Document Detail


A systematic study of site-specific GalNAc-type O-glycosylation modulating proprotein convertase processing.
MedLine Citation:
PMID:  21937429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Site-specific GalNAc-type O-glycosylation is emerging as an important co-regulator of proprotein convertase (PC) processing of proteins. PC processing is crucial in regulating many fundamental biological pathways and O-glycans in or immediately adjacent to processing sites may affect recognition and function of PCs. Thus, we previously demonstrated that deficiency in site-specific O-glycosylation in a PC site of the fibroblast growth factor, FGF23, resulted in marked reduction in secretion of active unprocessed FGF23, which cause familial tumoral calcinosis and hyperostosis hyperphosphatemia. GalNAc-type O-glycosylation is found on serine and threonine amino acids and up to 20 distinct polypeptide GalNAc transferases catalyze the first addition of GalNAc to proteins making this step the most complex and differentially regulated steps in protein glycosylation. There is no reliable prediction model for O-glycosylation especially of isolated sites, but serine and to a lesser extent threonine residues are frequently found adjacent to PC processing sites. In the present study we used in vitro enzyme assays and ex vivo cell models to systematically address the boundaries of the region within site-specific O-glycosylation affect PC processing. The results demonstrate that O-glycans within at least ±3 residues of the RXXR furin cleavage site may affect PC processing suggesting that site-specific O-glycosylation is a major co-regulator of PC processing.
Authors:
Katrine Ter-Borch Gram Schjoldager; Malene B Vester-Christensen; Christoffer K Goth; Thomas Nordahl Petersen; Søren Brunak; Eric P Bennett; Steven B Levery; Henrik Clausen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-09-20
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-14     Completed Date:  2012-01-05     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  40122-32     Citation Subset:  IM    
Affiliation:
Center for Glycomics, Department of Cellular and Molecular Medicine and School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Motifs
Animals
CHO Cells
Cricetinae
Cricetulus
Fibroblast Growth Factors / genetics,  metabolism*
Furin / genetics,  metabolism*
Glycosylation
Humans
Protein Modification, Translational / physiology*
Protein Processing, Post-Translational / physiology*
Proteolysis
Chemical
Reg. No./Substance:
0/fibroblast growth factor 23; 62031-54-3/Fibroblast Growth Factors; EC 3.4.21.75/Furin
Comments/Corrections

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