# PI3K/AKT pathway

The PI3K/AKT pathway is a central signaling line inside your cells. It is switched on by receptor tyrosine kinases (including the insulin and IGF-1 receptors), by G-protein-coupled receptors, and by other cues. PI3K (phosphoinositide 3-kinase) converts a membrane lipid, PIP2, into PIP3. PIP3 then recruits AKT (also known as protein kinase B) and its helper kinase PDK1. A second complex, mTORC2, fully switches AKT on by tagging it at Ser473. Active AKT then tags many targets. It pushes FOXO transcription factors out of the nucleus, blocks GSK-3β, promotes survival through BAD, and switches on mTORC1 through TSC2. Together these steps coordinate cell survival, glucose handling, protein building, and growth. A tumor-suppressor called PTEN opposes PI3K by stripping the phosphate back off PIP3. In worms and other animals, dialing this pathway down extends lifespan, by freeing FOXO. But in humans it is over-active in many cancers and in insulin resistance. So its role in aging is complex and depends on context.

## Sources

- Hoxhaj G, Manning BD. (2020). The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism. Nature Reviews Cancer. https://doi.org/10.1038/s41568-019-0216-7
- Porta C, Paglino C, Mosca A. (2014). Targeting PI3K/Akt/mTOR Signaling in Cancer. Frontiers in Oncology. https://doi.org/10.3389/fonc.2014.00064

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_Canonical: https://longevity-switzerland.com/en/glossary/pi3k-akt · Part of Longevity Cities · Updated 2026-06-22_