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Abstract #123592 Published in IGR 25-1
Membrane-anchored intracellular insulin receptor or insulin-like growth factor-1 receptor elicits ligand-independent downstream signaling
Sotozono A; Namekata K; Guo X; Shinozaki Y; Harada C; Noro T; Nakano T; Harada TBiochemistry and biophysics reports 2024; 39: 101799
Neurodegenerative diseases including glaucoma affect insulin signaling, and insulin treatment has been shown to reverse the neurodegenerative loss of dendritic complexity in retinal ganglion cells. Therefore, strategies for enhancing or maintaining insulin signaling are worth pursuing to establish new therapies for these diseases. In the present study, we generated constitutively active insulin receptor (F-iIR) and insulin-like growth factor-1 receptor (F-iIGF1R) using a system that forces membrane localization of the intracellular domains of these receptors by farnesylation. Immunohistochemistry and Western blot analysis revealed that F-iIR and F-iIGF1R caused the activation of ERK and AKT in the absence of ligands . Our results suggest that effects of F-iIR and F-iIGF1R on the progression of neurodegenerative diseases should be investigated in the future.
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