Signal transduction by CXC chemokine receptor 4. Stromal cell-derived factor 1 stimulates prolonged protein kinase B and extracellular signal-regulated kinase 2 activation in T lymphocytes
| Autor: | B, Tilton, L, Ho, E, Oberlin, P, Loetscher, F, Baleux, I, Clark-Lewis, M, Thelen |
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| Rok vydání: | 2000 |
| Předmět: |
Receptors
CXCR4 Time Factors T-Lymphocytes Down-Regulation PI 3-kinase Protein Serine-Threonine Kinases SDF-1 Mice Proto-Oncogene Proteins Animals Humans Enzyme Inhibitors Cells Cultured Phosphoinositide-3 Kinase Inhibitors Mitogen-Activated Protein Kinase 1 CXCR4 Dose-Response Relationship Drug Chemokine CXCL12 Androstadienes Enzyme Activation protein kinase B Original Article Wortmannin Chemokines CXC Proto-Oncogene Proteins c-akt signal transduction |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | We report that stromal cell-derived factor (SDF)-1 has the remarkable capacity to induce sustained signaling through CXC chemokine receptor 4 (CXCR4). In contrast to other chemokines, such as monocyte chemotactic protein 1 (CC chemokine receptor 2 [CCR2]), macrophage inflammatory protein 1beta (CCR5), liver and activation-regulated chemokine (LARC [CCR6]), Epstein-Barr virus-induced molecule 1 ligand chemokine (ELC [CCR7]), and IP10 (CXCR3), SDF-1 stimulates the prolonged activation of protein kinase B and extracellular signal-regulated kinase (ERK)-2. Activation of protein kinase B is reversed by displacement of SDF-1 from CXCR4 or inhibition of phosphatidylinositol 3-kinase. Although increasing concentrations of SDF-1 enhance CXCR4 internalization, kinase activation is prolonged. In addition, restimulation yields60% of initial protein kinase B activity, indicating that the remaining receptors are not desensitized. Furthermore, activation is prolonged by inhibiting SDF-1 degradation. The sustained activation of cell survival and mitogenic pathways may account for the unique role of SDF-1 and CXCR4 in embryogenesis and lymphopoiesis. |
| Databáze: | OpenAIRE |
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