Identification of zymogen and mature forms of human carboxypeptidase H. A processing enzyme for the synthesis of peptide hormones.
Carboxypeptidase H (CPH) is one of several processing enzymes required for the conversion of peptide hormone precursors into their smaller active forms. In this study, high levels of CPH activity was found in a liver metastasis of a human ileal carcinoid which expresses beta-preprotachykinin mRNA and the tachykinin neuropeptides, substance P and substance K. This human CPH showed properties of a zinc-metallopeptidase that is structurally similar to bovine and rat CPH. Immunoblots of the human ileal carcinoma with anti-bovine CPH showed that CPH activity is represented by two proteins of apparent molecular masses 57 and 55 kDa. Cell-free translation of poly(A)+ RNA followed by immunoprecipitation with anti-bovine CPH showed that human CPH mRNA encodes a precursor protein of apparent molecular mass 75 kDa. These data demonstrate that human CPH is synthesized as a zymogen, prepro-CPH, which must be cleaved to form catalytically active CPH.
Hook
V Y
VY
Department of Biochemistry, Uniformed Services University of the Health Sciences, Bethesda, MD 28014.
Affolter
H U
HU
D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002276:Carcinoid Tumor / Q000201:enzymology*; D004792:Enzyme Precursors / Q000032:analysis* / Q000378:metabolism; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007078:Ileal Neoplasms / Q000201:enzymology*; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000201:enzymology* / Q000556:secondary; D010455:Peptides / Q000378:metabolism*; D011061:Poly A / Q000378:metabolism; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger; D013373:Substance P / Q000378:metabolism; D013386:Succinates / Q000494:pharmacology; D015320:Tachykinins / Q000378:metabolism
D004792:Enzyme Precursors; D006728:Hormones; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D013386:Succinates; D015320:Tachykinins; C044206:preprotachykinin; D011061:Poly A; D013373:Substance P; D012313:RNA; C022015:guanidinopropylsuccinic acid; D002268:Carboxypeptidases; D043423:Carboxypeptidase H