Isolation of peptides arising from the specific posttranslational processing of chromogranin A and chromogranin B from human pheochromocytoma tissue.
An extract of human adrenal medullary pheochromocytoma tissue was fractionated by gel permeation chromatography, and peptides of major abundance in the approximate molecular mass range 1000-4000 were purified to apparent homogeneity by reverse phase HPLC. Determination of the primary structures of four such peptides demonstrated that they were fragments of either chromogranin A or chromogranin B. The peptide WSKMDQLAKELTAE represents chromogranin A(324-337), the peptide LGELFNPYYDPLQWKSSHFE represents chromogranin B(498-517), the peptide NLARVPKLDL represents chromogranin B(568-577), and the peptide QYDRVAQLDQLLHY (isolated as the N-terminal pyroglutamyl derivative) represents chromogranin B(580-593). Analysis of the nucleotide sequences of cDNAs complementary to human chromogranin A and B messenger RNAs indicates that each of these peptide sequences is flanked by pairs or groups of basic residues, suggesting that these fragments are the products of specific posttranslational processing. In addition, a peptide identified as chromogranin B(496-517) was isolated from extract. This component represents the product of incomplete proteolytic cleavage at the Lys494-Arg495-Lys496-Arg497 processing site in chromogranin B. A minor component in the extract was identified as chromogranin B(508-517), but this component probably represents an artifact of the extraction procedure arising from the hydrolysis of the acid labile Asp507-Pro508 bond. The study has shown that chromogranin A and B in pheochromocytoma tissue function as the precursors of several small peptides that may have a regulatory role.
Conlon
J M
JM
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178.
Hamberger
B
B
Grimelius
L
L
D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D053379:Chromogranin A; D053378:Chromogranin B; D002864:Chromogranins / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism; D010455:Peptides / Q000302:isolation & purification* / Q000378:metabolism; D010673:Pheochromocytoma / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D014020:Tissue Extracts / Q000737:chemistry
C506150:CHGA protein, human; C506134:CHGB protein, human; D053379:Chromogranin A; D053378:Chromogranin B; D002864:Chromogranins; D009363:Neoplasm Proteins; D010455:Peptides; D014020:Tissue Extracts