Cited by 102Cholesterol and Lipid MetabolismReceptor Mechanisms and SignalingProtease and Inhibitor Mechanisms

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Evidence for a second alpha 2-macroglobulin receptor.

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Misra, U.K., Chu, C.T., Gawdi, G., Pizzo, S.V.·1994·Journal of Biological Chemistry

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Abstract

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.

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Authors: Misra, U. K., Chu, C. T., Gawdi, G., & Pizzo, S. V.
Affiliations: Duke Medical Center (US)
ORCID: Misra, U.K.
Chu, C.T.
Pizzo, S.V.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1994-04
Volume: 269
Issue: 17
Pages: 12541-12547
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1016/s0021-9258(18)99909-6
OpenAlex: W1482079857
Cited by: 102
References: 53
Citations by year: 2021: 1 · 2019: 1 · 2018: 1 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 1
FWCI: 9.71
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 9713 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p01ca029589-13)
National Heart, Lung, and Blood Institute (HL24066)
National Cancer Institute (CA29589)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords: alpha2-macroglobulin, alpha2-macroglobulin receptor, low density lipoprotein receptor-related protein, receptor-associated protein, macrophages, G protein-coupled receptor signaling, intracellular calcium, inositol 1,4,5-trisphosphate, pertussis toxin-insensitive G protein, signal transduction
MeSH terms: Cyclic AMP, Adenosine Diphosphate Ribose, alpha-Macroglobulins, Animals, Cholera Toxin, Humans, Inositol Phosphates, Methylamines, Mice, Inbred C57BL, Peptide Fragments, Virulence Factors, Bordetella, Proteins, Receptors, Immunologic, Signal Transduction, Macrophages, Peritoneal, GTP-Binding Proteins, Low Density Lipoprotein Receptor-Related Protein-1, Pertussis Toxin, Mice

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Evidence for a second alpha 2-macroglobulin receptor.

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