Phosphoinositide 3-kinase class I enzyme (Class I PI3K)

Class I phosphoinositide 3-kinase enzymes are heterodimeric lipid kinases composed of a catalytic and a regulatory subunit, which function as key signal transducers downstream of activated cell surface receptors such as receptor tyrosine kinases and G-protein-coupled receptors. There are four human class I catalytic isoforms—p110α, p110β, p110δ (class IA, usually with p85 regulatory subunits), and p110γ (class IB, with p101 or p87/p84 regulatory subunits). They phosphorylate phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) to generate phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3), recruiting pleckstrin homology-domain proteins such as AKT and PDK1 to the membrane and activating downstream pathways that regulate cell growth, proliferation, metabolism, survival, and migration. Dysregulation and mutations of class I PI3Ks—especially PIK3CA (encoding p110α)—are frequent drivers in many cancers and are therapeutic targets of several approved and investigational drugs. Isoform-selective PI3K inhibitors are approved for use in certain cancers and under investigation for inflammatory or immune diseases, but clinical use is limited by immune suppression, metabolic, and other class-specific side effects.

Other names

Class I phosphoinositide 3-kinaseClass IA PI3KClass IB PI3KPI3Kα (PIK3CA)PI3Kβ (PIK3CB)PI3Kδ (PIK3CD)PI3Kγ (PIK3CG)p110αp110βp110δp110γ

Inhibition of PI3K enzymatic activity, reducing PIP3 production; Blocking PI3K-mediated AKT/mTOR signaling; Induction of apoptosis or cell cycle arrest in cancer cells; Modulation of immune cell function via decreased chemotaxis or cytokine production