Influence of phosphorylation of THR-3, SER-11, and SER-15 on deoxycytidine kinase activity and stability

Nucleosides Nucleotides Nucleic Acids. 2010 Jun;29(4-6):404-7. doi: 10.1080/15257771003741216.

Abstract

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.

MeSH terms

  • Cell Line
  • Deoxycytidine Kinase / chemistry
  • Deoxycytidine Kinase / genetics
  • Deoxycytidine Kinase / metabolism*
  • Enzyme Stability
  • Humans
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Serine / chemistry
  • Serine / metabolism*
  • Structure-Activity Relationship
  • Threonine / chemistry
  • Threonine / metabolism*

Substances

  • Threonine
  • Serine
  • Deoxycytidine Kinase