Binding analysis of amino-terminal and carboxyl-terminal regions of the 39-kDa protein to the low density lipoprotein receptor-related protein

Ilka Warshawsky, Guojun Bu, Alan L. Schwartz

Research output: Contribution to journalArticle

30 Scopus citations

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 languageEnglish (US)
Pages (from-to)3325-3330
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number5
StatePublished - Feb 4 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Binding analysis of amino-terminal and carboxyl-terminal regions of the 39-kDa protein to the low density lipoprotein receptor-related protein'. Together they form a unique fingerprint.

  • Cite this