Phosphoinositide 3-kinase regulatory subunit 5 (PIK3R5)

Phosphoinositide 3-kinase regulatory subunit 5 (PIK3R5), also known as p101, is the regulatory subunit of the class IB phosphoinositide 3-kinase γ (PI3Kγ) complex[1][2][3]. This protein acts as an adapter that couples the catalytic subunit p110γ to Gβγ proteins released from activated G protein-coupled receptors (GPCRs), thereby recruiting PI3Kγ to the plasma membrane for generation of the second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3)[1][2]. PIK3R5 plays crucial roles in leukocyte chemotaxis, inflammation, cell survival, and proliferation, as well as in neurodevelopment[1][2]. Genetic variations or altered expression of PIK3R5 have been implicated in human diseases such as cancer, neurodegenerative ataxias, and as an emerging biomarker for drug-induced hypertension and leukemia progression[2][3]. Inhibiting the p101/p110γ complex disrupts PI3Kγ-mediated intracellular signaling, with drugs in development targeting various PI3K isoforms for immunological, oncological, and cardiovascular indications; however, targeting this axis may raise safety concerns including immunosuppression and potential cardiac and neurological effects[1][2][3].

Other names

p101P101-PI3KFOAP-2F730038I15RikPtdIns-3-kinase regulatory subunitPI3-kinase p101 subunitPI3-kinase regulatory subunit 5PtdIns-3-kinase p101

Inhibition of PI3Kγ catalytic activity (by preventing p101/p110γ activation), inhibition of GPCR-driven PIP3 generation, modulation of downstream Akt and MAPK pathways