Phosphatidylinositol 3-kinase–protein kinase B–Bcl-2-associated death promoter signaling pathway (PI3K–Akt–Bad signaling pathway)

The phosphatidylinositol 3-kinase–protein kinase B–Bcl-2-associated death promoter (PI3K–Akt–Bad) signaling pathway is a critical intracellular signal transduction cascade that regulates cell survival, proliferation, apoptosis, and metabolism. Activation of PI3K leads to generation of lipid second messengers that recruit and activate Akt, a serine/threonine kinase, which in turn phosphorylates and inactivates pro-apoptotic proteins like Bad, thereby promoting cell survival. Dysregulation of this pathway—by genetic mutations, loss of tumor suppressors (e.g., PTEN), or aberrant upstream signaling—is a hallmark of many cancers and underlies resistance to chemotherapy, as well as roles in neurodegenerative and metabolic diseases. This pathway is commonly targeted in cancer therapy using specific inhibitors of PI3K or Akt, though its widespread physiological roles create therapeutic challenges regarding specificity and toxicity

Other names

PI3K–Akt pathwayPI3K–Akt–Bad axisPI3K/Akt signaling pathway (alternate, but excludes Bad)

Inhibition of PI3K activity (blocks generation of PI(3,4,5)P3, impeding downstream Akt activation) Inhibition of Akt activation (direct Akt inhibitors prevent phosphorylation of downstream targets, including Bad) Disruption of AKT-mediated phosphorylation of Bad (thereby promoting apoptosis)