Claus Munck Petersen

The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds lipoprotein lipase and beta-migrating very low density lipoprotein associated with the lipase

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds lipoprotein lipase and beta-migrating very low density lipoprotein associated with the lipase. / Nykjaer, A; Bengtsson-Olivecrona, G; Lookene, A; Moestrup, S K; Petersen, C M; Weber, W; Beisiegel, U; Gliemann, J.

In: Journal of Biological Chemistry, Vol. 268, No. 20, 1993, p. 15048-55.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Nykjaer, A, Bengtsson-Olivecrona, G, Lookene, A, Moestrup, SK, Petersen, CM, Weber, W, Beisiegel, U & Gliemann, J 1993, 'The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds lipoprotein lipase and beta-migrating very low density lipoprotein associated with the lipase', Journal of Biological Chemistry, vol. 268, no. 20, pp. 15048-55.

APA

CBE

MLA

Vancouver

Author

Nykjaer, A ; Bengtsson-Olivecrona, G ; Lookene, A ; Moestrup, S K ; Petersen, C M ; Weber, W ; Beisiegel, U ; Gliemann, J. / The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds lipoprotein lipase and beta-migrating very low density lipoprotein associated with the lipase. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 20. pp. 15048-55.

Bibtex

@article{38138fd45414422ab4068a6cc04c0929,
title = "The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds lipoprotein lipase and beta-migrating very low density lipoprotein associated with the lipase",
abstract = "Lipoprotein lipase (LPL) causes a marked increase in the cellular binding of beta-migrating very low density lipoprotein (beta-VLDL) to a large receptor compatible with the alpha 2-macroglobulin receptor (alpha 2MR)/low density lipoprotein receptor-related protein (LRP) (Beisiegel, U., Weber, W., and Bengtsson-Olivecrona, G. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 8342-8346). Here we demonstrate that LPL binds to the alpha-chain of purified alpha 2MR/LRP immobilized on microtiter plates. The binding, apparently to multiple sites, was blocked by heparin and inhibited by the alpha 2MR-associated protein (alpha 2MRAP) and by EDTA. Immobilized LPL bound alpha 2MR/LRP in solution as well as beta-VLDL prepared from cholesterol-fed rabbits. Both binding reactions were dependent on an intact carboxyl-terminal folding domain of LPL, but were independent of its dimeric structure and intact catalytical function. Dimeric LPL could mediate binding of beta-VLDL to immobilized alpha 2MR/LRP and to cells, e.g. monocytes. In contrast, LPL monomers were not able to mediate binding to immobilized alpha 2MR/LRP, presumably because of cross-inhibition due to close relation between the binding regions for the lipoprotein and for the receptor in the carboxyl-terminal domain of the LPL monomer. Heparin, but not alpha 2MRAP, inhibited cellular binding of 125I-LPL or 125I-beta-VLDL supplemented with LPL. However, alpha 2MRAP inhibited degradation of the two ligands by about 90{\%} and 40-50{\%}, respectively. The results show that LPL is a ligand for alpha 2MR/LRP and, because of its affinity for lipoprotein particles, dimeric LPL can mediate or strengthen binding of beta-VLDL to this receptor. It is proposed that LPL binds primarily to cell surface heparan sulfate in monocytes and is presented for endocytosis and degradation by alpha 2MR/LRP. Moreover, beta-VLDL may be further supplemented with LPL at the cell surface and achieve affinity for alpha 2MR/LRP.",
keywords = "Animals, Binding Sites, Cells, Cultured, Humans, Lipoprotein Lipase, Lipoproteins, VLDL, Low Density Lipoprotein Receptor-Related Protein-1, Rabbits, Receptors, Immunologic, alpha-Macroglobulins",
author = "A Nykjaer and G Bengtsson-Olivecrona and A Lookene and Moestrup, {S K} and Petersen, {C M} and W Weber and U Beisiegel and J Gliemann",
year = "1993",
language = "English",
volume = "268",
pages = "15048--55",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "20",

}

RIS

TY - JOUR

T1 - The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds lipoprotein lipase and beta-migrating very low density lipoprotein associated with the lipase

AU - Nykjaer, A

AU - Bengtsson-Olivecrona, G

AU - Lookene, A

AU - Moestrup, S K

AU - Petersen, C M

AU - Weber, W

AU - Beisiegel, U

AU - Gliemann, J

PY - 1993

Y1 - 1993

N2 - Lipoprotein lipase (LPL) causes a marked increase in the cellular binding of beta-migrating very low density lipoprotein (beta-VLDL) to a large receptor compatible with the alpha 2-macroglobulin receptor (alpha 2MR)/low density lipoprotein receptor-related protein (LRP) (Beisiegel, U., Weber, W., and Bengtsson-Olivecrona, G. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 8342-8346). Here we demonstrate that LPL binds to the alpha-chain of purified alpha 2MR/LRP immobilized on microtiter plates. The binding, apparently to multiple sites, was blocked by heparin and inhibited by the alpha 2MR-associated protein (alpha 2MRAP) and by EDTA. Immobilized LPL bound alpha 2MR/LRP in solution as well as beta-VLDL prepared from cholesterol-fed rabbits. Both binding reactions were dependent on an intact carboxyl-terminal folding domain of LPL, but were independent of its dimeric structure and intact catalytical function. Dimeric LPL could mediate binding of beta-VLDL to immobilized alpha 2MR/LRP and to cells, e.g. monocytes. In contrast, LPL monomers were not able to mediate binding to immobilized alpha 2MR/LRP, presumably because of cross-inhibition due to close relation between the binding regions for the lipoprotein and for the receptor in the carboxyl-terminal domain of the LPL monomer. Heparin, but not alpha 2MRAP, inhibited cellular binding of 125I-LPL or 125I-beta-VLDL supplemented with LPL. However, alpha 2MRAP inhibited degradation of the two ligands by about 90% and 40-50%, respectively. The results show that LPL is a ligand for alpha 2MR/LRP and, because of its affinity for lipoprotein particles, dimeric LPL can mediate or strengthen binding of beta-VLDL to this receptor. It is proposed that LPL binds primarily to cell surface heparan sulfate in monocytes and is presented for endocytosis and degradation by alpha 2MR/LRP. Moreover, beta-VLDL may be further supplemented with LPL at the cell surface and achieve affinity for alpha 2MR/LRP.

AB - Lipoprotein lipase (LPL) causes a marked increase in the cellular binding of beta-migrating very low density lipoprotein (beta-VLDL) to a large receptor compatible with the alpha 2-macroglobulin receptor (alpha 2MR)/low density lipoprotein receptor-related protein (LRP) (Beisiegel, U., Weber, W., and Bengtsson-Olivecrona, G. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 8342-8346). Here we demonstrate that LPL binds to the alpha-chain of purified alpha 2MR/LRP immobilized on microtiter plates. The binding, apparently to multiple sites, was blocked by heparin and inhibited by the alpha 2MR-associated protein (alpha 2MRAP) and by EDTA. Immobilized LPL bound alpha 2MR/LRP in solution as well as beta-VLDL prepared from cholesterol-fed rabbits. Both binding reactions were dependent on an intact carboxyl-terminal folding domain of LPL, but were independent of its dimeric structure and intact catalytical function. Dimeric LPL could mediate binding of beta-VLDL to immobilized alpha 2MR/LRP and to cells, e.g. monocytes. In contrast, LPL monomers were not able to mediate binding to immobilized alpha 2MR/LRP, presumably because of cross-inhibition due to close relation between the binding regions for the lipoprotein and for the receptor in the carboxyl-terminal domain of the LPL monomer. Heparin, but not alpha 2MRAP, inhibited cellular binding of 125I-LPL or 125I-beta-VLDL supplemented with LPL. However, alpha 2MRAP inhibited degradation of the two ligands by about 90% and 40-50%, respectively. The results show that LPL is a ligand for alpha 2MR/LRP and, because of its affinity for lipoprotein particles, dimeric LPL can mediate or strengthen binding of beta-VLDL to this receptor. It is proposed that LPL binds primarily to cell surface heparan sulfate in monocytes and is presented for endocytosis and degradation by alpha 2MR/LRP. Moreover, beta-VLDL may be further supplemented with LPL at the cell surface and achieve affinity for alpha 2MR/LRP.

KW - Animals

KW - Binding Sites

KW - Cells, Cultured

KW - Humans

KW - Lipoprotein Lipase

KW - Lipoproteins, VLDL

KW - Low Density Lipoprotein Receptor-Related Protein-1

KW - Rabbits

KW - Receptors, Immunologic

KW - alpha-Macroglobulins

M3 - Journal article

C2 - 7686910

VL - 268

SP - 15048

EP - 15055

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 20

ER -