Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-2-9
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1240-6
pubmed:dateRevised
2009-11-19
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
pubmed:year
1998
pubmed:articleTitle
Ligand binding to macrophage scavenger receptor-A induces urokinase-type plasminogen activator expression by a protein kinase-dependent signaling pathway.
pubmed:affiliation
Department of Medicine, Cornell University Medical College, New York, New York 10021, USA. hyhsu@ym.edu.tu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.