2.7.1.137: phosphatidylinositol 3-kinase
This is an abbreviated version!
For detailed information about phosphatidylinositol 3-kinase, go to the full flat file.
Word Map on EC 2.7.1.137
-
2.7.1.137
-
wortmannin
-
mapks
-
mtor
-
rapamycin
-
erk
-
endothelial
-
pten
-
signal-regulated
-
pkc
-
metastasis
-
bcl-2
-
sirna
-
caspase-3
-
agonist
-
glycogen
-
leukemia
-
actin
-
pik3ca
-
phospholipase
-
insulin-like
-
mitogen
-
cyclins
-
integrins
-
tumorigenesis
-
irs-1
-
tensin
-
tnf
-
neuroprotective
-
c-jun
-
pi3-kinase
-
dominant-negative
-
adipocytes
-
nf-kappab
-
anti-apoptotic
-
insulin-stimulated
-
gtpases
-
insulin-induced
-
akt1
-
transwell
-
platelet-derived
-
rac1
-
kinase-3
-
igf-i
-
sh2
-
substrate-1
-
pleckstrin
-
grb2
-
egf-induced
-
everolimus
-
tyrosine-phosphorylated
-
drug development
-
medicine
-
pharmacology
- 2.7.1.137
- wortmannin
- mapks
- mtor
- rapamycin
- erk
- endothelial
- pten
-
signal-regulated
- pkc
- metastasis
- bcl-2
- sirna
- caspase-3
- agonist
- glycogen
- leukemia
- actin
- pik3ca
- phospholipase
-
insulin-like
-
mitogen
- cyclins
- integrins
- tumorigenesis
- irs-1
-
tensin
- tnf
-
neuroprotective
- c-jun
- pi3-kinase
-
dominant-negative
- adipocytes
- nf-kappab
-
anti-apoptotic
-
insulin-stimulated
- gtpases
-
insulin-induced
- akt1
-
transwell
-
platelet-derived
- rac1
- kinase-3
- igf-i
- sh2
- substrate-1
-
pleckstrin
- grb2
-
egf-induced
-
everolimus
-
tyrosine-phosphorylated
- drug development
- medicine
- pharmacology
Reaction
Synonyms
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, hVps34 PI 3-kinase, kinase (phosphorylating), phosphatidylinositol 3-, kinase, phosphatidylinositol 3- (phosphorylating), lipid kinase Vps34, mammalian vacuolar protein sorting 34 homologue, More, p110a, p110delta I PI3K., p110g-related PI 3-kinase, p85/p110 phosphoinositide 3-kinase, p85/p110 type phosphatidylinositol kinase, p85a phosphoinositide 3-kinase, phosphatidyl-inositol-3-kinase, phosphatidylinositide 3-kinase, phosphatidylinositide 3-kinase C2alpha, phosphatidylinositol 3 kinase, phosphatidylinositol 3'-kinase, phosphatidylinositol 3-kinase, phosphoinositide 3'-kinase, phosphoinositide 3-kinase, phosphoinositide 3-kinase Dp110, phosphoinositide 3-kinase gamma, phosphoinositide-3-kinase, PI 3-K, PI 3-kinase, PI-3-K, PI-3K, PI3 K, PI3 kinase, PI3-K, PI3-K-related protein MEC1, PI3-kinase, PI3K, PI3K type III, PI3Kalpha, PI3Kbeta, PI3Kgamma, PI3K_59F, PI3K_68D, PIK3, PIK3C3, protein sorting mutant 34 protein, PtdIns 3'-kinase, PtdIns 3-kinase, PtdIns 3-kinase vacuolar protein sorting 34, receptor-linked phosphatidylinositol 3-kinase, Rickettsia intracellular secreted kinase-1, Risk1, RT0135, TcVps34, type III phosphatidylinositol 3-kinase, vacuolar protein sorting 34, VPS34, Vps34p
ECTree
2.7.1.137 phosphatidylinositol 3-kinaseAdvanced search results
results (
results (Engineering
Engineering on EC 2.7.1.137 - phosphatidylinositol 3-kinase
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
top
PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
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
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
H297A
D2243E
-
site-directed mutagenesis, no functional complementation of a yeast enzyme-knockout mutant strain
D749E
-
site-directed mutagenesis, no functional complementation of a yeast enzyme-knockout mutant strain
I670A
-
site-directed mutagenesis, functional complementation of a yeast enzyme-knockout mutant strain
I670G
-
site-directed mutagenesis, no functional complementation of a yeast enzyme-knockout mutant strain
L2129A
-
site-directed mutagenesis, functional complementation of a yeast enzyme-knockout mutant strain
L2129G
-
site-directed mutagenesis, functional complementation of a yeast enzyme-knockout mutant strain
additional information
H1047R
-
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
H1047R
-
HCT-116 cells are heterozygous for gain of function mutant PIK3CA catalytic subunit
H297A
site-directed mutagenesis, a kinase dead mutant. Overexpression of Risk1 H297A results in a significant reduction in colocalization with all tested PI sensors. Cells transfected with Risk1 H297A display a significant increase in apoptosis
H297A
-
site-directed mutagenesis, a kinase dead mutant. Overexpression of Risk1 H297A results in a significant reduction in colocalization with all tested PI sensors. Cells transfected with Risk1 H297A display a significant increase in apoptosis
-
H297A
-
site-directed mutagenesis, a kinase dead mutant. Overexpression of Risk1 H297A results in a significant reduction in colocalization with all tested PI sensors. Cells transfected with Risk1 H297A display a significant increase in apoptosis
-
additional information
-
a homozygous VPS34 T-DNA insertional knockout mutant shows defects in the development of male gametophyte, while heterozygous mutants show reduced root hair with 50% reduced hair length compared to wild-type growth, phenotypes, overview
additional information
the progeny of VPS34/vps34 heterozygous plants, harboring a T-DNA insertion, shows a segregation ratio of 1:1:0 for wild-type, heterozygous, and homozygous mutant plants, indicating a gametophytic defect. The abnormal segregation ratio is due to failure to transmit the mutant allele through the male gametophyte. A 2fold higher proportion of pollen grains in heterozygous plants are dead or show reduced numbers of nuclei compared to the wild-type, phenotype, overview. Pollen grains from VPS34/vps34 plants are defective in vacuolar reorganization following the first mitosis
additional information
-
a mutant with a deletion in the binding site of the p110 catalytic subunit is dominant negative
additional information
-
the Arg409Gln p85a subunit of a natural variant is associated with lower insulin-stimulated phosphoinositide 3-kinase activity compared with wild-type, 15% reduction. The recruitment of Arg409Gln p85a into phosphotyrosine complexes is not significantly impaired. The impaired phosphoinositide 3-kinase activity of the Arg409Gln mutant suggests that it could contribute to the insulin resistance seen in this family. The Met326Ile p85a variant appears to have no functional effect on the insulin-stimulated phosphoinositide 3-kinase activity
additional information
-
activating mutations of the enzyme are often identified at high frequency in several types of cancer
additional information
-
a mutant with a deletion in the binding site of the p110 catalytic subunit is dominant negative
additional information
-
deregulation of the PI3K pathway, either through loss-of-function mutations in PTEN or dominant activating mutations in PIK3CA, leads to lapatinib resistance, which can be effectively reversed by NVP-BEZ235. Constitutive activation of the PI3K pathway decreases sensitivity to trastuzumab and lapatinib, overview
additional information
-
identification of hot-spot mutations in gene PIK2CA encoding the catalytic subunit p110alpha of PI3K, gain-of-function mutations allowing the mutant enzyme to constitutvely activate AKT signaling and induce oncogenic transformation in vitro and in vivo, the mutations lead to exchanges in the helical and kinase domains, overview. The gain of function induced by helical domain mutations require RAS-Gtp binding, while the kinase domain mutation is active in absence of RAS-Gtp binding, but depends on the interaction with p85, moleculr mechanisms, overview
additional information
-
PI 3-kinase activity is not affected by Nrf2 knockdown. Overexpression of DELTAp85 inhibits the enzyme
additional information
-
RNA interference-mediated knockdown of Ron kinase in a highly tumorigenic colon cancer HCT116 cell line leads to reduced proliferation as compared with the control cells and inhibits mutant phosphatidylinositol 3-kinase, phenotype, overview. Ron kinase knockout reduces metastasis in diverse human cancer cell lines, overview
additional information
-
silencing by siRNA-mediated knockdown of Atg14 in HeLa cells suppresses autophagosome formation
additional information
silencing by siRNA-mediated knockdown of Atg14 in HeLa cells suppresses autophagosome formation
additional information
silencing by siRNA-mediated knockdown of Atg14 in HeLa cells suppresses autophagosome formation
additional information
-
silencing by siRNA-mediated knockdown of UVRAG in HeLa cells suppresses autophagosome formation
additional information
silencing by siRNA-mediated knockdown of UVRAG in HeLa cells suppresses autophagosome formation
additional information
silencing by siRNA-mediated knockdown of UVRAG in HeLa cells suppresses autophagosome formation
additional information
determmination of constitutional and mosaic mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria, genotying, targeted screening of gene PIK3R2 from 118 subjects, overview. Constitutional and mosaic mutations in the PIK3R2 gene are associated with developmental brain disorders ranging from BPP with a normal head size to the MPPH syndrome
additional information
-
determmination of constitutional and mosaic mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria, genotying, targeted screening of gene PIK3R2 from 118 subjects, overview. Constitutional and mosaic mutations in the PIK3R2 gene are associated with developmental brain disorders ranging from BPP with a normal head size to the MPPH syndrome
additional information
-
no JNK stimulation in enzyme-deficient mutant cells or by enzyme p110delta mutants
additional information
-
expression of a dominant negative enzyme mutant under control of the smooth muscle alpha-actin promoter in murine hepatic stellate cells using transfection via an adenoviral vector, Ad-SMAdnPI3K, results in reduced HSC activation and decreased extracellular matrix deposition, including collagen expression. A reduction in profibrogenic mediators, including transforming growth factor beta, tissue inhibitor of metalloproteinase 1, and connective tissue growth factor also occurs, however, liver damage, assessed by alanine aminotransferase levels, is not reduced
additional information
-
generation of PI3Kgamma knockout PI3K-/- mice displaying highly reduced activity, poorer functional recovery, and greater tissue injury following ischemic preconditioning compared to wild-type and PI3Kgamma-/+ mutant hearts. Mice expressing a cardiac-specific kinase-deleted PI3Kalpha are resistant to injury induced by 30 min of ischemia followed by 40 min of reperfusion, their to ischemia/reperfusion correlates with the persistent expression of p110gamma and is blocked by the PI3K inhibitor wortmannin, phosphorylation patterns in PI3K signaling in mutant mice, overview
additional information
phenotypes in knockout Vps34 mice: cardiomegaly, decreased contractility of the heart, reduced progression to maladaptive cardiac hypertrophy, impaired myoblast differentiation, murine muscular dystrophy, proteinuria, glomerular scarring, loss of dendritic spines, neurodegeneration, vacuolization in large diameter sensory neurons, increased lysosomes in small diameter neurons, neurodegeneration, increased amyloidogenic processing of amyloid precursor protein (APP), reduced sorting of APP to MVBs, reduced T-cell number, increased cell death and reduced IL-7 receptor expression, reduced T-cell survival, increased mitochondrial mass and ROS, reduced natural killer (NK) cells, and inflammatory wasting syndrome with reduced CD4+ Foxp3+ regulatory T-cells (Tregs)
additional information
-
generation of PI3Kgamma knockout PI3K-/- mice displaying highly reduced activity, poorer functional recovery, and greater tissue injury following ischemic preconditioning compared to wild-type and PI3Kgamma-/+ mutant hearts. Mice expressing a cardiac-specific kinase-deleted PI3Kalpha are resistant to injury induced by 30 min of ischemia followed by 40 min of reperfusion, their to ischemia/reperfusion correlates with the persistent expression of p110gamma and is blocked by the PI3K inhibitor wortmannin, phosphorylation patterns in PI3K signaling in mutant mice, overview
-
additional information
in TcVps34-overexpressing cells, the activities of vacuolar-H+-ATPase and vacuolar H+-pyrophosphatase are altered, suggesting defects in the acidification of intracellular compartments, phenotype, overview. Overexpressing cells show resistance to PI3K inhibitors. TcVps34-overexpressing epimastigotes show morphological alterations in the plasma membrane region between the cytostome and the flagellar pocket
additional information
-
in TcVps34-overexpressing cells, the activities of vacuolar-H+-ATPase and vacuolar H+-pyrophosphatase are altered, suggesting defects in the acidification of intracellular compartments, phenotype, overview. Overexpressing cells show resistance to PI3K inhibitors. TcVps34-overexpressing epimastigotes show morphological alterations in the plasma membrane region between the cytostome and the flagellar pocket
additional information
-
in TcVps34-overexpressing cells, the activities of vacuolar-H+-ATPase and vacuolar H+-pyrophosphatase are altered, suggesting defects in the acidification of intracellular compartments, phenotype, overview. Overexpressing cells show resistance to PI3K inhibitors. TcVps34-overexpressing epimastigotes show morphological alterations in the plasma membrane region between the cytostome and the flagellar pocket
-
