p120-catenin is an E-cadherin-associated protein that modulates E-cadherin function and stability. We describe here that p120-catenin is required for Wnt pathway signaling. p120-catenin binds and is phosphorylated by CK1ε in response to Wnt3a. p120-catenin also associates to the Wnt co-receptor LRP5/6, an interaction mediated by E-cadherin, showing an unexpected physical link between adherens junctions and a Wnt receptor. Depletion of p120-catenin abolishes CK1ε binding to LRP5/6 and prevents CK1ε activation upon Wnt3a stimulation. Elimination of p120-catenin also inhibits early responses to Wnt, such as LRP5/6 and Dvl-2 phosphorylation and axin recruitment to the signalosome, as well as later effects, such as β-catenin stabilization. Moreover, since CK1ε is also required for E-cadherin phosphorylation, a modification that decreases the affinity for β-catenin, p120-catenin depletion prevents the increase in β-catenin transcriptional activity even in the absence of β-catenin degradation. Therefore, these results demonstrate a novel and crucial function of p120-catenin in Wnt signaling and unveil additional points of regulation by this factor of β-catenin transcriptional activity different of β-catenin stability.

There was an error published in J. Cell Sci. 124, 2298-2309.Some of the blots presented in Fig. 4A were inadvertently duplicated in Fig. 6D. The blots in Fig. 4A are correct as presented. The correct Fig. 6 is presented below. There are no changes to the figure legend, which is accurate. This error does not affect the conclusions of the study.The authors apologise to the readers for any confusion that this error might have caused. . Kaiso also interacts with β-catenin and its binding is regulated by p120-catenin. (A) 2 pmol of recombinant GST-Kaiso or GST as a control was incubated with 1 pmol of full-length β-catenin or two deletion mutants comprising armadillo repeats 1-12 (amino acids 120-683) or 1-6 (amino acids 120-420). Protein complexes were affinity purified with glutathione-Sepharose and analyzed by western blotting (WB) with anti-β-catenin antibody. Blots were re-analyzed with anti-GST antibody to ensure that a similar amount of fusion protein was present. (B) 2 pmol of recombinant GST-Kaiso, or GST as a control, was incubated with 2 pmol of p120-catenin (amino acids 102-911) (left-hand panel) or 2 pmol of full-length β-catenin (right-hand panel). Protein complexes were affinity purified with glutathione-Sepharose and analyzed by western blotting with the indicated antibodies. 'St' indicates the signal obtained with known amounts of recombinant proteins used as control. (C) Pull-down assays were performed by incubating 7 pmol of GST-Kaiso with 400 μg of whole-cell extracts from SW-480 cells transfected with pcDNA3-Tcf-4-HA. When indicated, 35 pmols of p120-catenin or β-catenin was added to the incubation medium. Protein complexes were affinity purified and analyzed by western blotting with the indicated antibodies. (D) SW-480 cells were infected with scrambled shRNA (Ctl) or shRNA specific for p120-catenin, and were treated with control or Wnt3a-conditioned medium for 6 hours. Kaiso was immunoprecipitated (IP) and immunocomplexes were analyzed by western blotting. (E) SW480 cells were treated with control or Wnt3a-conditioned medium for 6 hours. β-catenin was immunoprecipitated from SW-480 total cell extracts and the immunocomplex was analyzed by western blotting. In the input lane, 5% of each total cell extract used is shown. (F) Kaiso was immunoprecipitated with a specific antibody from total cell extracts of HT29-M6 cells treated with control or Wnt3a-conditioned medium for 6 hours. Associated proteins were analyzed by western blotting. All the data presented in this figure are representative of at least three independent experiments. Irr IgG, an irrelevant IgG used as control in the immunoprecipitation. 873

There was an error published in J. Cell Sci. 124, 2298-2309.Some of the blots presented in Fig. 4A were inadvertently duplicated in Fig. 6D. The blots in Fig. 4A are correct as presented. The correct Fig. 6 is presented below. There are no changes to the figure legend, which is accurate. This error does not affect the conclusions of the study.The authors apologise to the readers for any confusion that this error might have caused. . Kaiso also interacts with β-catenin and its binding is regulated by p120-catenin. (A) 2 pmol of recombinant GST-Kaiso or GST as a control was incubated with 1 pmol of full-length β-catenin or two deletion mutants comprising armadillo repeats 1-12 (amino acids 120-683) or 1-6 (amino acids 120-420). Protein complexes were affinity purified with glutathione-Sepharose and analyzed by western blotting (WB) with anti-β-catenin antibody. Blots were re-analyzed with anti-GST antibody to ensure that a similar amount of fusion protein was present. (B) 2 pmol of recombinant GST-Kaiso, or GST as a control, was incubated with 2 pmol of p120-catenin (amino acids 102-911) (left-hand panel) or 2 pmol of full-length β-catenin (right-hand panel). Protein complexes were affinity purified with glutathione-Sepharose and analyzed by western blotting with the indicated antibodies. 'St' indicates the signal obtained with known amounts of recombinant proteins used as control. (C) Pull-down assays were performed by incubating 7 pmol of GST-Kaiso with 400 μg of whole-cell extracts from SW-480 cells transfected with pcDNA3-Tcf-4-HA. When indicated, 35 pmols of p120-catenin or β-catenin was added to the incubation medium. Protein complexes were affinity purified and analyzed by western blotting with the indicated antibodies. (D) SW-480 cells were infected with scrambled shRNA (Ctl) or shRNA specific for p120-catenin, and were treated with control or Wnt3a-conditioned medium for 6 hours. Kaiso was immunoprecipitated (IP) and immunocomplexes were analyzed by western blotting. (E) SW480 cells were treated with control or Wnt3a-conditioned medium for 6 hours. β-catenin was immunoprecipitated from SW-480 total cell extracts and the immunocomplex was analyzed by western blotting. In the input lane, 5% of each total cell extract used is shown. (F) Kaiso was immunoprecipitated with a specific antibody from total cell extracts of HT29-M6 cells treated with control or Wnt3a-conditioned medium for 6 hours. Associated proteins were analyzed by western blotting. All the data presented in this figure are representative of at least three independent experiments. Irr IgG, an irrelevant IgG used as control in the immunoprecipitation. 873