Molecular cloning of the human kidney differentiation antigen gp160: human aminopeptidase A

gp160 is a cell surface differentiation-related glycoprotein of 160 kDa expressed by epithelial cells of the glomerulus and proximal tubule cells of the human nephron but only by a subset of renal cell carcinomas (RCCs). We have reported that gp160 expression correlates with the resistance of cultured RCCs to the antiproliferative effects of alpha interferon, while lack of expression correlates with sensitivity to alpha interferon. In this study, we have purified gp160 protein, obtained partial sequences of random peptides, and isolated a full-length cDNA. The gp160 cDNA possesses 78% homology to the murine BP-1/6C3 antigen, a B-lymphocyte differentiation protein that exhibits aminopeptidase A (APA; EC 3.4.11.7) activity. Enzymatic assays on human RCC cell lines indicated a 100% concordance between APA activity and gp160 expression. APA activity of gp160-expressing RCC cells was increased or decreased by a panel of APA activators or inhibitors, respectively. Furthermore, anti-gp160 monoclonal antibodies immunoprecipitate APA activity from RCC cell lysates and selectively deplete APA activity from RCC cell extracts. These data indicate that the gp160 human kidney/RCC glycoprotein is human APA.