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rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
1996-3-1
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pubmed:abstractText |
Monocyte chemoattractant protein-1 (MCP-1) mediates monocyte migration into tissues in inflammatory diseases and atherosclerosis. We have investigated structure-activity relationships for human MCP-1. Mutations were introduced based upon differences between MCP-1 and the structurally related but functionally distinct molecule interleukin-8 (IL-8). Mutant proteins produced using the baculovirus/insect cell expression system were purified and their ability to stimulate monocyte chemotaxis and elevation of intracellular calcium in THP-1 monocytic leukaemia cells was measured. Two regions in MCP-1 were identified as important for its biological activity. One region consists of the sequence Thr-Cys-Cys-Tyr (amino acids 10-13). Point mutations of Thr-10 to Arg and Tyr-13 to Ile greatly lowered MCP-1 activity. The second functionally important region is formed by Ser-34 and Lys-35. Insertion of a Pro between these two residues, or their substitution by the sequence Gly-Pro-His, caused nearly complete loss of MCP-1 activity. Competition binding experiments showed that the mutations that affected activity also lowered the ability to compete with wild-type MCP-1 for receptors on THP-1 cells. Point mutations at positions 8, 15, 30, 37, 38 and 68 had little effect on MCP-1 activity. The important regions that we have identified in MCP-1 correspond with previously identified functionally important regions of IL-8, suggesting that the two molecules bind to their respective receptors by similar contacts.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8573103-14450081,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8573103-1681733,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/8573103-8512707
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0264-6021
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
313 ( Pt 2)
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
633-40
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8573103-Amino Acid Sequence,
pubmed-meshheading:8573103-Animals,
pubmed-meshheading:8573103-Baculoviridae,
pubmed-meshheading:8573103-Base Sequence,
pubmed-meshheading:8573103-Binding, Competitive,
pubmed-meshheading:8573103-Cell Line,
pubmed-meshheading:8573103-Chemokine CCL2,
pubmed-meshheading:8573103-Chromatography, Ion Exchange,
pubmed-meshheading:8573103-DNA Primers,
pubmed-meshheading:8573103-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:8573103-Humans,
pubmed-meshheading:8573103-Molecular Sequence Data,
pubmed-meshheading:8573103-Mutagenesis, Site-Directed,
pubmed-meshheading:8573103-Protein Conformation,
pubmed-meshheading:8573103-Recombinant Proteins,
pubmed-meshheading:8573103-Spodoptera
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pubmed:year |
1996
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pubmed:articleTitle |
Site-directed mutagenesis of monocyte chemoattractant protein-1 identifies two regions of the polypeptide essential for biological activity.
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pubmed:affiliation |
Neurobiotechnology Center, Ohio State University, Columbus 43210, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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