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PACAP type I receptor transactivation is essential for IGF-1 receptor signalling and antiapoptotic activity in neurons.: IGF-1 transactivates PACAP type I receptors

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.
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https://www.hal.inserm.fr/inserm-00151734
Contributor : Angie Madeuf <>
Submitted on : Friday, September 28, 2007 - 2:05:35 PM
Last modification on : Friday, March 6, 2020 - 4:54:02 PM
Long-term archiving on: : Thursday, April 8, 2010 - 6:54:46 PM

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Nicolas Delcourt, Eric Thouvenot, Benjamin Chanrion, Nathalie Galéotti, Patrick Jouin, et al.. PACAP type I receptor transactivation is essential for IGF-1 receptor signalling and antiapoptotic activity in neurons.: IGF-1 transactivates PACAP type I receptors. EMBO Journal, EMBO Press, 2007, 26 (6), pp.1542-51. ⟨10.1038/sj.emboj.7601608⟩. ⟨inserm-00151734⟩

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