Schmidt A, Hall M N, Koller A
Department of Biochemistry, Biozentrum, University of Basel, Switzerland.
Mol Cell Biol. 1994 Oct;14(10):6597-606. doi: 10.1128/mcb.14.10.6597-6606.1994.
The macrocyclic lactone FK506 exerts immunosuppressive effects on T lymphocytes by interfering with signal transduction leading to T-cell activation and also inhibits the growth of eukaryotic microorganisms, including Saccharomyces cerevisiae. We reported previously that an FK506-sensitive target in S. cerevisiae is required for amino acid import and that overexpression of two new genes, TAT1 and TAT2 (formerly called TAP1 and TAP2), confers resistance to the drug. Here we report that TAT1 and TAT2 encode novel members of the yeast amino acid permease family composed of integral membrane proteins that share 30 to 40% identity. TAT1 is the tyrosine high-affinity transporter, which also mediates low-affinity or low-capacity uptake of tryptophan. TAT2 is the tryptophan high-affinity transporter. FK506 does not reduce the levels of TAT1 and TAT2 transcripts, indicating that the inhibition of amino acid transport by the drug is posttranscriptional.
大环内酯类药物FK506通过干扰导致T细胞活化的信号转导对T淋巴细胞发挥免疫抑制作用，并且还能抑制包括酿酒酵母在内的真核微生物的生长。我们先前报道过，酿酒酵母中一个对FK506敏感的靶点是氨基酸转运所必需的，并且两个新基因TAT1和TAT2（以前称为TAP1和TAP2）的过表达赋予了对该药物的抗性。在此我们报道，TAT1和TAT2编码酵母氨基酸通透酶家族的新成员，这些成员由具有30%至40%同源性的整合膜蛋白组成。TAT1是酪氨酸高亲和力转运体，它也介导色氨酸的低亲和力或低容量摄取。TAT2是色氨酸高亲和力转运体。FK506不会降低TAT1和TAT2转录本的水平，这表明该药物对氨基酸转运的抑制作用是转录后水平的。
