Phosphatidylinositol 3-kinase catalytic subunit gamma (PI3Kγ (gene symbol: PIK3CG; catalytic subunit also referred to as p110γ))

Phosphatidylinositol 3-kinase catalytic subunit gamma (p110γ; gene PIK3CG) is the catalytic component of the class IB PI3K that partners with regulatory subunits p101 or p87/p84 to form PI3Kγ complexes activated primarily downstream of GPCRs via direct Gβγ binding and also by Ras, leading to production of PtdIns(3,4,5)P3 and activation of PI3K/AKT signaling pathways controlling chemotaxis, inflammation, cardiac β-adrenergic signaling, cell survival, and proliferation; dysregulation contributes to inflammatory disease, cardiovascular dysfunction, and cancer, and the catalytic site is druggable with small-molecule inhibitors as shown in human PI3Kγ crystal structures.

Other names

Phosphoinositide 3-kinase gammaPI3K gammap110 gamma (p110γ)PIK3CG (gene)Class IB PI3K catalytic subunit

Competitive inhibition of the ATP-binding site in the p110γ kinase domain, blocking phosphorylation of PtdIns(4,5)P2 to PtdIns(3,4,5)P3. Functional antagonism of GPCR→Gβγ→PI3Kγ signaling, reducing downstream AKT/PDK1 recruitment and signaling outputs. Modulation of Ras-augmented activation where inhibitors prevent Ras-enhanced PI3Kγ activity.