EXPRESSION CLONING OF AN INTERFERON-INDUCIBLE 17-KDA MEMBRANE-PROTEIN IMPLICATED IN THE CONTROL OF CELL-GROWTH
EXPRESSION CLONING OF AN INTERFERON-INDUCIBLE 17-KDA MEMBRANE-PROTEIN IMPLICATED IN THE CONTROL OF CELL-GROWTH
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DOI：
10.1074/jbc.270.40.23860
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发表时间：
1995-10-06
影响因子：
4.8
通讯作者：
WATHELET, MG
中科院分区：
文献类型：
--
作者：
DEBLANDRE, GA;MARINX, OP;WATHELET, MG
大约17kda的干扰素诱导膜蛋白被认为在干扰素的抗增殖活性中发挥作用，基于(1)它们在干扰素敏感和耐药细胞系中的诱导模式；(2)富含17kda蛋白的膜片段抑制细胞生长的能力。为了深入了解介导干扰素抗增殖活性的蛋白质的性质，产生了一种单克隆抗体13A5，它与17kda干扰素诱导的细胞表面蛋白特异性反应。这种17-kDa蛋白在人类细胞系中的表达模式与对干扰素抗增殖活性的敏感性相关。为了获得该蛋白的结构信息，我们利用13A5抗体对转染了人cDNA表达文库的COS细胞进行筛选。对全长cDNA克隆的序列分析显示，该克隆与先前通过差异筛选鉴定其干扰素诱导性而分离的9-27 cDNA同源。此外，9-27基因编码的17-kDa蛋白与Leu-13抗原相同。此前在白细胞和内皮细胞中发现了一种16kda的干扰素诱导蛋白，是参与抗增殖和同型粘附信号转导的多聚复合体的一个组成部分。这些结果表明，干扰素对细胞的调控涉及一种膜蛋白，这种膜蛋白由干扰素诱导的9-27基因编码，它与细胞表面的其他蛋白质结合，形成一个复杂的传递生长抑制和聚集信号。
Interferon-inducible membrane proteins of approximately 17 kDa have been suggested to play a role in the antiproliferative activity of interferons based on (1) their pattern of induction in interferon-sensitive and -resistant cell lines and (2) the ability of a membrane fraction enriched in 17-kDa proteins to inhibit cell growth. To gain insight into the nature of the proteins that mediate the antiproliferative activity of interferons, a monoclonal antibody, 13A5, was generated that reacted specifically with a 17-kDa interferon-inducible cell surface protein. The expression pattern of this 17-kDa protein by human cell lines correlated with sensitivity to the antiproliferative activity of interferons. To obtain information regarding the structure of this protein, the 13A5 antibody was used to screen COS cells transfected with a human cDNA expression library. Sequence analysis of a full-length cDNA clone revealed identity with the 9-27 cDNA, previously isolated on the basis of its interferon inducibility by differential screening. In addition, the 17-kDa protein encoded by the 9-27 gene was shown to be identical to the Leu-13 antigen. Leu-13 was previously identified as a 16-kDa interferon-inducible protein in leukocytes and endothelial cells and is a component of a multimeric complex involved in the transduction of antiproliferative and homotypic adhesion signals. These results suggest a novel level of cellular regulation by interferons involving a membrane protein, encoded by the interferon-inducible 9-27 gene, which associates with other proteins at the cell surface, forming a complex relaying growth inhibitory and aggregation signals.