Binding and Functional Properties of Recombinant and Endogenous CXCR3 Chemokine Receptors
| Autor: | Mary Jo Staruch, Salvatore J. Siciliano, Martin S. Springer, Sandra L. Gould, Kristine E. Waldburger, Bruce L. Daugherty, Anna Sirotina-Meisher, Julie A. DeMartino, Youmin Weng |
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| Rok vydání: | 1998 |
| Předmět: |
Chemokine CCL11
CCR1 Eotaxin Receptors CXCR3 Chemokine receptor CCR5 Chemotactic Factors Eosinophil T-Lymphocytes CHO Cells C-C chemokine receptor type 6 CCR8 Lymphocyte Activation CXCR3 Chemokine CXCL9 Biochemistry Interferon-gamma Chemokine receptor stomatognathic system immune system diseases Cricetinae Animals Humans Chemokine CCL7 Cloning Molecular Receptors Cytokine Chemokine CCL5 Molecular Biology biology Chemistry hemic and immune systems Cell Biology Recombinant Proteins Monocyte Chemoattractant Proteins Up-Regulation Cell biology Chemokine CXCL10 stomatognathic diseases Chemokines CC Immunology biology.protein Cytokines Intercellular Signaling Peptides and Proteins XCL2 Receptors Chemokine Chemokines CXC Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 273:18288-18291 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.273.29.18288 |
| Popis: | IP10 and MIG are two members of the CXC branch of the chemokine superfamily whose expression is dramatically up-regulated by interferon (IFN)-gamma. The proteins act largely on natural killer (NK)-cells and activated T-cells and have been implicated in mediating some of the effects of IFN-gamma and lipopolysaccharides (LPSs), as well as T-cell-dependent anti-tumor responses. Recently both chemokines have been shown to be functional agonists of the same G-protein-coupled receptor, CXCR3. We now report the pharmacological characterization of CXCR3 and find that, when heterologously expressed, CXCR3 binds IP10 and MIG with Ki values of 0.14 and 4.9 nM, respectively. The receptor has very modest affinity for SDF-1alpha and little or no affinity for other CXC-chemokines. The properties of the endogenous receptor expressed on activated T-cells are similar. Surprisingly, several CC-chemokines, particularly eotaxin and MCP-4, also compete with moderate affinity for the binding of IP10 to CXCR3. Eotaxin does not activate CXCR3 but, in CXCR3-transfected cells, can block IP10-mediated receptor activation. Eotaxin, therefore, may be a natural CXCR3 antagonist. |
| Databáze: | OpenAIRE |
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