Document Detail


Furin and prohormone convertase 1/3 are major convertases in the processing of mouse pro-growth hormone-releasing hormone.
MedLine Citation:
PMID:  14684599     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the proteolytic processing of mouse pro-GHRH [84 amino acids (aa)] by furin, PC1/3, PC2, and PC5/6A. We created six point mutations in the N- and C-terminal cleavage sites, RXXR decreased and RXRXXR decreased, respectively. The following results were obtained after transient transfection/cotransfection and metabolic pulse-chase labeling studies in several neuroendocrine cells. 1) Furin was the most efficient convertase in cleaving the N-terminal RXXR/RXRR site to generate intermediate I, 12-84aa, whereas PC1/3 was the most potent in processing the C-terminal RXRXXR site to yield mature GHRH, 12-53aa. 2) Both PC1/3 and PC5/6A also processed the N-terminal site but less efficiently than furin. 3) PC2 was much weaker in cleaving the C-terminal site relative to PC1/3 to generate mature GHRH. 4) The Q10R mutant was significantly more susceptible to furin cleavage at the N-terminal site than the wild-type pro-GHRH. And 5) the N- and C-terminal P1 Arg residues, R11 and R54, respectively, were essential for mature GHRH production. We also showed localization of the GHRH immunoreactive peptides in Golgi and secretory granules in neuroendocrine cells by an immunofluorescence assay. We conclude that the efficient production of mature GHRH from pro-GHRH is a stepwise process mediated predominantly by furin at the N-terminal cleavage site followed by PC1/3 at the C terminus.
Authors:
Arunangsu Dey; Christina Norrbom; Xiaorong Zhu; Jeffrey Stein; Chunling Zhang; Kazuya Ueda; Donald F Steiner
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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.     Date:  2003-12-18
Journal Detail:
Title:  Endocrinology     Volume:  145     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-03-17     Completed Date:  2004-04-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1961-71     Citation Subset:  AIM; IM    
Affiliation:
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Furin / metabolism*
Growth Hormone-Releasing Hormone / metabolism*
Mice
Models, Biological
Neurosecretory Systems / cytology,  metabolism
Peptide Fragments / metabolism
Proprotein Convertase 1 / metabolism*
Protein Precursors / metabolism*
Protein Processing, Post-Translational / physiology*
Subcellular Fractions / metabolism
Tissue Distribution
Grant Support
ID/Acronym/Agency:
DK13914/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Peptide Fragments; 0/Protein Precursors; 125200-87-5/pro-growth hormone releasing hormone, mouse; 9034-39-3/Growth Hormone-Releasing Hormone; EC 3.4.21.75/Furin; EC 3.4.21.93/Proprotein Convertase 1

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


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