Cellular Conditioning and Activation of β-Catenin Signaling by the FPB Prostanoid Receptor

FP prostanoid receptors have been identified as two isoforms named FP(A) and FP(B). We have shown that the FP(B) isoform, but not the FP(A), activates beta-catenin-mediated transcription. We now report that the mechanism of this FP(B)-specific activation of beta-catenin signaling occurs in two steps. The first is a conditioning step that involves an agonist-independent association of the FP(B) receptor with phosphatidylinositol 3-kinase followed by constitutive internalization of a receptor complex containing E-cadherin and beta-catenin. This constitutive internalization conditions the cell for subsequent beta-catenin signaling by increasing the cellular content of cytosolic beta-catenin. The second step involves agonist-dependent activation of Rho followed by cell rounding. Because of the conditioning step, this agonist-dependent step results in a stabilization of beta-catenin and activation of transcription. Although stimulation of the FP(A) isoform activates Rho and induces cellular shape change, it does not activate beta-catenin signaling, because the FP(A) does not undergo constitutive internalization and does not condition the cell for beta-catenin signaling. The cellular conditioning described here for the FP(B) illustrates the potential of the receptor to alter the signaling environment of a cell even in the absence of agonist and has general significance for understanding G-protein-coupled receptor signaling.