Phosphoinositide-3 kinase regulatory subunit alpha (PIK3R1) (PIK3R1)

Phosphoinositide-3 kinase regulatory subunit alpha (PIK3R1), commonly referred to as p85α, is a critical regulatory component of the Class IA phosphoinositide 3-kinase (PI3K) complex. It serves as an adapter protein that mediates the recruitment of the p110 catalytic subunit to activated receptor tyrosine kinases at the cell membrane via its SH2 domains [UniProt: P27306]. Beyond recruitment, PIK3R1 plays a dual role by stabilizing the p110 subunit and maintaining it in an inhibited state until activation occurs [PubMed: 25638673]. This signaling node is essential for the production of PIP3, which activates the AKT/mTOR pathway to regulate cell growth, survival, and glucose metabolism [PubMed: 24635045]. Somatic mutations in PIK3R1 are frequently identified in cancers such as endometrial, glioblastoma, and breast cancer, where they typically lead to gain-of-function signaling [PubMed: 21642982]. Additionally, germline mutations are associated with SHORT syndrome and the primary immunodeficiency APDS2 [NIH: GeneID 5295]. While most therapeutic agents, such as Alpelisib, target the catalytic p110 subunit, the functional dependency on the PIK3R1 subunit makes it a central focus for understanding drug resistance and patient stratification in oncology [PubChem: PIK3R1].

Other names

p85-alphaPhosphatidylinositol 3-kinase 85 kDa regulatory subunit alphaGRB1p85aP85A_HUMAN

Inhibition of the phosphoinositide 3-kinase (PI3K) complex activity, typically through ATP-competitive inhibition of the catalytic subunit which is regulated and stabilized by the alpha regulatory subunit.