Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2) (PIK3R2)

Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2), also known as p85-beta, is a critical regulatory component of the Class IA phosphoinositide 3-kinase (PI3K) enzyme complex (UniProt: P27986). It functions by binding to and stabilizing the p110 catalytic subunits, while also mediating the recruitment of the complex to activated receptor tyrosine kinases (RTKs) via its SH2 domains (NCBI Gene: 5296). This recruitment triggers the production of PIP3, which activates downstream effectors like AKT and mTOR to promote cell survival, growth, and metabolism. In pathology, germline mutations in PIK3R2 are the primary cause of Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, characterized by brain overgrowth (PMID: 22885924). Additionally, somatic mutations and overexpression of PIK3R2 are implicated in various cancers, including endometrial and colon cancers, by driving constitutive PI3K pathway activation (PMID: 19147581). Although most clinical PI3K inhibitors target the catalytic p110 subunits, PIK3R2 is essential for the assembly and localization of the drug-target complex, making it a key factor in therapeutic efficacy and resistance (DrugBank: DB11715).

Other names

p85-betaP85BPhosphoinositide-3-kinase regulatory subunit 2p85beta

Inhibition of the PI3K catalytic activity by targeting the PI3K complex (p110/p85) or preventing the recruitment of the complex to the plasma membrane.