Influence of phosphorylation of THR-3, SER-11, and SER-15 on deoxycytidine kinase activity and stability.
Deoxycytidine kinase (dCK) is a key enzyme in the salvage of deoxyribonucleosides and in the activation of several anticancer and antiviral nucleoside analogues. We have recently shown that dCK is a phosphoprotein. Four in vivo phosphorylation sites were identified: Thr-3, Ser-11, Ser-15, and Ser-74. Site-directed mutagenesis demonstrated that phosphorylation of Ser-74, the major phosphorylated residue, strongly influences dCK activity in eucaryotic cells. Here, we show that phosphorylation of the three other sites, located in the N-terminal extremity of the protein, does not significantly modify dCK activity, but phosphorylation of Thr-3 could promote dCK stability.
Smal
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C
Université Catholique de Louvain, de Duve Institute, Brussels, Belgium. caroline.smal@uclouvain.be
Ntamashimikiro
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S
Arts
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A
Van Den Neste
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E
Bontemps
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F
D002460:Cell Line; D003842:Deoxycytidine Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004795:Enzyme Stability; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D012694:Serine / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013912:Threonine / Q000737:chemistry / Q000378:metabolism*
D013912:Threonine; D012694:Serine; D003842:Deoxycytidine Kinase