dc.contributor.author |
Encinas Martín, Mario |
dc.contributor.author |
Rozen, Esteban Javier |
dc.contributor.author |
Dolcet Roca, Xavier |
dc.contributor.author |
Jain, Sanjay |
dc.contributor.author |
Comella i Carnicé, Joan Xavier |
dc.contributor.author |
Milbrandt, Jeffrey |
dc.contributor.author |
Johnson, Eugene M. |
dc.date |
2015-02-02T09:07:38Z |
dc.date |
2015-02-02T09:07:38Z |
dc.date |
2008 |
dc.identifier |
http://hdl.handle.net/10459.1/47782 |
dc.identifier |
https://doi.org/10.1038/cdd.2008.76 |
dc.identifier.uri |
http://hdl.handle.net/10459.1/47782 |
dc.description |
We analyzed the survival responses and downstream signaling elicited by GDNF on sympathetic
neurons from different Ret knockin mice. Lack of tyrosine 1062, a multidocking site in Ret,
completely prevented GDNF-mediated survival. Importantly lack of tyrosine 981, although
abrogating Akt phosphorylation, had no effect on neuronal survival, indicating that the PI 3-K/Akt
pathway is not necessary for survival of sympathetic neurons. In contrast, silencing of B-Raf
completely prevented not only GDNF-mediated but also NGF-mediated cell survival, independently
of MEK-1/2. We identified IKKs as the main effectors of the protective effects of B-Raf. First, BRaf
interacted with and activated IKKs. Second, knockdown of IKKs reversed the protection afforded
by a constitutively active form of B-Raf. Third, knockdown of IKKs prevented both NGF- and
GDNF-mediated survival. In conclusion, our data delineate a novel survival pathway for sympathetic
neurons linking B-Raf to IKKs, independently of both PI 3-K and MEK-1/2 pathways. |
dc.language |
eng |
dc.publisher |
Nature Publishing Group |
dc.relation |
Reproducció del document publicat a https://doi.org/10.1038/cdd.2008.76 |
dc.relation |
Cell Death and Differentiation, 2008, vol. 15, núm. 9, p. 1510-1521 |
dc.rights |
(c) ADMC Associazione Differenziamento e Morte Cellulare, 2008 |
dc.rights |
http://creativecommons.org/licenses/by-nc-nd/3.0/es/ |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Sistema nerviós--Malalties |
dc.title |
Analysis of Ret knockin mice reveals a critical role for IKKs, but not PI 3-K, in neurotrophic factor-induced survival of sympathetic neurons. |
dc.type |
article |
dc.type |
acceptedVersion |