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 Citations (Scopus)

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

Fingerprint

TCF Transcription Factors
Catenins
Dinoprost
Prostaglandins F
Dinoprostone
Prostaglandins
Protein Isoforms
Inositol Phosphates
Cells
Cell signaling
Second Messenger Systems
G-Protein-Coupled Receptors
Chemical activation
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

Prostaglandin E2 selectively antagonizes prostaglandin F -stimulated T-cell factor/β-catenin signaling pathway by the FPB prostanoid receptor. / Fujino, Hiromichi; Vielhauer, George A.; Regan, John W.

In: Journal of Biological Chemistry, Vol. 279, No. 42, 15.10.2004, p. 43386-43391.

Research output: Contribution to journalArticle

@article{a5b5311a140d4434931659c182cd74a8,
title = "Prostaglandin E2 selectively antagonizes prostaglandin F 2α-stimulated T-cell factor/β-catenin signaling pathway by the FPB prostanoid receptor",
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 F2α (PGF2α). Previously we have shown that both isoforms undergo Rho-mediated cell rounding following treatment with PGF2α. Following the removal of PGF 2α, however, FPA-expressing cells return to their original morphology, whereas FPB-expressing cells do not. It was also found that PGF2α-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 2α in cells expressing either the FPA or FP B isoforms. However, PGE2 has much lower efficacy as compared with PGF2α 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 PGF2α-stimulated Tcf/β-catenin signaling in a dose-dependent manner while having no effect on PGF 2α-stimulated inositol phosphates formation. Thus, the ratio of endogenous PGE2 and PGF2α 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.",
author = "Hiromichi Fujino and Vielhauer, {George A.} and Regan, {John W}",
year = "2004",
month = "10",
day = "15",
doi = "10.1074/jbc.M408276200",
language = "English (US)",
volume = "279",
pages = "43386--43391",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "42",

}

TY - JOUR

T1 - Prostaglandin E2 selectively antagonizes prostaglandin F 2α-stimulated T-cell factor/β-catenin signaling pathway by the FPB prostanoid receptor

AU - Fujino, Hiromichi

AU - Vielhauer, George A.

AU - Regan, John W

PY - 2004/10/15

Y1 - 2004/10/15

N2 - 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 F2α (PGF2α). Previously we have shown that both isoforms undergo Rho-mediated cell rounding following treatment with PGF2α. Following the removal of PGF 2α, however, FPA-expressing cells return to their original morphology, whereas FPB-expressing cells do not. It was also found that PGF2α-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 2α in cells expressing either the FPA or FP B isoforms. However, PGE2 has much lower efficacy as compared with PGF2α 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 PGF2α-stimulated Tcf/β-catenin signaling in a dose-dependent manner while having no effect on PGF 2α-stimulated inositol phosphates formation. Thus, the ratio of endogenous PGE2 and PGF2α 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.

AB - 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 F2α (PGF2α). Previously we have shown that both isoforms undergo Rho-mediated cell rounding following treatment with PGF2α. Following the removal of PGF 2α, however, FPA-expressing cells return to their original morphology, whereas FPB-expressing cells do not. It was also found that PGF2α-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 2α in cells expressing either the FPA or FP B isoforms. However, PGE2 has much lower efficacy as compared with PGF2α 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 PGF2α-stimulated Tcf/β-catenin signaling in a dose-dependent manner while having no effect on PGF 2α-stimulated inositol phosphates formation. Thus, the ratio of endogenous PGE2 and PGF2α 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.

UR - http://www.scopus.com/inward/record.url?scp=6344241868&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=6344241868&partnerID=8YFLogxK

U2 - 10.1074/jbc.M408276200

DO - 10.1074/jbc.M408276200

M3 - Article

VL - 279

SP - 43386

EP - 43391

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 42

ER -