title: Positive regulation of deoxycytidine kinase activity by phosphorylation of Ser-74 in B-cell chronic lymphocytic leukaemia lymphocytes.
abstract: 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.
authors.affiliation: Laboratory of Physiological Chemistry, Christian de Duve Institute of Cellular Pathology and Université catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Smal
authors.forename: Eric
authors.initials: E
authors.lastname: Van Den Neste
authors.forename: Marie
authors.initials: M
authors.lastname: Maerevoet
authors.forename: Xavier
authors.initials: X
authors.lastname: Poiré
authors.forename: Ivan
authors.initials: I
authors.lastname: Théate
authors.forename: Françoise
authors.initials: F
authors.lastname: Bontemps
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D003842:Deoxycytidine Kinase / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000276:immunology; D012694:Serine / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D010768:Phosphoserine; D012694:Serine; D003842:Deoxycytidine Kinase