Cellular conditioning and activation of β-catenin signaling by the FPB prostanoid receptor

Hiromichi Fujino, Dinesh Srinivasan, John W. Regan

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

FP prostanoid receptors have been identified as two isoforms named FPA and FPB. We have shown that the FPB isoform, but not the FPA, activates β-catenin-mediated transcription. We now report that the mechanism of this FPB-specific activation of β-catenin signaling occurs in two steps. The first is a conditioning step that involves an agonist-independent association of the FPB receptor with phosphatidylinositol 3-kinase followed by constitutive internalization of a receptor complex containing E-cadherin and β-catenin. This constitutive internalization conditions the cell for subsequent β-catenin signaling by increasing the cellular content of cytosolic β-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 β-catenin and activation of transcription. Although stimulation of the FPA isoform activates Rho and induces cellular shape change, it does not activate β-catenin signaling, because the FPA does not undergo constitutive internalization and does not condition the cell for β-catenin signaling. The cellular conditioning described here for the FPB 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.

Original languageEnglish (US)
Pages (from-to)48786-48795
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number50
DOIs
StatePublished - Dec 13 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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