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/L...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-09-01
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| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/8/10/1148 |
| Summary: | 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. |
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| ISSN: | 2073-4409 |