PIK3CG
Function
Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation, activation, and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway downstream of RASGRP4-mediated Ras-activation, to promote neutrophil functional responses (By similarity).
Involvement in disease
Immunodeficiency 97 with autoinflammation
IMD97
An autosomal recessive disorder with variable features. Affected individuals have childhood-onset antibody defects, cytopenias, and T lymphocytic pneumonitis and colitis. Some patients may have features of hemophagocytic lymphohistiocytosis.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.
Post-translational modifications
Autophosphorylation at Ser-1101 has no effect on the phosphatidylinositol-4,5-bisphosphate 3-kinase activity.
Sequence Similarities
Belongs to the PI3/PI4-kinase family.
Tissue Specificity
Pancreas, skeletal muscle, liver and heart.
Cellular localization
- Cytoplasm
- Cell membrane
Alternative names
PI3-kinase subunit gamma, PI3K-gamma, PI3Kgamma, PtdIns-3-kinase subunit gamma, Phosphoinositide-3-kinase catalytic gamma polypeptide, Serine/threonine protein kinase PIK3CG, p120-PI3K, PtdIns-3-kinase subunit p110-gamma, p110gamma, PIK3CG
Database links
swissprot:P48736 omim:601232 genbank:AF327656 entrezGene:5294
Other research areas
- Immuno-oncology