Isolation and primary structure of tumor-derived peptides related to human pancreastatin and chromogranin A.
Using an antiserum raised against a synthetic C-terminal peptide of porcine pancreastatin, we detected pancreastatin-like immunoreactivity (PLI) in human pancreatic islets, adrenal medulla, and endocrine tumors. From a carcinoid liver metastasis, human PLI was extracted and purified by HPLC. Two C-terminally amidated peptides were isolated and characterized by sequence analysis. The first peptide, hCgA-210-301, consists of 92 amino acid residues with glycinamide as C terminus. It is identical to the cDNA-derived sequence of human chromogranin A, positions 210-301, which is preceded by two basic residues indicating a putative processing site. The C-terminal part, positions 250-301, shows 70% sequence identity to porcine pancreastatin and represents the human pancreastatin-like sequence. The second peptide, hCgA-273-301, represents a C-terminally amidated fragment of the human pancreastatin sequence, generated by an Asp-Pro cleavage at the N terminus. Peptide hCgA-273-301 was synthesized to confirm the structure of the natural peptide. Two other peptides derived from human chromogranin A were isolated and partially characterized. They are generated by proteolytic cleavage after dibasic amino acids Lys-Arg (positions 338-339) and after Trp-376 of the human chromogranin A sequence, respectively. These results indicate that chromogranin A may represent the precursor for pancreastatin-related and possibly other yet-unidentified peptides of unknown physiological function.
Schmidt
W E
WE
Department of Medicine, Georg August University of Göttingen, Federal Republic of Germany.
Siegel
E G
EG
Kratzin
H
H
Creutzfeldt
W
W
D000595:Amino Acid Sequence; D000818:Animals; D002276:Carcinoid Tumor / Q000032:analysis / Q000556:secondary; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis*; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D010187:Pancreatic Hormones / Q000032:analysis*; D010446:Peptide Fragments / Q000032:analysis; D051381:Rats; D013552:Swine
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010187:Pancreatic Hormones; D010446:Peptide Fragments; C506153:chromogranin A, rat; C050836:pancreastatin