39-kDa protein modulates binding of ligands to low density lipoprotein receptor-related protein/α₂-macroglobulin receptor

A 39-kDa protein of unknown function has previously been reported to copurify with the low density lipoprotein receptor-related protein (LRP)/α₂-macroglobulin receptor. In this study we demonstrate that a recombinant 39-kDa fusion protein can reversibly bind to the 515-kDa subunit of the LRP/α₂-macroglobulin receptor. This interaction inhibits the binding and uptake of the receptor's two known ligands: 1) β-migrating very low density lipoproteins activated by enrichment with apoprotein E and 2) α₂-macroglobulin activated by incubation with plasma proteases or methylamine. A potential in vivo role of the 39-kDa protein is to modulate the uptake of apoE-enriched lipoproteins and activated α₂-macroglobulin in hepatic and extra-hepatic tissues.