PIK3CG - Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform - human protein (Function)
 
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PIK3CG »  Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform   [ EC 2.7.1.153 ]  (PI3Kgamma)
 
Protein also known as:  Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma (p110gamma).
Gene name:  PIK3CG
Family name: PI3/PI4-kinase
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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 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 ADRBK1 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.  
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  • UniProtKB
GO molecular function 
1-phosphatidylinositol-3-kinase activitydefinition[GO:0016303]  
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  • RefGenome
1-phosphatidylinositol-4-phosphate 3-kinase activitydefinition[GO:0035005]  
1
  • RefGenome
ATP bindingdefinition[GO:0005524]  
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  • UniProtKB KW
Ephrin receptor bindingdefinition[GO:0046875]  
1
  • UniProtKB
Phosphatidylinositol 3-kinase activitydefinition[GO:0035004]  
1
  • UniProtKB
Phosphatidylinositol-4,5-bisphosphate 3-kinase activitydefinition[GO:0046934]  
1
  • RefGenome
Protein bindingdefinition[GO:0005515]  
2
  • IntAct
Protein kinase activitydefinition[GO:0004672]  
1
  • UniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • UniProtKB KW
GO biological process 
Adaptive immune responsedefinition[GO:0002250]  
1
  • UniProtKB
Angiogenesisdefinition[GO:0001525]  
1
  • UniProtKB KW
Cytokine productiondefinition[GO:0001816]  
1
  • UniProtKB
Dendritic cell chemotaxisdefinition[GO:0002407]  
1
  • UniProtKB
Endocytosisdefinition[GO:0006897]  
1
  • UniProtKB KW
G-protein coupled receptor signaling pathwaydefinition[GO:0007186]  
1
  • UniProtKB
Hepatocyte apoptotic processdefinition[GO:0097284] silver  
1
  • Ortholog Compara
Inflammatory responsedefinition[GO:0006954]  
1
  • UniProtKB
Innate immune responsedefinition[GO:0045087]  
1
  • UniProtKB
Mast cell degranulationdefinition[GO:0043303]  
1
  • UniProtKB
Natural killer cell chemotaxisdefinition[GO:0035747]  
1
  • UniProtKB
Negative regulation of cardiac muscle contractiondefinition[GO:0055118]  
1
  • UniProtKB
Negative regulation of fibroblast apoptotic processdefinition[GO:2000270] silver  
1
  • Ortholog Compara
Negative regulation of triglyceride catabolic processdefinition[GO:0010897] silver  
1
  • Ortholog Compara
Neutrophil chemotaxisdefinition[GO:0030593]  
1
  • UniProtKB
Neutrophil extravasationdefinition[GO:0072672]  
1
  • UniProtKB
Phosphatidylinositol 3-kinase signalingdefinition[GO:0014065]  
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  • UniProtKB
Phosphatidylinositol phosphorylationdefinition[GO:0046854] silver  
1
  • Ortholog Compara
Phosphatidylinositol-3-phosphate biosynthetic processdefinition[GO:0036092] silver  
1
  • Ortholog Compara
Platelet aggregationdefinition[GO:0070527]  
1
  • UniProtKB
Positive regulation of acute inflammatory responsedefinition[GO:0002675] silver  
1
  • Ortholog Compara
Positive regulation of cytosolic calcium ion concentrationdefinition[GO:0007204] silver  
1
  • Ortholog Compara
Positive regulation of MAP kinase activitydefinition[GO:0043406]  
1
  • UniProtKB
Positive regulation of protein kinase B signalingdefinition[GO:0051897]  
1
  • UniProtKB
Protein phosphorylationdefinition[GO:0006468] silver  
1
  • Ortholog Compara
Regulation of cell adhesion mediated by integrindefinition[GO:0033628]  
1
  • UniProtKB
Respiratory burst involved in defense responsedefinition[GO:0002679]  
1
  • UniProtKB
Secretory granule localizationdefinition[GO:0032252] silver  
1
  • Ortholog Compara
T cell activationdefinition[GO:0042110]  
1
  • UniProtKB
T cell chemotaxisdefinition[GO:0010818]  
1
  • UniProtKB
T cell proliferationdefinition[GO:0042098]  
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  • UniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 2.7.1.153: ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate.  
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  • UniProtKB
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
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  • UniProtKB
It is regulated in the following manner
Activated by both the alpha and the beta-gamma G proteins following stimulation of G protein-coupled receptors (GPCRs). Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation. Inhibited by AS-604850 and AS-605240.  
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  • UniProtKB
 
More information is available from:
Pathways 
This protein is involved in the following pathway
Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis  
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  • UniProtKB
According to KEGG, this protein belongs to the following pathways:
Acute myeloid leukemia  hsa05221+5294  
Aldosterone-regulated sodium reabsorption  hsa04960+5294  
Amoebiasis  hsa05146+5294  
Apoptosis  hsa04210+5294  
B cell receptor signaling pathway  hsa04662+5294  
Bacterial invasion of epithelial cells  hsa05100+5294  
Carbohydrate digestion and absorption  hsa04973+5294  
Chagas disease (American trypanosomiasis)  hsa05142+5294  
Chemokine signaling pathway  hsa04062+5294  
Cholinergic synapse  hsa04725+5294  
Colorectal cancer  hsa05210+5294  
Endometrial cancer  hsa05213+5294  
ErbB signaling pathway  hsa04012+5294  
Fc epsilon RI signaling pathway  hsa04664+5294  
Fc gamma R-mediated phagocytosis  hsa04666+5294  
Focal adhesion  hsa04510+5294  
Glioma  hsa05214+5294  
Hepatitis C  hsa05160+5294  
HTLV-I infection  hsa05166+5294  
Influenza A  hsa05164+5294  
Inositol phosphate metabolism  hsa00562+5294  
Insulin signaling pathway  hsa04910+5294  
Jak-STAT signaling pathway  hsa04630+5294  
Leukocyte transendothelial migration  hsa04670+5294  
Measles  hsa05162+5294  
Melanoma  hsa05218+5294  
mTOR signaling pathway  hsa04150+5294  
Natural killer cell mediated cytotoxicity  hsa04650+5294  
Neurotrophin signaling pathway  hsa04722+5294  
Non-small cell lung cancer  hsa05223+5294  
Osteoclast differentiation  hsa04380+5294  
Pancreatic cancer  hsa05212+5294  
Pathways in cancer  hsa05200+5294  
Phosphatidylinositol signaling system  hsa04070+5294  
Progesterone-mediated oocyte maturation  hsa04914+5294  
Prostate cancer  hsa05215+5294  
Regulation of actin cytoskeleton  hsa04810+5294  
Renal cell carcinoma  hsa05211+5294  
Small cell lung cancer  hsa05222+5294  
T cell receptor signaling pathway  hsa04660+5294  
Toll-like receptor signaling pathway  hsa04620+5294  
Toxoplasmosis  hsa05145+5294  
Type II diabetes mellitus  hsa04930+5294  
VEGF signaling pathway  hsa04370+5294  
According to Reactome, this protein belongs to the following pathways:
G beta:gamma signalling through PI3Kgamma  REACT_19290  
GPVI-mediated activation cascade  REACT_1695  
Synthesis of PIPs at the plasma membrane  REACT_121025  
 
More information is available from:
Note 
Candidate target in therapy for inflammatory diseases. Selective inhibitors and protein ablation are anti-inflammatory in multiple disease models such as asthma, rheumatoid arthritis, allergy, systemic lupus erythematosus, airway inflammation, lung injury and pancreatitis (PubMed18278175).  
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  • UniProtKB
 

Keywords

Biological process 
Angiogenesis  definition   [KW-0037]
Chemotaxis  definition   [KW-0145]
Endocytosis  definition   [KW-0254]
Immunity  definition   [KW-0391]
Inflammatory response  definition   [KW-0395]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PIK3CG
GenomeRNAi: 5294
PRO: PR:P48736
Chemistry
GuidetoPHARMACOLOGY: 2156