E-cadherin phosphorylation occurs during its biosynthesis to promote its cell surface stability and adhesion

Mol Biol Cell. 2014 Aug 15;25(16):2365-74. doi: 10.1091/mbc.E14-01-0690. Epub 2014 Jun 25.


E-cadherin is highly phosphorylated within its β-catenin-binding region, and this phosphorylation increases its affinity for β-catenin in vitro. However, the identification of key serines responsible for most cadherin phosphorylation and the adhesive consequences of modification at such serines have remained unknown. In this study, we show that as few as three serines in the β-catenin-binding domain of E-cadherin are responsible for most radioactive phosphate incorporation. These serines are required for binding to β-catenin and the mutual stability of both E-cadherin and β-catenin. Cells expressing a phosphodeficient (3S>A) E-cadherin exhibit minimal cell-cell adhesion due to enhanced endocytosis and degradation through a lysosomal compartment. Conversely, negative charge substitution at these serines (3S>D) antagonizes cadherin endocytosis and restores wild-type levels of adhesion. The cadherin kinase is membrane proximal and modifies the cadherin before it reaches the cell surface. Together these data suggest that E-cadherin phosphorylation is largely constitutive and integral to cadherin-catenin complex formation, surface stability, and function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD
  • COS Cells
  • Cadherins / biosynthesis*
  • Cell Adhesion*
  • Cell Line
  • Cell Membrane / metabolism*
  • Chlorocebus aethiops
  • Endocytosis
  • Humans
  • Phosphorylation
  • Protein Binding
  • Serine / metabolism*
  • beta Catenin / metabolism*


  • Antigens, CD
  • CDH1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • beta Catenin
  • Serine