Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1

Research output: Contribution to journalJournal article – Annual report year: 2003Researchpeer-review

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Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1. / Gils, Ann; Pedersen, Katrine Egelund; Skottrup, Peter; Christensen, Anni; Naessens, Dominik; Deinum, Johanna; Enghild, Jan Johannes; Declerck, Paul; Andreasen, Peter.

In: Thrombosis and Haemostasis, Vol. 90, No. 2, 2003, p. 206-217.

Research output: Contribution to journalJournal article – Annual report year: 2003Researchpeer-review

Harvard

Gils, A, Pedersen, KE, Skottrup, P, Christensen, A, Naessens, D, Deinum, J, Enghild, JJ, Declerck, P & Andreasen, P 2003, 'Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1', Thrombosis and Haemostasis, vol. 90, no. 2, pp. 206-217. https://doi.org/10.1160/TH03-01-0034

APA

Gils, A., Pedersen, K. E., Skottrup, P., Christensen, A., Naessens, D., Deinum, J., ... Andreasen, P. (2003). Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1. Thrombosis and Haemostasis, 90(2), 206-217. https://doi.org/10.1160/TH03-01-0034

CBE

Gils A, Pedersen KE, Skottrup P, Christensen A, Naessens D, Deinum J, Enghild JJ, Declerck P, Andreasen P. 2003. Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1. Thrombosis and Haemostasis. 90(2):206-217. https://doi.org/10.1160/TH03-01-0034

MLA

Vancouver

Author

Gils, Ann ; Pedersen, Katrine Egelund ; Skottrup, Peter ; Christensen, Anni ; Naessens, Dominik ; Deinum, Johanna ; Enghild, Jan Johannes ; Declerck, Paul ; Andreasen, Peter. / Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1. In: Thrombosis and Haemostasis. 2003 ; Vol. 90, No. 2. pp. 206-217.

Bibtex

@article{1ec4e12314964b30b2206a19a7854ae2,
title = "Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1",
abstract = "The serpin plasminogen activator inhibitor-1 (PAI-1) is a potential target for anti-thrombotic and anti-cancer therapy. PAI-1 has 3 potential sites for N-linked glycosylation. We demonstrate here that PAI-1 expressed recombinantly or naturally by human cell lines display a heterogeneous glycosylation pattern of the sites at N209 and N265, while that at N329 is not utilised. The IC(50)-values for inactivation of PAI-1 by 4 monoclonal antibodies differed strongly between glycosylated PAI-1 and non-glycosylated PAI-1 expressed in E. coli. For 3 antibodies, an overlap of the epitopes with the glycosylation sites could be excluded as explanation for the differential reactivity. The latency transition of non-glycosylated, but not of glycosylated PAI-1, was strongly accelerated by a non-ionic detergent. The different biochemical properties of glycosylated and non-glycosylated PAI-1 depended specifically on glycosylation of either one or the other of the utilised sites. The PAI-1-binding protein vitronectin reversed the changes associated with the lack of glycosylation at one of the sites. Our results stress the importance of the source of PAI-1 when studying the mechanisms of action of PAI-1-inactivating compounds of potential clinical importance.",
author = "Ann Gils and Pedersen, {Katrine Egelund} and Peter Skottrup and Anni Christensen and Dominik Naessens and Johanna Deinum and Enghild, {Jan Johannes} and Paul Declerck and Peter Andreasen",
year = "2003",
doi = "10.1160/TH03-01-0034",
language = "English",
volume = "90",
pages = "206--217",
journal = "Thrombosis and Haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
number = "2",

}

RIS

TY - JOUR

T1 - Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1

AU - Gils, Ann

AU - Pedersen, Katrine Egelund

AU - Skottrup, Peter

AU - Christensen, Anni

AU - Naessens, Dominik

AU - Deinum, Johanna

AU - Enghild, Jan Johannes

AU - Declerck, Paul

AU - Andreasen, Peter

PY - 2003

Y1 - 2003

N2 - The serpin plasminogen activator inhibitor-1 (PAI-1) is a potential target for anti-thrombotic and anti-cancer therapy. PAI-1 has 3 potential sites for N-linked glycosylation. We demonstrate here that PAI-1 expressed recombinantly or naturally by human cell lines display a heterogeneous glycosylation pattern of the sites at N209 and N265, while that at N329 is not utilised. The IC(50)-values for inactivation of PAI-1 by 4 monoclonal antibodies differed strongly between glycosylated PAI-1 and non-glycosylated PAI-1 expressed in E. coli. For 3 antibodies, an overlap of the epitopes with the glycosylation sites could be excluded as explanation for the differential reactivity. The latency transition of non-glycosylated, but not of glycosylated PAI-1, was strongly accelerated by a non-ionic detergent. The different biochemical properties of glycosylated and non-glycosylated PAI-1 depended specifically on glycosylation of either one or the other of the utilised sites. The PAI-1-binding protein vitronectin reversed the changes associated with the lack of glycosylation at one of the sites. Our results stress the importance of the source of PAI-1 when studying the mechanisms of action of PAI-1-inactivating compounds of potential clinical importance.

AB - The serpin plasminogen activator inhibitor-1 (PAI-1) is a potential target for anti-thrombotic and anti-cancer therapy. PAI-1 has 3 potential sites for N-linked glycosylation. We demonstrate here that PAI-1 expressed recombinantly or naturally by human cell lines display a heterogeneous glycosylation pattern of the sites at N209 and N265, while that at N329 is not utilised. The IC(50)-values for inactivation of PAI-1 by 4 monoclonal antibodies differed strongly between glycosylated PAI-1 and non-glycosylated PAI-1 expressed in E. coli. For 3 antibodies, an overlap of the epitopes with the glycosylation sites could be excluded as explanation for the differential reactivity. The latency transition of non-glycosylated, but not of glycosylated PAI-1, was strongly accelerated by a non-ionic detergent. The different biochemical properties of glycosylated and non-glycosylated PAI-1 depended specifically on glycosylation of either one or the other of the utilised sites. The PAI-1-binding protein vitronectin reversed the changes associated with the lack of glycosylation at one of the sites. Our results stress the importance of the source of PAI-1 when studying the mechanisms of action of PAI-1-inactivating compounds of potential clinical importance.

U2 - 10.1160/TH03-01-0034

DO - 10.1160/TH03-01-0034

M3 - Journal article

VL - 90

SP - 206

EP - 217

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

IS - 2

ER -