Receptor-associated protein binding blocks ubiquitinylation of the low density lipoprotein receptor-related protein.

Published

Journal Article

The low density lipoprotein receptor-related protein (LRP) consists of two subunits, M(r) approximately 515,000 and 85,000. LRP is a receptor for activated alpha2-macrogobulin (alpha2M*), Pseudomonas exotoxin A, and many other proteins. We now report that ubiquitinylation of the LRP heavy chain occurred when either Pseudomonas exotoxin A or alpha2M* bound to LRP on macrophages. Ubiquitinylation was dose-dependent and maximal about 30 min after ligation of the receptor. Addition of the proteosome inhibitor MG-132 sustained the level of ubiquitin-LRP for longer time intervals in macrophages treated with either alpha2M* or Pseudomonas exotoxin A. By contrast, when receptor associated protein (RAP) bound to LRP, ubiquitinylation did not occur. While RAP is not found in the extracellular environment it binds to LRP and is believed to function as an intracellular chaperone. The presence of RAP within the cell may, therefore, contribute to the recycling of intact LRP which has ligated and internalized its ligands.

Full Text

Duke Authors

Cited Authors

  • Misra, UK; Pizzo, SV

Published Date

  • December 1, 2001

Published In

Volume / Issue

  • 396 / 1

Start / End Page

  • 106 - 110

PubMed ID

  • 11716468

Pubmed Central ID

  • 11716468

International Standard Serial Number (ISSN)

  • 0003-9861

Digital Object Identifier (DOI)

  • 10.1006/abbi.2001.2597

Language

  • eng

Conference Location

  • United States