The disruption of adherens junctions is associated with a decrease of E-cadherin phosphorylation by protein kinase CK2

The down-regulation of E-cadherin is a common event in carcinogenesis. Phos phorylation/dephosphorylation is one posttranscriptional process which may regulate intercellular junctions. Here we show that in okadaic acid-treated keratinocytes, E-cadherin expression is shifted from the membrane to the c ytoplasm, preventing cells from forming aggregates. These changes of E-cadh erin localization and function are associated with a decrease in its phosph orylation state, The decrease in E-cadherin phosphorylation was essentially detected in okadaic acid-treated cell lysates isolated from 0.5% Triton-so luble fraction and not in the Triton-insoluble fraction linked to the cytos keleton, suggesting a role of E-cadherin phosphorylation in cell-cell inter actions. E-cadherin was markedly phosphorylated by CK2, either the purified recombinant enzyme or the endogenous enzyme. Using specific CK2 inhibitors such as heparin and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, endo genous CK2 was confirmed as the main enzyme phosphorylating E-cadherin, The decrease in E-cadherin phosphorylation by endogenous CK2 was not restored by the addition of purified CK2, confirming that it is not due to a defect in CK2 expression or to its reduced activity, but rather to the incapacity of CK2 to phosphorylate E-cadherin. The co-immunoprecipitation and colocali zation of E-cadherin and CK2 suggests that CK2 may play a critical role in the maintenance of epidermis cohesion. (C) 2000 Academic Press.