FP Prostanoid Receptor Activation of a T-cell Factor/β-Catenin Signaling Pathway

Hiromichi Fujino, John W Regan

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

FP prostanoid receptors are G-protein-coupled receptors (GPCR) that consist of two known isoforms, FPA and FPB. These isoforms, which are generated by alternative mRNA splicing, are identical except for their carboxyl-terminal domains. Previously we have shown that stimulation of both isoforms with prostaglandin F2. (PGF) activates the small G-protein Rho, leading to morphological changes consisting of cell rounding and the formation of cell aggregates. Following the removal of PGF , however, FPA-expressing cells show rapid reversal of cell rounding, whereas FPB-expressing cells do not. We now show that acute treatment of FPB-expressing cells with PGF leads to a subcellular reorganization of β-catenin, a decrease in the phosphorylation of cytoplasmic β-catenin, and persistent stimulation of Tcf/Lef-mediated transcriptional activation. This does not occur in FPA-expressing cells and may underlie the differences between these isoforms with respect to the reversal of cell rounding. The Tcf/β-catenin signaling pathway is known to mediate the actions of Wnt acting through the heptahelical receptor, Frizzled, and has not been associated previously with GPCR activation. Our findings expand the signaling possibilities for GPCRs and suggest novel roles for FP receptors in normal tissue development and malignant transformation.

Original languageEnglish (US)
Pages (from-to)12489-12492
Number of pages4
JournalJournal of Biological Chemistry
Volume276
Issue number16
DOIs
StatePublished - Apr 20 2001

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TCF Transcription Factors
Catenins
Protein Isoforms
Chemical activation
Dinoprost
Prostaglandins F
G-Protein-Coupled Receptors
Cells
Frizzled Receptors
Phosphorylation
Monomeric GTP-Binding Proteins
Tissue
Messenger RNA
prostaglandin F2alpha receptor
Alternative Splicing
Transcriptional Activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

FP Prostanoid Receptor Activation of a T-cell Factor/β-Catenin Signaling Pathway. / Fujino, Hiromichi; Regan, John W.

In: Journal of Biological Chemistry, Vol. 276, No. 16, 20.04.2001, p. 12489-12492.

Research output: Contribution to journalArticle

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