PACAP type I receptor transactivation is essential for IGF-1 receptor signalling and antiapoptotic activity in neurons.
EMBO J
; 26(6): 1542-51, 2007 Mar 21.
Article
em En
| MEDLINE
| ID: mdl-17332755
ABSTRACT
Insulin-like growth factor-1 (IGF-1) and pituitary adenylyl cyclase activating polypeptide (PACAP) are both potent neurotrophic and antiapoptotic factors, which exert their effects via phosphorylation cascades initiated by tyrosine kinase and G-protein-coupled receptors, respectively. Here, we have adapted a recently described phosphoproteomic approach to neuronal cultures to characterize the phosphoproteomes generated by these neurotrophic factors. Unexpectedly, IGF-1 and PACAP increased the phosphorylation state of a common set of proteins in neurons. Using PACAP type 1 receptor (PAC1R) null mice, we showed that IGF-1 transactivated PAC1Rs constitutively associated with IGF-1 receptors. This effect was mediated by Src family kinases, which induced PAC1R phosphorylation on tyrosine residues. PAC1R transactivation was responsible for a large fraction of the IGF-1-associated phosphoproteome and played a critical role in the antiapoptotic activity of IGF-1. Hence, in contrast to the general opinion that the trophic activity of IGF-1 is solely mediated by tyrosine kinase receptor-associated signalling, we show that it involves a more complex signalling network dependent on the PAC1 Gs-protein-coupled receptor in neurons.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Insulin-Like I
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Transdução de Sinais
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Ativação Transcricional
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Apoptose
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Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
França