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Information on EC 2.7.1.137 - phosphatidylinositol 3-kinase and Organism(s) Homo sapiens and UniProt Accession O75747

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EC Tree
IUBMB Comments
One mammalian isoform is known.
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This record set is specific for:
Homo sapiens
UNIPROT: O75747
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
pi3k, phosphatidylinositol 3-kinase, pi3 kinase, vps34, phosphoinositide-3-kinase, phosphatidylinositol 3 kinase, ptdins 3-kinase, pik3c3, phosphatidylinositide 3-kinase, hvps34, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
class 3 phosphatidylinositol 3-kinase vacuolar protein sorting 34
-
class I phosphoinositide 3-kinase
-
-
class III phosphatidylinositol 3-kinase
-
class III phosphoinositide 3-kinase
-
class III PI3K
-
-
HsC2-PI3K
-
hVps34 PI 3-kinase
-
-
kinase (phosphorylating), phosphatidylinositol 3-
-
-
-
-
kinase, phosphatidylinositol 3- (phosphorylating)
-
-
-
-
p110a
-
-
p110delta I PI3K.
-
p85/p110 phosphoinositide 3-kinase
-
-
-
-
p85a phosphoinositide 3-kinase
-
-
phosphatidyl-inositol-3-kinase
-
-
phosphatidylinositide 3-kinase
-
-
phosphatidylinositol 3'-kinase
phosphatidylinositol 3-kinase
phosphoinositide 3'-kinase
-
-
-
-
phosphoinositide 3-kinase
phosphoinositide-3-kinase
-
PI 3-K
-
-
PI 3-kinase
PI-3K
-
-
PI3 K
-
-
PI3 kinase
-
-
PI3-kinase
PI3Kgamma
-
p110gamma catalytic subunit
protein sorting mutant 34 protein
-
-
PtdIns 3'-kinase
-
-
-
-
PtdIns 3-kinase
-
-
PtdIns 3-kinase vacuolar protein sorting 34
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type III phosphatidylinositol 3-kinase
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vacuolar protein sorting 34
-
Vps34p
-
-
additional information
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase
One mammalian isoform is known.
CAS REGISTRY NUMBER
COMMENTARY hide
115926-52-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
class I enzyme, preferred substrate of the class III enzyme
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
hVps34 plays a major role in generating phosphatidylinositol 3-phosphate for internal vesicle formation in multivesicular/late endosomes. The findings also unexpectedly suggest that other wortmannin-sensitive kinases and/or polyphosphoinositide phosphatases may be able to compensate for the loss of hVps34 and maintain phosphatidylinositol 3-phosphate levels required for vesicular trafficking in the early endocytic pathway or the trans-Golgi network
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
class I enzyme, preferred substrate in vivo, physiologic regulation and mode of action
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
show the reaction diagram
-
synthesis of a second messenger, enzyme is involved in several cellular signaling processes important for cell growth and survival, cell differentiation and motility
-
-
?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1E,4S,4aR,5R,6aS,7S)-5-(acetyloxy)-1-[[[3-(dimethylamino)-propyl](methyl)amino]methylene]-11-hydroxy-4-(methoxymethyl)-4a,6a-dimethyl-2,10-dioxo-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydroindeno[4,5-h]isochromen-7-yl-(1R,2R,4S)-4-[(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl]-2-methoxycyclohexyl octanedioate
-
-
(1Z,4S,4aR,6aS,9aR)-1-([[3-(dimethylamino)propyl](methyl)amino]methylidene)-5-ethoxy-7,11-dihydroxy-4-(methoxymethyl)-4a,6a-dimethyl-4a,5,6,6a,7,8,9,9a-octahydroindeno[4,5-h]isochromene-2,10(1H,4H)-dione
-
-
(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-3-[(2R)-1-[(1S,3R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone
-
-
(8S)-2-[(3R)-3-methylmorpholin-4-yl]-9-(3-methyl-2-oxobutyl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one
-
17-hydroxywortmannin
-
-
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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i.e. LY294002
2-morpholin-4-yl-3-phenylchromen-4-one
-
weak inhibition, IC50 is above 0.2 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
2-morpholin-4-yl-3-propylchromen-4-one
-
IC50 is 0.0031 mM for the recombinant wild-type enzyme and 0.068 mM for the recombinant mutant C838V/I848A
3-benzyl-2-morpholin-4-yl-chromen-4-one
-
weak inhibition, IC50 is above 0.2 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
3-butyl-2-morpholin-4-yl-chromen-4-one
-
IC50 is 0.025 mM for the recombinant wild-type enzyme and 0.048 mM for the recombinant mutant C838V/I848A
3-ethyl-2-morpholin-4-yl-chromen-4-one
-
IC50 is 0.028 mM for the recombinant wild-type enzyme and 0.0044 mM for the recombinant mutant C838V/I848A
3-isopropyl-2-morpholin-4-yl-chromen-4-one
-
IC50 is 0.051 mM for the recombinant wild-type enzyme and more than 0.2 mM for the recombinant mutant C838V/I848A
3-methyl-2-morpholin-4-yl-chromen-4-one
-
IC50 is 0.033 mM for the recombinant wild-type enzyme and 0.040 mM for the recombinant mutant C838V/I848A
3-Methyladenine
apocynin
-
specific PI3K inhibitor, restores vasorelaxation and hyperpolarization in response to an ATP-sensitive K+ channel opener levcromakalim
Ead125
-
-
GDC-0941
Gö6976
inhibitor directly targets phosphatidylinositol 3-kinase and confers profound inhibition of autophagic flux by inhibiting the formation of autophagosomes. It does not inhibit the cell survival promoting class I phosphoinositide 3-kinase-Akt signaling at the concentrations required for effective autophagy inhibition
IC87114
-
-
KU55933
inhibitor directly targets phosphatidylinositol 3-kinase and confers profound inhibition of autophagic flux by inhibiting the formation of autophagosomes. Inhibits wild-type activity in vitro almost as efficiently as LY294002. It does not inhibit the cell survival promoting class I phosphoinositide 3-kinase-Akt signaling at the concentrations required for effective autophagy inhibition
Ly-294002
-
-
LY292223
-
i.e. 2-morpholin-4-yl-chromen-4-one, IC50 is 0.0026 mM for the recombinant wild-type enzyme and 0.025 mM for the recombinant mutant C838V/I848A
LY294002
naloxone
-
-
noggin
-
-
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NVP-BEZ235
palmitate
-
-
peptide N24
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a peptide inhibitor derived from p55PIK phosphatidylinositol 3-kinase, N24, regulatory subunit acts as inhibitor in cancer therapy, it blocks cell proliferation and induces cell cycle arrest in all cancer cell lines tested. Modeling of mechanisms of Rb-dependent and Rb-independent cell cycle arrest by N24 peptide, overview
-
PIK-III
-
-
PWT-458
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i.e. poly(oxy-1,2-ethanediyl)-, R-[2-[[2-[[(1S,6bR,9S,9aS,11R,11bR)-11-(acetyloxy)-1,6,6b,7,8,9,9a,10,11,11b-decahydro-1-(methoxymethyl)-9a,11b-dimethyl-3,6-dioxo-3Hfuro[4,3,2-de]indeno[4,5-h]-2-benzopyran-9-yl]oxy]-2-oxoethyl]thio]ethyl]-omega-methoxy
PX-866
TGFbeta
-
significantly inhibits phosphorylation of both p85 and ERK1/2 in vivo. TGFbeta does not activate the ERK pathway but turns off the GM-CSF-induced ERK signal via inhibition of the PI3-kinase-Akt pathway in human leukemia cells, overview
-
Tiron
-
specific PI3K inhibitor, restores vasorelaxation and hyperpolarization in response to an ATP-sensitive K+ channel opener levcromakalim
Vps34-IN-1
-
-
Wortmannin
ZSTK474
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a phosphatidylinositol 3-kinase inhibitor, inhibited phosphorylation of Ser65, Thr70 and Thr37/46 in 4E-BP1 by PI3K. Identification of the ZSTK474-sensitive phosphoproteins in A-549 cells, overview
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
beta-catenin
-
tyrosine-phopshorylated
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bone morphogenetic protein-2
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activates Akt phopshorylation by PI3K. Cell treatment with BMP-2 exhibits dramatic changes in cell morphology, from a cuboid, epithelial-like shape to a spindle, fibroblastic-like appearance, consistent with epithelial-mesenchymal transition, EMT, overview
-
c-Src
-
-
-
Dlg
-
tyrosine-phopshorylated
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insulin-like growth factor-I
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strongly stimulates insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity about 54fold and total phosphatidylinositol 3-kinase activity abozut 6fold
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monosodium urate
-
interaction of monosodium urate crystals with human neutrophils leads to the stimulation of class Ia PI-3Ks by a mechanism that is dependent on the tyrosine kinase Syk. The activation of PI-3Ks by monosodium urate crystals is a critical element regulating phospholipase D activation and degranulation of human neutrophils
-
morphine
-
morphine treatment enhances the level of phosphorylated, rather than unphosphorylated, PI3K and AKT, which are synchronously recruited to membrane. Levels of PTEN and p53, which are negative regulators of these signal molecules, are reduced, and as a result, the interaction between PTEN and p53 is completely interrupted
oleate
-
activates
p38 mitogen-activated protein kinase
-
activates PI3K, and proteasome inactivation promotes p38 mitogen-activated protein kinase-dependent phosphatidylinositol 3-kinase activation in retinal piment epithelial cells
-
pioglitazone
-
a thiazolidinedione, activates PI3K 2-2.5fold at 0.002-0.010 mM, activates adiponectin secretion from adipocytes in vivo
Ron kinase
-
Ron plays an essential role in maintaining malignant phenotypes of colon cancer cells through regulating mutant PI3K activity
-
Syk
-
protein kinase Syk associates with clathrin and mediates phosphatidylinositol 3-kinase activation during human rhinovirus internalization in leukocytes
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011
phosphatidylinositol-4,5-bisphosphate
-
preferred free substrate
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000002
(8S)-2-[(3R)-3-methylmorpholin-4-yl]-9-(3-methyl-2-oxobutyl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one
Homo sapiens
pH and temperature not specified in the publication
0.2
2-morpholin-4-yl-3-phenylchromen-4-one
Homo sapiens
-
weak inhibition, IC50 is above 0.2 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
0.0031
2-morpholin-4-yl-3-propylchromen-4-one
Homo sapiens
-
IC50 is 0.0031 mM for the recombinant wild-type enzyme and 0.068 mM for the recombinant mutant C838V/I848A
0.2
3-benzyl-2-morpholin-4-yl-chromen-4-one
Homo sapiens
-
weak inhibition, IC50 is above 0.2 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
0.025
3-butyl-2-morpholin-4-yl-chromen-4-one
Homo sapiens
-
IC50 is 0.025 mM for the recombinant wild-type enzyme and 0.048 mM for the recombinant mutant C838V/I848A
0.028
3-ethyl-2-morpholin-4-yl-chromen-4-one
Homo sapiens
-
IC50 is 0.028 mM for the recombinant wild-type enzyme and 0.0044 mM for the recombinant mutant C838V/I848A
0.051
3-isopropyl-2-morpholin-4-yl-chromen-4-one
Homo sapiens
-
IC50 is 0.051 mM for the recombinant wild-type enzyme and more than 0.2 mM for the recombinant mutant C838V/I848A
0.033
3-methyl-2-morpholin-4-yl-chromen-4-one
Homo sapiens
-
IC50 is 0.033 mM for the recombinant wild-type enzyme and 0.040 mM for the recombinant mutant C838V/I848A
0.000036
3-Methyladenine
Homo sapiens
pH and temperature not specified in the publication
0.01
GDC-0941
Homo sapiens
above, pH and temperature not specified in the publication
0.0026
LY292223
Homo sapiens
-
i.e. 2-morpholin-4-yl-chromen-4-one, IC50 is 0.0026 mM for the recombinant wild-type enzyme and 0.025 mM for the recombinant mutant C838V/I848A
0.0011
LY294002
Homo sapiens
-
IC50 is 0.0011 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
0.000488
PI-103
Homo sapiens
pH and temperature not specified in the publication
0.000018
PIK-III
Homo sapiens
pH and temperature not specified in the publication
-
0.0000012
SAR405
Homo sapiens
pH and temperature not specified in the publication
0.000025
Vps34-IN-1
Homo sapiens
pH and temperature not specified in the publication
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0016
-
purified recombinant isozyme gamma, at phosphatidylinositol-4,5-bisphosphate surface concentration of 10 mol%
0.0017
-
purified recombinant isozyme beta, at phosphatidylinositol-4,5-bisphosphate surface concentration of 7.5 mol%
0.0028
-
purified recombinant isozyme delta, at phosphatidylinositol-4,5-bisphosphate surface concentration of 2.5 mol%
0.0086
-
purified recombinant isozyme alpha, at phosphatidylinositol-4,5-bisphosphate surface concentration of 10 mol%
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
assay at room temperature
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
colorectal tumors exhibit enhanced PI 3-kinase activity compared with normal colonic mucosa
Manually annotated by BRENDA team
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colorectal tumors exhibit enhanced PI 3-kinase activity compared with normal colonic mucosa
Manually annotated by BRENDA team
-
umbilical vein endothelial cells
Manually annotated by BRENDA team
-
primary tumor cell line
Manually annotated by BRENDA team
-
nodal metastasis cell line
Manually annotated by BRENDA team
-
primary glioblastoma
Manually annotated by BRENDA team
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HCT-116 cells are heterozygous for gain of function mutant PIK3CA H1047R
Manually annotated by BRENDA team
-
a promyelocytic leukemia cell line, expression of different PI3K isoforms during granulocyte differentiation of NB4 cells induced by all-trans-retinoic acid, 9-cis-retinoic acid or retinoic acid receptor agonists, overview
Manually annotated by BRENDA team
-
KF, KFTx, SHIN-3, KOC-2S, and SK-OV-3. Simultaneous inhibition of the mitogen-activated protein kinase kinase and phosphatidylinositol 3-kinase pathways enhances sensitivity to paclitaxel in ovarian carcinoma
Manually annotated by BRENDA team
-
a cell line overexpressing the HER2/c-erb-2 gene product
Manually annotated by BRENDA team
-
insulin-stimulated insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity is enhanced in human skeletal muscle after exercise
Manually annotated by BRENDA team
-
anaplastic and follicular thyroid carcinoma
Manually annotated by BRENDA team
-
ATCC CRTL-1486
Manually annotated by BRENDA team
additional information
-
isozymes Ia alpha and Ia beta are widely expressed in tissues
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
in quiescent cells, PI3-kinase is distributed through the cytoplasm, although a portion is present in the nucleus, following stimulation with IL-1, PI3-kinase is redistributed, increasing in the nuclear compartment. PI3-kinase translocation to the nucleus upon IL-1R activation is an early event in IL-1 signaling mechanism, and may be involved in transcriptional activation
Manually annotated by BRENDA team
-
cytosol is partly associated with the cytoskeletal filaments
Manually annotated by BRENDA team
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
vacuolar protein sorting 34 (Vps34) is a member of the phosphoinositide 3-kinase (PI3K) family of lipid kinases. Vps34 and its functions are highly conserved from yeast to mammals. The domain organization of Vps34 and Vps15 are highly conserved between yeast and humans
malfunction
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
P3C2G_HUMAN
1445
0
165715
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
110000
128900
-
1 * 128900, catalytic subunit, recombinant isozyme alpha, + 1 * 83400, regulatory subunit, recombinant isozyme alpha, mass spectrometry, 1 * 110000, catalytic subunit, + 1 * 85000, regulatory subunit, recombinant isozymes alpha-delta, SDS-PAGE
85000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
heterodimer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
for Vps34, phosphorylation sites within the C2 domain are inhibitory (Thr159, Thr163 and Ser165) as is phosphorylation of Thr668 in the kinase domain. Activating phosphorylation sites are in the C2-helical linker (Tyr231) or in the kinase domain (Tyr310 and Thr667). Inhibitory phosphorylation sites in Atg14 (Ser3, Ser223, Ser233, Ser383 and Ser440) are spread throughout the proteins. Ser90 phosphorylation regulates Vps34 activity
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of PI3K SH3 domain at 2.0 A resolution
-
in complex with inhibitor E5E2, hanging drop vapour diffusion method, 100 mM Tris pH 7.2, 200 mM ammonium sulfate, 21% PEG 4000
-
purified detagged recombinant PI3K SH3 domain, residues 1-83, crystallized in presence of peptide ligands PD1R or PD1, the crystals do not contain the PD1 ligand, instead, the ligand binding site is partially occupied by residues Arg18 and Trp55 from the symmetry-related PI3K SH3 molecule. Sitting drop vapor diffusion method by mixing of 0.001 ml of protein-peptide mixture and 0.001 ml of reservoir solution containing for PD1R crystals 100 mM CAPS buffer, pH 10.5, 2 M ammonium sulfate and 0.2 M lithium sulfate or for PD1 crystals 100 mM Na-citrate buffer, pH 5.5, 0.5 M ammonium sulfate and 1 M lithium sulfate, 17°C, several weeks, X-ray diffraction structure determination and analysis at 1.7 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C838C/I848A
-
site-directed mutagenesis, 10% activity compared to the wild-type enzyme
C838I/I848A
-
site-directed mutagenesis, below 10% activity compared to the wild-type enzyme
C838L/I848A
-
site-directed mutagenesis, highly reduced activity, 0.1% compared to the wild-type enzyme
D743N
kinase-dead catalytic loop mutant
E545K
-
a dominant activating mutation of the catalytic subunit PIK3CA that is prevalent in breast cancer and confers resistance to lapatinib, lapatinib effectively inhibits the transactivation of EGFR and HER2 by IGF-I signaling
G373R
naturally occuring mutation in gene PIK3R2 involved in bilateral perisylvian polymicrogyria
H1047R
I848A
-
site-directed mutagenesis, mutation of a catalytic subunit p110 residue, highly reduced activity, 1% compared to the wild-type enzyme
I848G
-
site-directed mutagenesis, mutation of a catalytic subunit p110 residue, highly reduced activity, 0.1% compared to the wild-type enzyme
K376E
naturally occuring mutation in gene PIK3R2 involved in bilateral perisylvian polymicrogyria
L750M
mutation in the ATP-binding pocket. Mutant is less sensitive to inhibition by KU55933 than wild-type, mutant is similarly sensitive to inhibition by LY294002 as wild-type
S90A
site-directed mutagenesis, basal Beclin-1-associated Vps34 activity is decreased in cells expressing S90A Beclin-1, and increased in cells expressing S90E Beclin-1
S90E
site-directed mutagenesis, basal Beclin-1-associated Vps34 activity is decreased in cells expressing S90A Beclin-1, and increased in cells expressing S90E Beclin-1
Y231F
Vps34 is activated in Src-transformed cells by phosphorylation at Tyr231 and Tyr310, and kinase-dead or Y231F Vps34 blocks Src-mediated transformation. Expression of Y231F Vps34 causes a reduction in insulin-stimulated activation of S6K1
Y836A
-
site-directed mutagenesis, completely inactive p110alpha mutant
Y836D
-
site-directed mutagenesis, completely inactive p110alpha mutant
Y836G
-
site-directed mutagenesis, completely inactive p110alpha mutant
Y836H
-
site-directed mutagenesis, completely inactive p110alpha mutant
Y836L
-
site-directed mutagenesis, completely inactive p110alpha mutant
Y836M
-
site-directed mutagenesis, completely inactive p110alpha mutant
Y836T
-
site-directed mutagenesis, completely inactive p110alpha mutant
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged PI3K SH3 domain from Escherichia coli strain BL21 by glutathione affinity chromatography, followed by removal of the tag and gel filtration
-
recombinant His-tagged class Ia isozymes and recombinant His-tagged p85 and p110 subunits from insect cells by nickel affinity chromatography to homogeneity
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
PIK3C2G is mapped to chromosome 12
C2 domain-containing phosphoinositide 3-kinase, HsC2-PI3K
class Ia isozymes, DNA sequence determination and analysis, expression of His-tagged isozymes or P85 and p110 subunits alone in Spodoptera frugiperda Sf9 insect cells utilizing the baculovirus infection system
-
class II phosphoinositide 3-kinase with a C2 domain, cloned from a U937 monocyte cDNA library, expression in mammalian and insect cells
class II phosphoinositide 3-kinase, PI 3-kinase C2b, with a C2 domain is cloned from a U937 monocyte cDNA library and expressed in mammalian and insect cells
cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin
-
construction of a tetracycline-inducible expression system by introducing a regulatory plasmid, which constitutively expresses tetracycline-sensitive transactivator, and a response plasmid, containing a tetracycline response element in form of a heptameric repeat of the tetR binding site, under control of a minimal CMV promotor, into Jurkat cells, individual and coexpression of the Myc-tagged enzyme subunits in the Jurkat cell system, determination of expression levels, overview
-
expressed in Escherichia coli
-
expression of GST-tagged PI3K SH3 domain in Escherichia coli strain Bl21
-
expression of the catalytic subunit p110alpha of the wild-type and mutant enzymes in COS-1 cells
-
expression of the wild-type p110 alpha protein in CHO cells
gene PIK3R2
genotyping
-
phosphoinositide-3 kinase isotype, p110 gamma
stable expression of GFP-tagged Atg14 in NIH3T3 cells, transient co-expression of N-terminally Myc-, HA-, or FLAG-tagged Atg14, Beclin 1, and UVRAG in HEK-293T cells
transient co-expression of N-terminally Myc-, HA-, or FLAG-tagged Beclin 1 in HEK-293T cells
transient co-expression of N-terminally Myc-, HA-, or FLAG-tagged UVRAG in HEK-293T cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
medicine
pharmacology
-
development of specific isozyme inhibitors may offer therapeutic benefit in a broad range of clinical settings related to cancer, inflammatory and immunological diseases
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Vanhaesebroeck, B.; Welham, M.J.; Kotani, K.; Stein, R.; Warne, P.H.; Zvelebil, M.J.; Higashi, K.; Volinia, S.; Downward, J.; Waterfield, M.D.
P110delta, a novel phosphoinositide 3-kinase in leukocytes
Proc. Natl. Acad. Sci. USA
94
4330-4335
1997
Homo sapiens (O00329)
Manually annotated by BRENDA team
Arcaro, A.; Zvelebil, M.J.; Wallasch, C.; Ullrich, A.; Waterfield, M.D.; Domin, J.
Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors
Mol. Cell. Biol.
20
3817-3830
2000
Homo sapiens
Manually annotated by BRENDA team
Arcaro, A.; Volinia, S.; Zvelebil, M.J.; Stein, R.; Watton, S.J.; Layton, M.J.; Gout, I.; Ahmadi, K.; Downward, J.; Waterfield, M.D.
Human phosphoinositide 3-kinase C2b, the role of calcium and the C2 domain in enzyme activity
J. Biol. Chem.
273
33082-33090
1998
Homo sapiens, Homo sapiens (O00750)
Manually annotated by BRENDA team
Axelsson, L.; Hellberg, C.; Melander, F.; Smith, D.; Zheng, L.; Andersson, T.
Clustering of b2-Integrins on Human Neutrophils Activates Dual Signaling Pathways to PtdIns 3-Kinase
Exp. Cell Res.
256
257-263
2000
Homo sapiens
Manually annotated by BRENDA team
Bavelloni, A.; Santi, S.; Sirri, A.; Riccio, M.; Faenza, I.; Zini, N.; Cecchi, S.; Ferri, A.; Auron, P.; Maraldi, N.M.; Marmiroli, S.
Phosphatidylinositol 3-kinase translocation to the nucleus is induced by interleukin 1 and prevented by mutation of interleukin 1 receptor in human osteosarcoma Saos-2 cells
J. Cell Sci.
112
631-640
1999
Homo sapiens
-
Manually annotated by BRENDA team
Baynes, K.C.R.; Beeton, C.A.; Panayotou, G.; Stein, R.; Soos, M.; Hansen, T.; Simpson, H.; O'Rahilly, S.; Shepherd, P.R.; Whitehead, J.P.
Natural variants of human p85a phosphoinositide 3-kinase in severe insulin resistance: a novel variant with impaired insulin-stimulated lipid kinase activity
Diabetologia
43
321-331
2000
Homo sapiens
Manually annotated by BRENDA team
Beckwith, M.; Fenton, R.G.; Katona, I.M.; Longo, D.L.
Phosphatidylinositol-3-kinase activity is required for the anti-Ig-mediated growth inhibition of a human b-lymphoma cell line
Blood
87
202-210
1996
Homo sapiens
Manually annotated by BRENDA team
Blondeau, F.; Laporte, J.; Bodin, S.; Superti-Furga, G.; Payrastre, B.; Mandel, J.L.
Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway
Hum. Mol. Genet.
9
2223-2229
2000
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Chantry, D.; Vojtek, A.; Kashishian, A.; Holtzman, D.A.; Wood, C.; Gray, P.W.; Cooper, J.A.; Hoekstra, M.F.
p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes
J. Biol. Chem.
272
19236-19241
1997
Homo sapiens, Homo sapiens (O00329), Mus musculus, Mus musculus (O35940)
Manually annotated by BRENDA team
Dadi, H.; Ke, S.; Roifman, C.M.
Activation of phosphatidylinositol-3 kinase by ligation of the interleukin-7 receptor is dependent on protein tyrosine kinase activity
Blood
84
1579-1586
1994
Homo sapiens
Manually annotated by BRENDA team
Domin, J.; Pages, F.; Volinia, S.; Rittenhouse, S.E.; Zvelebil, M.J.; Stein, R.C.; Waterfield, M.D.
Cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin
Biochem. J.
326
139-147
1997
Homo sapiens
-
Manually annotated by BRENDA team
Hardy, S.; Langelier, Y.; Prentki, M.
Oleate activates phosphatidylinositol 3-kinase and promotes proliferation and reduces apoptosis of MDA-MB-231 breast cancer cells, whereas palmitate has opposite effects
Cancer Res.
60
6353-6358
2000
Homo sapiens
Manually annotated by BRENDA team
Hauert, A.B.; Martinelli, S.; Marone, C.; Niggli, V.
Differentiated HL-60 cells are a valid model system for the analysis of human neutrophil migration and chemotaxis
Int. J. Biochem. Cell Biol.
34
838-854
2002
Homo sapiens
Manually annotated by BRENDA team
Herrera-Velit, P.; Reiner, N.E.
Bacterial lipopolysaccharide induces the association and coordinate activation of p53/56lyn and phosphatidylinositol 3-kinase in human monocytes
J. Immunol.
156
1157-1165
1996
Homo sapiens
Manually annotated by BRENDA team
Knall, C.; Young, S.; Nick, J.A.; Buhl, A.M.; Worthen, G.S.; Johnson, G.L.
Interleukin-8 regulation of the Ras/Raf/mitogen-activated protein kinase pathway in human neutrophils
J. Biol. Chem.
271
2832-2838
1996
Homo sapiens
Manually annotated by BRENDA team
Krymskaya, V.P.; Hoffman, R.; Eszterhas, A.; Kane, S.; Ciocca, V.; Panettieri, R.A., Jr.
EGF activates ErbB-2 and stimulates phosphatidylinositol 3-kinase in human airway smooth muscle cells
Am. J. Physiol.
276
L246-L255
1999
Homo sapiens
Manually annotated by BRENDA team
Liang, J.; Chen, J.K.; Schreiber, S.L.; Clardy, J.
Crystal structure of PI3K SH3 domain at 2.0.ANG. resolution
J. Mol. Biol.
257
632-643
1996
Homo sapiens
Manually annotated by BRENDA team
Marshall, A.J.; Krahn, A.K.; Ma, K.; Duronio, V.; Hou, S.
TAPP1 and TAPP2 are targets of phosphatidylinositol 3-kinase signaling in B cells: sustained plasma membrane recruitment triggered by the B-cell antigen receptor
Mol. Cell. Biol.
22
5479-5491
2002
Homo sapiens
Manually annotated by BRENDA team
Pellegatta, F.; Chierchia, S.L.; Zocchi, M.R.
Functional association of platelet endothelial cell adhesion molecule-1 and phosphoinositide 3-kinase in human neutrophils
J. Biol. Chem.
273
27768-27771
1998
Homo sapiens
Manually annotated by BRENDA team
Phillips, W.A.; St.Clair, F.; Munday, A.D.; Thomas, R.J.S.; Mitchell, C.A.
Increased levels of phosphatidylinositol 3-kinase activity in colorectal tumors
Cancer
83
41-47
1998
Homo sapiens
Manually annotated by BRENDA team
Rondinone, C.M.; Carvalho, E.; Rahn, T.; Manganiello, V.C.; Degerman, E.; Smith, U.P.
Phosphorylation of PDE3B by phosphatidylinositol 3-kinase associated with the insulin receptor
J. Biol. Chem.
275
10093-10098
2000
Homo sapiens
Manually annotated by BRENDA team
Stoyanov, B.; Volinia, S.; Hanck, T.; Rubio, I.; Loubtchenkov, M.; Malek, D.; Stoyanova, S.; Vanhaesebroeck, B.; Dhand, R.; et al.
Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase
Science
269
690-693
1995
Homo sapiens, Homo sapiens (P48736)
Manually annotated by BRENDA team
Volinia, S.; Dhand, R.; Vanhaesebroeck, B.; MacDougall, L.; Stein, R.; Zvelebil, M.J.; Domin, J.; Panaretou, C.; Waterfield, M.D.
A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system
EMBO J.
14
3339-3348
1995
Homo sapiens
Manually annotated by BRENDA team
Yu, Y.; Sato, J.D.
MAP kinases, phosphatidylinositol 3-kinase, and p70 S6 kinase mediate the mitogenic response of human endothelial cells to vascular endothelial growth factor
J. Cell. Physiol.
178
235-246
1999
Homo sapiens
Manually annotated by BRENDA team
Zhou, J.H.; Broussard, S.R.; Strle, K.; Freund, G.G.; Johnson, R.W.; Dantzer, R.; Kelley, K.W.
IL-10 inhibits apoptosis of promyeloid cells by activating insulin receptor substrate-2 and phosphatidylinositol 3'-kinase
J. Immunol.
167
4436-4442
2001
Homo sapiens
Manually annotated by BRENDA team
Zini, N.; Ognibene, A.; Bavelloni, A.; Santi, S.; Sabatelli, P.; Baldini, N.; Scotlandi, K.; Serra, M.; Maraldi, N.M.
Cytoplasmic and nuclear localization sites of phosphatidylinositol 3-kinase in human osteosarcoma sensitive and multidrug-resistant Saos-2 cells
Histochem. Cell Biol.
106
457-464
1996
Homo sapiens
Manually annotated by BRENDA team
Brown, R.A.; Ho, L.K.; Weber-Hall, S.J.; Shipley, J.M.; Fry, M.J.
Identification and cDNA cloning of a novel mammalian C2 domain-containing phosphoinositide 3-kinase, HsC2-PI3K
Biochem. Biophys. Res. Commun.
233
537-544
1997
Homo sapiens (O00750), Homo sapiens
Manually annotated by BRENDA team
McWhirter, J.R.; Galasso, D.L.; Wang, J.Y.
A coiled-coil oligomerization domain of Bcr is essential for the transforming function of Bcr-Abl oncoproteins
Mol. Cell. Biol.
13
7587-7595
1993
Homo sapiens (P42338)
Manually annotated by BRENDA team
Rozycka, M.; Lu, Y.J.; Brown, R.A.; Lau, M.R.; Shipley, J.M.; Fry, M.J.
cDNA cloning of a third human C2-domain-containing class II phosphoinositide 3-kinase, PI3K-C2gamma, and chromosomal assignment of this gene (PIK3C2G) to 12p12
Genomics
54
569-574
1998
Homo sapiens (O75747)
Manually annotated by BRENDA team
Stirdivant, S.M.; Ahern, J.; Conroy, R.R.; Barnett, S.F.; Ledder, L.M.; Oliff, A.; Heimbrook, D.C.
Cloning and mutagenesis of the p110 alpha subunit of human phosphoinositide 3'-hydroxykinase
Bioorg. Med. Chem.
5
65-74
1997
Homo sapiens (P42336)
Manually annotated by BRENDA team
Volinia, S.; Hiles, I.; Ormondroyd, E.; Nizetic, D.; Antonacci, R.; Rocchi, M.; Waterfield, M.D.
Molecular cloning, cDNA sequence, and chromosomal localization of the human phosphatidylinositol 3-kinase p110 alpha (PIK3CA) gene
Genomics
24
472-477
1994
Schizosaccharomyces pombe (O14356), Schizosaccharomyces pombe (Q9Y7K2), Homo sapiens (P42336), Homo sapiens
Manually annotated by BRENDA team
Srivastava, R.; Ratheesh, A.; Gude, R.K.; Rao, K.V.K.; Panda, D.; Subrahmanyam, G.
Resveratrol inhibits type II phosphatidylinositol 4-kinase: A key component in pathways of phosphoinositide turn over
Biochem. Pharmacol.
70
1048-1055
2005
Homo sapiens
Manually annotated by BRENDA team
Alaimo, P.J.; Knight, Z.A.; Shokat, K.M.
Targeting the gatekeeper residue in phosphoinositide 3-kinases
Bioorg. Med. Chem.
13
2825-2836
2005
Saccharomyces cerevisiae, Homo sapiens
Manually annotated by BRENDA team
Jones, D.R.; Paneda, C.; Villar, A.V.; Alonso, A.; Goni, F.M.; Butikofer, P.; Brodbeck, U.; Shepherd, P.R.; Varela-Nieto, I.
Phosphorylation of glycosyl-phosphatidylinositol by phosphatidylinositol 3-kinase changes its properties as a substrate for phospholipases
FEBS Lett.
579
59-65
2005
Homo sapiens
Manually annotated by BRENDA team
Anderson, K.E.; Jackson, S.P.
Class I phosphoinositide 3-kinases
Int. J. Biochem. Cell Biol.
35
1028-1033
2003
Homo sapiens, Mammalia
Manually annotated by BRENDA team
Curnock, A.P.; Ward, S.G.
Development and characterization of tetracycline-regulated phosphoinositide 3-kinase mutants: assessing the role of multiple phosphoinositide 3-kinases in chemokine signaling
J. Immunol. Methods
273
29-41
2003
Homo sapiens
Manually annotated by BRENDA team
Meier, T.I.; Cook, J.A.; Thomas, J.E.; Radding, J.A.; Horn, C.; Lingaraj, T.; Smith, M.C.
Cloning, expression, purification, and characterization of the human Class Ia phosphoinositide 3-kinase isoforms
Protein Expr. Purif.
35
218-224
2004
Homo sapiens
Manually annotated by BRENDA team
Zhang, X.; Mi, J.; Wetsel, W.C.; Davidson, C.; Xiong, X.; Chen, Q.; Ellinwood, E.H.; Lee, T.H.
PI3 kinase is involved in cocaine behavioral sensitization and its reversal with brain area specificity
Biochem. Biophys. Res. Commun.
340
1144-1150
2006
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Johnson, E.E.; Overmeyer, J.H.; Gunning, W.T.; Maltese, W.A.
Gene silencing reveals a specific function of hVps34 phosphatidylinositol 3-kinase in late versus early endosomes
J. Cell Sci.
119
1219-1232
2006
Homo sapiens (Q8NEB9), Homo sapiens
Manually annotated by BRENDA team
Zeng, X.; Overmeyer, J.H.; Maltese, W.A.
Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking
J. Cell Sci.
119
259-270
2006
Homo sapiens
Manually annotated by BRENDA team
Howlett, K.F.; Sakamoto, K.; Yu, H.; Goodyear, L.J.; Hargreaves, M.
Insulin-stimulated insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity is enhanced in human skeletal muscle after exercise
Metab. Clin. Exp.
55
1046-1052
2006
Homo sapiens
Manually annotated by BRENDA team
Vogt, P.K.; Kang, S.; Elsliger, M.A.; Gymnopoulos, M.
Cancer-specific mutations in phosphatidylinositol 3-kinase
Trends Biochem. Sci.
32
342-349
2007
Homo sapiens
Manually annotated by BRENDA team
Xing, C.; Zhu, B.; Liu, H.; Yao, H.; Zhang, L.
Class I phosphatidylinositol 3-kinase inhibitor LY294002 activates autophagy and induces apoptosis through p53 pathway in gastric cancer cell line SGC7901
Acta Biochim. Biophys. Sin. (Shanghai)
40
194-201
2008
Homo sapiens
Manually annotated by BRENDA team
von Vietinghoff, S.; Choi, M.; Rolle, S.; Luft, F.C.; Kettritz, R.
Febrile temperatures control antineutrophil cytoplasmic autoantibody-induced neutrophil activation via inhibition of phosphatidylinositol 3-kinase/Akt
Arthritis Rheum.
56
3149-3158
2007
Homo sapiens
Manually annotated by BRENDA team
Liu, P.; Xu, B.; Li, J.; Lu, H.
LY294002 inhibits leukemia cell invasion and migration through early growth response gene 1 induction independent of phosphatidylinositol 3-kinase-Akt pathway
Biochem. Biophys. Res. Commun.
377
187-190
2008
Homo sapiens
Manually annotated by BRENDA team
Tamburini, J.; Chapuis, N.; Bardet, V.; Park, S.; Sujobert, P.; Willems, L.; Ifrah, N.; Dreyfus, F.; Mayeux, P.; Lacombe, C.; Bouscary, D.
Mammalian target of rapamycin (mTOR) inhibition activates phosphatidylinositol 3-kinase/Akt by up-regulating insulin-like growth factor-1 receptor signaling in acute myeloid leukemia: rationale for therapeutic inhibition of both pathways
Blood
111
379-382
2008
Homo sapiens
Manually annotated by BRENDA team
Terragni, J.; Graham, J.R.; Adams, K.W.; Schaffer, M.E.; Tullai, J.W.; Cooper, G.M.
Phosphatidylinositol 3-kinase signaling in proliferating cells maintains an anti-apoptotic transcriptional program mediated by inhibition of FOXO and non-canonical activation of NFkappaB transcription factors
BMC Cell Biol.
9
6
2008
Homo sapiens
Manually annotated by BRENDA team
Opel, D.; Westhoff, M.A.; Bender, A.; Braun, V.; Debatin, K.M.; Fulda, S.
Phosphatidylinositol 3-kinase inhibition broadly sensitizes glioblastoma cells to death receptor- and drug-induced apoptosis
Cancer Res.
68
6271-6280
2008
Homo sapiens
Manually annotated by BRENDA team
Schnell, C.R.; Stauffer, F.; Allegrini, P.R.; OReilly, T.; McSheehy, P.M.; Dartois, C.; Stumm, M.; Cozens, R.; Littlewood-Evans, A.; Garcia-Echeverria, C.; Maira, S.M.
Effects of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imaging
Cancer Res.
68
6598-6607
2008
Homo sapiens
Manually annotated by BRENDA team
Kawaguchi, W.; Itamochi, H.; Kigawa, J.; Kanamori, Y.; Oishi, T.; Shimada, M.; Sato, S.; Shimogai, R.; Sato, S.; Terakawa, N.
Simultaneous inhibition of the mitogen-activated protein kinase kinase and phosphatidylinositol 3-kinase pathways enhances sensitivity to paclitaxel in ovarian carcinoma
Cancer Sci.
98
2002-2008
2007
Homo sapiens
Manually annotated by BRENDA team
Qureshi, H.Y.; Ahmad, R.; Sylvester, J.; Zafarullah, M.
Requirement of phosphatidylinositol 3-kinase/Akt signaling pathway for regulation of tissue inhibitor of metalloproteinases-3 gene expression by TGF-beta in human chondrocytes
Cell. Signal.
19
1643-1651
2007
Homo sapiens
Manually annotated by BRENDA team
Sabnis, G.; Goloubeva, O.; Jelovac, D.; Schayowitz, A.; Brodie, A.
Inhibition of the phosphatidylinositol 3-kinase/Akt pathway improves response of long-term estrogen-deprived breast cancer xenografts to antiestrogens
Clin. Cancer Res.
13
2751-2757
2007
Homo sapiens
Manually annotated by BRENDA team
Uchida, M.; Iwase, M.; Takaoka, S.; Yoshiba, S.; Kondo, G.; Watanabe, H.; Ohashi, M.; Nagumo, M.; Shintani, S.
Enhanced susceptibility to tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in oral squamous cell carcinoma cells treated with phosphatidylinositol 3-kinase inhibitors
Int. J. Oncol.
30
1163-1171
2007
Homo sapiens
Manually annotated by BRENDA team
Iwase, M.; Yoshiba, S.; Uchid, M.; Takaoka, S.; Kurihara, Y.; Ito, D.; Hatori, M.; Shintani, S.
Enhanced susceptibility to apoptosis of oral squamous cell carcinoma cells subjected to combined treatment with anticancer drugs and phosphatidylinositol 3-kinase inhibitors
Int. J. Oncol.
31
1141-1147
2007
Homo sapiens
Manually annotated by BRENDA team
Pan, M.H.; Lin, C.C.; Lin, J.K.; Chen, W.J.
Tea polyphenol (-)-epigallocatechin 3-gallate suppresses heregulin-beta1-induced fatty acid synthase expression in human breast cancer cells by inhibiting phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase cascade signaling
J. Agric. Food Chem.
55
5030-5037
2007
Homo sapiens
Manually annotated by BRENDA team
Tsoyi, K.; Park, H.B.; Kim, Y.M.; Chung, J.I.; Shin, S.C.; Lee, W.S.; Seo, H.G.; Lee, J.H.; Chang, K.C.; Kim, H.J.
Anthocyanins from black soybean seed coats inhibit UVB-induced inflammatory cylooxygenase-2 gene expression and PGE2 production through regulation of the nuclear factor-kappaB and phosphatidylinositol 3-kinase/Akt pathway
J. Agric. Food Chem.
56
8969-8974
2008
Homo sapiens
Manually annotated by BRENDA team
Tzatsos, A.; Tsichlis, P.N.
Energy depletion inhibits phosphatidylinositol 3-kinase/Akt signaling and induces apoptosis via AMP-activated protein kinase-dependent phosphorylation of IRS-1 at Ser-794
J. Biol. Chem.
282
18069-18082
2007
Homo sapiens
Manually annotated by BRENDA team
Havasi, A.; Li, Z.; Wang, Z.; Martin, J.L.; Botla, V.; Ruchalski, K.; Schwartz, J.H.; Borkan, S.C.
Hsp27 inhibits Bax activation and apoptosis via a phosphatidylinositol 3-kinase-dependent mechanism
J. Biol. Chem.
283
12305-12313
2008
Homo sapiens
Manually annotated by BRENDA team
Lindemann, M.J.; Hu, Z.; Benczik, M.; Liu, K.D.; Gaffen, S.L.
Differential regulation of the IL-17 receptor by gammac cytokines: inhibitory signaling by the phosphatidylinositol 3-kinase pathway
J. Biol. Chem.
283
14100-14108
2008
Homo sapiens
Manually annotated by BRENDA team
Mostefai, H.A.; Agouni, A.; Carusio, N.; Mastronardi, M.L.; Heymes, C.; Henrion, D.; Andriantsitohaina, R.; Martinez, M.C.
Phosphatidylinositol 3-kinase and xanthine oxidase regulate nitric oxide and reactive oxygen species productions by apoptotic lymphocyte microparticles in endothelial cells
J. Immunol.
180
5028-5035
2008
Homo sapiens
Manually annotated by BRENDA team
Popa-Nita, O.; Rollet-Labelle, E.; Thibault, N.; Gilbert, C.; Bourgoin, S.G.; Naccache, P.H.
Crystal-induced neutrophil activation. IX. Syk-dependent activation of class Ia phosphatidylinositol 3-kinase
J. Leukoc. Biol.
82
763-773
2007
Homo sapiens
Manually annotated by BRENDA team
Ren, M.; Guan, Q.; Zhong, X.; Gong, B.; Sun, Y.; Xin, W.; Guo, J.; Wang, H.; Gao, L.; Zhao, J.
Phosphatidylinositol 3-kinase/nuclear factor-kappaB signaling pathway is involved in the regulation of IGF-I on Fas-associated death domain-like interleukin-1-converting enzyme-inhibitory protein expression in cultured FRTL thyroid cells
J. Mol. Endocrinol.
38
619-625
2007
Homo sapiens
Manually annotated by BRENDA team
Ito, K.; Caramori, G.; Adcock, I.M.
Therapeutic potential of phosphatidylinositol 3-kinase inhibitors in inflammatory respiratory disease
J. Pharmacol. Exp. Ther.
321
1-8
2007
Homo sapiens
Manually annotated by BRENDA team
Howes, A.L.; Chiang, G.G.; Lang, E.S.; Ho, C.B.; Powis, G.; Vuori, K.; Abraham, R.T.
The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures
Mol. Cancer Ther.
6
2505-2514
2007
Homo sapiens
Manually annotated by BRENDA team
Maira, S.M.; Stauffer, F.; Brueggen, J.; Furet, P.; Schnell, C.; Fritsch, C.; Brachmann, S.; Chene, P.; De Pover, A.; Schoemaker, K.; Fabbro, D.; Gabriel, D.; Simonen, M.; Murphy, L.; Finan, P.; Sellers, W.; Garcia-Echeverria, C.
Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity
Mol. Cancer Ther.
7
1851-1863
2008
Homo sapiens
Manually annotated by BRENDA team
Shen, J.; Jiang, J.; Wei, Y.; Zhou, L.; Liu, D.; Zhou, J.; Gu, J.
Two specific inhibitors of the phosphatidylinositol 3-kinase LY294002 and wortmannin up-regulate beta1,4-galactosyltransferase I and thus sensitize SMMC-7721 human hepatocarcinoma cells to cycloheximide-induced apoptosis
Mol. Cell. Biochem.
304
361-367
2007
Homo sapiens
Manually annotated by BRENDA team
Wang, X.; Yue, P.; Chan, C.B.; Ye, K.; Ueda, T.; Watanabe-Fukunaga, R.; Fukunaga, R.; Fu, H.; Khuri, F.R.; Sun, S.Y.
Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3-kinase-dependent and Mnk-mediated eukaryotic translation initiation factor 4E phosphorylation
Mol. Cell. Biol.
27
7405-7413
2007
Homo sapiens
Manually annotated by BRENDA team
Xie, P.; Williams, D.S.; Atilla-Gokcumen, G.E.; Milk, L.; Xiao, M.; Smalley, K.S.; Herlyn, M.; Meggers, E.; Marmorstein, R.
Structure-based design of an Organoruthenium phosphatidyl-inositol-3-kinase inhibitor reveals a switch governing lipid kinase potency and selectivity
ACS Chem. Biol.
3
305-316
2008
Homo sapiens
Manually annotated by BRENDA team
Mitchell, C.; Kabolizadeh, P.; Ryan, J.; Roberts, J.D.; Yacoub, A.; Curiel, D.T.; Fisher, P.B.; Hagan, M.P.; Farrell, N.P.; Grant, S.; Dent, P.
Low-dose BBR3610 toxicity in colon cancer cells is p53-independent and enhanced by inhibition of epidermal growth factor receptor (ERBB1)-phosphatidyl inositol 3 kinase signaling
Mol. Pharmacol.
72
704-714
2007
Homo sapiens
Manually annotated by BRENDA team
Ding, Y.; Choi, K.J.; Kim, J.H.; Han, X.; Piao, Y.; Jeong, J.H.; Choe, W.; Kang, I.; Ha, J.; Forman, H.J.; Lee, J.; Yoon, K.S.; Kim, S.S.
Endogenous hydrogen peroxide regulates glutathione redox via nuclear factor erythroid 2-related factor 2 downstream of phosphatidylinositol 3-kinase during muscle differentiation
Am. J. Pathol.
172
1529-1541
2008
Homo sapiens
Manually annotated by BRENDA team
Liu, H.; Li, H.; Guo, L.; Li, M.; Li, C.; Wang, S.; Jiang, W.; Liu, X.; McNutt, M.A.; Li, G.
Mechanisms involved in phosphatidylinositol 3-kinase pathway mediated up-regulation of the mu opioid receptor in lymphocytes
Biochem. Pharmacol.
79
516-523
2010
Homo sapiens
Manually annotated by BRENDA team
Batra-Safferling, R.; Granzin, J.; Moedder, S.; Hoffmann, S.; Willbold, D.
Structural studies of the phosphatidylinositol 3-kinase (PI3K) SH3 domain in complex with a peptide ligand: role of the anchor residue in ligand binding
Biol. Chem.
391
33-42
2009
Homo sapiens
Manually annotated by BRENDA team
Wu, J.; Ding, W.G.; Matsuura, H.; Tsuji, K.; Zang, W.J.; Horie, M.
Inhibitory actions of the phosphatidylinositol 3-kinase inhibitor LY294002 on the human Kv1.5 channel
Br. J. Pharmacol.
156
377-387
2009
Homo sapiens
Manually annotated by BRENDA team
Sarveswaran, S.; Myers, C.E.; Ghosh, J.
MK591, a leukotriene biosynthesis inhibitor, induces apoptosis in prostate cancer cells: Synergistic action with LY294002, an inhibitor of phosphatidylinositol 3'-kinase
Cancer Lett.
291
167-176
2009
Homo sapiens
Manually annotated by BRENDA team
Eichhorn, P.J.; Gili, M.; Scaltriti, M.; Serra, V.; Guzman, M.; Nijkamp, W.; Beijersbergen, R.L.; Valero, V.; Seoane, J.; Bernards, R.; Baselga, J.
Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235
Cancer Res.
68
9221-9230
2008
Homo sapiens
Manually annotated by BRENDA team
Baryawno, N.; Sveinbjoernsson, B.; Eksborg, S.; Chen, C.S.; Kogner, P.; Johnsen, J.I.
Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth
Cancer Res.
70
266-276
2010
Homo sapiens
Manually annotated by BRENDA team
Zhao, L.; Vogt, P.K.
Hot-spot mutations in p110alpha of phosphatidylinositol 3-kinase (PI3K): Differential interactions with the regulatory subunit p85 and with RAS
Cell Cycle
9
596-600
2010
Homo sapiens
Manually annotated by BRENDA team
Montenegro, D.E.; Franklin, T.; Moscinski, L.C.; Zuckerman, K.S.; Hu, X.T.
TGFbeta inhibits GM-CSF-induced phosphorylation of ERK and MEK in human myeloid leukaemia cell lines via inhibition of phosphatidylinositol 3-kinase (PI3-k)
Cell Prolif.
42
1-9
2009
Homo sapiens
Manually annotated by BRENDA team
Kang, M.H.; Kim, J.S.; Seo, J.E.; Oh, S.C.; Yoo, Y.A.
BMP2 accelerates the motility and invasiveness of gastric cancer cells via activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway
Exp. Cell Res.
316
24-37
2010
Homo sapiens
Manually annotated by BRENDA team
Rivard, N.
Phosphatidylinositol 3-kinase: a key regulator in adherens junction formation and function
Front. Biosci.
14
510-522
2009
Canis lupus familiaris, Homo sapiens
Manually annotated by BRENDA team
Kinoshita, H.; Matsuda, N.; Kaba, H.; Hatakeyama, N.; Azma, T.; Nakahata, K.; Kuroda, Y.; Tange, K.; Iranami, H.; Hatano, Y.
Roles of phosphatidylinositol 3-kinase-Akt and NADPH oxidase in adenosine 5-triphosphate-sensitive K+ channel function impaired by high glucose in the human artery
Hypertension
52
507-513
2008
Homo sapiens
Manually annotated by BRENDA team
Wang, J.; Rajput, A.; Kan, J.L.; Rose, R.; Liu, X.Q.; Kuropatwinski, K.; Hauser, J.; Beko, A.; Dominquez, I.; Sharratt, E.A.; Brattain, L.; Levea, C.; Sun, F.L.; Keane, D.M.; Gibson, N.W.; Brattain, M.G.
Knockdown of Ron kinase inhibits mutant phosphatidylinositol 3-kinase and reduces metastasis in human colon carcinoma
J. Biol. Chem.
284
10912-10922
2009
Homo sapiens
Manually annotated by BRENDA team
Scholl, S.; Bondeva, T.; Liu, Y.; Clement, J.H.; Hoeffken, K.; Wetzker, R.
Additive effects of PI3-kinase and MAPK activities on NB4 cell granulocyte differentiation: potential role of phosphatidylinositol 3-kinase gamma
J. Cancer Res. Clin. Oncol.
134
861-872
2008
Homo sapiens
Manually annotated by BRENDA team
McLaughlin, N.J.; Banerjee, A.; Khan, S.Y.; Lieber, J.L.; Kelher, M.R.; Gamboni-Robertson, F.; Sheppard, F.R.; Moore, E.E.; Mierau, G.W.; Elzi, D.J.; Silliman, C.C.
Platelet-activating factor-mediated endosome formation causes membrane translocation of p67phox and p40phox that requires recruitment and activation of p38 MAPK, Rab5a, and phosphatidylinositol 3-kinase in human neutrophils
J. Immunol.
180
8192-8203
2008
Homo sapiens
Manually annotated by BRENDA team
Lau, C.; Wang, X.; Song, L.; North, M.; Wiehler, S.; Proud, D.; Chow, C.W.
Syk associates with clathrin and mediates phosphatidylinositol 3-kinase activation during human rhinovirus internalization
J. Immunol.
180
870-880
2008
Homo sapiens
Manually annotated by BRENDA team
Ayral-Kaloustian, S.; Gu, J.; Lucas, J.; Cinque, M.; Gaydos, C.; Zask, A.; Chaudhary, I.; Wang, J.; Di, L.; Young, M.; Ruppen, M.; Mansour, T.S.; Gibbons, J.J.; Yu, K.
Hybrid inhibitors of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR): design, synthesis, and superior antitumor activity of novel wortmannin-rapamycin conjugates
J. Med. Chem.
53
452-459
2009
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Pereira, R.I.; Leitner, J.W.; Erickson, C.; Draznin, B.
Pioglitazone acutely stimulates adiponectin secretion from mouse and human adipocytes via activation of the phosphatidylinositol 3-kinase
Life Sci.
83
638-643
2008
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Itakura, E.; Kishi, C.; Inoue, K.; Mizushima, N.
Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG
Mol. Biol. Cell
19
5360-5372
2008
Homo sapiens, Homo sapiens (Q6ZNE5), Homo sapiens (Q9P2Y5)
Manually annotated by BRENDA team
Fernandes, A.F.; Bian, Q.; Jiang, J.K.; Thomas, C.J.; Taylor, A.; Pereira, P.; Shang, F.
Proteasome inactivation promotes p38 mitogen-activated protein kinase-dependent phosphatidylinositol 3-kinase activation and increases interleukin-8 production in retinal pigment epithelial cells
Mol. Biol. Cell
20
3690-3699
2009
Homo sapiens
Manually annotated by BRENDA team
Hu, J.; Xia, X.; Cheng, A.; Wang, G.; Luo, X.; Reed, M.F.; Fojo, T.; Oetting, A.; Gong, J.; Yen, P.M.
A peptide inhibitor derived from p55PIK phosphatidylinositol 3-kinase regulatory subunit: a novel cancer therapy
Mol. Cancer Ther.
7
3719-3728
2008
Homo sapiens
Manually annotated by BRENDA team
Akashi, T.; Yamori, T.
Proteomic analysis of phosphoproteins sensitive to a phosphatidylinositol 3-kinase inhibitor, ZSTK474, by using SELDI-TOF MS
Proteome Sci.
7
14
2009
Homo sapiens
Manually annotated by BRENDA team
Marwick, J.A.; Chung, K.F.; Adcock, I.M.
Phosphatidylinositol 3-kinase isoforms as targets in respiratory disease
Ther. Adv. Respir. Dis.
2009
1-16
2010
Homo sapiens
Manually annotated by BRENDA team
Chan, G.; Bivins-Smith, E.R.; Smith, M.S.; Yurochko, A.D.
NF-kappaB and phosphatidylinositol 3-kinase activity mediates the HCMV-induced atypical M1/M2 polarization of monocytes
Virus Res.
144
329-333
2009
Homo sapiens
Manually annotated by BRENDA team
Karam, M.; Lassarre, C.; Legay, C.; Ricort, J.M.
Phosphatidylinositol 3-kinase and protein kinase D1 specifically cooperate to negatively regulate the insulin-like growth factor signaling pathway
Biochim. Biophys. Acta
1823
558-569
2012
Homo sapiens
Manually annotated by BRENDA team
Zheng, W.; Gorre, N.; Shen, Y.; Noda, T.; Ogawa, W.; Lundin, E.; Liu, K.
Maternal phosphatidylinositol 3-kinase signalling is crucial for embryonic genome activation and preimplantation embryogenesis
EMBO Rep.
11
890-895
2010
Homo sapiens (Q8NEB9)
Manually annotated by BRENDA team
Wu, Y.; Tan, H.; Shui, G.; Bauvy, C.; Huang, Q.; Wenk, M.; Ong, C.; Codogno, P.; Shen, H.
Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase
J. Biol. Chem.
285
10850-10861
2010
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Venkatareddy, M.; Verma, R.; Kalinowski, A.; Patel, S.R.; Shisheva, A.; Garg, P.
Distinct requirements for vacuolar protein sorting 34 downstream effector phosphatidylinositol 3-phosphate 5-kinase in podocytes versus proximal tubular cells
J. Am. Soc. Nephrol.
27
2702-2719
2016
Homo sapiens (Q8NEB9)
Manually annotated by BRENDA team
Mirzaa, G.M.; Conti, V.; Timms, A.E.; Smyser, C.D.; Ahmed, S.; Carter, M.; Barnett, S.; Hufnagel, R.B.; Goldstein, A.; Narumi-Kishimoto, Y.; Olds, C.; Collins, S.; Johnston, K.; Deleuze, J.F.; Nitschke, P.; Friend, K.; Harris, C.; Goetsch, A.; Martin, B.; Boyle, E.A.; Parrini, E.; Mei, D.; Tattini, L.; Slavotinek, A.; Blair, E.; Barnett, C.; Shendure, J.; Chelly, J.; Dobyns, W.B.; Guerrini, R.
Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study
Lancet Neurol.
14
1182-1195
2015
Homo sapiens (O00459), Homo sapiens
Manually annotated by BRENDA team
Burrows, N.; Williams, J.; Telfer, B.A.; Resch, J.; Valentine, H.R.; Fitzmaurice, R.J.; Eustace, A.; Irlam, J.; Rowling, E.J.; Hoang-Vu, C.; West, C.M.; Brabant, G.; Williams, K.J.
Phosphatidylinositide 3-kinase (PI3K) and PI3K-related kinase (PIKK) activity contributes to radioresistance in thyroid carcinomas
Oncotarget
7
63106-63123
2016
Homo sapiens
Manually annotated by BRENDA team
Backer, J.M.
The intricate regulation and complex functions of the Class III phosphoinositide 3-kinase Vps34
Biochem. J.
473
2251-2271
2016
Saccharomyces cerevisiae (P22543), Mus musculus (Q6PF93), Homo sapiens (Q8NEB9)
Manually annotated by BRENDA team