catalytic subunit of the PI3/PI4-kinase family of phospholipid-kinases. Phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. Phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 recruits proteins with PH domains to the membrane, including AKT1 and PDPK1, and plays a critical pleiotropic role in regulating membrane signaling. Activated by both the alpha and the beta:gamma G proteins following stimulation of G protein-coupled receptors (GPCRs), linking GPCR activation to PIP3 production.. Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6), leading to the translocation from the cytosol to the plasma membrane. Inhibited by AS-604850 and AS-605240. Activates signaling cascades involved in cell growth, survival, proliferation, motility and morphology. 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, it regulates many cellular functions: it is involved in natural killer (NK) cell development and migration towards the sites of inflammation; participates in T-lymphocyte development and migration; required for B-lymphocyte development and signaling; regulates lymphocyte cytokine production; participates in neutrophil respiratory burst, chemotaxis and extravasation; 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; involved in endothelial progenitor cell migration; 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 ADRBK1 and by non-muscle tropomyosin phosphorylation; and contributes to cardiac hypertrophy under pathological stress. Possesses serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. 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. Holoenzyme is a trimer composed of a heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or PIK3R6 regulatory subunit. Interacts with HRAS1; the interaction is required for membrane recruitment and beta-gamma G protein dimer-dependent activation of the PI3K gamma complex PIK3CG:PIK3R6. Note: This description may include information from UniProtKB.
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.