The human E48 antigen, highly homologous to the murine Ly-6 antigen ThB, is a GPI-anchored molecule apparently involved in keratinocyte cell-cell adhesion.
The human E48 antigen, highly homologous to the murine Ly-6 antigen ThB, is a GPI-anchored molecule apparently involved in keratinocyte cell-cell adhesion.
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DOI：
10.1083/jcb.129.6.1677
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发表时间：
1995-06
期刊：
影响因子：
--
通讯作者：
van Dongen GA
中科院分区：
文献类型：
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作者：
Brakenhoff RH;Gerretsen M;Knippels EM;van Dijk M;van Essen H;Weghuis DO;Sinke RJ;Snow GB;van Dongen GA
E48抗原是牛口鼻部桥粒制剂中存在的一种20 - kD蛋白的假定人类同源物，以前被称为桥粒芯糖蛋白III（dg4），是人类鳞状细胞癌抗体治疗的一个有前景的靶抗原。为了预测高剂量抗体治疗的效果，并评估该抗原在致癌过程中可能的生物学作用，我们着手对该抗原进行分子特性鉴定。通过在COS细胞中进行表达克隆，分离出了一个编码E48抗原的cDNA克隆。序列分析显示，该克隆包含一个128个氨基酸的开放阅读框，编码一个13286 kD的核心蛋白。数据库搜索表明，E48抗原与小鼠ThB抗原（Ly - 6抗原家族的一个成员）具有高度的序列相似性。磷脂酰肌醇特异性（PI特异性）磷脂酶 - C处理表明，E48抗原是通过糖基磷脂酰肌醇锚定（GPI锚定）在质膜上的。编码E48抗原的基因是一个单拷贝基因，位于人类8号染色体8q24 - qter区域。该基因的表达局限于角质形成细胞和鳞状肿瘤细胞。假定的小鼠同源物ThB抗原最初被鉴定为淋巴细胞谱系细胞上的一种抗原，结果显示它在小鼠鳞状上皮细胞中高度表达。此外，与淋巴细胞中的情况不同，角质形成细胞中的ThB表达水平与小鼠品系无关。用E48 cDNA转染小鼠SV40 - 多瘤病毒转化的小鼠NIH/3T3细胞，证实该抗原可能参与细胞 - 细胞间的黏附。
The E48 antigen, a putative human homologue of the 20-kD protein present in desmosomal preparations of bovine muzzle, and formerly called desmoglein III (dg4), is a promising target antigen for antibody- based therapy of squamous cell carcinoma in man. To anticipate the effect of high antibody dose treatment, and to evaluate the possible biological involvement of the antigen in carcinogenesis, we set out to molecularly characterize the antigen. A cDNA clone encoding the E48 antigen was isolated by expression cloning in COS cells. Sequence analysis revealed that the clone contained an open reading frame of 128 amino acids, encoding a core protein of 13,286 kD. Database searching showed that the E48 antigen has a high level of sequence similarity with the mouse ThB antigen, a member of the Ly-6 antigen family. Phosphatidylinositol-specific (PI-specific) phospholipase-C treatment indicated that the E48 antigen is glycosylphosphatidylinositol-anchored (GPI-anchored) to the plasma membrane. The gene encoding the E48 antigen is a single copy gene, located on human chromosome 8 in the 8q24-qter region. The expression of the gene is confined to keratinocytes and squamous tumor cells. The putative mouse homologue, the ThB antigen, originally identified as an antigen on cells of the lymphocyte lineage, was shown to be highly expressed in squamous mouse epithelia. Moreover, the ThB expression level is in keratinocytes, in contrast to that in lymphocytes, not mouse strain related. Transfection of mouse SV40-polyoma transformed mouse NIH/3T3 cells with the E48 cDNA confirmed that the antigen is likely to be involved in cell-cell adhesion.