Phosphatidylinositol 3-Kinase Gamma (PI3Kγ)

Phosphatidylinositol 3-kinase gamma (PI3Kγ) is a member of the class I phosphoinositide 3-kinases (PI3Ks). It is unique as the only class IB PI3K and plays a central role in immune cell signaling, inflammation, and various physiological and pathological processes. It is activated downstream of G protein–coupled receptors (GPCRs) via Gβγ subunits. It is highly expressed in cells of the myeloid lineage, as well as lymphoid-derived immune cells. In non-leukocyte structural airway cells under normal conditions expression is low but upregulated during stress or inflammation. It is involved in airway inflammation/disease including asthma and pulmonary fibrosis. Mutations affecting either catalytic or regulatory subunits can cause primary immunodeficiency disorders. Somatic/germline mutations have been linked to cancer development/metabolic syndromes/overgrowth syndromes/inflammatory diseases due to dysregulated signaling through this pathway.

Phosphorylates phosphatidylinositol(4,5)bisphosphate [PI(4,5)P₂] to generate phosphatidylinositol(3,4,5)trisphosphate [PI(3,4,5)P₃], which recruits PH domain-containing proteins for downstream signaling. Also functions as a scaffold protein regulating cAMP levels.