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 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/β-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/β-catenin pathway often interacts with the FGF and TGF-β pathways. In adults, Wnt function in homeostasis, and inappropriate activation of the Wnt/β-catenin pathway is implicated in a variety of cancer.
Article reproduced from Signalway Antibody