PI3K/Akt

The PI3K/Akt pathway is a central regulator of cell growth, survival, metabolism and proliferation. It is one of the most frequently dysregulated pathways in cancer, which makes it a major drug target.

How the pathway works

1. A growth-factor receptor (e.g. an RTK) activates PI3K, which converts membrane PIP₂ to PIP₃.
2. PIP₃ recruits Akt (PKB) and PDK1 to the membrane; Akt is phosphorylated and activated (PDK1 and mTORC2).
3. Active Akt phosphorylates many targets to promote survival, growth and metabolism, including activation of mTORC1 (protein synthesis) and inhibition of pro-apoptotic factors.

Key regulator: PTEN

PTEN is the main brake on the pathway — it dephosphorylates PIP₃ back to PIP₂. Loss of PTEN (common in cancer) leaves the pathway constitutively active.

Why it matters

Activating mutations in PIK3CA, loss of PTEN, and Akt/mTOR dysregulation drive many cancers and overgrowth syndromes. PI3K, Akt and mTOR inhibitors are used or in trials across oncology, and the pathway is central to metabolism and insulin signalling.

Explore the pathway

• KEGG: PI3K–Akt signalling pathway
• Reactome — search “PI3K/AKT”.
• Cell Signaling Technology pathways

Frequently asked questions

What does the PI3K/Akt pathway control?

Cell survival, growth, proliferation and metabolism, partly through activation of mTORC1.

What is the role of PTEN?

PTEN is the negative regulator that converts PIP₃ back to PIP₂; its loss leaves the pathway constitutively active.

Why is PI3K/Akt important in cancer?

Activating PIK3CA mutations and PTEN loss are common oncogenic events, and PI3K/Akt/mTOR inhibitors are used or in development in oncology.