FP Prostanoid Receptor Activation of a T-cell Factor/β-Catenin Signaling Pathway

Abstract

FP prostanoid receptors are G-protein-coupled receptors (GPCR) that consist of two known isoforms, FPA and FPB. These isoforms, which are generated by alternative mRNA splicing, are identical except for their carboxyl-terminal domains. Previously we have shown that stimulation of both isoforms with prostaglandin F2. (PGF2α) activates the small G-protein Rho, leading to morphological changes consisting of cell rounding and the formation of cell aggregates. Following the removal of PGF 2α, however, FPA-expressing cells show rapid reversal of cell rounding, whereas FPB-expressing cells do not. We now show that acute treatment of FPB-expressing cells with PGF 2α leads to a subcellular reorganization of β-catenin, a decrease in the phosphorylation of cytoplasmic β-catenin, and persistent stimulation of Tcf/Lef-mediated transcriptional activation. This does not occur in FPA-expressing cells and may underlie the differences between these isoforms with respect to the reversal of cell rounding. The Tcf/β-catenin signaling pathway is known to mediate the actions of Wnt acting through the heptahelical receptor, Frizzled, and has not been associated previously with GPCR activation. Our findings expand the signaling possibilities for GPCRs and suggest novel roles for FP receptors in normal tissue development and malignant transformation.