Title
Nuclear stabilization of <tex>$\beta$</tex>-catenin and inactivation of glycogen synthase kinase-3 <tex>$\beta$</tex> by gonadotropin releasing hormone : targeting Wnt signaling in the pituitary gonadotrope Nuclear stabilization of <tex>$\beta$</tex>-catenin and inactivation of glycogen synthase kinase-3 <tex>$\beta$</tex> by gonadotropin releasing hormone : targeting Wnt signaling in the pituitary gonadotrope
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Baltimore, Md ,
Subject
Human medicine
Source (journal)
Molecular endocrinology. - Baltimore, Md, 1987, currens
Volume/pages
21(2007) :12 , p. 3028-3038
ISSN
0888-8809
ISI
000251243900015
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
The GnRH receptor is a G protein-coupled receptor ( GPCR), and its ligand GnRH is the central regulator of the reproductive system. GnRH receptors are known to target a wide variety of signal transduction pathways. Several recent studies have shown that activation of GPCRs can impact on beta-catenin signaling. beta-Catenin is the main effecter of the Wnt signaling pathway where it acts with the transcription factors T cell factor/lymphoid enhancer factor to mediate the transcription of Wnt target genes. We show that GnRH treatment promotes the nuclear accumulation of beta-catenin, activation of T cell factor-dependent transcription, and up-regulation of Wnt target genes, c-Jun, Fra-1, and c-Myc. These results are observed in human embryonic kidney 293/GnRH receptor-expressing cells and have been recapitulated in L beta T2 and alpha T3-1 mouse gonadotrope cells. In addition to these findings, we show that GnRH treatment mediates the inactivation of glycogen synthase kinase-3, a protein serine/threonine kinase that regulates beta-catenin degradation within the Wnt signaling pathway. Our findings extend the number of GPCRs that can target beta-catenin signaling through diverse pathways. Furthermore, this is the first demonstration of the targeting of Wnt/beta-catenin signaling by a peptide hormone GPCR.
E-info
https://repository.uantwerpen.be/docman/iruaauth/0f90f4/57f9054.pdf
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