Neuropeptide-processing carboxypeptidases.
Neuropeptides are generally produced from precursor proteins by selective cleavage at specific sites, usually involving basic amino acids. Enzymes such as the prohormone convertases and carboxypeptidase E are highly specific for these basic amino acid-containing sites. In addition to this "traditional" pathway, several neuropeptides are known to be cleaved at non-basic sites, and the enzymes responsible for these cleavages have not been conclusively identified. In a recent search for novel members of the metallocarboxypeptidase family, we found three human genes. One of these, named "CPA-5," has a specificity for C-terminal hydrophobic amino acids and mRNA expression in brain, pituitary, and testis. To test whether CPA-5 protein has a distribution pattern in pituitary that is consistent with a role for this enzyme in the non-basic processing of proopiomelanocortin-derived peptides such as beta-endorphin and adrenocorticotropin, we examined the distribution of CPA-5 using immunocytochemistry. In the pituitary, CPA-5 is detected in the neurointermediate lobe and in scattered cells in the anterior lobe. In the AtT-20 corticotroph cell line, CPA-5 has a perinuclear distribution. Taken together, these results are consistent with a role for CPA-5 in the intracellular processing of proopiomelanocortin-derived peptides at non-basic sites.
Wei
Suwen
S
Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Feng
Yun
Y
Kalinina
Elena
E
Fricker
Lloyd D
LD
D000818:Animals; D002268:Carboxypeptidases / Q000096:biosynthesis*; D043422:Carboxypeptidases A; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism*; D010902:Pituitary Gland / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley
D009479:Neuropeptides; D011498:Protein Precursors; D002268:Carboxypeptidases; D043422:Carboxypeptidases A