Human transferrin receptor: expression of the receptor is assigned to chromosome 3.

Abstract

Human chromosome 3 has been identified as responsible for expression of the transferrin receptor in mouse-human lymphocyte hybrids. The receptor was detected by immunoprecipitation with anti-human receptor antibody of "MI-labeled cells. This method also detected a similar 94,000-dalton protein in mouse cells. A radioimmunoassay developed for the human transferrin receptor measured 10% crossreactivity with the mouse protein. The two proteins were distinguished by NaDodSO4/ polyacrylamide gel patterns of partial proteolytic digests of the immunoprecipitated proteins. Mouse-human hybrids were generated by fusing a mouse thymoma (BW5147) cell line to either concanavalin A-or pokeweed mitogen-activated human peripheral blood lymphocytes or a mouse myeloma (NS-1) to uncultured human peripheral blood lymphocytes. Each hybrid was karyotyped with respect to both mouse and human chromosomes. In every case, expression of the human transferrin receptor correlated only with human chromosome 3.The genes for a number of human cell surface proteins have been assigned to specific chromosomes and chromosome regions by studying somatic cell hybrids between human and rodent cells (1-4). Several of these genes have been assigned to the human X chromosome (1, 2, 5-7); others have been assigned to the autosomes (3,4,(8)(9)(10)(11).In most cases, the antigens have been defined only by reactivity with human cells and mouse-human hybrid clones containing certain human chromosomes (1, 5, 10) although, in a few, the marker molecules have been characterized as well (7, 9).In this paper, we describe expression of the human transferrin receptor in mouse-human lymphocyte cell hybrids and assign the gene for this receptor to human chromosome 3. Assignment is based on identification of the transferrin receptor by its molecular and immunochemical properties. Partial digestion patterns were used to distinguish the human transferrin receptor from the mouse transferrin receptor. We have also identified and characterized molecular and immunochemical properties of the mouse transferrin receptor.MATERIALS gle's medium (GIBCO)/15% newborn calf serum (GIBCO)/ 0.1 mM hypoxanthine/0.4 tuM aminopterine/13 tLM thymidine containing penicillin at 100 pug/ml and streptomycin at 100 units/ml] and cloned by limiting dilution on human fibroblast feeders. A hypoxanthine/aminopterin/thymidine-sensitive BALB/c myeloma (NS-1) was fused with human peripheral blood lymphocytes, and the hybrids were cultured and cloned as T-cell hybrids.The hybrid clones and the cell lines were cultured in Dulbecco's modified Eagle's medium/15% newborn calfserum, the human erythroid cell line K562 was cultured in RPMI 1640 (GIBCO)/10% fetal calf serum, and BeWo cells were cultured in BeWo medium (12). All cultures were grown in the presence of penicillin (100 tug/ml) and streptomycin (100 units/ml) (GIBCO).Karyotypes and Clones. Chromosome preparations were made from the hybrid clones on multiple occasions (see Table 2) and once from the BW5147 and NS-1 cell lines. Giemsa bands...

Transferrin receptor: Its biological significance

“…The TR has been characterized biochemically (Enns & Sussman, 1981;Schneider et al, 1982) and also the gene for the human TR has been cloned recently and the primary structure determined (McClelland et al, 1984;Schneider et al, 1984). While the gene for both the human TR and transferrin has been localized to chromosome 3 (Goodfellow et al, 1982;Enns et al, 1982), this coincidence appears to be of no particular functional significance.…”

“…For instance, the C-terminus region of the polypeptide was found to be facing the extracellular environment and the Nterminus domain, consisting of approximately 62 amino acids, represents the cytoplasmic tail of the receptor ( Figure). In general, secreted and transmembrane proteins studied thus far have been Sutherland et al (1981), Trowbridge and Omary (1981), Enns, Suomalainen et al (1982), Goodfellow et al (1982), Schneider et al (1982Schneider et al ( , 1984, McClelland, Kuhn and Ruddle (1984). O, High mannose oligosaccharide chain; O, complex oligosaccharide chain; ,~, acylated fatty acid moiety; ( ), estimated mol wt in kilodaltons; AA, approximate number of amino acids found to be synthesized with an N-terminus region facing the extracellular environment.…”

“…The transferrin receptor (TR) has been characterized biochemically (Sutherland et al, 1981) and the gene for the human TR has been localized to chromosome 3 (Enns et al, 1982;Goodfellow et al, 1982) and has been cloned and sequenced revealing important structural information about this transmembrane protein (McClelland, Kuhn & Ruddle, 1984;Schneider, Owen, Banville & Williams, 1984). The TR is a crucial surface membrane component which is present in high levels on most rapidly proliferating normal and transformed cells (Larrick & Cresswell, 1979;Shindleman, Ortmeyer & Sussman, 1981;Sutherland et al, 1981; and drastically diminishes when cells are induced to terminally differentiate (Rovera et al, 1982;Yeh, Papamichael & Faulk, 1982;Pan, Blotstein & Johnstone, 1983).…”

Human transferrin: cDNA characterization and chromosomal localization.

“…Earlier work of Naylor, et al (29) predicted that in mice Tf mapped to chromosome 9, a homologue of human chromosome 3. The genes encoding the Tf receptor and melanoma antigen p97 have also been assigned to chromosome 3 (30)(31)(32), and the Tf receptor gene has been localized to the 3q22 -+ ter region (33). A heretofore unmapped linkage group (34) consisting of ceruloplasmin, pseudocholinesterase-1, a2Hs-glycoprotein (and Tf) can now be mapped to chromosome 3. In summary, Tf cDNA has been identified and characterized from a human liver cDNA library.…”

Report of the committee on the genetic constitution of chromosomes 2, 3, 4, and 5

“…With monoclonal antisera the transferrin receptor gene (T F R C ) could be assigned to chromosome 3 (Goodfellow et al, 1982), confirmed (Enns et al, 1982), and regionally mapped to SRO 3q23->qter (Jones et al, 1984;van de Rijn et al, 1983) . Homology of regions in mouse chromosome 9 and human chromosome 3, to which the aminoacylase 1 gene ACY1 and the beta-galactosidase 1 gene GLB1 have been assigned, as well as the mapping of the mouse transferrin gene (T F R ) to this region, raises the possibility that the structural loci for the transferrin receptor and for transferrin may also be linked in man (Goodfellow et al, 1982;Naylor et al, 1982).…”