canonical Wnt signaling pathway

Definition

Target type: biologicalprocess

A type of Wnt signaling pathway in which Wnt binding to its receptor on the surface of a target cell results in the by propagation of the molecular signals via beta-catenin, and end with a change in transcription of target genes. In this pathway, the activated receptor signals via downstream effectors that result in the inhibition of beta-catenin phosphorylation, thereby preventing degradation of beta-catenin. Stabilized beta-catenin can then accumulate and travel to the nucleus to trigger changes in transcription of target genes. [PMID:11532397, PMID:19619488]

The canonical Wnt signaling pathway, also known as the β-catenin pathway, is a fundamental signaling cascade involved in embryonic development, tissue homeostasis, and various cellular processes. Its activation is critical for regulating cell fate decisions, proliferation, differentiation, and migration. The pathway is initiated by the binding of Wnt proteins, a family of secreted glycoproteins, to their cognate receptors, Frizzled (FZD) and LRP5/6. Upon Wnt binding, the cytoplasmic protein Dishevelled (DVL) is recruited to the receptor complex, triggering a cascade of events that ultimately leads to the stabilization and nuclear translocation of β-catenin.

In the absence of Wnt signaling, β-catenin is continuously phosphorylated by a destruction complex composed of Axin, APC (adenomatous polyposis coli), CK1α (casein kinase 1α), and GSK3β (glycogen synthase kinase 3β). This phosphorylation targets β-catenin for ubiquitination by the E3 ubiquitin ligase β-TrCP, leading to its proteasomal degradation and low levels of β-catenin in the cytoplasm.

However, when Wnt ligands bind to their receptors, the destruction complex is inactivated. DVL, through its interaction with FZD and LRP5/6, triggers the recruitment of Axin to the membrane, sequestering it from the destruction complex. This event, coupled with the phosphorylation of LRP5/6 by CK1α and GSK3β, initiates a cascade of events that leads to the inhibition of GSK3β activity, thus preventing β-catenin phosphorylation and degradation.

The stabilized β-catenin accumulates in the cytoplasm and translocates into the nucleus. In the nucleus, it interacts with TCF/LEF (T cell factor/lymphoid enhancer factor) transcription factors, displacing the transcriptional repressor Groucho. This interaction activates the transcription of Wnt target genes, which encode a diverse array of proteins involved in cell growth, proliferation, differentiation, and migration.

Disruption of the canonical Wnt signaling pathway has been implicated in various human diseases, including cancer, developmental disorders, and neurodegenerative diseases. Deregulated Wnt signaling can contribute to uncontrolled cell proliferation, tumor growth, and metastasis. Conversely, insufficient Wnt signaling can lead to developmental defects and impaired tissue regeneration.'
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Proteins (24)

Compounds (504)