Smal Caroline, Van Den Neste Eric, Maerevoet Marie, Poiré Xavier, Théate Ivan, Bontemps Françoise
Laboratory of Physiological Chemistry, Christian de Duve Institute of Cellular Pathology and Université catholique de Louvain, B-1200 Brussels, Belgium.
Cancer Lett. 2007 Aug 8;253(1):68-73. doi: 10.1016/j.canlet.2007.01.013. Epub 2007 Mar 9.
Deoxycytidine kinase (dCK) activates several antileukaemic nucleoside analogues. We have recently reported that the activity of dCK, overexpressed in HEK 293T cells, correlates with its phosphorylation level on Ser-74. Here, we show that dCK from B-cell chronic lymphocytic leukaemia (B-CLL) lymphocytes can be detected by an anti-phospho-Ser-74 antibody and that interindividual variability in dCK activity is related to its phosphorylation level on Ser-74. Moreover, pharmacological intervention modified Ser-74 phosphorylation, in close parallel with changes in dCK activity. These results suggest that activation of dCK via phosphorylation of Ser-74 might constitute a new therapeutic strategy to enhance activation and efficacy of nucleoside analogues.
脱氧胞苷激酶（dCK）可激活多种抗白血病核苷类似物。我们最近报道，在HEK 293T细胞中过表达的dCK的活性与其Ser-74位点的磷酸化水平相关。在此，我们表明，抗磷酸化Ser-74抗体可检测到B细胞慢性淋巴细胞白血病（B-CLL）淋巴细胞中的dCK，且dCK活性的个体间差异与其Ser-74位点的磷酸化水平有关。此外，药物干预改变了Ser-74的磷酸化，这与dCK活性的变化密切相关。这些结果表明，通过Ser-74磷酸化激活dCK可能构成一种新的治疗策略，以增强核苷类似物的激活和疗效。
