Protein phosphatase 2A regulates deoxycytidine kinase activity via Ser-74 dephosphorylation
Amsailale, Rachid Beyaert, Maxime Smal, Caroline Janssens, Veerle Van Den Neste, Eric Bontemps, Françoise # ×
Elsevier on behalf of the Federation of European Biochemical Societies
FEBS Letters vol:588 issue:5 pages:727-732
Deoxycytidine kinase (dCK) is a critical enzyme for activation of anticancer nucleoside analogs. Its activity is controlled via Ser-74 phosphorylation. Here, we investigated which Ser/Thr phosphatase dephosphorylates Ser-74. In cells, the PP1/PP2A inhibitor okadaic acid increased both dCK activity and Ser-74 phosphorylation at concentrations reported to specifically target PP2A. In line with this, purified PP2A, but not PP1, dephosphorylated recombinant pSer-74-dCK. In cell lysates, the Ser-74-dCK phosphatase activity was found to be latent, Mn2+-activated, responsive to PP2A inhibitors, and diminished after PP2A-immunodepletion. Use of siRNAs allowed concluding definitively that PP2A constitutively dephosphorylates dCK in cells and negatively regulates its activity.