FP prostanoid receptor activation of a T-cell factor/beta-catenin signaling pathway

FP prostanoid receptors are G-protein-coupled receptors (GPCR) that consist of two known isoforns, FPA and FPB. These isoforms, which are generated by alternative mRNA splicing, are identical except for their carboxyl-termina l domains. Previously we have shown that stimulation of both isoforms with prostaglandin F-2 alpha (PGF(2 alpha)) activates the small G-protein Rho, l eading to morphological changes consisting of cell rounding and the formati on of cell aggregates. Following the removal of PGF(2 alpha), however, FPA- expressing cells show rapid reversal of cell rounding, whereas FPB-expressi ng cells do not. We now show that acute treatment of FPB-expressing cells w ith PGF(2 alpha) leads to a subcellular reorganization of beta -catenin, a decrease in the phosphorylation of cytoplasmic beta -catenin, and persisten t stimulation of Tcf/Lef-mediated transcriptional activation. This does not occur in FPA-expressing cells and may underlie the differences between the se isoforms with respect to the reversal of cell rounding. The Tcf/beta -ca tenin signaling pathway is known to mediate the actions of Wnt acting throu gh the heptahelical receptor, Frizzled, and has not been associated previou sly with GPCR activation. Our findings expand the signaling possibilities f or GPCRs and suggest novel roles for FP receptors in normal tissue developm ent and malignant transformation.