PIK3CG
Description
The PIK3CG (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma) is a protein-coding gene located on chromosome 7.
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform is an enzyme that in humans is encoded by the PIK3CG gene.
== Function == This gene encodes a protein that belongs to the pi3/pi4-kinase family of proteins. The gene product is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. It is an important modulator of extracellular signals, including those elicited by E-cadherin-mediated cell-cell adhesion, which plays an important role in maintenance of the structural and functional integrity of epithelia. In addition to its role in promoting assembly of adherens junctions, the protein is thought to play a pivotal role in the regulation of cytotoxicity in NK cells. The gene is located in a commonly deleted segment of chromosome 7 previously identified in myeloid leukemias.
== Interactions == PIK3CG has been shown to interact with:
BCR gene, KRAS, PIK3CD, and PIK3R5.
The PIK3CG gene encodes a protein known as Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, also called PI3-kinase subunit gamma, PI3K-gamma, PI3Kgamma, PtdIns-3-kinase subunit gamma, Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma, Phosphoinositide-3-kinase catalytic gamma polypeptide, Serine/threonine protein kinase PIK3CG, or p120-PI3K. This protein functions as a 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 in recruiting PH domain-containing proteins like AKT1 and PDPK1 to the membrane, ultimately activating signaling cascades involved in various cellular functions such as growth, survival, proliferation, motility, and morphology. This enzyme links G-protein coupled receptor activation to PIP3 production. It is involved in immune, inflammatory, and allergic responses, modulating leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. PIK3CG may also control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by organizing F-actin formation and integrin-based adhesion at the leading edge. Furthermore, it controls the motility of dendritic cells. In collaboration with PIK3CD, this gene is involved in natural killer (NK) cell development and migration towards inflammatory sites. It participates in T-lymphocyte migration, regulates T-lymphocyte proliferation, activation, and cytokine production, and, together with PIK3CD, participates in T-lymphocyte development. PIK3CG is also required for B-lymphocyte development and signaling, and, together with PIK3CD, participates in neutrophil respiratory burst and is involved in neutrophil chemotaxis and extravasation. Along with PIK3CB, it promotes platelet aggregation and thrombosis. It regulates the adhesive function of alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism and may also play a lipid kinase activity-dependent role in platelet aggregation. PIK3CG is involved in endothelial progenitor cell migration. It acts as a negative regulator of cardiac contractility, modulating it by anchoring protein kinase A (PKA) and PDE3B activation, ultimately reducing cAMP levels. It also regulates cardiac contractility by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. PIK3CG possesses serine/threonine protein kinase activity, and both its lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. It may also have a scaffolding role in modulating cardiac contractility and contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6, this gene is assembled in a signaling complex where the PI3K gamma complex is activated by RAPGEF3 and is involved in angiogenesis. Within neutrophils, it participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway downstream of RASGRP4-mediated Ras-activation, promoting neutrophil functional responses.
PIK3CG is also known as IMD97, PI3CG, PI3K, PI3Kgamma, PIK3, p110gamma, p120-PI3K.
