Phosphoinositide 3-kinase gamma isoform (PI3Kγ)

Phosphoinositide 3‑kinase gamma isoform (PI3Kγ) is a member of the class I phosphoinositide 3‑kinases distinguished by its unique regulatory mechanism via G protein-coupled receptors. It consists of a catalytic subunit p110γ paired with regulatory subunits p101 or p84/p87. Unlike other class I isoforms that respond primarily to receptor tyrosine kinases, PI3Kγ is activated by signals from GPCRs through Gβγ subunits. It is highly expressed in hematopoietic cells where it regulates key aspects of immune cell development, recruitment, activation—including T-cell activation and neutrophil chemotaxis—and inflammatory responses. Recent studies also implicate it in cardiovascular biology through its role in vascular smooth muscle cells. Dysregulation or aberrant signaling via this enzyme contributes to cancer progression—particularly hematologic malignancies—as well as chronic inflammatory diseases and cardiovascular remodeling processes.

Other names

PI3KγPhosphatidylinositol 3-kinase catalytic subunit gammap110γ

Drugs targeting PI3Kγ typically act as ATP‑competitive inhibitors of the kinase domain, blocking the phosphorylation of phosphatidylinositols at the plasma membrane. This prevents downstream activation of Akt/PKB signaling pathways involved in immune cell activation, proliferation, migration, and survival.