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. Phosphorylation/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 cytoplasm, preventing cells from forming aggregates. These changes of E-cadherin localization and function are associated with a decrease in its phosphorylation state. The decrease in E-cadherin phosphorylation was essentially detected in okadaic acid-treated cell lysates isolated from 0.5% Triton-soluble fraction and not in the Triton-insoluble fraction linked to the cytoskeleton, suggesting a role of E-cadherin phosphorylation in cell-cell interactions. 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, endogenous 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 colocalization of E-cadherin and CK2 suggests that CK2 may play a critical role in the maintenance of epidermis cohesion.
Serres
M
M
INSERM U 346, Hôpital E. Herriot, Lyon Cedex 03, 69437, France. serres@lyon151.inserm.fr
Filhol
O
O
Lickert
H
H
Grangeasse
C
C
Chambaz
E M
EM
Stappert
J
J
Vincent
C
C
Schmitt
D
D
D015820:Cadherins / Q000378:metabolism*; D047390:Casein Kinase II; D002448:Cell Adhesion; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism
D015820:Cadherins; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D019319:Okadaic Acid; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases