The relationship between low density lipoprotein-related protein/alpha 2-macroglobulin (alpha 2M) receptors and the newly described alpha 2M signaling receptor.
alpha 2-Macroglobulin (alpha 2M)-methylamine binding to macrophages appears to involve two receptors. Binding of alpha 2M-methylamine to low density lipoprotein-related protein (LRP) results in cellular uptake and degradation, while binding to a newly described alpha 2M signaling receptor elevates intracellular calcium ([Ca2+]i) and inositol phosphates. We now demonstrate that binding of lactoferrin, Pseudomonas exotoxin A, and lipoprotein lipase to LRP on macrophages results in increased [Ca2+]i and inositol 1,4,5-triphosphate. Receptor-associated protein, which binds to LRP but not the alpha 2M signaling receptor, blocks the lactoferrin signal but has no effect on alpha 2M-methylamine signaling. The latter observation supports our hypothesis that a distinct signaling receptor binds alpha 2M-methylamine. We further demonstrate that the signaling events induced by lactoferrin may involve a pertussis toxin-sensitive G protein, while the alpha 2M signaling receptor appears to be coupled to a pertussis toxin-insensitive G protein.
Misra
U K
UK
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
Chu
C T
CT
Gawdi
G
G
Pizzo
S V
SV
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D007781:Lactoferrin / Q000494:pharmacology; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D037342:Pertussis Toxin; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000378:metabolism* / Q000494:pharmacology*
D007295:Inositol Phosphates; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D010566:Virulence Factors, Bordetella; D000511:alpha-Macroglobulins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D037342:Pertussis Toxin; D007781:Lactoferrin; D002118:Calcium