positive regulation of Wnt signaling pathway, calcium modulating pathway

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of the series of molecular signals initiated by binding of a Wnt protein to a receptor on the surface of the target cell where activated receptors leads to an increase in intracellular calcium and activation of protein kinase C (PKC). [GOC:go_curators]

The positive regulation of Wnt signaling pathway, calcium modulating pathway, is a complex process involving a delicate interplay of molecular events, ultimately leading to the activation of downstream genes that influence cell fate, proliferation, and development. Here's a breakdown of the key steps involved:

**1. Wnt Ligand Binding and Receptor Activation:**
- The process starts with the binding of Wnt proteins, secreted signaling molecules, to their cognate receptors on the cell surface, Frizzled (Fz) proteins.
- This interaction triggers a cascade of intracellular events.

**2. Dishevelled (Dsh) Activation:**
- Fz receptor activation leads to the recruitment and activation of Dishevelled (Dsh), a cytoplasmic protein that acts as a crucial intermediary in Wnt signaling.
- Dsh activation is often accompanied by the phosphorylation of its amino-terminal region, facilitating its association with other signaling components.

**3. β-Catenin Stabilization and Nuclear Translocation:**
- Dsh, in turn, triggers a series of events that ultimately result in the stabilization of β-catenin, a key effector molecule in Wnt signaling.
- In the absence of Wnt signaling, β-catenin is targeted for degradation by a protein complex containing the proteins Axin, APC, and GSK3β (Glycogen Synthase Kinase 3β).
- Wnt signaling disrupts this complex, leading to β-catenin stabilization and its accumulation in the cytoplasm.
- Stabilized β-catenin then translocates into the nucleus, where it acts as a transcription factor.

**4. Calcium-Modulating Pathways and Wnt Signaling Intersection:**
- Calcium signaling pathways, such as the PLC-IP3-Ca2+ signaling pathway, can influence Wnt signaling by modulating the activity of key components like GSK3β.
- Calcium influx can activate CaMKII (Calcium/Calmodulin-dependent protein kinase II), which can phosphorylate GSK3β, thereby inhibiting its activity and promoting β-catenin stabilization.
- Conversely, calcium-dependent signaling can also activate calcineurin, which can dephosphorylate GSK3β, leading to its activation and β-catenin degradation.

**5. Gene Expression and Cellular Responses:**
- Once in the nucleus, β-catenin interacts with TCF/LEF (T-cell factor/Lymphoid enhancer factor) transcription factors, forming a complex that activates the transcription of Wnt target genes.
- These target genes play diverse roles in developmental processes, including cell proliferation, cell differentiation, and tissue morphogenesis.

**6. Tight Regulation of Wnt Signaling:**
- The Wnt signaling pathway is tightly regulated to ensure its proper functioning.
- Negative regulatory mechanisms, such as the degradation of β-catenin in the absence of Wnt signals, prevent aberrant activation of the pathway.

**7. Wnt Signaling Dysregulation and Disease:**
- Aberrant activation of Wnt signaling has been linked to a variety of human diseases, including cancer.
- Conversely, defects in Wnt signaling can contribute to developmental disorders and other diseases.

**8. Calcium-Dependent Regulation of Wnt Signaling in Different Contexts:**
- The interplay between Wnt signaling and calcium signaling is context-dependent.
- In some cell types, calcium signaling can promote Wnt signaling, while in others, it can inhibit it.
- The specific roles of calcium signaling in modulating Wnt signaling are still being investigated.

This detailed description highlights the intricate interplay between Wnt signaling and calcium-modulating pathways, emphasizing the importance of calcium signaling in fine-tuning Wnt pathway activity. The regulation of this complex interplay is crucial for proper cellular function and development.'
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