A conserved phosphorylation switch controls the interaction between cadherin and β-catenin in vitro and in vivo

Dev Cell. 2015 Apr 6;33(1):82-93. doi: 10.1016/j.devcel.2015.02.005.


In metazoan adherens junctions, β-catenin links the cytoplasmic tail of classical cadherins to the F-actin-binding protein α-catenin. Phosphorylation of a Ser/Thr-rich region in the cadherin tail dramatically enhances affinity for β-catenin and promotes cell-cell adhesion in cell culture systems, but its importance has not been demonstrated in vivo. Here, we identify a critical phosphorylated serine in the C. elegans cadherin HMR-1 required for strong binding to the β-catenin homolog HMP-2. Ablation of this phosphoserine interaction produces developmental defects that resemble full loss-of-function (Hammerhead and Humpback) phenotypes. Most metazoans possess a single gene for β-catenin, which is also a transcriptional coactivator in Wnt signaling. Nematodes and planaria, however, have a set of paralogous β-catenins; for example, C. elegans HMP-2 functions only in cell-cell adhesion, whereas SYS-1 mediates transcriptional activation through interactions with POP-1/Tcf. Our structural data define critical sequence differences responsible for the unique ligand specificities of these two proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adherens Junctions / physiology
  • Amino Acid Sequence
  • Animals
  • Cadherins / chemistry
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Adhesion / physiology*
  • Crystallography, X-Ray
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism
  • Image Processing, Computer-Assisted
  • In Vitro Techniques
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Serine / chemistry
  • Serine / metabolism*
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • beta Catenin / metabolism*


  • Cadherins
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Sys-1 protein, C elegans
  • Transcription Factors
  • beta Catenin
  • hmr-1 protein, C elegans
  • pop-1 protein, C elegans
  • Serine

Associated data

  • PDB/4R0Z
  • PDB/4R10
  • PDB/4R11