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 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.
Brakenhoff
R H
RH
Department of Otorhinolaryngology, Free University Hospital, The Netherlands.
Gerretsen
M
M
Knippels
E M
EM
van Dijk
M
M
van Essen
H
H
Weghuis
D O
DO
Sinke
R J
RJ
Snow
G B
GB
van Dongen
G A
GA
D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly / Q000737:chemistry*; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell; D002417:Cattle; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism; D017931:DNA Primers; D051184:Desmoglein 3; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000378:metabolism*; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006258:Head and Neck Neoplasms; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology*; D007668:Kidney; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
D000950:Antigens, Ly; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D051184:Desmoglein 3; D051182:Desmogleins; D051180:Desmoplakins; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D017261:Glycosylphosphatidylinositols; C094237:LY6D protein, human; D015345:Oligonucleotide Probes; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase