THE 39-KDA PROTEIN REGULATES LRP ACTIVITY IN CULTURED ENDOTHELIAL ANDSMOOTH-MUSCLE CELLS

The low density lipoprotein receptor-related protein (LRP) has been pr oposed to function as an endocytosis receptor for chylomicron remnants and protease-inhibitor complexes so that these particles can be clear ed from the plasma or extracellular fluid. The kidney glycoprotein 330 (gp330) may have an analogous role to LRP in the kidney. A 39-kDa pro tein which copurifies with LRP and gp330 inhibits the binding and/or c ellular uptake of ligands to these receptors and may regulate LRP and gp330 activity in vivo. Recently, LRP has been immunochemically locali zed to endothelial and vascular smooth muscle cells. In the present st udy, the biology of the 39-kDa protein was studied in cultured endothe lial cells and vascular smooth muscle cells. The 39-kDa protein is syn thesized 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 i ntracellular localization with enrichment in the perinuclear region. T issue-type plasminogen activator (t-PA), a plasma serine protease that binds specifically and with high affinity to LRP on hepatoma cells, a lso binds to endothelial cells and vascular smooth muscle cells. I-125 -t-PA binding to both cell types is inhibited by the 39-kDa protein. H owever, only the endothelial cells are capable of rapidly internalizin g and degrading I-125-t-pA. These data thus suggest that LRP may funct ion as a clearance receptor for t-PA on endothelial cells.