MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Van Rompay, A. R.
Right arrow Articles by Karlsson, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Van Rompay, A. R.
Right arrow Articles by Karlsson, A.

Vol. 59, Issue 5, 1181-1186, May 2001

Phosphorylation of Uridine and Cytidine Nucleoside Analogs by Two Human Uridine-Cytidine Kinases

An R. Van Rompay, Ameli Norda, Karin Lindén, Magnus Johansson, and Anna Karlsson

Division of Clinical Virology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden

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 approx 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 approx 1.8 and approx 2.7 kb. The 2.7-kb band was ubiquitously expressed in the investigated tissues. The band of approx 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, N4-acetylcytidine, N4-benzoylcytidine, 5-fluorocytidine, 2-thiocytidine, 5-methylcytidine, and N4-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.

Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
K. Klumpp, G. Kalayanov, H. Ma, S. Le Pogam, V. Leveque, W.-R. Jiang, N. Inocencio, A. De Witte, S. Rajyaguru, E. Tai, et al.
2'-Deoxy-4'-azido Nucleoside Analogs Are Highly Potent Inhibitors of Hepatitis C Virus Replication Despite the Lack of 2'-{alpha}-Hydroxyl Groups
J. Biol. Chem., January 25, 2008; 283(4): 2167 - 2175.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
E. Murakami, H. Bao, M. Ramesh, T. R. McBrayer, T. Whitaker, H. M. Micolochick Steuer, R. F. Schinazi, L. J. Stuyver, A. Obikhod, M. J. Otto, et al.
Mechanism of Activation of {beta}-D-2'-Deoxy-2'-Fluoro-2'-C-Methylcytidine and Inhibition of Hepatitis C Virus NS5B RNA Polymerase
Antimicrob. Agents Chemother., February 1, 2007; 51(2): 503 - 509.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. M. Fortier and J. Kornbluth
NK Lytic-Associated Molecule, Involved in NK Cytotoxic Function, Is an E3 Ligase.
J. Immunol., June 1, 2006; 176(11): 6454 - 6463.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
G. Belliot, S. V. Sosnovtsev, K.-O. Chang, V. Babu, U. Uche, J. J. Arnold, C. E. Cameron, and K. Y. Green
Norovirus Proteinase-Polymerase and Polymerase Are Both Active Forms of RNA-Dependent RNA Polymerase
J. Virol., February 15, 2005; 79(4): 2393 - 2403.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
D. Murata, Y. Endo, T. Obata, K. Sakamoto, Y. Syouji, M. Kadohira, A. Matsuda, and T. Sasaki
A CRUCIAL ROLE OF URIDINE/CYTIDINE KINASE 2 IN ANTITUMOR ACTIVITY OF 3'-ETHYNYL NUCLEOSIDES
Drug Metab. Dispos., October 1, 2004; 32(10): 1178 - 1182.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics