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discounted EARLY registration ends Dec 31, 2014
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discounted EARLY registration ends Dec 31, 2014
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discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
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MetaCyc Polypeptide: phosphatidylinositol 3 kinase catalytic subunit p110γ

Gene: PIK3CG Accession Number: HS02818 (MetaCyc)

Synonyms: PI3Kgamma, PI3CG, PIK3, PI3K, PI3-kinase P110 subunit γ, phosphoinositide-3-kinase, catalytic, gamma polypeptide, PI3-kinase, p110-gamma, PTDINS-3-kinase, phosphatidylinositol 3-kinase catalytic subunit, gamma isoform, phosphoinositide-3-kinase gamma catalytic subunit, phosphatidylinositol 3-kinase catalytic 110-kD gamma, phosphatidylinositol 3-kinase, catalytic, gamma polypeptide

Species: Homo sapiens

Component of:
phosphatidylinositol 3-kinase, class IB, p110γ/p87 (extended summary available)
phosphatidylinositol 3-kinase, class IB, p110γ/p101 (extended summary available)

Summary:
A cDNA encoding the phosphatidylinositol 3 kinase catalytic subunit p110γ was isolated, and the protein was expressed in Sf9 cells as a GST-fusion. The recombinant protein was purified and characterized [Stoyanov95]. The protein was clearly different from the class IA subunits, as it did not bind to p85 regulatory subunits.

It was subsequently shown that p100γ 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 [Laprise02]. 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 PIK3CG gene is located in a commonly deleted segment of chromosome 7 previously identified in myeloid leukemias [Kratz02].

Map Position: [104,989,627 -> 105,031,295]

Molecular Weight of Polypeptide: 126.45 kD (from nucleotide sequence), 110.0 kD (experimental) [Stoyanov95 ]

Unification Links: ArrayExpress:P48736 , DIP:DIP-37781N , Entrez-Nucleotide:X83368 , Mint:MINT-155782 , PhosphoSite:P48736 , PhylomeDB:P48736 , Pride:P48736 , Protein Model Portal:P48736 , SMR:P48736 , String:9606.ENSP00000352121 , UniProt:P48736

Relationship Links: InterPro:IN-FAMILY:IPR000008 , InterPro:IN-FAMILY:IPR000341 , InterPro:IN-FAMILY:IPR000403 , InterPro:IN-FAMILY:IPR001263 , InterPro:IN-FAMILY:IPR002420 , InterPro:IN-FAMILY:IPR003113 , InterPro:IN-FAMILY:IPR011009 , InterPro:IN-FAMILY:IPR015433 , InterPro:IN-FAMILY:IPR016024 , InterPro:IN-FAMILY:IPR018936 , Panther:IN-FAMILY:PTHR10048 , PDB:Structure:1E8Y , PDB:Structure:1E8Z , PDB:Structure:1HE8 , PDB:Structure:2A4Z , PDB:Structure:2A5U , PDB:Structure:2CHW , PDB:Structure:2CHX , PDB:Structure:2CHZ , PDB:Structure:2V4L , PDB:Structure:3APC , PDB:Structure:3APD , PDB:Structure:3APF , PDB:Structure:3CSF , PDB:Structure:3CST , PDB:Structure:3DBS , PDB:Structure:3DPD , PDB:Structure:3ENE , PDB:Structure:3IBE , PDB:Structure:3L08 , PDB:Structure:3L13 , PDB:Structure:3L16 , PDB:Structure:3L17 , PDB:Structure:3L54 , PDB:Structure:3LJ3 , PDB:Structure:3MJW , PDB:Structure:3ML8 , PDB:Structure:3ML9 , PDB:Structure:3NZS , PDB:Structure:3NZU , PDB:Structure:3OAW , PDB:Structure:3P2B , PDB:Structure:3PRE , PDB:Structure:3PRZ , PDB:Structure:3PS6 , PDB:Structure:3QAQ , PDB:Structure:3QAR , PDB:Structure:3QJZ , PDB:Structure:3QK0 , PDB:Structure:3R7Q , PDB:Structure:3R7R , PDB:Structure:3S2A , PDB:Structure:3SD5 , PDB:Structure:3T8M , PDB:Structure:3TJP , PDB:Structure:3TL5 , PDB:Structure:3ZVV , PDB:Structure:3ZW3 , PDB:Structure:4ANU , PDB:Structure:4ANV , PDB:Structure:4ANW , PDB:Structure:4ANX , PDB:Structure:4AOF , PDB:Structure:4DK5 , PDB:Structure:4EZJ , PDB:Structure:4EZK , PDB:Structure:4EZL , PDB:Structure:4F1S , PDB:Structure:4FA6 , PDB:Structure:4FAD , PDB:Structure:4FHJ , PDB:Structure:4FHK , PDB:Structure:4FJY , PDB:Structure:4FJZ , PDB:Structure:4FLH , PDB:Structure:4FUL , PDB:Structure:4G11 , PDB:Structure:4GB9 , PDB:Structure:4HLE , PDB:Structure:4KZ0 , PDB:Structure:4KZC , Pfam:IN-FAMILY:PF00454 , Pfam:IN-FAMILY:PF00613 , Pfam:IN-FAMILY:PF00792 , Pfam:IN-FAMILY:PF00794 , Prosite:IN-FAMILY:PS00915 , Prosite:IN-FAMILY:PS00916 , Prosite:IN-FAMILY:PS50290 , Prosite:IN-FAMILY:PS51544 , Prosite:IN-FAMILY:PS51545 , Prosite:IN-FAMILY:PS51546 , Prosite:IN-FAMILY:PS51547 , Smart:IN-FAMILY:SM00142 , Smart:IN-FAMILY:SM00144 , Smart:IN-FAMILY:SM00145 , Smart:IN-FAMILY:SM00146

Gene-Reaction Schematic: ?

Credits:
Created 14-Oct-2009 by Caspi R , SRI International


Subunit of: phosphatidylinositol 3-kinase, class IB, p110γ/p87

Species: Homo sapiens

Subunit composition of phosphatidylinositol 3-kinase, class IB, p110γ/p87 = [PIK3R6][PIK3CG]
         phosphoinositide 3-kinase regulatory subunit p87 = PIK3R6 (extended summary available)
         phosphatidylinositol 3 kinase catalytic subunit p110γ = PIK3CG (summary available)

Summary:
The Class I PI 3-kinases, which can be subdivided into IA and IB, are known to be activated by receptors. Although they can phosphorylate an L-1-phosphatidyl-inositol, a 1-phosphatidyl-1D-myo-inositol 4-phosphate, and a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate in vitro, these enzymes utilize mainly a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate as a substrate in vivo [Stephens91, Hawkins92].

The Class IB PI 3-kinase phosphatidylinositol 3 kinase catalytic subunit p110γ is associated with either a p101 or a p87 regulatory subunits (encoded by PIK3R5 and PIK3R6, respectively), which may link the kinase to serpentine receptors by the βγ subunits of heterotrimeric G-proteins and thus mediate p110γ activation [Stoyanov95].

Most of our knowledge about the physiological role of PI3Kγ is derived from the characterization of p110γ knockout mice, which show defects in chemoattractant-induced neutrophil migration and oxidative burst, thymocyte development [Li00b, Hirsch00, Sasaki00a, Koyasu03], macrophage and dendritic cell migration [Del04], and the GPCR-dependent autocrine amplification of FceRI-mediated mast cell degranulation [Laffargue02]. In addition, characterization of these knockout mice revealed a role for the enzyme both in the regulation of myocardial contractility and in cardiac remodeling processes [Oudit04, Crackower02].

Credits:
Created 14-Oct-2009 by Caspi R , SRI International


Enzymatic reaction of: phosphatidylinositol-4,5-bisphosphate 3-kinase (phosphatidylinositol 3-kinase, class IB, p110γ/p87)

EC Number: 2.7.1.153

a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + ATP <=> 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + ADP + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: 3-phosphoinositide biosynthesis

Inhibitors (Unknown Mechanism): wortmanin [Stoyanov95]


Subunit of: phosphatidylinositol 3-kinase, class IB, p110γ/p101

Species: Homo sapiens

Subunit composition of phosphatidylinositol 3-kinase, class IB, p110γ/p101 = [PIK3R5][PIK3CG]
         phosphoinositide-3-kinase regulatory subunit p101 = PIK3R5 (extended summary available)
         phosphatidylinositol 3 kinase catalytic subunit p110γ = PIK3CG (summary available)

Summary:
The Class I PI 3-kinases, which can be subdivided into IA and IB, are known to be activated by receptors. Although they can phosphorylate an L-1-phosphatidyl-inositol, a 1-phosphatidyl-1D-myo-inositol 4-phosphate, and a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate in vitro, these enzymes utilize mainly a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate as a substrate in vivo [Stephens91, Hawkins92].

The Class IB PI 3-kinase phosphatidylinositol 3 kinase catalytic subunit p110γ is associated with either a p101 or a p87 regulatory subunits (encoded by PIK3R5 and PIK3R6, respectively), which may link the kinase to serpentine receptors by the βγ subunits of heterotrimeric G-proteins and thus mediate p110γ activation [Stoyanov95].

Most of our knowledge about the physiological role of PI3Kγ is derived from the characterization of p110γ knockout mice, which show defects in chemoattractant-induced neutrophil migration and oxidative burst, thymocyte development [Li00b, Hirsch00, Sasaki00a, Koyasu03], macrophage and dendritic cell migration [Del04], and the GPCR-dependent autocrine amplification of FceRI-mediated mast cell degranulation [Laffargue02]. In addition, characterization of these knockout mice revealed a role for the enzyme both in the regulation of myocardial contractility and in cardiac remodeling processes [Oudit04, Crackower02].

Credits:
Created 14-Oct-2009 by Caspi R , SRI International


Enzymatic reaction of: phosphatidylinositol-4,5-bisphosphate 3-kinase (phosphatidylinositol 3-kinase, class IB, p110γ/p101)

EC Number: 2.7.1.153

a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + ATP <=> 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + ADP + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: 3-phosphoinositide biosynthesis

Exons/Introns:


References

Brock03: Brock C, Schaefer M, Reusch HP, Czupalla C, Michalke M, Spicher K, Schultz G, Nurnberg B (2003). "Roles of G beta gamma in membrane recruitment and activation of p110 gamma/p101 phosphoinositide 3-kinase gamma." J Cell Biol 160(1);89-99. PMID: 12507995

Crackower02: Crackower MA, Oudit GY, Kozieradzki I, Sarao R, Sun H, Sasaki T, Hirsch E, Suzuki A, Shioi T, Irie-Sasaki J, Sah R, Cheng HY, Rybin VO, Lembo G, Fratta L, Oliveira-dos-Santos AJ, Benovic JL, Kahn CR, Izumo S, Steinberg SF, Wymann MP, Backx PH, Penninger JM (2002). "Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways." Cell 110(6);737-49. PMID: 12297047

Del04: Del Prete A, Vermi W, Dander E, Otero K, Barberis L, Luini W, Bernasconi S, Sironi M, Santoro A, Garlanda C, Facchetti F, Wymann MP, Vecchi A, Hirsch E, Mantovani A, Sozzani S (2004). "Defective dendritic cell migration and activation of adaptive immunity in PI3Kgamma-deficient mice." EMBO J 23(17);3505-15. PMID: 15318168

Hawkins92: Hawkins PT, Jackson TR, Stephens LR (1992). "Platelet-derived growth factor stimulates synthesis of PtdIns(3,4,5)P3 by activating a PtdIns(4,5)P2 3-OH kinase." Nature 358(6382);157-9. PMID: 1319558

Hirsch00: Hirsch E, Katanaev VL, Garlanda C, Azzolino O, Pirola L, Silengo L, Sozzani S, Mantovani A, Altruda F, Wymann MP (2000). "Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation." Science 287(5455);1049-53. PMID: 10669418

Koyasu03: Koyasu S (2003). "The role of PI3K in immune cells." Nat Immunol 4(4);313-9. PMID: 12660731

Kratz02: Kratz CP, Emerling BM, Bonifas J, Wang W, Green ED, Le Beau MM, Shannon KM (2002). "Genomic structure of the PIK3CG gene on chromosome band 7q22 and evaluation as a candidate myeloid tumor suppressor." Blood 99(1);372-4. PMID: 11756194

Laffargue02: Laffargue M, Calvez R, Finan P, Trifilieff A, Barbier M, Altruda F, Hirsch E, Wymann MP (2002). "Phosphoinositide 3-kinase gamma is an essential amplifier of mast cell function." Immunity 16(3);441-51. PMID: 11911828

Laprise02: Laprise P, Chailler P, Houde M, Beaulieu JF, Boucher MJ, Rivard N (2002). "Phosphatidylinositol 3-kinase controls human intestinal epithelial cell differentiation by promoting adherens junction assembly and p38 MAPK activation." J Biol Chem 277(10);8226-34. PMID: 11756422

Lecompte08: Lecompte O, Poch O, Laporte J (2008). "PtdIns5P regulation through evolution: roles in membrane trafficking?." Trends Biochem Sci 33(10);453-60. PMID: 18774718

Li00b: Li Z, Jiang H, Xie W, Zhang Z, Smrcka AV, Wu D (2000). "Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction." Science 287(5455);1046-9. PMID: 10669417

Oudit04: Oudit GY, Sun H, Kerfant BG, Crackower MA, Penninger JM, Backx PH (2004). "The role of phosphoinositide-3 kinase and PTEN in cardiovascular physiology and disease." J Mol Cell Cardiol 37(2);449-71. PMID: 15276015

Rohde02: Rohde G, Wenzel D, Haucke V (2002). "A phosphatidylinositol (4,5)-bisphosphate binding site within mu2-adaptin regulates clathrin-mediated endocytosis." J Cell Biol 158(2);209-14. PMID: 12119359

Sasaki00a: Sasaki T, Irie-Sasaki J, Jones RG, Oliveira-dos-Santos AJ, Stanford WL, Bolon B, Wakeham A, Itie A, Bouchard D, Kozieradzki I, Joza N, Mak TW, Ohashi PS, Suzuki A, Penninger JM (2000). "Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration." Science 287(5455);1040-6. PMID: 10669416

Stephens91: Stephens LR, Hughes KT, Irvine RF (1991). "Pathway of phosphatidylinositol(3,4,5)-trisphosphate synthesis in activated neutrophils." Nature 351(6321);33-9. PMID: 1851250

Stoyanov95: Stoyanov B, Volinia S, Hanck T, Rubio I, Loubtchenkov M, Malek D, Stoyanova S, Vanhaesebroeck B, Dhand R, Nurnberg B (1995). "Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase." Science 269(5224);690-3. PMID: 7624799

Voigt06a: Voigt P, Dorner MB, Schaefer M (2006). "Characterization of p87PIKAP, a novel regulatory subunit of phosphoinositide 3-kinase gamma that is highly expressed in heart and interacts with PDE3B." J Biol Chem 281(15);9977-86. PMID: 16476736


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Nov 27, 2014, BIOCYC14A.