Rat preprocarboxypeptidase H. Cloning, characterization, and sequence of the cDNA and regulation of the mRNA by corticotropin-releasing factor

J Biol Chem. 1989 Apr 5;264(10):5988-95.


Carboxypeptidase H is a putative post-translational processing enzyme which removes basic amino acid residues from intermediates during protein hormone biosynthesis. A 2.2-kilobase pair cDNA was shown to contain the complete amino acid sequence of rat carboxypeptidase H. The deduced amino acid sequence revealed that the enzyme was synthesized as preprocarboxypeptidase H, a precursor form of 476 amino acid residues. Preprocarboxypeptidase H contained a putative hydrophobic signal peptide and a short propeptide which contained 5 adjacent Arg residues at its C terminus. Northern blot analysis identified a single carboxypeptidase H mRNA of approximately 2.3 kilobases in brain, pituitary, and heart, as well as in mouse AtT20 cells. No carboxypeptidase H mRNA was detected in rat liver, spleen, kidney, lung, and mammary gland. Sequence analysis of cDNAs obtained from different rat tissues suggested that a single mRNA encodes an identical carboxypeptidase in several tissues. Treatment of AtT20 cells with dexamethasone decreased the levels of both carboxypeptidase H and preproopiomelanocortin (POMC) mRNAs by approximately 30%. Exposure of the dexamethasone-treated cells to corticotropin-releasing factor effected a 2- to 3-fold increase in the carboxypeptidase H and POMC mRNA levels relative to those of dexamethasone-treated cells exposed to control medium. This suggests that the mRNA levels of POMC and one of its putative post-translational processing enzymes, carboxypeptidase H, are co-regulated by corticotropin-releasing factor and steroid hormones.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Carboxypeptidases / genetics*
  • Cloning, Molecular*
  • Corticotropin-Releasing Hormone / pharmacology*
  • DNA / genetics*
  • Enzyme Precursors / genetics*
  • Gene Expression Regulation / drug effects*
  • Genes
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • Protein Conformation
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics*
  • Rats
  • Restriction Mapping


  • Enzyme Precursors
  • Oligonucleotide Probes
  • RNA, Messenger
  • DNA
  • Corticotropin-Releasing Hormone
  • Carboxypeptidases
  • preprocarboxypeptidase H

Associated data

  • GENBANK/J04625