Publicação
IL-7 induces rapid clathrin-mediated internalization and JAK3-dependent degradation of IL-7Rα in T cells
| dc.contributor.author | Henriques, Catarina M. | |
| dc.contributor.author | Rino, José | |
| dc.contributor.author | Nibbs, Robert J. | |
| dc.contributor.author | Graham, Gerry J. | |
| dc.contributor.author | Barata, João T. Barata | |
| dc.date.accessioned | 2013-02-01T12:13:31Z | |
| dc.date.available | 2013-02-01T12:13:31Z | |
| dc.date.issued | 2010 | |
| dc.description | © 2010 by The American Society of Hematology | eng |
| dc.description.abstract | Interleukin-7 (IL-7) is an essential cytokine for T-cell development and homeostasis. It is well established that IL-7 promotes the transcriptional down-regulation of IL7RA, leading to decreased IL-7Rα surface expression. However, it is currently unknown whether IL-7 regulates the intracellular trafficking and early turnover of its receptor on ligand binding. Here, we show that, in steady-state T cells, IL-7Rα is slowly internalized and degraded while a significant fraction recycles back to the surface. On IL-7 stimulation, there is rapid IL-7Rα endocytosis via clathrin-coated pits, decreased receptor recycling, and accelerated lysosome and proteasome-dependent degradation. In accordance, the half-life of IL-7Rα decreases from 24 hours to approximately 3 hours after IL-7 treatment. Interestingly, we further demonstrate that clathrin-dependent endocytosis is necessary for efficient IL-7 signal transduction. In turn, pretreatment of T cells with JAK3 or pan-JAK inhibitors suggests that IL-7Rα degradation depends on the activation of the IL-7 signaling effector JAK3. Overall, our findings indicate that IL-7 triggers rapid IL-7Rα endocytosis, which is required for IL-7–mediated signaling and subsequent receptor degradation. | eng |
| dc.description.sponsorship | This work was supported by Instituto de Medicina Molecular startup funds and by Fundação para a Ciência e a Tecnologia (grant PTDC/SAU-OBD/104816/2008; J.T.B.). C.M.H. has an FCTSFRH PhD fellowship. | eng |
| dc.identifier.citation | Blood, 22 April 2010 . Volume 115, Number 16 | eng |
| dc.identifier.issn | 0006-4971 | |
| dc.identifier.uri | http://dx.doi.org/10.1182/blood-2009-10-246876 | |
| dc.identifier.uri | http://hdl.handle.net/10451/7628 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | American Society of Hematology | eng |
| dc.title | IL-7 induces rapid clathrin-mediated internalization and JAK3-dependent degradation of IL-7Rα in T cells | eng |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 3277 | por |
| oaire.citation.startPage | 3269 | por |
| oaire.citation.title | Blood | eng |
| oaire.citation.volume | 115 | por |
| rcaap.rights | restrictedAccess | por |
| rcaap.type | article | por |