Isolation and Primary Structure of Tumor-Derived Peptides Related to Human Pancreastatin and Chromogranin A

• Published in: Proceedings of the National Academy of Sciences - PNAS 1988-11, Vol.85 (21), p.8231-8235
• Main Authors: Schmidt, Wolfgang E., Siegel, Erhard G., Kratzin, Hartmut, Creutzfeldt, Werner
• Format: Article
• Language: English
• Subjects: Amides; Amino Acid Sequence; Amino acids; Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; Animals; Antiserum; Biological and medical sciences; Carcinoid Tumor - analysis; Carcinoid Tumor - secondary; Carcinoid tumors; Cattle; Chromatography, High Pressure Liquid; Chromogranin A; Chromogranins; Chromogranins - analysis; Endocrine cells; Fundamental and applied biological sciences. Psychology; Humans; Molecular Sequence Data; Neoplasm Proteins - analysis; Nerve Tissue Proteins - analysis; pancreastatin; Pancreatic Hormones - analysis; Peptide Fragments - analysis; Professional liability insurance; Proteins; Rats; Solvents; Swine; Tumors; Ungulates
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.21.8231

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.