ISOLATION OF AN MESSENGER-RNA ENCODING A SOLUBLE FORM OF THE HUMAN INTERLEUKIN-6 RECEPTOR

ISOLATION OF AN MESSENGER-RNA ENCODING A SOLUBLE FORM OF THE HUMAN INTERLEUKIN-6 RECEPTOR
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DOI:
10.1016/1043-4666(92)90043-q
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发表时间:
1992-03-01
期刊:
影响因子:
3.8
通讯作者:
MAIHLE, NJ
MAIHLE, NJ
中科院分区:
医学3区
文献类型:
--
作者:
LUST, JA;DONOVAN, KA;MAIHLE, NJ

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已经描述了缺乏跨膜结构域的可溶形式的白介素(IL)-2、IL-4和IL-7受体。IL-6是在B细胞最终分化为浆细胞和多发性骨髓瘤的发病机制中重要的生长因子。为了确定IL-6的受体是否可以作为可溶性分子存在,分析了来自转化的B细胞系U266、CESS和Daudi、来自两名骨髓瘤患者的骨髓和来自正常白细胞的RNA。使用聚合酶链反应,选择跨膜结构域侧翼的寡核苷酸引物以产生339 bp的片段。除Daudi外,所有样品均产生等量的预期339 bp片段加上较小的245 bp片段,Daudi表现出实际上不存在这两种片段。对来自五个样品中的每一个的较小片段的序列分析证明了从密码子356(G-TG)至387(AG-G)的整个跨膜区的缺失。这种删除的界限在所有情况下都是相同的。对U266配体结合结构域的部分序列分析表明,IL-6受体cDNA的膜结合形式和可溶形式的序列相同。总之,编码可溶形式的IL-6受体的mRNA在正常细胞和骨髓瘤细胞中都表达。
Soluble forms of the interleukin (IL)-2, IL-4 and IL-7 receptors which lack the transmembrane domain have been described. IL-6 is a growth factor important in the final differentiation of B-cells into plasma cells and in the pathogenesis of multiple myeloma. To determine whether the receptor for IL-6 may exist as a soluble molecule, RNA was analysed from the transformed B-cell lines U266, CESS and Daudi, from bone marrow from two myeloma patients, and from normal leukocytes. Using polymerase chain reaction, oligonucleotide primers which flank the transmembrane domain were selected to generate a 339 bp fragment. All samples produced equivalent amounts of the expected 339 bp fragment plus a smaller 245 bp fragment except Daudi which exhibited virtual absence of both. Sequence analysis of the smaller fragments from each of the five samples demonstrated the deletion of the entire transmembrane region from codons 356 (G-TG) to 387 (AG-G). The boundaries of this deletion were identical in all cases. Partial sequence analysis of the ligand-binding domain for U266 demonstrated identical sequences for the membrane-bound and soluble forms of the IL-6 receptor cDNAs. In summary, an mRNA which encodes a soluble form of the IL-6 receptor is expressed in both normal and myeloma cells.