title: Cellular conditioning and activation of beta-catenin signaling by the FPB prostanoid receptor.
abstract: 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.
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism*; D000077191:Wortmannin; D051176:beta Catenin
chemical_list: D000730:Androstadienes; D003598:Cytoskeletal Proteins; D015237:Dinoprost; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011982:Receptors, Prostaglandin; D015534:Trans-Activators; D000077191:Wortmannin; D051176:beta Catenin; C495270:CTNNB1 protein, human; C034671:prostaglandin F2alpha receptor