Identification of domains on the 39-kDa protein that inhibit the binding of ligands to the low density lipoprotein receptor-related protein

I. Warshawsky, Guojun D Bu, A. L. Schwartz

Research output: Contribution to journalArticle

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Abstract

The low density lipoprotein receptor-related protein/α 2-macroglobulin receptor (LRP/α 2MR) binds and internalizes several plasma proteins including tissue-type plasminogen activator (t-PA) and α 2-macroglobulin- protease complexes (α 2M*). A 39-kDa protein that copurifies with LRP/α 2MR inhibits the binding and uptake of ligands by LRP/α 2MR, including t-PA and α 2M*. To define domains on the 39-kDa protein which are essential for inhibition of t-PA and α 2M* binding to LRP/α 2MR, 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 α 2M* binding to LRP/α 2MR on rat hepatoma MH 1C 1 cells are shown to require amino acid residues 18-24 and 100-107 on the 39-kDa protein. Inhibition of t-PA but not α 2M* binding to LRP/α 2MR is also mediated by residues 200-225 and 311-319. The same 39-kDa protein constructs that inhibit α 2M* and t-PA binding to MH 1C 1 cells are able to bind directly to purified LRP/α 2MR 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 α 2M* binding to LRP/α 2MR.

Original languageEnglish (US)
Pages (from-to)22046-22054
Number of pages9
JournalJournal of Biological Chemistry
Volume268
Issue number29
StatePublished - 1993
Externally publishedYes

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LDL-Receptor Related Proteins
LDL Receptors
Protein Binding
Macroglobulins
Lipoprotein Receptors
Ligands
Plasminogen Activators
Proteins
Low Density Lipoprotein Receptor-Related Protein-2
Collodion
Tissue Plasminogen Activator

ASJC Scopus subject areas

  • Biochemistry

Cite this

Identification of domains on the 39-kDa protein that inhibit the binding of ligands to the low density lipoprotein receptor-related protein. / Warshawsky, I.; Bu, Guojun D; Schwartz, A. L.

In: Journal of Biological Chemistry, Vol. 268, No. 29, 1993, p. 22046-22054.

Research output: Contribution to journalArticle

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AB - The low density lipoprotein receptor-related protein/α 2-macroglobulin receptor (LRP/α 2MR) binds and internalizes several plasma proteins including tissue-type plasminogen activator (t-PA) and α 2-macroglobulin- protease complexes (α 2M*). A 39-kDa protein that copurifies with LRP/α 2MR inhibits the binding and uptake of ligands by LRP/α 2MR, including t-PA and α 2M*. To define domains on the 39-kDa protein which are essential for inhibition of t-PA and α 2M* binding to LRP/α 2MR, 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 α 2M* binding to LRP/α 2MR on rat hepatoma MH 1C 1 cells are shown to require amino acid residues 18-24 and 100-107 on the 39-kDa protein. Inhibition of t-PA but not α 2M* binding to LRP/α 2MR is also mediated by residues 200-225 and 311-319. The same 39-kDa protein constructs that inhibit α 2M* and t-PA binding to MH 1C 1 cells are able to bind directly to purified LRP/α 2MR 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 α 2M* binding to LRP/α 2MR.

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