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A carboxylterminal fragment of lipoprotein lipase binds to the low density lipoprotein receptor-related protein and inhibits lipase-mediated uptake of lipoproteins to cells
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Nykjaer A, Nielsen M, Lookene A, Meyer N, Roigaard H, Etzerodt M, Beisiegel U, Olivecrona G, Gliemann J: A carboxylterminal fragment of lipoprotein lipase binds to the low density lipoprotein receptor-related protein and inhibits lipase-mediated uptake of lipoproteins to cells. J Biol Chem 1994, 269:31747-31755. The LRP binding site has been located within residues 378-423 in human LPL. Studies performed with fragments containing these residues demonstrated that these fragments were able to inhibit the binding of LPL to LRP and LPL-mediated binding of lipoprotein to cells.
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Willnow E, Sheng Z, Ishibashi S, Herz J: Inhibition of hepatic chylomicron remnant uptake by gene transfer of a receptor antagonist. Science 1994, 264:1471-1474. The importance of this model is that it represents the first demonstration of the function of LRP as a lipoprotein receptor in vivo. It has also shed some light on the open question of the role of the LDL receptor in remnant catabolism in vivo. The data suggest that both the LDL receptor and LRP could be involved in remnant clearance in mice.
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Mokuno H, Brady S, Kotite L, Herz J, Havel J: Effect of the 39-kDa receptor-associated protein on the hepatic uptake and endocytosis of chylomicron remnants and low density lipoproteins in the rat. J Biol Chem 1994, 269:13238-13243. The pathway by which chylomicron remnants are taken up in the liver is shown to be clearly inhibited by RAP. This finding is very important because it might have decisive relevance for the regulation of this pathway. The authors also demonstrate that RAP interferes not only with LRP binding but also with the binding of ligands to the LDL receptor.
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Battey FD, Gafvels ME, FitzGerald DJ, Argraves WS, Chappell DA, Strauss JF, Strickland DK: The 39-kDa receptor-associated protein regulates ligand binding by the very low density lipoprotein receptor. J Biol Chem 1994, 269.23268-23273. The purified VLDL receptor (130kDa) bound VLDL on nitrocellulose membranes but not LDL VLDL binding was completely inhibited by RAP, and this protein also inhibited the uptake of VLDL by cells over-expressing the VLDL receptor. This suggests a common functional role for RAP in modulating ligand binding by members of the LDL receptor gene family.
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Shimano H, Namba Y, Ohsuga J, Kawamura M, Yamamoto K, Shimada M, Gotoda T, Harada K, Yazaki Y, Yamada N: Secretion-recapture process of apolipoprotein E in hepatic uptake of chylomicron remnants in transgenic mice. J Clin Invest 1994, 93:2215-2223. Surplus rat apoE, demonstrated on the surface of hepatocytes in transgenic mice, was markedly reduced after chylomicron infusion. This indicated that chylomicrons were captured by apoE on the cell surface, and the chylomicron-apoE complex was subsequently taken up through receptor-mediated endocytosis. This mechanism could only be demonstrated for chylomicrons, but not for VLDL or LDL. It might, therefore, be an important step in the rapid clearance of chylomicron remnants.
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Hofer F, Gruenberger M, Kowalski H, Machat H, Huettinger M, Kuechler E, Blaas D: Members of the low density lipoprotein receptor family mediate cell entry of a minor-group common cold virus. Proc Natl Acad Sci USA 1994, 91:1839-1842.
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2-macroglobulin receptor/low density lipoprotein receptor-related protein and scavenger receptor in human atherosclerotic lesions. J Clin Invest 1994, 93.2014-2021. The first demonstration of the possible importance of LRP in atherogenesis. Like the scavenger receptor, LRP might contribute significantly to the development of lesions. In particular, it was shown that smooth muscle cells express LRP, which might be responsible for their transformation into foam cells.
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Human very-low-density lipoprotein receptor complentary DNA and deduced amino acid sequence and localization of its gene (VLDLR) to chromosome band 9p24 by fluorescence in situ hybridization
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Nimpf J Stifani S, Bilous PT, Schneider WJ: The somatic cell-specific low density lipoprotein receptor-related protein of the chicken. J Biol Chem 1994, 269:212-219. In the chicken, both the LDL receptor and LRP occur in two distinct forms that are different in somatic tissues and in growing follicles. The 600 kDa somatic LRP has an overall identity of 83% with human LRP. The second avian LRP is detected as a 380kDa vitellogenin-binding protein in the growing follicle. The chicken model indicates that the LRP genes have emerged from an ancestor that was designed to ensure an important event in reproduction.
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J Biol Chem
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