Phosphatidylinositol 3-kinase–Akt–mammalian target of rapamycin pathway (PI3K–Akt–mTOR pathway)

The phosphatidylinositol 3-kinase–Akt–mammalian target of rapamycin pathway—commonly known as the PI3K–Akt–mTOR pathway—is a key intracellular signaling cascade that regulates cellular processes including cycle progression, survival, proliferation, metabolism, and growth[1][2][3]. It is activated by extracellular stimuli such as growth factors and cytokines that act through receptor tyrosine kinases, leading first to PI3K activation and subsequent AKT phosphorylation and activation at the plasma membrane[1][3][4]. Activated AKT phosphorylates several downstream effectors, notably mTOR (mechanistic target of rapamycin), thereby promoting protein synthesis, cell growth, and survival while inhibiting apoptosis[1][2][4]. Overactivity or mutation of this pathway is a prominent feature of many cancers, making it a prime therapeutic target, although inhibition can present metabolic and immunological safety concerns[1][2][5][6][7]. Note on is_incorrect: This is not a single molecule or a membrane-bound "receptor", but rather a multi-component intracellular signaling pathway encompassing several distinct molecular targets (PI3K isoforms, AKT isoforms, mTOR complexes). For structure-activity or drug development databases that require targets to be single molecules/proteins, this designation is overly broad and not technically precise. Individual components (e.g., "Phosphatidylinositol 3-kinase catalytic subunit alpha", "AKT1", "mechanistic target of rapamycin") are typically the precise entries.

Other names

PI3K–Akt pathwayPI3K–Akt–mTOR signaling pathwayPhosphatidylinositol 3-kinase–protein kinase B–mTOR pathwayPI3K/AKT/mTOR pathwayPI3K/Akt pathway

Inhibition of PI3K enzymatic activity; Inhibition of mTOR kinase activity; Blockade of downstream protein phosphorylation; Suppression of cell cycle progression; Induction of apoptosis