| First Author | Delcourt N | Year | 2007 |
| Journal | EMBO J | Volume | 26 |
| Issue | 6 | Pages | 1542-51 |
| PubMed ID | 17332755 | Mgi Jnum | J:341313 |
| Mgi Id | MGI:7466453 | Doi | 10.1038/sj.emboj.7601608 |
| Citation | Delcourt N, et al. (2007) PACAP type I receptor transactivation is essential for IGF-1 receptor signalling and antiapoptotic activity in neurons. EMBO J 26(6):1542-51 |
| abstractText | 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. |
