Activation of deoxycytidine kinase during inhibition of DNA synthesis by 2-chloro-2′-deoxyadenosine (cladribine) in human lymphocytes

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

“…The first mechanism reported to control dCK activity was retro-inhibition by dCTP, although its physiological relevance is questionable [4][5][6]. Thereafter, several studies [7][8][9][10] suggested that dCK activity could be regulated by posttranslational modification, which was definitively confirmed by our group. We established that dCK is a phosphoprotein containing at least four phosphorylation sites: Thr-3, Ser-11, Ser-15 and Ser-74, the latter being the major phosphorylated residue and the only one to play a role in the regulation of dCK activity [11].…”

Nucleoside analogues: mechanisms of drug resistance and reversal strategies

“…It has been shown that dCK activity is stimulated after treatment with 2-CdA, as well as with fludarabine and ara-C in normal human lymphocytes and various leukemic cell lines. 190,191 The increase of dCK activity induced by NA was considered to result from posttranslational modifications of dCK during inhibition of DNA synthesis. 192,193 The importance of the ratio of nucleoside analogues to normal nucleosides has been recognized more recently.…”

Structure and function of cellular deoxyribonucleoside kinases

“…This was verified by determination of the structure of the bound nucleoside using nuclear magnetic resonance (NMR) methods with complexes of 13 C/ 2 H double-labeled dC and dA and dCK [83]. Synergistic effects of certain combinations of nucleosides, e. g. AraC and FArA [84], have been shown to at least in part be due to activation of dCK [85]. Incubation of cells with several of the nucleosides phosphorylated by dCK as well as with unrelated agents, such as the topoisomerase inhibitor etoposide, leads to higher dCK activity without a concomitant increase in dCK mRNA or protein levels [86].…”