Immunochemical characterization of a novel secretory protein (defined by monoclonal antibody HISL-19) of peptide hormone producing cells which is distinct from chromogranin A, B, and C.
In this study we have investigated the biochemical properties as well as the subcellular localization of a 67 kD (35/32 kD dimer) polypeptide detected by a monoclonal antibody (HISL-19), which was generated after immunization of BALB/c mice with human islet cell preparations. This protein is expressed by neuronal and peptide hormone producing cells and shares many biochemical and molecular key features with the chromogranin proteins. As demonstrated by one-dimensional and two-dimensional gel electrophoresis, immunoblotting, monoclonal antibody HISL-19 immunoaffinity chromatography, and immunoelectron microscopy, it is a water-soluble, acidic protein stored within secretory granules of peptide hormone-producing cells, and it is released in detectable amounts into the serum of patients bearing neuroendocrine carcinomas. Differences of the HISL-19 protein and chromogranins A, B, and C are indicated by their different tissue distribution, the discrepancy of their apparent molecular weights in sodium dodecyl sulfate gels and isoelectric points, and by the lack of cross-reactivity of their specific antibodies. The protein detected by monoclonal antibody HISL-19 represents therefore a novel component of the soluble compartments of neurosecretory granules, which is distinct from chromogranin A, B, and C.
Krisch
K
K
Department of Pathology, University of Vienna Medical School, Austria.
Horvat
G
G
Krisch
I
I
Wengler
G
G
Alibeik
H
H
Neuhold
N
N
Ulrich
W
W
Braun
O
O
Hochmeister
M
M
D000313:Adrenal Medulla / Q000032:analysis; D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000032:analysis* / Q000276:immunology; D002417:Cattle; D002846:Chromatography, Affinity; D002864:Chromogranins / Q000032:analysis* / Q000276:immunology; D003594:Cytoplasmic Granules / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007118:Immunoassay; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007340:Insulinoma / Q000032:analysis / Q000378:metabolism; D007515:Islets of Langerhans / Q000032:analysis; D009369:Neoplasms / Q000032:analysis* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009490:Neurosecretory Systems / Q000032:analysis*; D010455:Peptides / Q000032:analysis* / Q000276:immunology; D010673:Pheochromocytoma / Q000032:analysis / Q000378:metabolism; D003969:Vipoma / Q000032:analysis / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000941:Antigens; D002864:Chromogranins; D009419:Nerve Tissue Proteins; D010455:Peptides