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Title
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Nuclear stabilization of -catenin and inactivation of glycogen synthase kinase-3 by gonadotropin releasing hormone : targeting Wnt signaling in the pituitary gonadotrope
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Molecular endocrinology / Endocrine Society. - Baltimore, Md, 1987 - 2016
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Publication
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Baltimore, Md
:
2007
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ISSN
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0888-8809
[print]
1944-9917
[online]
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DOI
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10.1210/ME.2007-0268
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Volume/pages
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21
:12
(2007)
, p. 3028-3038
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ISI
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000251243900015
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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