Prostaglandin E2 selectively antagonizes prostaglandin F -stimulated T-cell factor/β-catenin signaling pathway by the FPB prostanoid receptor

Hiromichi Fujino, George A. Vielhauer, John W. Regan

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

FP prostanoid receptors are G-protein-coupled receptors that consist of two isoforms named FPA and FPB. Both isoforms activate inositol phosphate second messenger signaling pathways by their endogenous ligand prostaglandin F (PGF). Previously we have shown that both isoforms undergo Rho-mediated cell rounding following treatment with PGF. Following the removal of PGF , however, FPA-expressing cells return to their original morphology, whereas FPB-expressing cells do not. It was also found that PGF-could activate T-cell factor (Tcf)/β-catenin signaling in cells expressing the FPB isoform but not in cells expressing the FPA isoform. We now show that prostaglandin E2 (PGE2) can induce cell rounding and stimulate the formation of inositol phosphates to the same extent as PGF in cells expressing either the FPA or FP B isoforms. However, PGE2 has much lower efficacy as compared with PGF for the activation of Tcf/β-catenin signaling in FPB-expressing cells, and the cell rounding is reversible. Interestingly, pretreatment of FPB-expressing cells with PGE2-attenuated PGF-stimulated Tcf/β-catenin signaling in a dose-dependent manner while having no effect on PGF -stimulated inositol phosphates formation. Thus, the ratio of endogenous PGE2 and PGF has the potential to selectively regulate one signaling pathway over another. This represents a novel mechanism for the regulation of cell signaling that is distinct from regulation occurring at the level of the receptor and its effector pathways.

Original languageEnglish (US)
Pages (from-to)43386-43391
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number42
DOIs
StatePublished - Oct 15 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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