PKC regulation of the human equilibrative nucleoside transporter, hENT1.
Regulation of nucleoside transporters is poorly understood. We show that acute stimulation of protein kinase C (PKC) causes a rapid increase in S-(4-nitrobenzyl)-6-thioinosine-sensitive (human equilibrative nucleoside transporter 1, hENT1) nucleoside uptake, in human cultured cells, which is not due to increased metabolism and which can be blocked by PKC inhibitors. Use of isoform-specific inhibitors indicates that PKC delta and/or epsilon (but not alpha, beta or gamma) are responsible for the acute effects. Down-regulation of PKC decreases hENT1-dependent uridine uptake. These are the first data to show rapid PKC delta/epsilon-dependent stimulation of hENT1 transport by a mechanism that may involve activation of transporters at the membrane possibly by post-translational modification of the protein.
Coe
Imogen
I
Department of Biology, York University, Toronto, Canada. coe@yorku.ca
Zhang
Ying
Y
McKenzie
Tamara
T
Naydenova
Zlatina
Z
D000661:Amphetamine / Q000494:pharmacology*; D000662:Amphetamines; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D033721:Equilibrative Nucleoside Transporter 1; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000378:metabolism*
D000662:Amphetamines; D004791:Enzyme Inhibitors; D033721:Equilibrative Nucleoside Transporter 1; D007527:Isoenzymes; D026901:Membrane Transport Proteins; C438649:SLC29A1 protein, human; D000661:Amphetamine; C497258:PRKCD protein, human; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; C100230:4-methoxyamphetamine; D014529:Uridine