PI3K-AKT-mTOR-FoxO1 Signaling Pathway

The IRS-PI3K-AKT-mTORC1/FoxO1 pathway is a major intracellular signaling axis that mediates the effects of insulin and growth factor binding to cell surface receptors, leading to activation of IRS proteins, recruitment and activation of PI3K, downstream phosphorylation and activation of AKT, and further engagement of mTORC1 and FoxO1 controls. The pathway governs a wide spectrum of cellular responses, including glucose and lipid metabolism, cell growth, protein synthesis, autophagy, and survival. Dysregulation is integral to metabolic diseases (diabetes, obesity), cancer, cardiovascular disease, and other pathological conditions. Each major node (PI3K, AKT, mTOR, FoxO1) is a validated therapeutic target, and modulation of signaling through this axis is central to many drug discovery efforts.

Other names

PI3K-AKT-mTOR pathwayIRS1/PI3K/AKT/mTOR pathwayInsulin signaling pathwayIGF-1/PI3K/AKT signaling axisFoxO signaling pathwayInsulin/IGF-1-PI3K-AKT-mTORC1/FoxO1 axis

Inhibition of kinase activity (PI3K, AKT, mTOR); blockade of metabolic adaptation and cell growth signals; regulation of transcription factor nuclear/cytoplasmic localization (FoxO1 retention or exclusion); and modulation of cell cycle progression and apoptosis.