Identification of the bile canalicular cell surface molecule GP110 as the ectopeptidase dipeptidyl peptidase IV: An analysis by tissue distribution, purification and N-terminal amino acid sequence

Authors

  • Dr. Geoffrey W. McCaughan,

    Corresponding author
    1. A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia
    • A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia
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  • Julie E. Wickson,

    1. A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia
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  • Paul F. Creswick,

    1. A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia
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  • Mark D. Gorrell

    1. A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia
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Abstract

This paper describes the tissue distribution, purification and N-terminal amino acid sequence of the bile canalicular cell surface molecule dipeptidyl peptidase IV. Immunoperoxidase staining of cryostat sections of rat liver with a monoclonal antibody, Medical Research Council OX-61, indicated specific binding to hepatocyte bile canalicular domains and brush borders of bile ducts. Additional staining was seen in other epithelial brush borders (small intestine, kidney, colon, pancreatic duct); acinar structures in salivary glands; endothelial structures and T cell areas in thymus, spleen and lymph node. The tissue distribution suggested that monoclonal antibody OX-61 binds to the ectoenzyme dipeptidyl peptidase IV. This was confirmed by depletion of dipeptidyl peptidase IV activity from tissue homogenates by monoclonal antibody OX-61 coupled to Sepharose. The molecule recognized by OX-61 was then purified from liver and kidney by monoclonal antibody affinity chromatography. The molecule had a molecular weight of 110 kD under reducing conditions. The purified molecule was subsequently analyzed for amino acid composition and N-terminal amino acid sequence. Thirty-one N-terminal amino acids were sequenced and indicated identity with part of the predicted N-terminus of the previously cloned bile canalicular molecule GP110. On review, other similarities between dipeptidyl peptidase IV and GP110 were detected: molecular weight, deglycosylated from and metabolic half-life. Finally, the recent cloning of dipeptidyl peptidase IV permitted a comparison between the molecule recognized by monoclonal antibody OX-61, GP110 and dipeptidyl peptidase IV. It is concluded that these three molecules are almost certainly identical.(HEPATOLOGY 1990; 11:534:544.)

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