Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3Kα) (PI3Kα)

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3Kα) is a class IA PI3K enzyme consisting of a p110α catalytic subunit and a p85 regulatory subunit (UniProt: P42336). It plays a central role in the PI3K/AKT/mTOR signaling pathway, which is vital for regulating cell proliferation, survival, and intracellular trafficking (PubMed: 29735994). PI3Kα is particularly significant in oncology as the PIK3CA gene is frequently mutated or amplified in various cancers, including breast, lung, and colorectal cancers (NIH: National Cancer Institute). In addition to its role in cancer, PI3Kα is a key mediator of insulin signaling, and its inhibition often leads to metabolic side effects such as hyperglycemia (StatPearls: Phosphoinositide 3 Kinase Inhibitors). Drugs like alpelisib are specifically designed to target this isoform to treat PIK3CA-mutated advanced breast cancer (FDA: Piqray). Understanding the wild-type function is crucial for managing the therapeutic window and safety profile of these inhibitors.

Other names

PIK3CAp110αPhosphoinositide-3-kinase catalytic alpha polypeptidep110-alphaPhosphatidylinositol 3-kinase catalytic subunit alpha

Inhibition of the catalytic activity of the p110α subunit, preventing the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3), thereby downregulating the AKT/mTOR signaling pathway (PubMed: 30545854).