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. 2019 Jun 19;7(2):44. doi: 10.3390/biomedicines7020044

Figure 1.

Figure 1

The Wnt and R-spondin signaling pathway: In the absence of R-spondin (-Rspo), the membrane ubiquitinase zinc and ring finger 3/ ring finger 43 (ZNRF3/RNF43) associates with the Wnt receptor complex Frizzled/ Low-density lipoprotein receptor-related protein 5/6 (Fzd/LRP5/6), inducing its internalization and preventing its Wnt dependent phosphorylation, thereby inhibiting the downstream Wnt signaling cascade. In the presence of R-spondin (+Rspo), the ubiquitinase ZNRF3/RNF43 is internalized, enabling Wnt dependent phosphorylation of LRP5/6 and Dishevelled (DVL) as well as inhibition of glycogen synthase kinase-3 beta (GSK3beta). This then leads to the stabilization of the transcription factor beta-catenin (β-cat), its translocation in the nucleus and the subsequent expression of Wnt target genes.