Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) (PI3Kα)

The Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, commonly known as PI3Kα or p110α, is a critical lipid kinase that serves as a central node in the PI3K/AKT/mTOR signaling pathway (UniProt P42336). It functions by phosphorylating phosphatidylinositol 4,5-bisphosphate (PIP2) to generate the second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3) at the plasma membrane, which recruits and activates downstream effectors like AKT to promote cell growth, survival, and metabolism (Fruman et al., 2017). PIK3CA is one of the most frequently mutated oncogenes in human cancers, with 'hotspot' mutations in the helical (e.g., E542K, E545K) and kinase (e.g., H1047R) domains leading to constitutive enzyme activation (PubMed: 29033130). These mutations are particularly prevalent in hormone receptor-positive breast cancer, where they contribute to endocrine therapy resistance (Andre et al., 2019). Therapeutic targeting of PI3Kα with selective inhibitors like alpelisib has demonstrated clinical efficacy, leading to FDA approval for specific breast cancer indications (FDA, 2019). However, because PI3Kα is essential for insulin-mediated glucose uptake, its inhibition frequently results in systemic hyperglycemia, which remains a significant clinical management challenge (StatPearls: Phosphoinositide 3-kinase Inhibitors).

Other names

PIK3CAp110αp110-alphaPhosphoinositide-3-kinase catalytic alpha polypeptidePtdIns-3-kinase subunit alpha

Selective or pan-class I inhibition of the PI3K catalytic activity by competing with ATP for the binding site within the p110α subunit, thereby preventing the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3) and inhibiting downstream AKT/mTOR signaling.