The low density lipoprotein receptor-related protein/α2-macroglobulin receptor (LRP/α2MR) binds and internalizes several plasma proteins including tissue-type plasminogen activator (t-PA) and α2-macroglobulin- protease complexes (α2M*). A 39-kDa protein that copurifies with LRP/α2MR inhibits the binding and uptake of ligands by LRP/α2MR, including t-PA and α2M*. To define domains on the 39-kDa protein which are essential for inhibition of t-PA and α2M* binding to LRP/α2MR, we have generated bacterial expression constructs encoding discrete regions of the 39-kDa protein as fusion proteins with glutathione S-transferase. Inhibition of t-PA and α2M* binding to LRP/α2MR on rat hepatoma MH1C1 cells are shown to require amino acid residues 18-24 and 100-107 on the 39-kDa protein. Inhibition of t-PA but not α2M* binding to LRP/α2MR is also mediated by residues 200-225 and 311-319. The same 39-kDa protein constructs that inhibit α2M* and t-PA binding to MH1C1 cells are able to bind directly to purified LRP/α2MR immobilized on nitrocellulose. Thus, our studies demonstrate several specific regions on the 39-kDa protein which are required for the inhibition of t-PA and α2M* binding to LRP/α2MR.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Biological Chemistry|
|State||Published - Jan 1 1993|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology