Deoxycytidine kinase is phosphorylated in vitro by protein kinase C alpha.
Deoxycytidine (dCyd) kinase was effectively phosphorylated by protein kinase C. The reaction was rapid, occurring at 4 degrees C as well as at 37 degrees C and approximately 0.7 mol of phosphate could be incorporated per mol of deoxycytidine kinase. Phosphoserine was the primary amino acid to be phosphorylated. Phosphorylation of deoxycytidine kinase resulted in a 100% increase in the Vmax using dCyd as a substrate (52.16 +/- 1.3 versus 104.47 +/- 11.4 nmol/min/mg protein), and an increase in the apparent Km (2.0 +/- 0.2 microM versus 6.9 +/- 1.2 microM). The inactive antimetabolite, ara-C, is activated within a cell by deoxycytidine kinase phosphorylation of the prodrug. Recent studies have shown that ara-C activates protein kinase C in vivo [1]. Furthermore, ara-C has been shown to be metabolized to ara-CDP-choline via reversal of the cholinephosphotransferase [2] producing diglyceride, a cellular activator of protein kinase C. Thus, in situ, deoxycytidine kinase may be phosphorylated by protein kinase C with the result that self-potentiation of ara-C toxicity may occur via increased activity of deoxycytidine kinase.
Wang
L M
LM
Comprehensive Cancer Center of Wake Forest University, Bowman Gray School of Medicine, Winston-Salem, NC 27157.
Kucera
G L
GL
D003561:Cytarabine / Q000378:metabolism; D003842:Deoxycytidine Kinase / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D013696:Temperature
D007527:Isoenzymes; D003561:Cytarabine; D003842:Deoxycytidine Kinase; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha