Differential chemokine activation of CC chemokine receptor 1-regulated pathways: ligand selective activation of Gα 14-coupled pathways
| Autor: | Patrick M. Slocombe, David C. New, Maggie M. K. Lee, Yung Hou Wong, Yaji Tian, Lisa Y. Yung, Breda Twomey, Rodger A. Allen |
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| Rok vydání: | 2004 |
| Předmět: |
CCR1
Immunology Receptors CCR1 C-C chemokine receptor type 6 Biology Ligands Transfection CCL7 Cell Line Chemokine receptor Chlorocebus aethiops Animals Humans Immunology and Allergy CCL17 Phosphorylation Chemokine CCL4 CCL13 Chemokine CCL3 JNK Mitogen-Activated Protein Kinases Macrophage Inflammatory Proteins GTP-Binding Protein alpha Subunits Cell biology Chemotaxis Leukocyte COS Cells Receptors Chemokine Chemokines Mitogen-Activated Protein Kinases CCL23 Signal Transduction CCL21 |
| Zdroj: | European Journal of Immunology. 34:785-795 |
| ISSN: | 0014-2980 |
| Popis: | Chemokines regulate the chemotaxis, development, and differentiation of many cell types enabling the regulation of routine immunosurveillance and immunological adaptation. CC chemokine receptor 1 (CCR1) is the target of 11 chemokines. This promiscuity of receptor-ligand interactions and the potential for functional redundancy has led us to investigate the selective activation of CCR1-coupled pathways by known CCR1 agonists. Chemokines leukotactin-1, macrophage inflammatory protein (MIP)-1alpha, monocyte chemotactic peptide (MCP)-3, RANTES, and MIP-1delta all inhibited adenylyl cyclase activity in cells transiently transfected with CCR1. In contrast, only MIP-1delta was unable to signal via G14-, G16- or chimeric 16z44-coupled pathways. In a stable cell line expressing CCR1 and Galpha14, all of these five chemokines along with hemofiltrate CC chemokine (HCC)-1 and myeloid progenitor inhibitory factor (MPIF)-1 were able to stimulate G(i/o)-coupled pathways, but MIP-1delta, HCC-1 and MPIF-1 were unable to activate G14-mediated stimulation of phospholipase Cbeta activity. In addition, MIP-1delta was unable to promote the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase. This suggests that different chemokines are able to selectively activate CCR1-coupled pathways, probably because of different intrinsic ligand efficacies. CCR1 and Galpha14 or Galpha16 are co-expressed in several cell types and we hypothesize that selective activation of chemokine receptors provides a mechanism by which chemokines are able to fine-tune intracellular signaling pathways. |
| Databáze: | OpenAIRE |
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