Altered interaction of Cis-dichlorodiammineplatinum(II)--modified alpha 2-macroglobulin (alpha 2M) with the low density lipoprotein receptor-related protein/alpha 2M receptor but not the alpha 2M signaling receptor.

Published

Journal Article

Receptor-recognized forms of alpha 2-macroglobulin (alpha 2M*) bind to two macrophage receptors: an endocytic receptor, the low density lipoprotein receptor-related protein/alpha 2M receptor (LRP/alpha 2MR), and a G protein-coupled receptor, the alpha 2M signaling receptor (alpha 2MSR). Binding of alpha 2M* to LRP/alpha 2MR but not alpha 2MSR is inhibited by receptor-associated protein. We now present binding characteristics of alpha 2MSR (kD approximately 50 pm; 1,530 sites/cell) using Scatchard analysis. We also demonstrate that chemical modification of alpha 2M* with cis-dichlorodiammineplatinum (cis-DDP) does not significantly alter binding to either receptor or signaling characteristics as compared with unmodified alpha 2M*. However, internalization by LRP/alpha 2MR is greatly affected. Cis-DDP-modified alpha 2M* (cis-DDP-alpha 2M*) and alpha 2M* show comparable internalization during a single round of endocytosis; however, cis-DDP modification of alpha 2M* results in a > or = 82% reduction in internalization involving receptor recycling and multiple rounds of endocytosis. Results from pH 5.0 dissociation and receptor recycling experiments suggest that the mechanism of decreased internalization of cis-DDP-alpha 2M* involves poor dissociation from the receptor in endosomes and a decrease in available surface receptors over the time of exposure to the ligand.

Full Text

Duke Authors

Cited Authors

  • Howard, GC; Misra, UK; DeCamp, DL; Pizzo, SV

Published Date

  • March 1, 1996

Published In

Volume / Issue

  • 97 / 5

Start / End Page

  • 1193 - 1203

PubMed ID

  • 8636430

Pubmed Central ID

  • 8636430

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI118533

Language

  • eng

Conference Location

  • United States