Complete amino acid sequence of the epidermal desmoglein precursor polypeptide and identification of a second type of...

The amino acid sequence of the precursor to desmoglein, a major desmosomal cadherin, has been determined from a cDNA clone from bovine muzzle epithelium, and the transcription start site, i.e., the beginning of the approximately 7.6 kb mRNA, identified by primer extension analysis. The precursor segment of 49 amino acids starts with a relatively hydrophobic stretch of 17 amino acids, conforming to the typical features of signal peptides, displays no sequence homology to the corresponding portion of other cadherins. The isolation of the complete cDNA has allowed the cloning of a desmoglein cDNA construct, which under the control of the human beta-actin promoter, was successfully used in cell transfection. In addition, a major N-glycosylation site has been identified by lectin affinity chromatography and amino acid sequencing at amino acid position 61, i.e., in the middle of the first extracellular domain. In the course of these studies we have identified, in colon carcinoma and other simple epithelial cells, another kind of desmoglein which by partial cDNA-derived sequence and by Southern blotting is clearly the product of a different gene. This suggests that there are multiple desmogleins which can be differentially expressed in various epithelia.