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.
Misra
U K
UK
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Adlakha
C L
CL
Gawdi
G
G
McMillian
M K
MK
Pizzo
S V
SV
Laskowitz
D T
DT
D000818:Animals; D001057:Apolipoproteins E / Q000494:pharmacology*; D001667:Binding, Competitive; D020013:Calcium Signaling; D002478:Cells, Cultured; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007700:Kinetics; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009532:Nickel / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D011971:Receptors, Immunologic / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001057:Apolipoproteins E; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010455:Peptides; D011971:Receptors, Immunologic; D010566:Virulence Factors, Bordetella; D009532:Nickel; D015544:Inositol 1,4,5-Trisphosphate; D037342:Pertussis Toxin