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A systematic study of site-specific GalNAc-type O-glycosylation modulating proprotein convertase processing

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A systematic study of site-specific GalNAc-type O-glycosylation modulating proprotein convertase processing. / Gram Schjoldager, Katrine Ter-Borch; Vester-Christensen, Malene B; Goth, Christoffer K; Petersen, Thomas Nordahl; Brunak, Søren; Bennett, Eric P; Levery, Steven B; Clausen, Henrik.

I: Journal of Biological Chemistry, Bind 286, Nr. 46, 18.11.2011, s. 40122-32.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Gram Schjoldager, KT-B, Vester-Christensen, MB, Goth, CK, Petersen, TN, Brunak, S, Bennett, EP, Levery, SB & Clausen, H 2011, 'A systematic study of site-specific GalNAc-type O-glycosylation modulating proprotein convertase processing', Journal of Biological Chemistry, bind 286, nr. 46, s. 40122-32. https://doi.org/10.1074/jbc.M111.287912

APA

Gram Schjoldager, K. T-B., Vester-Christensen, M. B., Goth, C. K., Petersen, T. N., Brunak, S., Bennett, E. P., ... Clausen, H. (2011). A systematic study of site-specific GalNAc-type O-glycosylation modulating proprotein convertase processing. Journal of Biological Chemistry, 286(46), 40122-32. https://doi.org/10.1074/jbc.M111.287912

Vancouver

Gram Schjoldager KT-B, Vester-Christensen MB, Goth CK, Petersen TN, Brunak S, Bennett EP o.a. A systematic study of site-specific GalNAc-type O-glycosylation modulating proprotein convertase processing. Journal of Biological Chemistry. 2011 nov 18;286(46):40122-32. https://doi.org/10.1074/jbc.M111.287912

Author

Gram Schjoldager, Katrine Ter-Borch ; Vester-Christensen, Malene B ; Goth, Christoffer K ; Petersen, Thomas Nordahl ; Brunak, Søren ; Bennett, Eric P ; Levery, Steven B ; Clausen, Henrik. / A systematic study of site-specific GalNAc-type O-glycosylation modulating proprotein convertase processing. I: Journal of Biological Chemistry. 2011 ; Bind 286, Nr. 46. s. 40122-32.

Bibtex

@article{386a85292fc341cbb74555b4e68ea950,
title = "A systematic study of site-specific GalNAc-type O-glycosylation modulating proprotein convertase processing",
abstract = "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.",
keywords = "Amino Acid Motifs, Animals, CHO Cells, Cricetinae, Cricetulus, Fibroblast Growth Factors, Furin, Glycosylation, Humans, Protein Modification, Translational, Protein Processing, Post-Translational, Proteolysis",
author = "{Gram Schjoldager}, {Katrine Ter-Borch} and Vester-Christensen, {Malene B} and Goth, {Christoffer K} and Petersen, {Thomas Nordahl} and S{\o}ren Brunak and Bennett, {Eric P} and Levery, {Steven B} and Henrik Clausen",
year = "2011",
month = "11",
day = "18",
doi = "10.1074/jbc.M111.287912",
language = "English",
volume = "286",
pages = "40122--32",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "46",

}

RIS

TY - JOUR

T1 - A systematic study of site-specific GalNAc-type O-glycosylation modulating proprotein convertase processing

AU - Gram Schjoldager, Katrine Ter-Borch

AU - Vester-Christensen, Malene B

AU - Goth, Christoffer K

AU - Petersen, Thomas Nordahl

AU - Brunak, Søren

AU - Bennett, Eric P

AU - Levery, Steven B

AU - Clausen, Henrik

PY - 2011/11/18

Y1 - 2011/11/18

N2 - 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.

AB - 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.

KW - Amino Acid Motifs

KW - Animals

KW - CHO Cells

KW - Cricetinae

KW - Cricetulus

KW - Fibroblast Growth Factors

KW - Furin

KW - Glycosylation

KW - Humans

KW - Protein Modification, Translational

KW - Protein Processing, Post-Translational

KW - Proteolysis

U2 - 10.1074/jbc.M111.287912

DO - 10.1074/jbc.M111.287912

M3 - Journal article

C2 - 21937429

VL - 286

SP - 40122

EP - 40132

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 46

ER -

ID: 36070543