Phosphoproteomics Analysis of Insulin-like Growth Factor‑1 Signaling in Neuronal Cells

Phosphorylation is a key post-translational modification
that can
impact the function of a protein and the outcome of cell signaling
pathways. Using phosphoproteomics to characterize the phosphorylation
changes downstream of trophic factor signaling is important for better
understanding the pleiotropic actions of this class of molecules.
Insulin-like growth factor-1 (IGF-1) is a trophic factor that can
influence cellular growth and differentiation, and IGF-1 signaling
in the brain has been linked to cognitive processes. While its main
signaling molecules are well characterized, we sought to perform a
more in-depth and unbiased analysis of the IGF-1 phosphoproteome in
neuronal cells. To obtain insight into the IGF-1 signaling pathway
in neuronal cells, we performed a quantitative mass spectrometric
phosphoproteomics analysis in rat pheochromocytoma (PC-12) cells.
Our results illustrate a diverse phosphoproteome downstream of IGF-1,
with insight into novel phosphoprotein sites, such as Plcβ3
(Ser1105), that likely influence IGF-1 signaling in neuronal
cells. We also identify a robust upregulation of the Rho GTPase cycle
and an activation of synaptogenesis signaling downstream of IGF-1.
These results pave the way for more targeted studies on specific phosphoprotein
sites, which will facilitate a better understanding of how these phosphorylation
events impact IGF-1-related signaling outcomes in neuronal cells.