Tyrosine phosphorylation of human keratinocyte beta-catenin and plakoglobin reversibly regulates their binding to E-cadherin and alpha-catenin.
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.
Hu
P
P
Department of Dermatology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599-7287, USA.
O'Keefe
E J
EJ
Rubenstein
D S
DS
D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D051180:Desmoplakins; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D012016:Reference Values; D014018:Tissue Distribution; D015534:Trans-Activators; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
D015703:Antigens, CD; C050361:CDH2 protein, human; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin; C069276:peroxovanadate; D014638:Vanadates; D014443:Tyrosine