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) which contains three copies of the PDZ protein-protein interaction domain. The gene encoding PDZ-73 mapped to chromosome 11p15.4-p15.1. Additional tissue-specific isoforms were identified: PDZ-45, which lacks the third PDZ domain and the putative PEST protein degradation motif, is expressed in kidney, colon, small intestine, brain and testis; PDZ-54 and PDZ-59, which also lack the third PDZ domains, have unique carboxyl terminal amino acids and are expressed in brain, kidney, bladder, colon cancer and renal cancer; and a putative PDZ-37 isoform, containing only the third PDZ domain, that is expressed in the central nervous system. Immunohistochemical staining with anti-PDZ 73 monoclonal antibodies showed strong cytoplasmic reactivity in epithelial cells of the small intestine, colon and kidney tubules, with a prominent apical staining pattern in cells of the small intestine. The reactivity pattern of the antibodies with various tissues correlated with the mRNA expression pattern of the PDZ-45 isoform. The existence of multiple PDZ-73 isoforms with variations in tissue distribution, PDZ domains, protein degradation sequences and carboxyl terminal structure indicate that these isoforms have distinct tissue-specific functions.
Scanlan
M J
MJ
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. scanlanm@mskcc.org
Williamson
B
B
Jungbluth
A
A
Stockert
E
E
Arden
K C
KC
Viars
C S
CS
Gure
A O
AO
Gordan
J D
JD
Chen
Y T
YT
Old
L J
LJ
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003110:Colonic Neoplasms; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013737:Testis / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D020033:Protein Isoforms; D012333:RNA, Messenger; C118970:USH1C protein, human