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. 2020 Jul 9;21(14):4852. doi: 10.3390/ijms21144852

Figure 1.

Figure 1

Simplified scheme of canonical WNT -signaling pathway. (A) In the absence of WNT ligands (WNT OFF state), β-catenin is phosphorylated by a destruction complex consisting of AXIN, APC, GSK3β and CK1α to be further ubiquitinated for proteasomal degradation. In the absence of R-spondins, E3 ubiquitin ligases RNF43/ZNRF3 target FZD for lysosomal degradation; (B) binding of WNT ligands to FZD receptors and LRP co-receptors activates WNT-signaling (WNT ON state). AXIN is associated with LRP5/6, whereas DVL is recruited to FZD, which results in dissociation of the destructive complex. β-catenin is accumulated and stabilized in the cytosol, and then unphosphorylated β-catenin is translocated to the nucleus to activate the expression of WNT target genes. APC—adenomatosis polyposis coli; AXIN—axis inhibition protein; BCL—B-cell CLL/lymphoma protein; BRG-1—brahma-related gene-1; CBP—(CREB)-binding protein; CK1α—casein kinase 1α; CK1γ—casein kinase 1γ; CK1ε—casein kinase 1ε; DKK1—Dickkopf-1; DVL—disheveled; FZD—frizzled receptor; GSK3β—glycogen synthase kinase 3β; LEF—lymphoid enhancer-binding factor 1; LGR—leucine-rich repeat-containing G-protein coupled receptor; LRP—low-density lipoprotein receptor related protein; MAK—metastasis associated kinase; PAR1—protease-activated receptor 1; PKC—protein kinase C; PYGO—pygopus; RNF43—ring finger protein 43; sFRP—secreted frizzled-related proteins; TCF—T cell factor; β-TrCP—beta-transducin repeats-containing proteins; WIF1—WNT inhibitory factor 1; WISE—WNT modulator in surface ectoderm; Ub; ubiquitin; ZNRF3—zinc and ring finger protein 3.