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. (PGF2α) 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 2α, 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 2α 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 language | English (US) |
|---|---|
| Pages (from-to) | 12489-12492 |
| Number of pages | 4 |
| Journal | Journal of Biological Chemistry |
| Volume | 276 |
| Issue number | 16 |
| DOIs | |
| State | Published - Apr 20 2001 |
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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 journal › Article
}
TY - JOUR
T1 - FP Prostanoid Receptor Activation of a T-cell Factor/β-Catenin Signaling Pathway
AU - Fujino, Hiromichi
AU - Regan, John W
PY - 2001/4/20
Y1 - 2001/4/20
N2 - 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. (PGF2α) 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 2α, 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 2α 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.
AB - 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. (PGF2α) 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 2α, 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 2α 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0035918222&partnerID=8YFLogxK
U2 - 10.1074/jbc.C100039200
DO - 10.1074/jbc.C100039200
M3 - Article
C2 - 11278257
AN - SCOPUS:0035918222
VL - 276
SP - 12489
EP - 12492
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 16
ER -