Phosphoinositide-3-kinase regulatory subunit 1 (PI3KR1) (PI3KR1)

Phosphoinositide-3-kinase regulatory subunit 1 (PI3KR1), also known as p85α, is a critical adapter protein that regulates the activity and stability of Class IA phosphoinositide 3-kinase (PI3K) catalytic subunits [3, 11]. It plays a central role in the PI3K/AKT/mTOR signaling pathway, which is essential for cell growth, survival, metabolism, and immune function [3, 7]. In response to growth factor or insulin stimulation, PI3KR1 binds to phosphorylated receptor tyrosine kinases or adapter proteins, relieving its basal inhibitory effect on the p110 catalytic subunit and facilitating the production of the second messenger PIP3 [6, 7]. Mutations in the PIK3R1 gene are frequently observed in various cancers, such as endometrial, breast, and ovarian cancer, where they often lead to constitutive pathway activation and oncogenic transformation [2, 8, 9]. Additionally, germline mutations are linked to developmental disorders like SHORT syndrome and primary immunodeficiencies like Activated PI3K-delta Syndrome type 2 (APDS2) [1, 3]. While most current therapies target the catalytic subunits or downstream effectors, PI3KR1 status serves as a vital biomarker for patient stratification and drug sensitivity [4, 10].

Other names

p85 alphaPIK3R1Phosphatidylinositol 3-kinase regulatory subunit alphaGRB1p85AGM7IMD36

Inhibition of the PI3K/AKT/mTOR signaling pathway, stabilization and regulation of the p110 catalytic subunit, and modulation of PTEN activity [2, 4, 6].