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rdf:type |
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lifeskim:mentions |
umls-concept:C0007577,
umls-concept:C0037083,
umls-concept:C0282554,
umls-concept:C0301714,
umls-concept:C0535298,
umls-concept:C0936012,
umls-concept:C1167622,
umls-concept:C1439296,
umls-concept:C1514562,
umls-concept:C1709915,
umls-concept:C1710082,
umls-concept:C1880177,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
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pubmed:issue |
24
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pubmed:dateCreated |
2001-6-11
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pubmed:abstractText |
Fractalkine (FKN/CX3CL1) is a unique member of the chemokine gene family and contains a chemokine domain (CD), a mucin-like stalk, a single transmembrane region, and a short intracellular C terminus. This structural distinction affords FKN the property of mediating capture and firm adhesion of FKN receptor (CX3CR1)-expressing cells under physiological flow conditions. Shed forms of FKN also exist, and these promote chemotaxis of CX3CR1-expressing leukocytes. The goal of the present study was to identify specific residues within the FKN-CD critical for FKN-CX3CR1 interactions. Two residues were identified in the FKN-CD, namely Lys-7 and Arg-47, that are important determinants in mediating an FKN-CX3CR1 interaction. FKN-K7A and FKN-R47A mutants exhibited 30-60-fold decreases in affinity for CX3CR1 and failed to arrest efficiently CX3CR1-expressing cells under physiological flow conditions. However, these mutants had differential effects on chemotaxis of CX3CR1-expressing cells. The FKN-K7A mutant acted as an equipotent partial agonist, whereas the FKN-R47A mutant had marked decreased potency and efficacy in measures of chemotactic activity. These data identify specific structural features of the FKN-CD that are important in interactions with CX3CR1 including steady state binding, signaling, and firm adhesion of CX3CR1-expressing cells.
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pubmed:grant |
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acids, Diamino,
http://linkedlifedata.com/resource/pubmed/chemical/CX3CL1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CX3CL1,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CX3C,
http://linkedlifedata.com/resource/pubmed/chemical/Cx3cl1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cx3cl1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytokine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, HIV,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/V28 receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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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 |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
21632-41
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:11278650-Amino Acid Sequence,
pubmed-meshheading:11278650-Amino Acid Substitution,
pubmed-meshheading:11278650-Amino Acids, Diamino,
pubmed-meshheading:11278650-Animals,
pubmed-meshheading:11278650-Binding Sites,
pubmed-meshheading:11278650-Calcium,
pubmed-meshheading:11278650-Cell Adhesion,
pubmed-meshheading:11278650-Cell Line,
pubmed-meshheading:11278650-Chemokine CX3CL1,
pubmed-meshheading:11278650-Chemokines, CX3C,
pubmed-meshheading:11278650-Chemotaxis,
pubmed-meshheading:11278650-Humans,
pubmed-meshheading:11278650-Kinetics,
pubmed-meshheading:11278650-Membrane Proteins,
pubmed-meshheading:11278650-Mice,
pubmed-meshheading:11278650-Models, Molecular,
pubmed-meshheading:11278650-Molecular Sequence Data,
pubmed-meshheading:11278650-Mutagenesis, Site-Directed,
pubmed-meshheading:11278650-Polymerase Chain Reaction,
pubmed-meshheading:11278650-Protein Structure, Secondary,
pubmed-meshheading:11278650-Rats,
pubmed-meshheading:11278650-Receptors, Cytokine,
pubmed-meshheading:11278650-Receptors, HIV,
pubmed-meshheading:11278650-Recombinant Proteins,
pubmed-meshheading:11278650-Sequence Alignment,
pubmed-meshheading:11278650-Sequence Homology, Amino Acid,
pubmed-meshheading:11278650-Signal Transduction,
pubmed-meshheading:11278650-Transfection
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pubmed:year |
2001
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pubmed:articleTitle |
Mutational analysis of the fractalkine chemokine domain. Basic amino acid residues differentially contribute to CX3CR1 binding, signaling, and cell adhesion.
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pubmed:affiliation |
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610-0267, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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