Phosphatidylinositol 3-kinase alpha, beta, gamma, or delta (PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ)

Phosphatidylinositol 3-kinase (PI3K) is a family of lipid kinases that phosphorylate the 3' hydroxyl group of the inositol ring of phosphoinositides, generating important second messengers for intracellular signal transduction. Class I PI3Ks include four catalytic subunit isoforms in humans: alpha (PIK3CA), beta (PIK3CB), gamma (PIK3CG), and delta (PIK3CD). Each of these enzymes partners with distinct regulatory subunits and exhibits distinct tissue-specific expression and biological functions: PI3Kα and PI3Kβ are widely expressed, whereas PI3Kγ and PI3Kδ are predominantly found in leukocytes[1][2][3][6][7]. They are central regulators of the PI3K/AKT/mTOR pathway, influencing cell proliferation, growth, survival, and metabolism. Genetic mutations and/or aberrant activation of PI3K, especially PI3Kα, are common drivers in many cancers. The isoforms are considered important therapeutic targets, and multiple PI3K isoform-selective inhibitors have been developed and approved for oncology and immunology indications, though their clinical use is complicated by significant toxicity[1][3][4][5].

Other names

PI3KClass I PI3Kp110α (alpha)p110β (beta)p110γ (gamma)p110δ (delta)Phosphoinositide 3-kinase

Inhibition of PI3K activity (block phosphorylation of phosphoinositides, thereby blocking signal transduction through the PI3K/AKT/mTOR pathway)