Abstract
A 39-kDa protein binds to the low density lipoprotein receptor-related protein/α2-macroglobulin receptor (LRP/α2MR) and inhibits the binding of ligands to this receptor. We recently reported that inhibition of tissue- type plasminogen activator binding to LRP/α2MR is mediated by both amino- terminal and carboxyl-terminal regions of the 39-kDa protein, whereas inhibition of α2-macroglobulin-proteinase binding is mediated only by amino-terminal regions. In this report we show that amino-terminal and carboxyl-terminal regions of the 39-kDa protein bind specifically and with high affinity to LRP/α2MR on rat hepatoma MH1C1 cells. Following binding, these amino-terminal and carboxyl-terminal regions of the 39-kDa protein are each rapidly endocytosed and degraded with kinetics identical to the full- length 39-kDa protein. Competition binding experiments with these constructs demonstrate that amino-terminal and carboxyl-terminal regions of the 39-kDa protein compete with one another for binding to LRP/α2MR. A model is proposed in which amino-terminal and carboxyl-terminal regions of the 39-kDa protein bind to different sites on LRP/α2MR in order to inhibit ligand binding.
Original language | English |
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Pages (from-to) | 3325-3330 |
Number of pages | 6 |
Journal | Journal of Biological Chemistry |
Volume | 269 |
Issue number | 5 |
State | Published - Feb 4 1994 |