A p120-catenin-CK1¿ complex regulates Wnt signaling Articles uri icon

authors

  • Casagolda, D.
  • Del Valle-Pérez, B.
  • Valls, G.
  • Lugilde, E.
  • Vinyoles, M.
  • CASADO VELA, JUAN
  • Solanas, G.
  • Batlle, E.
  • Reynolds, A.B.
  • Casal, J.I.
  • García De Herreros, A.
  • Duñach, M.

publication date

  • January 2010

start page

  • 2621

end page

  • 2631

issue

  • 15

volume

  • 123

International Standard Serial Number (ISSN)

  • 0021-9533

Electronic International Standard Serial Number (EISSN)

  • 1477-9137

abstract

  • 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 CK1¿ 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 CK1¿ binding to LRP5/6 and prevents CK1¿ 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 ß-catenin stabilization. Moreover, since CK1¿ is also required for E-cadherin phosphorylation, a modification that decreases the affinity for ß-catenin, p120-catenin depletion prevents the increase in ß-catenin transcriptional activity even in the absence of ß-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 ß-catenin transcriptional activity different of ß-catenin stability.

keywords

  • ck1¿ e-cadherin p120-catenin wnt axin beta catenin casein kinase iepsilon catenin dishevelled 2 frizzled protein lipoprotein receptor p120 catenin unclassified drug uvomorulin wnt protein wnt3a protein cadherin delta catenin dishevelled proteins lipoprotein receptor related protein 5 low density lipoprotein receptor related protein lrp6 protein; human phosphoprotein signal transducing adaptor protein wnt protein article complex formation controlled study gene activation genetic transcription human human cell in vivo study priority journal protein binding protein degradation protein interaction protein phosphorylation drug effect genetics immunoprecipitation mass spectrometry metabolism phosphorylation signal transduction tumor cell line adaptor proteins; signal transducing cadherins casein kinase iepsilon catenins cell line; tumor humans immunoprecipitation ldl-receptor related proteins mass spectrometry phosphoproteins phosphorylation protein binding signal transduction wnt proteins