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.

Abstract

Abstract. 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.

Ly-6I, a New Member of the Murine Ly-6 Superfamily with a Distinct Pattern of Expression

“…Certainly, CD59 homologues have been characterized in rabbit (14), rat (15), pig (16), and mouse (17). At the present time human homologues for several mouse Ly-6SF members are known, including ThB (18), Ly-6H (19), and TSA-1/Sca-2/RIG-E (20,21). In addition, the human urokinase plasminogen activator receptor (uPAR) consists of three Ly6SF domains (22,23).…”

The Regulatory Mechanism of the LY6K Gene Expression in Human Breast Cancer Cells

“…The human LY6K (lymphocyte antigen 6 complex locus K) belongs to the Ly-6/urokinase-type plasminogen activator receptor (uPAR) 2 superfamily, which can be divided into two subfamilies based on the glycosylphosphatidylinositol-anchoring signal sequence: one is the glycosylphosphatidylinositolanchored transmembrane proteins, which include the retinoic acid-induced gene E (human LY6E), the E48 antigen (human LY6D), LY6H, prostate stem cell antigen, CD59, or protectin, lynxl, and uPAR (1)(2)(3). The other is a secretory protein without a glycosylphosphatidylinositol-anchoring signal sequence, which includes SLURP-1 and SLURP-2 (4).…”

Human Ly‐6 antigen E48 (Ly‐6D) regulates important interaction parameters between endothelial cells and head‐and‐neck squamous carcinoma cells

“…8 It recognizes an outer membrane antigen, expressed by HNSCC. This antigen was characterized by cDNA cloning 9 and proved to be a GPIanchored membrane protein expressed by squamous cells. E48 is highly (nearly 70%) homologous to the murine ThB protein, a member of the Ly-6 gene family.…”

“…E48 is highly (nearly 70%) homologous to the murine ThB protein, a member of the Ly-6 gene family. 9 -11 E48 maps on human chromosome 8q24, 9 the syntenic locus of mouse chromosome 15E, to which the mouse Ly-6 gene family has been mapped. 11 Whereas both E48 and ThB are expressed on keratinocytes of squamous epithelia, 9 they differ in lymphocyte expression.…”

“…12 The function of E48 on keratinocytes of squamous epithelia remains unclear, though it might be involved in cellular adhesion. 9 Shortly after the cloning of cDNA encoding the E48 antigen, several additional human Ly-6 genes were cloned. [13][14][15][16][17] Our laboratory reported previously on a linkage between the overexpression of certain Ly-6 proteins on mouse tumor cells and a high-malignancy phenotype of such cells.…”