Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma (PI3K gamma) (PI3K gamma)

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma (PI3Kγ) is a class IB phosphoinositide 3-kinase that plays a pivotal role in transducing signals from G protein-coupled receptors (GPCRs) [UniProt, NIH]. Unlike class IA PI3Ks, which are primarily activated by receptor tyrosine kinases, PI3Kγ is uniquely regulated by Gβγ subunits and Ras, facilitating the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) to the second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3) [UniProt, ResearchGate]. This enzyme is predominantly expressed in hematopoietic cells, where it modulates critical immune functions such as leukocyte chemotaxis, neutrophil activation, and T-cell migration [UniProt, NIH]. In the context of oncology, PI3Kγ is a key regulator of the tumor microenvironment; its inhibition can reprogram tumor-associated macrophages from a pro-tumorigenic M2-like phenotype to a pro-inflammatory M1-like phenotype, enhancing anti-tumor immunity [NIH, Wikipedia]. Clinically, drugs like duvelisib and eganelisib target PI3Kγ to treat hematologic malignancies and solid tumors, while its role in inflammatory diseases like asthma and COPD makes it a target for respiratory therapies [Cell Stress, YouTube]. However, therapeutic targeting must balance efficacy with safety concerns, including potential immune-related toxicities and effects on cardiac contractility [NIH, UniProt].

Other names

PIK3CGp110gammap120-PI3KPhosphoinositide-3-kinase catalytic gamma polypeptideIMD97

Inhibition of the catalytic activity of the p110γ subunit, preventing the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3), thereby disrupting downstream AKT/mTOR signaling and modulating immune cell recruitment and macrophage polarization.