[PDF] Wnt signalling: What The X@# is WTX? | Semantic Scholar (2024)

The current knowledge of Frizzled and LRP5/6 is reviewed, including their structures and interactions with Wnt proteins, and signaling mechanisms from receptor activation to the engagement of intracellular partners Dishevelled and Axin, and finally to the inhibition of β-catenin phosphorylation and ensuing β- catenin stabilization.

These findings suggest that sustained activation of Wnt/β-catenin signaling due to abrogation of Merlin-mediated inhibition of LRP6 phosphorylation may be a cause of NF2 disease.

Functional data suggest WTX to be an inhibitor of the Wnt/β‐catenin signaling pathway, and deletion of Wtx in mouse leads to perinatal death, impeding the analysis of its physiological role.

The signal transduction mechanism of the Hippo signaling pathway is discussed, along with cross-talk between the regulators of the Wnt/β-catenin and HippO signaling pathways.

It is demonstrated that amer1 was essential for the craniofacial development of zebrafish by interacting with the Wnt/β-catenin pathway and exerted an antagonistic effect on the Wnt/β-catenin pathway.

Findings indicate that Rspo1 is a negative regulator of andbgr;-cell neogenesis, development, and survival in the face of STZ-induced diabetes, providing a therapeutic target for the enhancement of &bgr ;-cell mass.

The immunohistochemical expression of Parkin and Adenomatous Polyposis Coli, Human Apurinic/Apyrimidinic endonuclease 1 (APE1), and B-cell lymphoma-extra-large (Bcl-xL; oncogenic proteins) in sporadic colorectal polyps with clinical, endoscopic, and diagnostic data is correlated to the biological role proposed for these proteins in cellular functions.

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Adenomatous polyposis coli membrane recruitment 1 (Amer1) (also called WTX), a membrane associated PtdIns(4,5)P2‐binding protein, is essential for the activation of Wnt signalling at the LRP6 receptor level.

Functional analyses in cultured cells, Xenopus, and zebrafish demonstrate that WTX promotes β-catenin ubiquitination and degradation, which antagonize WNT/β- catenin signaling, which provides a possible mechanistic explanation for the tumor suppressor activity of WTX.

The identification of Xenopus Casein kinase 1 γ (CK1γ), a membrane-bound member of the CK1 family is described, revealing an evolutionarily conserved mechanism that couples Wnt receptor activation to the cytoplasmic signal transduction apparatus.

It is proposed that Wnts induce coclustering of receptors and Dvl in LRP6-signalosomes, which in turn triggers LRP 6 phosphorylation to promote Axin recruitment and β-catenin stabilization.

The identification of Xenopus Casein kinase 1 gamma (CK1gamma), a membrane-bound member of the CK1 family, and an evolutionarily conserved mechanism that couples Wnt receptor activation to the cytoplasmic signal transduction apparatus are revealed.

The results suggest a model that upon Wnt-induced Fz-Lrp 6 complex formation, Fz recruitment of Dvl in turn recruits the axin-Gsk3 complex, thereby promoting Lrp6 phosphorylation to initiate β-catenin signaling.

Functional analyses in cultured cells, Xenopus, and zebrafish demonstrate that WTX promotes beta-catenin ubiquitination and degradation, which antagonize WNT/beta- catenin signaling, which provides a possible mechanistic explanation for the tumor suppressor activity of WTX.

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