Differential involvement of ERK1-2 and p38MAPK activation on Swiss3T3 cell proliferation induced by prostaglandin F2a

DEKANTY, A.; GIULIANELI, S.; COSO, O. A.; RUDLAND, P. S.; JIMENEZ DE ASUA, L.

FEBS LETTERS

Año: 2006 p. 2512 - 2516

0014-5793

Abstract Prostaglandin F2a (PGF2a) induces cyclin D1 expression and DNA synthesis in Swiss 3T3 cells. In order to assess which signaling mechanisms are implicated in these processes, we have used both a pharmacological approach and interfering mutants. We demonstrate that PGF2a induces extracellular-signal- regulated kinase (ERK1-2) and p38MAPK activation, and inhibition of any of these signaling pathways completely blocks PGF2a-stimulated DNA synthesis. We also show that ERK1-2, but not p38MAPK activation is required to induce cyclin D12a (PGF2a) induces cyclin D1 expression and DNA synthesis in Swiss 3T3 cells. In order to assess which signaling mechanisms are implicated in these processes, we have used both a pharmacological approach and interfering mutants. We demonstrate that PGF2a induces extracellular-signal- regulated kinase (ERK1-2) and p38MAPK activation, and inhibition of any of these signaling pathways completely blocks PGF2a-stimulated DNA synthesis. We also show that ERK1-2, but not p38MAPK activation is required to induce cyclin D12a induces extracellular-signal- regulated kinase (ERK1-2) and p38MAPK activation, and inhibition of any of these signaling pathways completely blocks PGF2a-stimulated DNA synthesis. We also show that ERK1-2, but not p38MAPK activation is required to induce cyclin D11-2) and p38MAPK activation, and inhibition of any of these signaling pathways completely blocks PGF2a-stimulated DNA synthesis. We also show that ERK1-2, but not p38MAPK activation is required to induce cyclin D12a-stimulated DNA synthesis. We also show that ERK1-2, but not p38MAPK activation is required to induce cyclin D1MAPK activation is required to induce cyclin D1 expression, strongly suggesting that the concerted action of cyclin D1 gene expression and other events are required to induce complete phosphorylation of retinoblastoma protein and S-phase entry in response to PGF2a.1 gene expression and other events are required to induce complete phosphorylation of retinoblastoma protein and S-phase entry in response to PGF2a.2a.