The Gßγ-Src signaling pathway regulates TNF-induced necroptosis via control of necrosome translocation.
Cell Res
; 24(4): 417-32, 2014 Apr.
Article
en En
| MEDLINE
| ID: mdl-24513853
ABSTRACT
Formation of multi-component signaling complex necrosomes is essential for tumor necrosis factor α (TNF)-induced programmed necrosis (also called necroptosis). However, the mechanisms of necroptosis are still largely unknown. We isolated a TNF-resistant L929 mutant cell line generated by retrovirus insertion and identified that disruption of the guanine nucleotide-binding protein γ 10 (Gγ10) gene is responsible for this phenotype. We further show that Gγ10 is involved in TNF-induced necroptosis and Gß2 is the partner of Gγ10. Src is the downstream effector of Gß2γ10 in TNF-induced necroptosis because TNF-induced Src activation was impaired upon Gγ10 knockdown. Gγ10 does not affect TNF-induced activation of NF-κB and MAPKs and the formation of necrosomes, but is required for trafficking of necrosomes to their potential functioning site, an unidentified subcellular organelle that can be fractionated into heterotypic membrane fractions. The TNF-induced Gßγ-Src signaling pathway is independent of RIP1/RIP3 kinase activity and necrosome formation, but is required for the necrosome to function.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor de Necrosis Tumoral alfa
/
Apoptosis
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Familia-src Quinasas
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Vesículas Citoplasmáticas
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Subunidades beta de la Proteína de Unión al GTP
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Subunidades gamma de la Proteína de Unión al GTP
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Res
Año:
2014
Tipo del documento:
Article
País de afiliación:
China