TA1/LAT-1/CD98 Light Chain and System L Activity, but Not 4F2/CD98 Heavy Chain, Respond to Arginine Availability in Rat Hepatic Cells

TA1/LAT-1/CD98 Light Chain and System L Activity, but Not 4F2/CD98 Heavy Chain, Respond to Arginine Availability in Rat Hepatic Cells
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TA1/LAT-1/CD98 轻链和 System L 活性(但不是 4F2/CD98 重链)对大鼠肝细胞中精氨酸的可用性有反应

DOI:
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发表时间:
2000
影响因子:
4.8
通讯作者:
N. Thompson
N. Thompson
中科院分区:
生物学2区
文献类型:
--
作者:
W. Campbell;Deborah E. Sah;M. M. Medina;J. Albina;W. Coleman;N. Thompson

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肿瘤相关基因-1/L氨基酸转运蛋白-1(TA 1/LAT-1)是新近发现的一种CD 98轻链氨基酸转运蛋白,是细胞活化的标志物。我们以前的研究表明,原代大鼠肝细胞培养物的TA 1 RNA水平是响应介质的氨基酸浓度,这表明适应性调节。与转化细胞相关的高水平TA 1表达也表明在肿瘤进展中的作用。本研究探讨了TA 1/CD 98的表达,适应性反应,相关的氨基酸转运肿瘤转化的关系,使用一个面板的特点大鼠肝细胞系。我们发现:1)TA 1的表达增加,对精氨酸而非谷氨酰胺有特异性反应; 2)在γ-谷氨酰转肽酶阳性转化细胞和致瘤细胞中,TA 1对精氨酸的反应丧失; 3)4F 2/CD 98重链对精氨酸水平无明显反应;精氨酸诱导的L系统氨基酸转运活性与TA 1/LAT-1 mRNA的变化相关,而与总免疫反应蛋白的变化无关。我们的研究结果表明,这CD 98轻链可能作为一个环境传感器,响应氨基酸的可用性,其调节是复杂的。我们假设TA 1表达的改变是肝癌发生的早期事件,使肿瘤细胞具有生长或存活优势,特别是在氨基酸可用性有限的条件下。
Tumor associated gene-1/L amino acid transporter-1 (TA1/LAT-1) was recently identified as a light chain of the CD98 amino acid transporter and cellular activation marker. Our previous studies with primary rat hepatocyte cultures demonstrated that TA1 RNA levels were responsive to media amino acid concentrations, suggesting adaptive regulation. High level TA1 expression associated with transformed cells also suggested a role in tumor progression. The present study examined the relationship of TA1/CD98 expression, adaptive response, and associated amino acid transport to neoplastic transformation using a panel of well characterized rat hepatic cell lines. We found 1) increased expression of TA1 in response to amino acid depletion, specific for arginine but not glutamine; 2) loss of TA1 response to arginine in γ-glutamyl transpeptidase-positive transformed and tumorigenic cells; 3) no appreciable response of 4F2/CD98 heavy chain to arginine levels; and 4) correlation of system L amino acid transport activity in response to arginine with changes in TA1/LAT-1 mRNA but not total immunoreacting protein. Our results suggest this CD98 light chain may act as an environmental sensor, responding to amino acid availability and that its regulation is complex. We hypothesize that altered TA1 expression is an early event in hepatocarcinogenesis giving neoplastic cells a growth or survival advantage, particularly under conditions of limited amino acid availability.
天冬酰胺在变异小鼠神经母细胞瘤细胞系中调节鸟氨酸脱羧酶基因表达的机制。
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影响因子: 11.2
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