The 39-kDa protein regulates LRP activity in cultured endothelial and smooth muscle cells.
The low density lipoprotein receptor-related protein (LRP) has been proposed to function as an endocytosis receptor for chylomicron remnants and protease-inhibitor complexes so that these particles can be cleared from the plasma or extracellular fluid. The kidney glycoprotein 330 (gp330) may have an analogous role to LRP in the kidney. A 39-kDa protein which copurifies with LRP and gp330 inhibits the binding and/or cellular uptake of ligands to these receptors and may regulate LRP and gp330 activity in vivo. Recently, LRP has been immunochemically localized to endothelial and vascular smooth muscle cells. In the present study, the biology of the 39-kDa protein was studied in cultured endothelial cells and vascular smooth muscle cells. The 39-kDa protein is synthesized by both cell types and has an average half-life of 15 hours. Immunofluorescence shows the major part of the 39-kDa protein has an intracellular localization with enrichment in the perinuclear region. Tissue-type plasminogen activator (t-PA), a plasma serine protease that binds specifically and with high affinity to LRP on hepatoma cells, also binds to endothelial cells and vascular smooth muscle cells. 125I-t-PA binding to both cell types is inhibited by the 39-kDa protein. However, only the endothelial cells are capable of rapidly internalizing and degrading 125I-t-PA. These data thus suggest that LRP may function as a clearance receptor for t-PA on endothelial cells.
Warshawsky
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Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
Schwartz
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D000818:Animals; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006207:Half-Life; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008657:Metabolic Clearance Rate; D008970:Molecular Weight; D011233:Precipitin Tests; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000378:metabolism*; D011973:Receptors, LDL; D013552:Swine; D010959:Tissue Plasminogen Activator / Q000378:metabolism / Q000493:pharmacokinetics
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D010959:Tissue Plasminogen Activator