Evidence for a second alpha 2-macroglobulin receptor.
alpha 2-Macroglobulin (alpha 2M)-methylamine binds to purified low density lipoprotein receptor-related protein (LRP), and it is assumed that LRP functions as the alpha 2M receptor in vivo. Binding of alpha 2M-methylamine to macrophage receptors elevates intracellular calcium ([Ca2+]i), inositol phosphates, and cyclic AMP. We have employed human alpha 2M-methylamine and recombinant receptor binding fragment (RBF) to study transduction mechanisms. Macrophages exposed to either ligand demonstrated a rapid rise in [Ca2+]i. Since the 39-kDa LRP/alpha 2M receptor-associated protein (RAP) blocks alpha 2M binding to LRP, we explored the effects of RAP upon signaling. Pretreatment of macrophages with RAP did not block the increase in [Ca2+]i elicited by alpha 2M-methylamine or RBF, suggesting a distinct binding site. RBF also elicited a transient 1.5-2.0-fold increase in inositol 1,4,5-triphosphate. In permeabilized macrophages, GTP gamma S and Gp-p(NH)p potentiated and sustained this inositol 1,4,5-triphosphate increase. Preincubation of permeabilized macrophages with GDP beta S abrogated the effects of GTP gamma S. Our results suggest that the signaling alpha 2M receptor is coupled to a pertussis toxin-insensitive G protein and possibly to a cholera toxin-sensitive G protein. We conclude that macrophages contain a second alpha 2M receptor that is G protein-coupled.
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
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008744:Methylamines / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism; D037342:Pertussis Toxin; D011506:Proteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000378:metabolism*
D007295:Inositol Phosphates; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008744:Methylamines; D010446:Peptide Fragments; D011506:Proteins; D011971:Receptors, Immunologic; D010566:Virulence Factors, Bordetella; D000511:alpha-Macroglobulins; D000246:Adenosine Diphosphate Ribose; D002772:Cholera Toxin; C027451:methylamine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins