Yoshimoto T, Yoshimoto E, Meruelo D
Department of Pathology, New York University Medical Center, New York 10016.
J Virol. 1992 Jul;66(7):4377-81. doi: 10.1128/JVI.66.7.4377-4381.1992.
The receptor for gp70 envelope glycoprotein of murine ecotropic leukemia virus is essential for virus entry into the host cell and has been recently demonstrated to function as a cationic amino acid transporter. In the experiments reported herein, we compared the gene expression of the murine ecotropic retroviral receptor (ERR) and its human homolog (H13) in rapidly proliferating cells versus resting cells using four different systems. (i) The expression of ERR gene is enhanced during activation of T and B lymphocytes by concanavalin A and lipopolysaccharide, respectively. Similar enhancement is observed by adding phorbol 12-myristate 13-acetate (PMA) or calcium ionophore (A23187). These phenomena appear to involve protein kinase C; two PMA analogs, 4 alpha-phorbol and 4 alpha-PMA, lacking the ability to activate protein kinase C fail to induce elevated levels of gene expression, and the protein kinase C inhibitor, H7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride[, inhibits the enhancement induced by PMA. (ii) Friend murine leukemia virus induces rapid splenomegaly, and acute erythroleukemia in sensitive mice. Concomitantly with splenomegaly, ERR gene expression in spleen cells increases dramatically. (iii) The level of expression of the ERR or H13 gene in a variety of tumor cells is highly elevated compared with the level in noncancerous cells. (iv) H13 gene expression decreases upon terminal differentiation of the human promyelocytic leukemia cell line HL-60 into granulocytes or macrophages by dimethyl sulfoxide or PMA, respectively. These results suggest that ERR and H13 genes play an important role in cellular proliferation.
小鼠嗜亲性白血病病毒gp70包膜糖蛋白的受体是病毒进入宿主细胞所必需的，最近已证明其具有阳离子氨基酸转运蛋白的功能。在本文报道的实验中，我们使用四种不同的系统比较了快速增殖细胞与静息细胞中小鼠嗜亲性逆转录病毒受体（ERR）及其人类同源物（H13）的基因表达。（i）ERR基因的表达在分别用刀豆球蛋白A和脂多糖激活T淋巴细胞和B淋巴细胞的过程中增强。通过添加佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）或钙离子载体（A23187）也观察到类似的增强。这些现象似乎涉及蛋白激酶C；两种缺乏激活蛋白激酶C能力的PMA类似物，4α - 佛波醇和4α - PMA，不能诱导基因表达水平升高，并且蛋白激酶C抑制剂H7 [1 - （5 - 异喹啉磺酰基） - 2 - 甲基哌嗪二盐酸盐] 可抑制PMA诱导的增强作用。（ii）弗氏小鼠白血病病毒可诱导敏感小鼠迅速出现脾肿大和急性红白血病。伴随脾肿大，脾细胞中ERR基因表达急剧增加。（iii）与非癌细胞中的水平相比，多种肿瘤细胞中ERR或H13基因的表达水平高度升高。（iv）人早幼粒细胞白血病细胞系HL - 60分别通过二甲基亚砜或PMA终末分化为粒细胞或巨噬细胞后，H13基因表达降低。这些结果表明ERR和H13基因在细胞增殖中起重要作用。
