A neuroendocrine peptide derived from the amino-terminal half of rat procalcitonin.
The sequence of rat procalcitonin reveals that calcitonin is located within the precursor's midregion, flanked by two potential polybasic cleavage sites that separate it from amino- and carboxyl-terminal domains. Cleavage at the polybasic sites during precursor processing to generate the 32-residue calcitonin should also generate 57- and 16-residue peptides from the amino- and carboxyl-terminal flanking regions. The carboxyl-terminal flanking hexadecapeptide and its coordinate secretion from C cells with calcitonin have been previously reported. In the present study we have focused on the predicted 57-residue amino-terminal procalcitonin cleavage peptide (N-proCT). We raised antisera to synthetic peptides homologous to the carboxyl- and amino-terminal regions of the putative 57-amino-acid N-proCT and screened calcitonin-rich neoplastic and nonneoplastic C-cells for these two immunoreactivities. A single species of 7.4 kilodaltons detected in C cells by gel filtration and reversed-phase HPLC analyses accounts for most of the carboxyl- and amino-terminal immunoreactivities and possesses the biochemical and biological features predicted for N-proCT. When C cell hyperplasia is induced by a high fat diet, thyroidal levels of calcitonin and N-proCT increase in parallel. In neoplastic C cell cultures, N-proCT and calcitonin concentrations are nearly equimolar in both cellular extracts and basal medium; dexamethasone increases both the cellular and secreted concentration of these peptides. Basal and dexamethasone-treated cultures show calcium-dependent, parallel secretion of N-proCT and calcitonin. Thus, the 57-residue N-proCT predicted from analysis of the procalcitonin sequence is a secretory peptide that appears to be present in equimolar amounts and coordinately regulated with calcitonin in vivo and in vitro.
Burns
D M
DM
Department of Medicine, University of Washington, Seattle 98195.
Birnbaum
R S
RS
Roos
B A
BA
D000818:Animals; D000918:Antibody Specificity; D002116:Calcitonin / Q000032:analysis* / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide; D002277:Carcinoma / Q000032:analysis; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006965:Hyperplasia; D007106:Immune Sera / Q000276:immunology; D010446:Peptide Fragments / Q000032:analysis* / Q000378:metabolism; D011498:Protein Precursors / Q000032:analysis* / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D013961:Thyroid Gland / Q000032:analysis* / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000032:analysis; D014407:Tumor Cells, Cultured
C000606591:Calca protein, rat; D007106:Immune Sera; D010446:Peptide Fragments; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide