Phosphoinositide 3-kinase catalytic subunit alpha (PI3Kα)

Phosphoinositide 3-kinase catalytic subunit alpha (PI3Kα, gene: PIK3CA) is a lipid kinase belonging to the Class I PI3K family of enzymes.[2][4] It catalyzes the phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2) to generate phosphatidylinositol (3,4,5)-trisphosphate (PIP3), a key step in the activation of the AKT signaling pathway that regulates diverse cellular functions including survival, growth, proliferation, and metabolism.[2][3][4] PI3Kα functions as the catalytic subunit in a heterodimer with a regulatory subunit (usually p85 in Class IA PI3Ks), and is frequently mutated or hyperactivated in many tumor types, making it a validated and important therapeutic target in cancer biology.[2][3][4] The protein structure includes an adaptor-binding domain, Ras-binding domain, C2 domain, helical domain, and a kinase domain.[2][4] The most common mutations (such as H1047R, E542K, E545K) drive oncogenesis by increasing catalytic activity or altering regulatory subunit interactions.[2][4] PI3Kα inhibitors are now approved for certain PIK3CA-mutant cancers, though side effects related to normal tissue PI3K signaling remain a challenge.[2][4]

Other names

p110αPI3K alphaPI3K-APIK3CA (gene)phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform

PI3K inhibitors block ATP binding or catalytic activity, preventing phosphorylation of phosphatidylinositols and downstream AKT pathway activation