated ERK1/2 phosphorylation was: (a) completely blocked by PD098059, a mitogen-activated protein kinase (MEK) inhibitor or by W-7, a Ca 2+-calmodulin (CaM) antagonist; (b) reduced by GF109203X, inhibitor of PKCs, or AG1478, inhibitor of EGFR tyrosine kinase, or LY294002/wortmannin, inhibitors of phosphoinositide 3-kinases, or cytochalasin D, inhibitor of actin microfilament bundles polymerization. The c-Fos induction was greatly diminished by Gö6976 or PD098059, and completely abolished when combined. In conclusion, data indicate that the P2Y2-induced phosphorylation of ERK1/2 and the induction of c-Fos are due to the operation of CaM, with PKC, PI3K, EGFR and receptor endocytosis mechanisms endorsing the signalling. On the other hand, no mitogenic effects of P2Y2 are whatsoever noticed in PC Cl3 cells.

Original languageEnglish
Pages (from-to)739-749
Number of pages11
JournalCellular Signalling
Volume17
Issue number6
DOIs
Publication statusPublished - Jun 2005

Keywords

  • ATP
  • c-Fos
  • ERK
  • P2Y
  • PC Cl3
  • PKC
  • Proliferation
  • Thyroid
  • UTP

ASJC Scopus subject areas

  • Cell Biology

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