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Título:
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Analysis of Ret knockin mice reveals a critical role for IKKs, but not PI 3-K, in neurotrophic factor-induced survival of sympathetic neurons.
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Autor/a:
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Encinas Martín, Mario; Rozen, Esteban Javier; Dolcet Roca, Xavier; Jain, Sanjay; Comella i Carnicé, Joan Xavier; Milbrandt, Jeffrey; Johnson, Eugene M.
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Notas:
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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. |
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Materia(s):
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-Sistema nerviós--Malalties |
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Derechos:
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(c) ADMC Associazione Differenziamento e Morte Cellulare, 2008
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
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Tipo de documento:
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article
acceptedVersion |
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Editor:
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Nature Publishing Group
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Compartir:
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