Regulation of equilibrative nucleoside uptake by protein kinase inhibitors.
The uptake of nucleosides and nucleoside analogs into human leukemia K562 cells is facilitated by the equilibrative transporters ENT1 and ENT2. Incubation of K562 cells with a variety of protein kinase inhibitors inhibited the transport of both uridine (ARA-C) and cytidine (CPEC) analogs. These inhibitory effects were observed for a large number of kinase inhibitors including those against p38 MAPK, the EGF receptor kinase, protein kinase C, TOR and others. Thus these results suggest that the nucleoside transporters are unexpected targets for kinase inhibitors and may influence the design and application of combinatorial approaches of nucleoside analogs and kinase inhibitors in clinical applications.
Huang
Min
M
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Wang
Yanhong
Y
Mitchell
Beverly S
BS
Graves
Lee M
LM
D000818:Animals; D001692:Biological Transport; D003562:Cytidine / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D033705:Equilibrative Nucleoside Transport Proteins / Q000378:metabolism*; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism; D033722:Equilibrative-Nucleoside Transporter 2 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy; D009705:Nucleosides / Q000493:pharmacokinetics*; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004791:Enzyme Inhibitors; D033705:Equilibrative Nucleoside Transport Proteins; D033721:Equilibrative Nucleoside Transporter 1; D033722:Equilibrative-Nucleoside Transporter 2; D009705:Nucleosides; D047428:Protein Kinase Inhibitors; D003562:Cytidine; D066246:ErbB Receptors; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases