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. 2014 Mar 3;588(5):727-32.
doi: 10.1016/j.febslet.2014.01.016. Epub 2014 Jan 23.

Protein phosphatase 2A regulates deoxycytidine kinase activity via Ser-74 dephosphorylation

Rachid Amsailale  1 , Maxime Beyaert  1 , Caroline Smal  1 , Veerle Janssens  2 , Eric Van Den Neste  3 , Françoise Bontemps  4
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Free article

Protein phosphatase 2A regulates deoxycytidine kinase activity via Ser-74 dephosphorylation

Rachid Amsailale et al. FEBS Lett. .
Free article

Abstract

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, Mn(2+)-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.

Keywords: Deoxycytidine kinase; Nucleoside analog; Protein phosphatase; Ser-74 phosphorylation; Ser/Thr protein phosphatase 2A.

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