TI - Cadherin mediated cell - cell adhesion is regulated by tyrosine phosphatases in human keratinocytes . AB - Normal Human Keratinocytes express on their cell surface E - and P-cadherins , two Ca2+ dependent homophilic cell adhesion molecules that mediate keratinocyte-keratinocyte adherens junctions . In other cell types , adherens-type junctions are reported to be major subcellular targets for tyrosine specific protein phosphorylation involving tyrosine kinases and tyrosine phosphatases . We investigated the role of tyrosine phosphatases in the regulation of cadherin mediated keratinocyte-keratinocyte adhesion . We report the results of a wide tyrosine phosphatase inhibition using pervanadate , a modified vanadate derivative known to inhibit most tyrosine phosphatases . Keratinocytes treated with pervanadate , exhibit an important change in cellular morphology and cadherins/catenins localization as shown by phase contrast microscopy and immunocytochemistry . In this conditions , cadherins and catenins no longer colocalize with the actin cytoskeleton of cells and the amount of E-cadherin bound to the cytoskeleton decreases . A more intense phosphotyrosine labelling is seen at the edges of the treated cells , suggesting that an increase in the phosphorylation rate of some cadherin-catenin complex proteins induces a diminished intercellular adhesion . Finally immunoprecipitation experiments of the E-cadherin/catenin complex from pervanadate treated keratinocytes reveal an increase in the tyrosine phosphorylation rate of E-cadherin , beta catenin and probably gamma catenin . These data suggest an essential role for the protein tyrosine phosphatases in keratinocyte intercellular junctions .