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Originally published In Press as doi:10.1074/jbc.C100039200 on February 13, 2001

J. Biol. Chem., Vol. 276, Issue 16, 12489-12492, April 20, 2001
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ACCELERATED PUBLICATION
FP Prostanoid Receptor Activation of a T-cell Factor/beta -Catenin Signaling Pathway*

Hiromichi Fujino and John W. ReganDagger

From the Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona 85721-80207

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 F2alpha (PGF2alpha ) activates the small G-protein Rho, leading to morphological changes consisting of cell rounding and the formation of cell aggregates. Following the removal of PGF2alpha , 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 PGF2alpha leads to a subcellular reorganization of beta -catenin, a decrease in the phosphorylation of cytoplasmic beta -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/beta -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.

* This work was supported in part by grants from the National Institutes of Health (EY11291) and Allergan Inc.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed. Tel.: 520-626-2181; Fax: 520-626-2466; E-mail: regan@pharmacy.arizona.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.