Oh J W, Revel M, Chebath J
Department of Molecular Genetics and Virology, Weizmann Institute of Sciences, Rehovot, Israel.
Cytokine. 1996 May;8(5):401-9. doi: 10.1006/cyto.1996.0055.
The human interleukin 6 receptor (IL-6R) is expressed on cells as a transmembrane protein of 80 kDa (gp80, ligand binding unit), or as a smaller soluble counterpart (sIL-6R, approximately 55 kDa). Recombinant or natural sIL-6Rs bind IL-6 and stimulate biological activity by association with the signal transducing subunit gp130 at the cell surface. The origin of sIL-6Rs is not clear. Haematopoietic cells express, in addition to the gp80 mRNA, an IL-6R mRNA where the transmembrane domain is spliced out, predicting a shorter protein with a modified basic sequence at the C-terminus. We show that the spliced mRNA is expressed in human T47D breast carcinoma cells and soluble IL-6R protein is indeed secreted by these cells. An antibody against the C-terminus of the spliced protein detects a 55-65 kDa glycosylated species in sIL-6R purified from T47D supernatant by classical and immunoaffinity chromatography. The spliced T47D IL-6R, glycosylated or after removal of O- and N-linked polysaccharides, has the same size as a recombinant spliced IL-6R from CHO cells. The recombinant spliced IL-6R acts on cells as an IL-6 agonist to stimulate transcription from IL-6 inducible enhancers.
人白细胞介素6受体（IL-6R）在细胞上作为一种80 kDa的跨膜蛋白（gp80，配体结合单位）表达，或作为一种较小的可溶性对应物（sIL-6R，约55 kDa）表达。重组或天然的sIL-6R结合IL-6，并通过与细胞表面的信号转导亚基gp130缔合来刺激生物活性。sIL-6R的来源尚不清楚。造血细胞除了表达gp80 mRNA外，还表达一种IL-6R mRNA，其中跨膜结构域被剪接掉，预测会产生一种在C端具有修饰碱性序列的较短蛋白质。我们发现这种剪接后的mRNA在人T47D乳腺癌细胞中表达，并且这些细胞确实分泌可溶性IL-6R蛋白。一种针对剪接蛋白C端的抗体在通过经典和免疫亲和层析从T47D上清液中纯化的sIL-6R中检测到一种55 - 65 kDa的糖基化物种。糖基化的或去除O - 连接和N - 连接多糖后的剪接T47D IL-6R与来自CHO细胞的重组剪接IL-6R大小相同。重组剪接IL-6R作为IL-6激动剂作用于细胞，以刺激IL-6诱导型增强子的转录。
