Seligman P A, Butler C D, Massey E J, Kaur J A, Brown J P, Plowman G D, Miller Y, Jones C
Am J Hum Genet. 1986 Apr;38(4):540-8.
Since the p97 antigen, a membrane-associated iron-binding protein, has extensive amino acid sequence with homology with transferrin, is functionally related to the transferrin receptor, and has been previously mapped to chromosome 3, we have performed additional studies for regional mapping of the gene expressing p97 antigen. In these experiments, Chinese hamster-human cell lines were chosen that contained a large spectrum of autosomal human chromosomes, but mainly consisted of clones expressing all or a part of chromosome 3. These cell lines included a clone that previously allowed for mapping of human transferrin receptor to q22-qter region. Human p97 expression was assessed by specific binding of [125I]monoclonal antibody 96.5, and human transferrin receptor expression was tested by specific [125I]human transferrin binding and [125I]monoclonal antibody OKT-9 specific for human transferrin receptor. Based on these analyses, both human p97 antigenic expression and human transferrin receptor are mapped concordantly to the q24-qter region. These data and previous reports, therefore, suggest that the related iron-transport proteins are closely linked and may be under coordinate regulation. However, studies of several cell lines that exhibit up-regulation of human transferrin receptor expression with cellular proliferation, and down-regulation of receptor with increased transferrin-iron in the media, showed no change in expression of p97 antigen. p97 antigenic expression increased when melanocyte-stimulating hormone was added to a human melanoma cell line in tissue culture. These latter studies suggest that in mammalian cells the two proteins do not show coordinate regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
由于p97抗原是一种膜相关铁结合蛋白,其氨基酸序列与转铁蛋白有广泛的同源性,在功能上与转铁蛋白受体相关,且先前已被定位到3号染色体,我们对表达p97抗原的基因进行了区域定位的进一步研究。在这些实验中,选用了含有广泛常染色体人类染色体的中国仓鼠-人类细胞系,但主要由表达全部或部分3号染色体的克隆组成。这些细胞系包括一个先前可将人类转铁蛋白受体定位到q22-qter区域的克隆。通过[125I]单克隆抗体96.5的特异性结合来评估人类p97的表达,通过[125I]人转铁蛋白的特异性结合以及对人类转铁蛋白受体具有特异性的[125I]单克隆抗体OKT-9来检测人类转铁蛋白受体的表达。基于这些分析,人类p97抗原表达和人类转铁蛋白受体均被一致地定位到q24-qter区域。因此,这些数据和先前的报道表明,相关的铁转运蛋白紧密相连,可能受协同调节。然而,对几个细胞系的研究表明,随着细胞增殖人类转铁蛋白受体表达上调,而培养基中转铁蛋白-铁增加时受体表达下调,但p97抗原的表达没有变化。当在组织培养中将促黑素细胞激素添加到人类黑色素瘤细胞系时,p97抗原表达增加。这些后期研究表明,在哺乳动物细胞中这两种蛋白不显示协同调节。(摘要截短于250词)