Relationship of multiple forms of chromogranin.

Chromogranin polypeptides of Mr 100,000, Mr 85,000, Mr 75,000, and Mr 65,000 have been detected in adrenal medulla chromaffin granules using anti-chromogranin antiserum. Monoclonal antibodies to this protein also detect the multiple molecular weight chromogranin polypeptides. Analysis of phosphorylated amino acids gives a value of 5 phosphoserine residues/mol of Mr 75,000 chromogranin polypeptide. Immunological analysis of dephosphorylated chromogranin shows that the anti-chromogranin serum reacts with both the phosphorylated and unphosphorylated forms of the protein. Each of the chromogranin polypeptides has been isolated using a combination of DEAE-cellulose chromatography and reverse phase high pressure liquid chromatography. Sequencer analysis of each protein revealed a high degree of amino acid identities at the amino terminal of these proteins. Amino-terminal Sequencer analysis of chromogranin fragments also provides evidence for a gene duplication event. Preliminary studies also show that chromogranin may be degraded in the chromaffin granules by a calcium-dependent mechanism.