A p120-catenin-CK1epsilon complex regulates Wnt signaling

J Cell Sci. 2010 Aug 1;123(Pt 15):2621-31. doi: 10.1242/jcs.067512.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Casein Kinase 1 epsilon / genetics
  • Casein Kinase 1 epsilon / metabolism*
  • Catenins / genetics
  • Catenins / metabolism*
  • Cell Line, Tumor
  • Delta Catenin
  • Dishevelled Proteins
  • Humans
  • Immunoprecipitation
  • LDL-Receptor Related Proteins / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Mass Spectrometry
  • Phosphoproteins / metabolism
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • Protein Binding / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Wnt Proteins / pharmacology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cadherins
  • Catenins
  • DVL2 protein, human
  • Dishevelled Proteins
  • LDL-Receptor Related Proteins
  • LRP5 protein, human
  • LRP6 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Phosphoproteins
  • Wnt Proteins
  • Casein Kinase 1 epsilon
  • Delta Catenin
  • CTNND1 protein, human