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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Mellado, Mario Miranda-carús, María Eugenia Gómez-cabañas, Laura González-bethencourt, Ivan Luis Delgado-martín, Cristina Regueiro, José Ramón López-cotarelo, Pilar Deguiz, María Laura Rodríguez-fernández, José Luis Escribano-díaz, Cristina Gómez-moreira, Carolina Torres-bacete, Jesús Fernández-barrera, Jaime |
| Description | Author Affiliation: López-Cotarelo P ( From the CIB/CSIC (Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas), 28040 Madrid.); Escribano-Díaz C ( From the CIB/CSIC (Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas), 28040 Madrid.); González-Bethencourt IL ( From the CIB/CSIC (Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas), 28040 Madrid.); Gómez-Moreira C ( From the CIB/CSIC (Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas), 28040 Madrid.); Deguiz ML ( From the CIB/CSIC (Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas), 28040 Madrid.); Torres-Bacete J ( From the CIB/CSIC (Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas), 28040 Madrid.); Gómez-Cabañas L ( From the CIB/CSIC (Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas), 28040 Madrid.); Fernández-Barrera J ( From the CIB/CSIC (Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas), 28040 Madrid.); Delgado-Martín C ( From the CIB/CSIC (Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas), 28040 Madrid.); Mellado M ( the CNB/CSIC (Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas,) 28049 Madrid.); Regueiro JR ( the School of Medicine, Universidad Complutense, 28040 Madrid, and.); Miranda-Carús ME ( the Department of Rheumatology, Hospital La Paz, 28046 Madrid, Spain.); Rodríguez-Fernández JL ( From the CIB/CSIC (Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas), 28040 Madrid, rodrifer@cib.csic.es.) |
| Abstract | Chemokine receptor CCR7 directs mature dendritic cells (mDCs) to secondary lymph nodes where these cells regulate the activation of T cells. CCR7 also promotes survival in mDCs, which is believed to take place largely through Akt-dependent signaling mechanisms. We have analyzed the involvement of the AMP-dependent kinase (AMPK) in the control of CCR7-dependent survival. A pro-apoptotic role for AMPK is suggested by the finding that pharmacological activators induce apoptosis, whereas knocking down of AMPK with siRNA extends mDC survival. Pharmacological activation of AMPK also induces apoptosis of mDCs in the lymph nodes. Stimulation of CCR7 leads to inhibition of AMPK, through phosphorylation of Ser-485, which was mediated by G(i)/Gßγ, but not by Akt or S6K, two kinases that control the phosphorylation of AMPK on Ser-485 in other settings. Using selective pharmacological inhibitors, we show that CCR7-induced phosphorylation of AMPK on Ser-485 is mediated by MEK and ERK. Coimmunoprecipitation analysis and proximity ligation assays indicate that AMPK associates with ERK, but not with MEK. These results suggest that in addition to Akt-dependent signaling mechanisms, CCR7 can also promote survival of mDCs through a novel MEK1/2-ERK1/2-AMPK signaling axis. The data also suggest that AMPK may be a potential target to modulate mDC lifespan and the immune response. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 2 |
| Volume Number | 290 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2015-01-09 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | AMP-Activated Protein Kinases Genetics Immunity, Innate MAP Kinase Kinase 1 MAP Kinase Kinase 2 Receptors, CCR7 Metabolism Apoptosis Cell Survival Dendritic Cells Immunology Mitogen-Activated Protein Kinase 3 Phosphorylation Signal Transduction T-Lymphocytes Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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