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Intracellular Signals Activated by Canonical Wnt Ligands Independent of GSK3 Inhibition and β-Catenin Stabilization
In contrast to non-canonical ligands, canonical Wnts promote the stabilization of β-catenin, which is a prerequisite for formation of the TCF4/β-catenin transcriptional complex and activation of its target genes. This pathway is initiated by binding of Wnt ligands to the Frizzled/LRP5/6 receptor com...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829497/ https://www.ncbi.nlm.nih.gov/pubmed/31557964 http://dx.doi.org/10.3390/cells8101148 |
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author | García de Herreros, Antonio Duñach, Mireia |
author_facet | García de Herreros, Antonio Duñach, Mireia |
author_sort | García de Herreros, Antonio |
collection | PubMed |
description | In contrast to non-canonical ligands, canonical Wnts promote the stabilization of β-catenin, which is a prerequisite for formation of the TCF4/β-catenin transcriptional complex and activation of its target genes. This pathway is initiated by binding of Wnt ligands to the Frizzled/LRP5/6 receptor complex, and it increases the half-life of β-catenin by precluding the phosphorylation of β-catenin by GSK3 and its binding to the βTrCP1 ubiquitin ligase. Other intercellular signals are also activated by Wnt ligands that do not inhibit GSK3 and increase β-catenin protein but that either facilitate β-catenin transcriptional activity or stimulate other transcriptional factors that cooperate with it. In this review, we describe the layers of complexity of these signals and discuss their crosstalk with β-catenin in activation of transcriptional targets. |
format | Online Article Text |
id | pubmed-6829497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68294972019-11-18 Intracellular Signals Activated by Canonical Wnt Ligands Independent of GSK3 Inhibition and β-Catenin Stabilization García de Herreros, Antonio Duñach, Mireia Cells Review In contrast to non-canonical ligands, canonical Wnts promote the stabilization of β-catenin, which is a prerequisite for formation of the TCF4/β-catenin transcriptional complex and activation of its target genes. This pathway is initiated by binding of Wnt ligands to the Frizzled/LRP5/6 receptor complex, and it increases the half-life of β-catenin by precluding the phosphorylation of β-catenin by GSK3 and its binding to the βTrCP1 ubiquitin ligase. Other intercellular signals are also activated by Wnt ligands that do not inhibit GSK3 and increase β-catenin protein but that either facilitate β-catenin transcriptional activity or stimulate other transcriptional factors that cooperate with it. In this review, we describe the layers of complexity of these signals and discuss their crosstalk with β-catenin in activation of transcriptional targets. MDPI 2019-09-25 /pmc/articles/PMC6829497/ /pubmed/31557964 http://dx.doi.org/10.3390/cells8101148 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review García de Herreros, Antonio Duñach, Mireia Intracellular Signals Activated by Canonical Wnt Ligands Independent of GSK3 Inhibition and β-Catenin Stabilization |
title | Intracellular Signals Activated by Canonical Wnt Ligands Independent of GSK3 Inhibition and β-Catenin Stabilization |
title_full | Intracellular Signals Activated by Canonical Wnt Ligands Independent of GSK3 Inhibition and β-Catenin Stabilization |
title_fullStr | Intracellular Signals Activated by Canonical Wnt Ligands Independent of GSK3 Inhibition and β-Catenin Stabilization |
title_full_unstemmed | Intracellular Signals Activated by Canonical Wnt Ligands Independent of GSK3 Inhibition and β-Catenin Stabilization |
title_short | Intracellular Signals Activated by Canonical Wnt Ligands Independent of GSK3 Inhibition and β-Catenin Stabilization |
title_sort | intracellular signals activated by canonical wnt ligands independent of gsk3 inhibition and β-catenin stabilization |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829497/ https://www.ncbi.nlm.nih.gov/pubmed/31557964 http://dx.doi.org/10.3390/cells8101148 |
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