PT  - JOURNAL ARTICLE
AU  - An R. Van Rompay
AU  - Ameli Norda
AU  - Karin Lindén
AU  - Magnus Johansson
AU  - Anna Karlsson
TI  - Phosphorylation of Uridine and Cytidine Nucleoside Analogs by Two Human Uridine-Cytidine Kinases
AID  - 10.1124/mol.59.5.1181
DP  - 2001 May 01
TA  - Molecular Pharmacology
PG  - 1181--1186
VI  - 59
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/59/5/1181.short
4100  - http://molpharm.aspetjournals.org/content/59/5/1181.full
SO  - Mol Pharmacol2001 May 01; 59
AB  - Uridine-cytidine kinases (UCK) have important roles for the phosphorylation of nucleoside analogs that are being investigated for possible use in chemotherapy of cancer. We have cloned the cDNA of two human UCKs. The ≈30-kDa proteins, named UCK1 and UCK2, were expressed in Escherichia coli and shown to catalyze the phosphorylation of Urd and Cyd. The enzymes did not phosphorylate deoxyribonucleosides or purine ribonucleosides. UCK1 mRNA was detected as two isoforms of ≈1.8 and ≈2.7 kb. The 2.7-kb band was ubiquitously expressed in the investigated tissues. The band of ≈1.8 kb was present in skeletal muscle, heart, liver, and kidney. The two isoforms of UCK2 mRNA of 1.2 and 2.0 kb were only detected in placenta among the investigated tissues. The genes encoding UCK1 and UCK2 were mapped to chromosome 9q34.2-9q34.3 and 1q22-1q23.2, respectively. We tested 28 cytidine and uridine nucleoside analogs as possible substrates of the enzymes. The enzymes phosphorylated several of the analogs, such as 6-azauridine, 5-fluorouridine, 4-thiouridine, 5-bromouridine, N 4-acetylcytidine,N 4-benzoylcytidine, 5-fluorocytidine, 2-thiocytidine, 5-methylcytidine, andN 4-anisoylcytidine. The cloning and recombinant expression of the two human UCKs will be important for development of novel pyrimidine ribonucleoside analogs and the characterization of their pharmacological activation.