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

Hiromichi Fujino, Dinesh Srinivasan, John W. Regan

Research output: Contribution to journalArticle

29 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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