Tyrosine Phosphorylation of Human Keratinocyte Beta-Catenin and Plakoglobin Reversibly Regulates Their Binding to E-cadherin and Alpha-Catenin

J Invest Dermatol. 2001 Nov;117(5):1059-67. doi: 10.1046/j.0022-202x.2001.01523.x.

Abstract

We show that tyrosine phosphorylation, produced by incubation of normal human keratinocytes with the tyrosine phosphatase inhibitor peroxovanadate, directly and reversibly regulates the association of beta-catenin and plakoglobin with E-cadherin and alpha-catenin. Prior studies have demonstrated a correlative, but not causal, association between increased tyrosine phosphorylation and decreased adherens junction mediated cell-cell adhesion. We observed that (i) binding of tyrosine phosphorylated beta-catenin and plakoglobin to E-cadherin and to alpha-catenin was substantially reduced, but could be restored in vitro by removal of phosphate from beta-catenin and plakoglobin with added tyrosine phosphatase, and (ii) tyrosine phosphorylation of beta-catenin and plakoglobin was associated with decreased cell-cell adhesion. These findings support a direct and causal role for tyrosine phosphorylation of beta-catenin and plakoglobin in regulating adherens junction mediated cell-cell adhesion. We propose that tyrosine phosphorylation of specific and probably different residues is responsible for regulating the binding of beta-catenin or plakoglobin to (i) E-cadherin and (ii) alpha-catenin. Additionally, because beta-catenin and plakoglobin have both structural and regulatory functions, the data raise the possibility that beta-catenin or plakoglobin released from the adherens junctions by tyrosine phosphorylation may transduce a signal to the nucleus regarding the adhesive state of the cell.

Publication types

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

MeSH terms

  • Antigens, CD
  • Cadherins / metabolism*
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Cytoskeletal Proteins / metabolism*
  • Desmoplakins
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Keratinocytes / physiology
  • Phosphorylation
  • Reference Values
  • Tissue Distribution
  • Trans-Activators*
  • Tyrosine / metabolism*
  • Vanadates / pharmacology
  • alpha Catenin
  • beta Catenin
  • gamma Catenin

Substances

  • Antigens, CD
  • CDH2 protein, human
  • CTNNA1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • Desmoplakins
  • Trans-Activators
  • alpha Catenin
  • beta Catenin
  • gamma Catenin
  • peroxovanadate
  • Vanadates
  • Tyrosine