Phosphatidylinositol 3-kinase–protein kinase B signaling pathway (PI3K-Akt pathway) (PI3K-Akt pathway)

The Phosphatidylinositol 3-kinase (PI3K)–protein kinase B (Akt) signaling pathway is a central intracellular signal transduction system that regulates a diverse array of cellular processes, including growth, motility, survival, and metabolism (PMID: 29633453). The pathway is typically activated by the binding of extracellular signals, such as growth factors or insulin, to receptor tyrosine kinases (RTKs) or G protein-coupled receptors (GPCRs), which then recruit PI3K to the plasma membrane (StatPearls, NBK557544). Once activated, PI3K generates the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3), which facilitates the recruitment and activation of the serine/threonine kinase Akt and its downstream effectors like mTOR (KEGG, hsa04151). Dysregulation of this pathway is one of the most frequent alterations in human cancers, often resulting from gain-of-function mutations in PIK3CA or the loss of the tumor suppressor PTEN, which normally acts as a negative regulator by dephosphorylating PIP3 (PMID: 19448670). While the pathway is a high-priority target for oncology therapeutics, drug development is complicated by the pathway's essential role in systemic glucose homeostasis, frequently leading to metabolic side effects such as hyperglycemia and insulin resistance (PMID: 31065115).

Other names

PI3K/Akt/mTOR pathwayPI3K-Akt signaling cascadePhosphatidylinositol 3-kinase signalingAkt signaling pathway

Inhibition of specific enzymatic nodes within the pathway, such as PI3K isoforms (alpha, delta, gamma), Akt, or the downstream mTOR complex, to disrupt signaling cascades that drive tumor growth and survival (PMID: 30675020).