Griffiths M, Beaumont N, Yao S Y, Sundaram M, Boumah C E, Davies A, Kwong F Y, Coe I, Cass C E, Young J D, Baldwin S A
Department of Biochemistry and Molecular Biology, University of Leeds, UK.
Nat Med. 1997 Jan;3(1):89-93. doi: 10.1038/nm0197-89.
In most mammalian cells nucleoside uptake occurs primarily via broad-specificity, es (e, equilibrative; 5, sensitive to NBMPR inhibition) transporters that are potently inhibited by nitrobenzylthioinosine (NBMPR). These transporters are essential for nucleotide synthesis by salvage pathways in hemopoietic and other cells that lack de novo pathways and are the route of cellular uptake for many cytotoxic nucleosides used in cancer and viral chemotherapy. They play an important role in adenosine-mediated regulation of many physiological processes, including neurotransmission and platelet aggregation, and are a target for coronary vasodilator drugs. We have previously reported the purification of the prototypic es transporter from human erythrocytes and have shown that this glycoprotein of apparent M, 55,000 is immunologically related to nucleoside transporters from several other species and tissues, including human placenta. Here we report the isolation of a human placental cDNA encoding a 456-residue glycoprotein with functional characteristics typical of an es-type transporter. It is predicted to possess 11 membrane-spanning regions and is homologous to several proteins of unknown function in yeast, nematodes, plants and mammals. Because of its central role in the uptake both of adenosine and of chemotherapeutic nucleosides, study of this protein should not only provide insights into the physiological roles of nucleoside transport but also open the way to improved therapies.
在大多数哺乳动物细胞中，核苷摄取主要通过具有广泛特异性的易化性（e，易化性；5，对NBMPR抑制敏感）转运体进行，这些转运体可被硝基苄硫肌苷（NBMPR）有效抑制。这些转运体对于造血细胞和其他缺乏从头合成途径的细胞通过补救途径进行核苷酸合成至关重要，并且是癌症和病毒化疗中使用的许多细胞毒性核苷的细胞摄取途径。它们在腺苷介导的许多生理过程的调节中起重要作用，包括神经传递和血小板聚集，并且是冠状动脉血管扩张药物的作用靶点。我们先前已报道了从人红细胞中纯化出原型易化性转运体，并表明这种表观分子量为55,000的糖蛋白与包括人胎盘在内的其他几种物种和组织中的核苷转运体存在免疫相关性。在此，我们报告分离出一种人胎盘cDNA，其编码一种具有456个残基的糖蛋白，具有易化性转运体类型的典型功能特征。预计它具有11个跨膜区域，并且与酵母、线虫、植物和哺乳动物中几种功能未知的蛋白质同源。由于其在腺苷和化疗核苷摄取中的核心作用，对该蛋白质的研究不仅应能深入了解核苷转运的生理作用，还应为改进治疗方法开辟道路。
