Intracellular Domains of CXCR3 That Mediate CXCL9, CXCL10, and CXCL11 Function
| Autor: | Gabriele S. V. Campanella, Andrew D. Luster, Jieti Sun, Richard A. Colvin |
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| Rok vydání: | 2004 |
| Předmět: |
Chemokine
Arrestins Ligands CXCR3 Chemokine CXCL9 Biochemistry immune system diseases Phosphorylation skin and connective tissue diseases Internalization beta-Arrestins media_common biology Chemistry Chemotaxis hemic and immune systems Recombinant Proteins Cell biology medicine.anatomical_structure Intercellular Signaling Peptides and Proteins CXCL9 Receptors Chemokine Chemokines CXC Plasmids Protein Binding Dynamins DNA Complementary Receptors CXCR3 media_common.quotation_subject T cell Blotting Western Molecular Sequence Data Transfection Cell Line Inhibitory Concentration 50 stomatognathic system medicine Humans CXCL10 CXCL11 Amino Acid Sequence Endothelium Molecular Biology Binding Sites Dose-Response Relationship Drug Cell Membrane Cell Biology Precipitin Tests Chemokine CXCL11 Protein Structure Tertiary Chemokine CXCL10 stomatognathic diseases Mutation Mutagenesis Site-Directed biology.protein Calcium |
| Zdroj: | Journal of Biological Chemistry. 279:30219-30227 |
| ISSN: | 0021-9258 |
| Popis: | The chemokine receptor CXCR3 is a G protein-coupled receptor found predominantly on T cells that is activated by three ligands as follows: CXCL9 (Mig), CXCL10 (IP-10), and CXCL11 (I-TAC). Previously, we have found that of the three ligands, CXCL11 is the most potent inducer of CXCR3 internalization and is the physiologic inducer of CXCR3 internalization after T cell contact with activated endothelial cells. We have therefore hypothesized that these three ligands transduce different signals to CXCR3. In light of this hypothesis, we sought to determine whether regions of CXCR3 are differentially required for CXCL9, CXCL10, and CXCL11 function. Here we identified two distinct domains that contributed to CXCR3 internalization. The carboxyl-terminal domain and beta-arrestin1 were predominantly required by CXCL9 and CXCL10, and the third intracellular loop was predominantly required by CXCL11. Chemotaxis and calcium mobilization induced by all three CXCR3 ligands were dependent on the CXCR3 carboxyl terminus and the DRY sequence in the third trans-membrane domain. Our findings demonstrate that distinct domains of CXCR3 mediate its functions and suggest that the differential requirement of these domains contributes to the complexity of the chemokine system. |
| Databáze: | OpenAIRE |
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