Yu Pei Xiao
N-linked glycosylation regulates human proteinase-activated receptor-1 cell surface expression and disarming via neutrophil proteinases and thermolysin
Xiao, Yu Pei; Morice, Alyn H.; Compton, Steven J.; Sadofsky, Laura
Authors
Professor Alyn Morice A.H.Morice@hull.ac.uk
Foundation Chair and Professor of Respiratory Medicine
Steven J. Compton
Dr Laura Sadofsky L.R.Sadofsky@hull.ac.uk
Senior Lecturer in Respiratory Medicine
Abstract
Proteinase-activated receptor 1 (PAR1) induces activation of platelet and vascular cells after proteolytic cleavage of its extracellular N terminus by thrombin. In pathological situations, other proteinases may be generated in the circulation and might modify the responses of PAR1 by cleaving extracellular domains. In this study, epitope-tagged wild-type human PAR1 (hPAR1) and a panel of N-linked glycosylation-deficient mutant receptors were permanently expressed in epithelial cells (Kirsten murine sarcoma virus-transformed rat kidney cells and CHO cells). We have analyzed the role of N-linked glycosylation in regulating proteinase activation/disarming and cell global expression of hPAR1. We reported for the first time that glycosylation in the N terminus of hPAR1 downstream of the tethered ligand (especially Asn75) governs receptor disarming to trypsin, thermolysin, and the neutrophil proteinases elastase and proteinase 3 but not cathepsin G. In addition, hPAR1 is heavily N-linked glycosylated and sialylated in epithelial cell lines, and glycosylation occurs at all five consensus sites, namely, Asn35, Asn62, Asn75, Asn250, and Asn259. Removing these N-linked glycosylation sequons affected hPAR1 cell surface expression to varying degrees, and N-linked glycosylation at extracellular loop 2 (especially Asn250) of hPAR1 is essential for optimal receptor cell surface expression and receptor stability.
Citation
Xiao, Y. P., Morice, A. H., Compton, S. J., & Sadofsky, L. (2011). N-linked glycosylation regulates human proteinase-activated receptor-1 cell surface expression and disarming via neutrophil proteinases and thermolysin. Journal of Biological Chemistry, 286(26), 22991-23002. https://doi.org/10.1074/jbc.M110.204271
Journal Article Type | Article |
---|---|
Online Publication Date | May 6, 2011 |
Publication Date | Jul 1, 2011 |
Deposit Date | Nov 13, 2014 |
Publicly Available Date | Nov 23, 2017 |
Journal | Journal of biological chemistry |
Print ISSN | 0021-9258 |
Electronic ISSN | 1083-351X |
Publisher | American Society for Biochemistry and Molecular Biology |
Peer Reviewed | Peer Reviewed |
Volume | 286 |
Issue | 26 |
Pages | 22991-23002 |
DOI | https://doi.org/10.1074/jbc.M110.204271 |
Keywords | Cell Biology; Biochemistry; Molecular Biology |
Public URL | https://hull-repository.worktribe.com/output/473014 |
Publisher URL | http://www.jbc.org/content/286/26/22991 |
Additional Information | Copy of article first published in Journal of biological chemistry, 2011, v.286, issue 26 |
Files
PAR1 Glycosylation paperJBC 23032011.pdf
(643 Kb)
PDF
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