Hanson D A, Kaspar A A, Poulain F R, Krensky A M
Department of Pediatrics, Stanford University School of Medicine, CA 94305-5208, USA.
Mol Immunol. 1999 May;36(7):413-22. doi: 10.1016/s0161-5890(99)00063-2.
Granulysin is a newly described lytic molecule expressed by CTL and NK cells. Three mRNA (519, 520, and 522) and two protein products of 15 and 9 kDa are encoded by the granulysin gene. Stable transfectants overexpressing the predominate 520 mRNA were generated to determine the protein products originating from the translation of this message. A transfectant of the NK cell tumor YT overexpressed both 15 and 9 kDa proteins while a transfectant of the T cell tumor HuT78 produced mainly 15 kDa granulysin. Thus the 520 mRNA is sufficient for production of both 15 and 9 kDa granulysin. 9 kDa granulysin accumulated via post-translational processing of 15 kDa protein and was present intracellularly but not in the cell culture supernatant, indicating specific retention of the 9 kDa protein. An inhibitor of granule acidification, concanamycin A, blocked the processing of 15 kDa granulysin to the 9 kDa form. A deduced structural difference between the two forms of the protein and a decrease in lytic activity of 9 kDa granulysin at granule pH suggest two mechanisms by which a granulysin expressing cell is protected from autolysis during the biosynthesis of this potentially harmful molecule.
颗粒溶素是一种新描述的由细胞毒性T淋巴细胞（CTL）和自然杀伤细胞（NK细胞）表达的溶细胞分子。颗粒溶素基因编码三种信使核糖核酸（mRNA，分别为519、520和522）以及两种蛋白质产物，分子量分别为15 kDa和9 kDa。构建了过表达主要的520 mRNA的稳定转染细胞系，以确定源自该信使翻译的蛋白质产物。NK细胞肿瘤YT的一个转染细胞系过表达了15 kDa和9 kDa两种蛋白质，而T细胞肿瘤HuT78的一个转染细胞系主要产生15 kDa的颗粒溶素。因此，520 mRNA足以产生15 kDa和9 kDa的颗粒溶素。9 kDa的颗粒溶素通过15 kDa蛋白质的翻译后加工积累，存在于细胞内，但不在细胞培养上清液中，表明9 kDa蛋白质有特异性滞留。颗粒酸化抑制剂 concanamycin A可阻断15 kDa颗粒溶素加工成9 kDa形式。两种形式蛋白质之间推测的结构差异以及9 kDa颗粒溶素在颗粒pH值下溶细胞活性的降低，提示了颗粒溶素表达细胞在这种潜在有害分子生物合成过程中免受自溶的两种机制。
