Anti-apoptotic signaling of the insulin-like growth factor-I receptor through mitochondrial translocation of c-Raf and Nedd4.
J Biol Chem
; 276(28): 25990-6, 2001 Jul 13.
Article
en En
| MEDLINE
| ID: mdl-11352919
ABSTRACT
The type 1 insulin-like growth factor receptor (IGF-IR) sends a strong anti-apoptotic signal by at least three different pathways. By using mutants of the IGF-IR, we showed that one of the pathways depends on residues of the IGF-IR (serines 1280--1283) that interact with 14.3.3 proteins. The result is the activation of Raf-1 and the mitochondrial translocation of both Raf-1 and Nedd4, a target of caspases. A mutant IGF-IR in which the serines at positions 1280--1283 have been mutated to alanine does not protect from apoptosis and fails to translocate Nedd4 or Raf-1 to the mitochondria. This failure is accompanied by a loss of cytochrome c from the mitochondria. The 14.3.3/Raf-1/Nedd4 pathway is operative in the presence or absence of the insulin receptor substrate-1.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Unión al Calcio
/
Receptor IGF Tipo 1
/
Apoptosis
/
Proteínas Proto-Oncogénicas c-raf
/
Ubiquitina-Proteína Ligasas
/
Ligasas
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos