Figure 3.

Comparative analysis of the regulation of the insulin/IGF1–AKT–mTOR pathway in clinical and preclinical studies. Upon receptor activation, IRS1 promotes the phosphorylation of phosphatidylinositol 4,5‐bisphosphate into phosphatidylinositol 3,4,5‐triphosphate at the plasma membrane by recruiting the kinase PI3K. Phospholipid phosphorylation promotes AKT recruitment and activation by PDK1. AKT positively or negatively regulates multiple targets including mTOR from the mTORC1 complex (not represented) and FOXO transcription factors. AMPK, whose activity is increased by energy stress, is another important modulator of the pathway. Black arrows indicate post‐translational regulation. Red arrows indicate transcriptional regulation. Significant variations are reported in red (increase) or blue (decrease). Unchanged levels are reported in white.