Prostaglandin E2 selectively antagonizes prostaglandin F2α-stimulated T-cell factor/β-catenin signaling pathway by the FPB prostanoid receptor

FP prostanoid receptors are G-protein-coupled receptors ;that consist of two isoforms named FPA and FPB. Both isoforms activate inositol phosphate second messenger signaling pathways by their endogenous ligand prostaglandin F-2alpha (PGF(2alpha)). Previously we have shown that both isoforms undergo Rho-mediated cell rounding following treatment with PGF(2alpha). Following the removal of PGF(2alpha), however, FPA-expressing cells return to their original morphology, whereas FPB-expressing cells do not. It was also found that PGF(2alpha)-could activate T-cell factor (Tcf)/beta-catenin signaling in cells expressing the FPB isoform but not in cells expressing the FPA isoform. We now show that prostaglandin E-2 (PGE(2)) can induce cell rounding and stimulate the formation of inositol phosphates to the same extent as PGF(2alpha) in cells expressing either the FPA or FPB isoforms. However, PGE2 has much lower efficacy as compared with PGF(2alpha) for the activation of Tcf/beta-catenin signaling in FPB-expressing cells, and the cell rounding is reversible. Interestingly, pretreatment of FPB-expressing cells with PGE(2)-attenuated PGF(2alpha)-stimulated Tcf/beta-catenin signaling in a dose-dependent manner while having no effect on PGF(2alpha)-stimulated inositol phosphates formation. Thus, the ratio of endogenous PGE(2) and PGF(2alpha) has the potential to selectively regulate one signaling pathway over another. This represents a novel mechanism for the regulation of cell signaling that is distinct from regulation occurring at the level of the receptor and its effector pathways.