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Neuroanatomical and functional studies of peptide precursor-processing enzymes. Enzyme 1991;45(5-6):285-300

Date

01/01/1991

Pubmed ID

1843282

DOI

10.1159/000468902

Scopus ID

2-s2.0-0026351028 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

An overview of in situ hybridization mapping studies comparing the brain distributions of mRNA transcripts encoding the proprotein convertase Furin, PC1 and PC2 in relation to transcripts encoding carboxypeptidase H (CPE) and peptidylglycine alpha-amidating monooxygenase (PAM) is presented. Furin mRNA was detected in both neurons and non-neuronal cells throughout all brain areas. The cellular localization of PC1 and PC2 was primarily neuronal, with PC2 generally more widely distributed, although many regional variations were detected. The detection of specific combinations of the convertases, CPE and PAM in peptide-rich brain regions suggests that specific enzymatic pathways are involved in neuropeptide processing. Results are also described from a series of functional studies on the processing of pro-opiomelanocortin (POMC) in a heterologous neuronal cell line, Neuro-2A, which expresses low levels of PC2 mRNA but no detectable PC1 mRNA. Two contrasting POMC-processing patterns were observed: one where the precursor was processed at a number of cleavage sites to produce several peptides, and another where POMC was processed at a single cleavage site to produce beta E only. If PC2 is responsible for POMC processing in transfected cells, this enzyme may have favored cleavage of the amino terminal-processing site above other sites in the latter type of cell line.

Author List

Cullinan WE, Day NC, Schäfer MK, Day R, Seidah NG, Chrétien M, Akil H, Watson SJ

Author

William E. Cullinan PhD Adjunct Associate Professor in the Neurosurgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Brain
Carboxypeptidase H
Carboxypeptidases
Cell Line
Endopeptidases
In Situ Hybridization
Male
Neurons
Peptide Biosynthesis
Pro-Opiomelanocortin
Proprotein Convertase 2
Protein Precursors
Protein Processing, Post-Translational
RNA, Messenger
Rats
Rats, Sprague-Dawley
Serine Endopeptidases