PHC320H1 Lecture : Wnt and Hedgehog Signalling Pathways
11 Apr 2012
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Document Summary
Normal roles: multiple wnt pathways regulate cell proliferation, cell fates, stem cell renewal and cell behavior in both embryos and adults. Diseases: cancers, bone density, neurodegenerative diseases, retinal disease. Ent development of dorsal axis, stem cell renewal. 19 members in man and mice: cystine rich glycoproteins, lipid modified. 7 transmembrane receptrs not sure if they engage g proteins activate cytoplasmic protein dishevelled, but mechanism unclear. Wnt transduction: scfb-trcp ubiquitin lifase regulates wnt signaling, mutations within wnt signaling pathway members leads to constitutive activation of the pathway and cancers, wnt prevents ubiquinitation of b-catenin buildupp of b-catenin. Wnt signaling in intestinal homeostasis: epithelial cells constant turnover. Stem cells at base of crypt: wnt pathway controls stem cell renewal, differentiation. Uncontrolled wnt signaling: abberant expansion of stem cells. If apc not mutated: axin (scaffolding proteins) can be mutated, or activating/oncogenic point mutation in b-catenin remove n-term serine/threonine phosphorylation sites required for its recruitment for ubiquitin-mediated proteolysis.
