Analysis of Ret knockin mice reveals a critical role for IKKs, but not PI 3-K, in neurotrophic factor-induced survival of sympathetic neurons.
Rozen, Esteban Javier
Comella i Carnicé, Joan Xavier
Johnson, Eugene M.
MetadataShow full item record
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.
Is part ofCell Death and Differentiation, 2008, vol. 15, núm. 9, p. 1510-1521
European research projects
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as (c) ADMC Associazione Differenziamento e Morte Cellulare, 2008
Showing items related by title, author, creator and subject.
Egea Navarro, Joaquim; Espinet Mestre, Carme; Soler i Tatché, Rosa Ma.; Dolcet Roca, Xavier; Yuste Mateos, Víctor J. (Víctor José); Encinas Martín, Mario; Iglesias Durán, Montserrat; Rocamora Ibars, Nativitat; Comella i Carnicé, Joan Xavier (Rockefeller University Press, 2001)It has been reported that phosphoinositide 3-kinase (PI 3-kinase) and its downstream target, protein kinase B (PKB), play a central role in the signaling of cell survival triggered by neurotrophins (NTs). In this report, ...
Activation of Phosphatidylinositol 3-Kinase, but Not Extracellular-Regulated Kinases, Is Necessary to Mediate BrainDerived Neurotrophic Factor-Induced Motoneuron Survival Dolcet Roca, Xavier; Egea Navarro, Joaquim; Soler i Tatché, Rosa Ma.; Martin-Zanca, Dionisio; Comella i Carnicé, Joan Xavier (Wiley, 1999)Chick embryo spinal cord motoneurons develop a trophic response to some neurotrophins when they are maintained in culture in the presence of muscle extract. Thus, after 2 days in culture, brain-derived neurotrophic factor ...
The prevention of the staurosporine-induced apoptosis by Bcl-XL, but not by Bcl-2 or caspase inhibitors, allows the extensive differentiation of human neuroblastoma cells Yuste Mateos, Víctor J. (Víctor José); Sánchez-López, Isabel; Solé Serra, Carme; Encinas Martín, Mario; Bayascas Ramírez, José Ramón; Boix Torras, Jacint; Comella i Carnicé, Joan Xavier (Wiley, 2002)Staurosporine is one of the best apoptotic inducers in different cell types including neuroblastomas. In this study we have compared the efficiency and final outcome of three different anti-apoptotic strategies in ...