Document Detail


Kex2-like endoproteases PC2 and PC3 accurately cleave a model prohormone in mammalian cells: evidence for a common core of neuroendocrine processing enzymes.
MedLine Citation:
PMID:  1647029     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Two mammalian gene products, PC2 and PC3, have been proposed as candidate neuroendocrine-precursor processing enzymes based on the structural similarity of their catalytic domains to that of the yeast precursor-processing endoprotease Kex2. In this report we demonstrate that these two proteases can cleave proopiomelanocortin (POMC) in the secretory pathway of mammalian cells. Similarly to pituitary corticotrophs, PC3 expressed in processing-deficient BSC-40 cells cleaved native mouse POMC at the -Lys-Arg- sites flanking corticotropin. The -Lys-Arg- within beta-lipotropin was less efficiently cleaved to release beta-endorphin. Expression of PC2 together with PC3 resulted in efficient conversion of beta-lipotropin, as occurs in pituitary melanotrophs. Furthermore, coexpression of PC2 together with mouse POMC in bovine adrenomedullary chromaffin cells resulted in conversion of beta-lipotropin to gamma-lipotropin and beta-endorphin in the regulated secretory pathway. Finally, the processing selectivities of PC3 and PC2 expressed together in BSC-40 cells were determined by using a series of mutant mouse POMCs containing all possible pairs of basic residues at certain sites. The observed pattern of cleavage site selectivities mimicked that of the endogenous endoproteases of the insulinoma and bovine adrenomedullary chromaffin cells, suggesting that PC2 and PC3 may represent important core endoproteases in the catalysis of prohormone processing in many neuroendocrine cell types.
Authors:
L Thomas; R Leduc; B A Thorne; S P Smeekens; D F Steiner; G Thomas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  88     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1991 Jun 
Date Detail:
Created Date:  1991-07-19     Completed Date:  1991-07-19     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5297-301     Citation Subset:  IM    
Affiliation:
Vollum Institute, Oregon Health Sciences University, Portland 97201.
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MeSH Terms
Descriptor/Qualifier:
Adrenocorticotropic Hormone / metabolism
Animals
Cells, Cultured
Chromatography, High Pressure Liquid
DNA / genetics
Mammals
Plasmids
Pro-Opiomelanocortin / metabolism*
Proprotein Convertase 2
Proprotein Convertases
Protein-Tyrosine Kinases*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins c-fes
Radioimmunoassay
Serine Endopeptidases / metabolism*
Substrate Specificity
beta-Endorphin / metabolism
beta-Lipotropin / metabolism
Grant Support
ID/Acronym/Agency:
DK-37274/DK/NIDDK NIH HHS; DK13914/DK/NIDDK NIH HHS; DK20505/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins; 60617-12-1/beta-Endorphin; 66796-54-1/Pro-Opiomelanocortin; 9002-60-2/Adrenocorticotropic Hormone; 9007-49-2/DNA; 9035-55-6/beta-Lipotropin; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Proto-Oncogene Proteins c-fes; EC 3.4.-/Proprotein Convertases; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.94/Proprotein Convertase 2
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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