Phosphoinositide 3-kinase–Akt signaling pathway (PI3K–Akt pathway)

The phosphoinositide 3‑kinase–Akt signaling pathway is an evolutionarily conserved intracellular signal transduction network that regulates fundamental cellular processes including transcription, translation, proliferation, growth and survival in response to extracellular cues such as growth factors or hormones. Activation typically begins at membrane-bound receptors like RTKs or GPCRs which stimulate class I PI3Ks; these generate phosphatidylinositol-(3,4,5)-trisphosphate at the plasma membrane. This lipid second messenger recruits Akt via its pleckstrin homology domain; subsequent phosphorylation events fully activate Akt. Activated Akt phosphorylates numerous substrates involved in metabolism regulation (including glucose uptake), protein synthesis via mTORC1 activation/inhibition pathways controlling apoptosis/cell cycle progression. Dysregulation—often through mutation/loss of negative regulators like PTEN—leads to pathological states including cancer progression/resistance mechanisms as well as metabolic diseases like diabetes mellitus.

Other names

PI3K–Akt pathwayAkt/PKB signaling pathwayPhosphatidylinositol 3'-kinase–protein kinase B (PKB) pathway

Inhibition of catalytic activity of PI3Ks to block PIP₃ production and downstream activation. Direct inhibition of AKT phosphorylation/activity. Inhibition of mTOR complexes downstream in the cascade. These mechanisms lead to reduced cell proliferation/survival signals in cancer cells.