Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (p110α) (p110α)

The Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (p110α), encoded by the PIK3CA gene, is the catalytic subunit of class IA phosphoinositide 3-kinase (PI3K), a lipid kinase that phosphorylates phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) at the 3-position of the inositol ring to generate phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3). This second messenger recruits and activates downstream effectors like AKT (PKB) and PDK1 via pleckstrin homology domains, driving the PI3K/AKT/mTOR pathway central to cellular processes including growth, proliferation, survival, motility, and metabolism. p110α forms a heterodimer with regulatory subunits such as p85α (PIK3R1), which inhibit basal activity until relieved by receptor tyrosine kinase (RTK) signaling or other stimuli. Gain-of-function PIK3CA mutations, common in cancers like breast, colorectal, and endometrial tumors, hyperactivate the pathway, promoting oncogenesis and resistance to therapies. As a validated therapeutic target, isoform-selective or pan-class I PI3K inhibitors like alpelisib (approved for PIK3CA-mutant breast cancer) block this hyperactivity, though challenges include metabolic toxicities from insulin pathway interference. Ubiquitously expressed, p110α also influences immune responses and neuronal functions, with dysregulation linked to immunodeficiencies and neurodegeneration.

Other names

PI3K catalytic subunit alphaphosphatidylinositol 3-kinase catalytic alpha polypeptidep110-alphaphosphoinositide-3-kinase catalytic alpha polypeptide

Inhibition of lipid kinase activity, preventing phosphorylation of phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate, blocking PI3K/AKT/mTOR pathway activation