CLONING AND EXPRESSION OF CDNAS FOR 2 DISTINCT MURINE TUMOR-NECROSIS-FACTOR RECEPTORS DEMONSTRATE ONE RECEPTOR IS SPECIES-SPECIFIC
CLONING AND EXPRESSION OF CDNAS FOR 2 DISTINCT MURINE TUMOR-NECROSIS-FACTOR RECEPTORS DEMONSTRATE ONE RECEPTOR IS SPECIES-SPECIFIC
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DOI：
10.1073/pnas.88.7.2830
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发表时间：
1991-04-01
影响因子：
11.1
通讯作者：
GOEDDEL, DV
中科院分区：
文献类型：
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作者：
LEWIS, M;TARTAGLIA, LA;GOEDDEL, DV
从小鼠巨噬细胞cDNA文库中分离到编码两种不同的肿瘤坏死因子受体的互补DNA克隆。小鼠肿瘤坏死因子受体1型(mtnf-r1)预测的成熟多肽由425个氨基酸组成，与人的成熟多肽的同源性为%，而小鼠肿瘤坏死因子受体2型(mtnf-r2)的cDNA预测的成熟蛋白由452个氨基酸组成，与人的肿瘤坏死因子受体2型的同源性为62%。这两个小鼠肿瘤坏死因子受体在胞外区有有限的序列同源性(几乎等于20%的同源性)，但在细胞质部分没有明显的相似性。Northern(RNA)分析表明mtnf-R1有一个2.6kb的转录本；mtnf-R2有一个3.6kb的转录本和一个更主要的4.5kb的转录本。用mtnf-r1或mtnf-r2表达载体转染的人细胞系与I-125标记的重组小鼠肿瘤坏死因子-α(TNF-α)特异性结合。尽管mtnf-R1对重组小鼠肿瘤坏死因子-α和人肿瘤坏死因子-α具有相似的亲和力，但mtnf-R2对重组小鼠肿瘤坏死因子-α表现出很强的特异性。这一结果表明，在小鼠或小鼠细胞系中报道的人肿瘤坏死因子-α的各种活性可能是由mtnf-R1介导的。
Complementary DNA clones encoding two distinct tumor necrosis factor receptors were isolated from a mouse macrophage cDNA library. The cDNA for murine tumor necrosis factor receptor type 1 (mTNF-R1) predicts a mature polypeptide of 425 amino acids that is 64% identical to its human counterpart, whereas the cDNA of murine tumor necrosis factor receptor type 2 (mTNF-R2) predicts a mature protein of 452 amino acids that is 62% identical to human tumor necrosis factor receptor type 2. The two murine tumor necrosis factor receptors have limited sequence homology (almost-equal-to 20% identity) in their extracellular regions but no apparent similarity in their cytoplasmic portions. Northern (RNA) analysis indicates a single 2.6-kilobase (kb) transcript for mTNF-R1; a 3.6-kb and a more predominant 4.5-kb transcript are observed for mTNf-R2. A human cell line transfected with either mTNF-R1 or mTNF-R2 expression vectors specifically bound I-125-labeled recombinant murine tumor necrosis factor-alpha (TNF-alpha). Although mTNF-R1 had a similar affinity for both recombinant murine TNF-alpha and human TNF-alpha, mTNF-R2 showed strong specificity for recombinant murine TNF-alpha. This result suggests that the various activities of human tumor necrosis factor-alpha reported in mice or in murine cell lines are probably mediated by mTNF-R1.