| Summary: | 碩士 === 中國醫藥大學 === 分子系統生物醫學研究所碩士班 === 101 === Wnt are secreted lipoglycoproteins that function as signaling molecules to regulate embryonic development at different stages and adult tissue homeostasis. Without Wnt stimulation, Axin serves as a platform and forms a protein complex with MACF1, GSK3β, CK1, and β-catenin in the cytoplasm. GSK3β and CK1 will phosphorylate β-catenin and target β-catenin for proteasome degradation. Upon Wnt stimulation, Wnt binds to its receptor Frizzled and co-receptor LRP5/6, and MACF1 helps Axin complex translocation from the cytoplasm to the cell membrane, then Axin is degraded and in some way β-catenin is accumulated in the cytoplasm for transducing Wnt signaling. Our previous studies have shown that Wnt treatment can activate a calcium-dependent protease to degrade Axin on the cell membrane and this degradation is indispensible for transducing Wnt signals. However, what signaling pathway is involved in the activation of the enzyme and Axin degradation is not known. In this research, we have performed experiments including treatments of cells with either specific inhibitors to components of Trimeric G protein signaling pathway, or over-expression of GRK2 C terminus or knockdown of Gαq through RNAi to show that, with these treatments, Axin degradation and β-catenin acumulation were inhibited, and TCF/β-caenin-mediated transcriptional activity was reduced upon Wnt stimulation. These results suggested that, upon Wnt stimulation, trimeric G protein signaling is involved in the activation of this protease to degrade Axin for transducing Wnt signals.
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