Phosphatidylinositol 3-kinase gamma isoform (PI3Kγ)

Phosphatidylinositol 3‑kinase gamma isoform is a member of the class IB phosphoinositide 3‑kinases. It functions as a heterodimer composed of a catalytic subunit p110γ encoded by the PIK3CG gene and regulatory subunits p101 or p84/p87. Unlike class IA enzymes activated by receptor tyrosine kinases, PI3Kγ is primarily activated downstream of G protein-coupled receptors via Gβγ subunits at cellular membranes. It catalyzes phosphorylation at the D‑position on phosphoinositides—most notably converting PIP₂ into PIP₃—which recruits pleckstrin homology domain-containing proteins like Akt to propagate intracellular signals controlling cell growth, survival, motility/migration and immune responses. Highly expressed in hematopoietic cells but also present in vascular tissues and cardiomyocytes, it plays critical roles in inflammation regulation—including leukocyte recruitment—and has been implicated in cancer progression through its influence on tumor microenvironment immunity. Selective inhibition has shown promise for treating inflammatory diseases and certain cancers while minimizing broader toxicity seen with less selective agents.

Other names

PI3KγPhosphoinositide 3-kinase gammaPIK3CG (gene symbol)p110γ (catalytic subunit)Class IB PI3K

Drugs targeting PI3Kγ typically act as ATP‑competitive inhibitors of the lipid kinase domain. This blocks the conversion of phosphatidylinositol-(4,5)-bisphosphate to phosphatidylinositol-(3,4,5)-trisphosphate at the plasma membrane—thereby inhibiting downstream signaling pathways such as Akt/mTOR that drive cell survival, proliferation, migration, and immune responses.