TY - JOUR
T1 - Neuropeptide-processing carboxypeptidases
AU - Wei, Suwen
AU - Feng, Yun
AU - Kalinina, Elena
AU - Fricker, Lloyd D.
N1 - Funding Information:
This work was supported in part by National Institutes of Health grant R01 DA-04494 and Research Scientist Development Award DA-00194 (L.D.F.). Photography was performed in the Analytical Imaging Facility and in the laboratory of Dr. Jonathan Backer, Albert Einstein College of Medicine.
PY - 2003/6/27
Y1 - 2003/6/27
N2 - 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.
AB - 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.
KW - Carboxypeptidase A-5
KW - Carboxypeptidase E
KW - Enkephalin convertase
KW - Metallocarboxypeptidase
KW - Peptide processing
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U2 - 10.1016/S0024-3205(03)00386-2
DO - 10.1016/S0024-3205(03)00386-2
M3 - Article
C2 - 12801587
AN - SCOPUS:0037836013
SN - 0024-3205
VL - 73
SP - 655
EP - 662
JO - Life Sciences
JF - Life Sciences
IS - 6
ER -