Isoforms of the human PDZ-73 protein exhibit differential tissue expression

Patients with renal and colon cancer frequently develop IgG autoantibodies toward the NY-CO-38/PDZ-73 antigen, a protein of 652 amino acids (73 kDa) w hich contains three copies of the PDZ protein-protein interaction domain. T he gene encoding PDZ-73 mapped to chromosome 11p15.4-p15.1. Additional tiss ue-specific isoforms were identified: PDZ-45, which lacks the third PDZ dom ain and the putative PEST protein degradation motif, is expressed in kidney , colon, small intestine, brain and testis; PDZ-54 and PDZ-59, which also l ack the third PDZ domains, have unique carboxyl terminal amino acids and ar e expressed in brain, kidney, bladder, colon cancer and renal cancer; and a putative PDZ-37 isoform, containing only the third PDZ domain, that is exp ressed in the central nervous system. Immunohistochemical staining with ant i-PDZ 73 monoclonal antibodies showed strong cytoplasmic reactivity in epit helial cells of the small intestine, colon and kidney tubules, with a promi nent apical staining pattern in cells of the small intestine. The reactivit y pattern of the antibodies with various tissues correlated with the mRNA e xpression pattern of the PDZ-45 isoform. The existence of multiple PDZ-73 i soforms with variations in tissue distribution, PDZ domains, protein degrad ation sequences and carboxyl terminal structure indicate that these isoform s have distinct tissue-specific functions. (C) 1999 Elsevier Science B.V. A ll rights reserved.