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-alpha, -betaI and -epsilon; (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 Ca2+-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 Go6976 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.
Effects of extracellular nucleotides in the thyroid: P2Y(2) receptor-mediated ERK1/2 activation and c-Fos induction in PC Cl3 cells
MUSCELLA, Antonella;DI JESO, Bruno;VERRI, Tiziano;STORELLI, Carlo;MARSIGLIANTE, Santo
2005-01-01
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-alpha, -betaI and -epsilon; (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 Ca2+-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 Go6976 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
