Apolipoprotein E and mimetic peptide initiate a calcium-dependent signaling response in macrophages.
Apolipoprotein E (ApoE) is a 34-kDa cholesterol transport protein that also possesses immunomodulatory properties. In this study, we demonstrate that ApoE initiates a signaling cascade in murine peritoneal macrophages that leads to increased production of inositol triphosphate with mobilization of intracellular Ca(2+) stores. This cascade is inhibited by pretreatment with receptor-associated protein and Ni(2+), and it is mediated by a pertussis toxin-sensitive G protein. These properties are characteristic of signal transduction induced via ligand binding to the cellular receptor, lipoprotein receptor-related protein. A peptide derived from the receptor-binding region of ApoE also initiates signal transduction in a manner similar to that of the intact protein, suggesting that this isolated region is sufficient for signal transduction. The ApoE-mimetic peptide competed for binding with the intact protein, confirming that they both interact with the same site. ApoE-dependent signal transduction might play a role in mediating the functional properties of this lipoprotein.
Duke Scholars
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Related Subject Headings
- Virulence Factors, Bordetella
- Receptors, Immunologic
- Pertussis Toxin
- Peptides
- Nickel
- Mice
- Macrophages
- Low Density Lipoprotein Receptor-Related Protein-1
- Kinetics
- Inositol 1,4,5-Trisphosphate
Citation
Published In
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Virulence Factors, Bordetella
- Receptors, Immunologic
- Pertussis Toxin
- Peptides
- Nickel
- Mice
- Macrophages
- Low Density Lipoprotein Receptor-Related Protein-1
- Kinetics
- Inositol 1,4,5-Trisphosphate