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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1998-2-9
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pubmed:abstractText |
Macrophage scavenger receptor-type A (MSR-A) has been implicated in the transmission of cell signals and the regulation of diverse cellular functions (Falcone, D. J., and Ferenc, M. J. (1988) J. Cell. Physiol. 135, 387-396; Falcone, D. J., McCaffrey, T. A., and Vergilio, J. A. (1991) J. Biol. Chem. 266, 22726-22732; Palkama, T. (1991) Immunology 74, 432-438; Krieger, M., and Herz, J. (1994) Annu. Rev. Biochem. 63, 601-637); however, the signaling mechanisms are unknown. In studies reported here, we demonstrate that binding of both lipoprotein and non-lipoprotein ligands to MSR-A induced protein tyrosine phosphorylation and increased protein kinase C (PKC) activity leading to up-regulated urokinase-type plasminogen activator (uPA) expression. Specifically, the binding of acetylated low density lipoprotein and fucoidan to MSR-A in human THP-1 macrophages triggered tyrosine phosphorylation of many proteins including phospholipase C-gamma1 and phosphatidylinositol-3-OH kinase. Inhibitors of tyrosine kinase dramatically reduced MSR-induced protein tyrosine phosphorylation and PKC activity. Moreover, inhibitors of tyrosine kinase and PKC reduced uPA activity expressed by THP-1 macrophages exposed to MSR-A ligands. The intracellular signaling response for tyrosine phosphorylation following ligand binding was further demonstrated by using the stable MSR-transfected Bowes cells that express surface MSR-A. These findings establish for the first time a signaling pathway induced by ligand binding to MSR-A and suggest a molecular model for the regulation of macrophage uPA expression by specific ligands of the MSR-A.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/MSR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Polysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Scavenger,
http://linkedlifedata.com/resource/pubmed/chemical/Scavenger Receptors, Class A,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator,
http://linkedlifedata.com/resource/pubmed/chemical/acetyl-LDL,
http://linkedlifedata.com/resource/pubmed/chemical/fucoidan
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1240-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9422792-Cell Line,
pubmed-meshheading:9422792-Enzyme Inhibitors,
pubmed-meshheading:9422792-Humans,
pubmed-meshheading:9422792-Ligands,
pubmed-meshheading:9422792-Lipoproteins, LDL,
pubmed-meshheading:9422792-Melanoma,
pubmed-meshheading:9422792-Phosphorylation,
pubmed-meshheading:9422792-Polysaccharides,
pubmed-meshheading:9422792-Protein Binding,
pubmed-meshheading:9422792-Protein Kinase C,
pubmed-meshheading:9422792-Protein-Tyrosine Kinases,
pubmed-meshheading:9422792-Receptors, Immunologic,
pubmed-meshheading:9422792-Receptors, Scavenger,
pubmed-meshheading:9422792-Scavenger Receptors, Class A,
pubmed-meshheading:9422792-Signal Transduction,
pubmed-meshheading:9422792-Tyrosine,
pubmed-meshheading:9422792-Up-Regulation,
pubmed-meshheading:9422792-Urokinase-Type Plasminogen Activator
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pubmed:year |
1998
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pubmed:articleTitle |
Ligand binding to macrophage scavenger receptor-A induces urokinase-type plasminogen activator expression by a protein kinase-dependent signaling pathway.
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pubmed:affiliation |
Department of Medicine, Cornell University Medical College, New York, New York 10021, USA. hyhsu@ym.edu.tu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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