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Wnt/Notch/Hedgehog Pathway


Pathway description:
During development, Wnt (Wingless-Type MMTV Integration Site Family) have diverse roles in governing cell fates, proliferation, migration, polarity, and death. In the absence of Wnt signaling, β-Catenin is associated with a cytoplasmic complex containing CK1, GSK3, Axin, APC and PP2A. This promotes phosphorylation of course β-Catenin and its interaction with β-TRCP, leading to the ubiquitination of β-Catenin and its degradation by the proteosome. In the presence of Wnt signaling, secreted Wnt glycoproteins bind to the receptor Frizzled, which leads to activation of the Dishevelled (Dsh) protein, a PDZ domain protein. Dsh acts to inhibit a cytoplasmic complex involving GSK3, Axin and APC that acts to degrade β-Catenin. GSK3 phosphorylates β-Catenin leading to ubiquitination and degradation by the proteosome. Activation of the Wnt/beta-catenin pathway inhibits degradation of β-Catenin allowing its nuclear transport and gene induction via bindng to TCF. During the elaboration of cell types and tissues, the Wnt/beta-catenin pathway often interacts with the FGF and TGF-β pathways. In adults, Wnt function in homeostasis, and inappropriate activation of the Wnt/beta-catenin pathway is implicated in a variety of cancer. 

Selected Reviews:
Li F,Chong zz,et al.(2006)Winding through the WNT pathway during cellular development and demise.Histol Histopathol.21(1),103.
Katoh M.(2005)Comparative genomics on Wnt5a and Wnt5b genes.Int J Mol Med.15(4),749.
Li F,Chong zz,et al.(2005)Vital elements of the Wnt-Firizzled signaling pathway in the nervous system.Curr Neurovasc Res.2(4),331.
Urano T.(2006)Wnt- beta-catenin signaling in bone metabolism.Clin Calcium. 16 (1),54.
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