Biology 3316A/B Lecture Notes - Lecture 10: Wnt Signaling Pathway, Pdz Domain, Dishevelled

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Egl10 and pleckstrin are modular proteins: analogous to bcl2, all you have to do is swap out one domain, put in another, and you change fate of the protein. Ck1 (common kinase) phosphorylates b-catenin; it primes it: gsk3 then recognizes that and hyperphosphorylates b-catenin (gsk3 is involved in glycogen breakdown and storage) That"s the cue to have the acl complex ubiquitinate the protein: b-catenin then gets targeted to proteasome & gets degraded completely (basically, phosphorylation leads to degradation) See it in cell migration: binds to cadherins. It"s a tumour suppressor; if you mutate it, will get colorectal polyps. It"s one of the genes that is mutated in colorectal cancer. When wnt is present: wnt (palmitoleic acid) binds to lrp. So axin is recruited, binds to dsh & scaffold is broken. Ck1 is no longer coming into contact with b-catenin: gsk3 is no longer able to phosphorylate b-catenin, apc is floating around cytosol, b-catenin isnt degraded by the proteasome, levels accumulate.

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