Coe Imogen, Zhang Ying, McKenzie Tamara, Naydenova Zlatina
Department of Biology, York University, Toronto, Canada.
FEBS Lett. 2002 Apr 24;517(1-3):201-5. doi: 10.1016/s0014-5793(02)02622-4.
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.
核苷转运体的调控机制目前还知之甚少。我们发现，在人类培养细胞中，蛋白激酶C（PKC）的急性刺激会导致对S-(4-硝基苄基)-6-硫代肌苷敏感的（人类平衡核苷转运体1，hENT1）核苷摄取迅速增加，这并非由于代谢增加所致，且可被PKC抑制剂阻断。使用亚型特异性抑制剂表明，PKCδ和/或ε（而非α、β或γ）负责这些急性效应。PKC的下调会降低hENT1依赖的尿苷摄取。这些是首批数据，表明通过一种可能涉及膜上转运体激活（可能通过蛋白质的翻译后修饰）的机制，PKCδ/ε可快速依赖地刺激hENT1转运。
