Information on EC 2.7.1.137 - phosphatidylinositol 3-kinase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
2.7.1.137
-
RECOMMENDED NAME
GeneOntology No.
phosphatidylinositol 3-kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
3-phosphoinositide biosynthesis
-
-
Inositol phosphate metabolism
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase
One mammalian isoform is known.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
class I phosphoinositide 3-kinase
-
-
class III phosphatidylinositol 3-kinase
Q6ZNE5, Q9P2Y5
-
class III PI3K
-
-
HsC2-PI3K
O00750
-
hVps34
-
-
hVps34 PI 3-kinase
-
-
kinase (phosphorylating), phosphatidylinositol 3-
-
-
-
-
p110a
-
-
p110delta I PI3K.
O00329
-
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 C2alpha
-
-
phosphatidylinositol 3 kinase
-
-
phosphatidylinositol 3'-kinase
-
-
-
-
phosphatidylinositol 3'-kinase
-
-
phosphatidylinositol 3-kinase
-
-
-
-
phosphatidylinositol 3-kinase
-
-
phosphatidylinositol 3-kinase
-
-
phosphatidylinositol 3-kinase
-
-
phosphatidylinositol 3-kinase
-
-
phosphoinositide 3'-kinase
-
-
-
-
phosphoinositide 3-kinase
-
-
-
-
phosphoinositide 3-kinase
-
-
phosphoinositide 3-kinase
-
-
phosphoinositide 3-kinase
-
-
phosphoinositide 3-kinase Dp110
P91634
-
phosphoinositide 3-kinase gamma
-
-
phosphoinositide-3-kinase
-
-
PI 3-K
-
-
PI 3-kinase
-
-
-
-
PI 3-kinase
-
-
PI 3-kinase
-
-
PI 3-kinase
-
-
PI-3K
-
-
PI3 K
-
-
PI3 kinase
-
-
PI3 kinase
-
-
PI3 kinase
-
-
PI3-K
-
-
PI3-K-related protein MEC1
-
-
PI3-kinase
Q6ZNE5, Q9P2Y5
-
PI3-kinase
-
-
PI3K
-
-
-
-
PI3K
-
-
PI3K
Mus musculus C57BL/6
-
;
-
PI3K
A9QWR8
-
PI3K
Trypanosoma cruzi CL Brener
A9QWR8
-
-
PI3Kalpha
-
-
PI3Kalpha
Mus musculus C57BL/6
-
-
-
PI3Kbeta
-
-
PI3Kbeta
Mus musculus C57BL/6
-
-
-
PI3Kgamma
-
p110gamma catalytic subunit
PI3Kgamma
-
-
PI3Kgamma
Mus musculus C57BL/6
-
-
-
PI3K_59F
P91635
-
PI3K_68D
Q9VTN5
-
protein sorting mutant 34 protein
-
-
PtdIns 3'-kinase
-
-
-
-
PtdIns 3-kinase
-
-
PtdIns 3-kinase
-
-
receptor-linked phosphatidylinositol 3-kinase
-
-
TcVps34
A9QWR8
-
TcVps34
Trypanosoma cruzi CL Brener
A9QWR8
-
-
type III phosphatidylinositol 3-kinase
-
-
VPS34
P42339
-
VPS34
Q8NEB9
gene name
Vps34p
-
-
kinase, phosphatidylinositol 3- (phosphorylating)
-
-
-
-
additional information
-
class III PI3K consists of a single family member, vacuolar protein sorting mutant 34 protein, Vps34p, which is associated with Vsp15
additional information
-
the enzyme belongs to the PI3-K family
additional information
-
the phosphatidylinositol 3-kinase, PI3K, family is a family of conserved lipid and protein kinases that are ubiquitously expressed in many cells, including the heart
additional information
Mus musculus C57BL/6
-
the phosphatidylinositol 3-kinase, PI3K, family is a family of conserved lipid and protein kinases that are ubiquitously expressed in many cells, including the heart
-
additional information
-
the enzyme belongs to the PI3-K family
additional information
A9QWR8
TcVps34 belongs to the class III PI3K family
additional information
Trypanosoma cruzi CL Brener
A9QWR8
TcVps34 belongs to the class III PI3K family
-
CAS REGISTRY NUMBER
COMMENTARY
115926-52-8
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene VPS34
-
-
Manually annotated by BRENDA team
PI3K is encoded by a single-copy gene, AtVPS34
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
Chlamydomonas sp.
-
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
Atg14; Vps34, p150, Beclin 1, Atg14, and UVRAG form two distinct class III phosphatidylinositol 3-kinase complexes
UniProt
Manually annotated by BRENDA team
catalytic subunit type 3
Uniprot
Manually annotated by BRENDA team
class I isozymes
-
-
Manually annotated by BRENDA team
class Ia phosphoinositide 3-kinase isozymes alpha, beta, gamma, and delta
-
-
Manually annotated by BRENDA team
class II phosphoinositide 3-kinase, PI 3-kinase C2b
-
-
Manually annotated by BRENDA team
clinical samples from Schwedish patients
-
-
Manually annotated by BRENDA team
enzyme form PI3K-C2a and PI3K-C2b
-
-
Manually annotated by BRENDA team
gene PIK3CA encoding the catalytic subunit p110alpha of PI3K
-
-
Manually annotated by BRENDA team
isozyme alpha
-
-
Manually annotated by BRENDA team
UVRAG; Vps34, p150, Beclin 1, Atg14, and UVRAG form two distinct class III phosphatidylinositol 3-kinase complexes
UniProt
Manually annotated by BRENDA team
Vps34, p150, Beclin 1, Atg14, and UVRAG form two distinct class III phosphatidylinositol 3-kinase complexes
-
-
Manually annotated by BRENDA team
class I isozymes, 2 subgroups Ia and Ib, subgroup Ia contains 3 isozymes alpha, beta, and gamma, different splicing variants of subunits
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
C57BL/6 mice
-
-
Manually annotated by BRENDA team
isozyme gamma
-
-
Manually annotated by BRENDA team
isozyme PI 3-kinase gamma
-
-
Manually annotated by BRENDA team
lean and obese animals
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
C57BL/6 mice
-
-
Manually annotated by BRENDA team
adult male Wistar rats
-
-
Manually annotated by BRENDA team
genetically obese, fa/fa, Zucker rats
-
-
Manually annotated by BRENDA team
high fat-fed rats
-
-
Manually annotated by BRENDA team
high-salt diet-fed
-
-
Manually annotated by BRENDA team
male Sprague–Dawley rats
-
-
Manually annotated by BRENDA team
Sprague Dawley rats
-
-
Manually annotated by BRENDA team
Sprague-Dawley
-
-
Manually annotated by BRENDA team
Wistar rats
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
Rattus norvegicus Wistar
Wistar
-
-
Manually annotated by BRENDA team
enzyme VPS34 and a PI3-K-related protein MEC1
-
-
Manually annotated by BRENDA team
CL Brener strain
UniProt
Manually annotated by BRENDA team
Trypanosoma cruzi CL Brener
CL Brener strain
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
Co-treatment of NB4 cells with either LY294002 to inhibit PI3Ks or PD98059 in order to suppress MEK activity lead to significant reduction of CD11b surface expression during all-trans-retinoic acid, 9-cis-retinoic acid or retinoic acid receptor agonist Ro40-6055 dependent NB4 cells granulocyte differentiation
malfunction
-
disruption of PDGFRbeta-PI3K signaling in mice reduces atherosclerosis. Disorganization of the actin cytoskeleton in LRP1-deficient smooth muscle cells is prevented by blocking PI3K activation by PDGFRbeta
malfunction
-
gene PIK3CA, encoding the catalytic subunit p110alpha of PI3K, is mutated in about 12% of all human cancers, as single point mutations of hot-spot mutation with exchange of three positions, overview
malfunction
A9QWR8
inhibition of TcVps34 with specific PI3K inhibitors, such as wortmannin and LY294000, result in reduced regulatory volume decrease after hyposmotic stress
malfunction
-
phosphatidylinositol 3-kinase signaling is involved in progression of hepatic fibrosis in hepatic stellate cells. Inhibition of phosphatidylinositol 3-kinase signaling in hepatic stellate cells, by either a pharmacological or by a genetic approach, blocks the progression of hepatic fibrosis inhibiting extracellular matrix deposition, including synthesis of type I collagen, and reducing expression of profibrogenic factors, mechanism, overview. Inhibition of PI3K signaling is also associated with reduced activation of Akt, p70 S6 kinase, and extracellular regulated kinase signaling as well as reduced cyclin D1 expression
malfunction
-
PI3K is part of the PI3K/Akt pathway, e.g. responsible for promoting motility and invasion of gastric cancer cells in epithelial-mesenchymal transition and metastasis, after activation and signaling by bone morphogenetic protein 2, BMP-2, with Snail induction, E-cadherin delocalization and down-regulation, and up-regulation of mesenchymal and invasiveness markers, overview
malfunction
-
the phosphatidylinositol 3-kinase/Akt signaling pathway is crucial to sustain the pathophysiology of medulloblastoma, a primitive neuroectodermal tumor and the most common malignant pediatric brain tumor. Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth. The inhibitors affect beta-catenin signaling by inhibition of GSK-3beta activity, resulting in cytoplasmic retention of beta-catenin and reduced expression of its target genes cyclin D1 and c-Myc
malfunction
-
upregulation of expression of the close homologue of adhesion molecule L1, CHL1, by reactive astrocytes in the glial scar requires the activation of PI3K/PKCdelta-dependent pathways reduces axonal regeneration and inhibits functional recovery after spinal cord injury, overview
malfunction
Trypanosoma cruzi CL Brener
-
inhibition of TcVps34 with specific PI3K inhibitors, such as wortmannin and LY294000, result in reduced regulatory volume decrease after hyposmotic stress
-
malfunction
Mus musculus C57BL/6
-
upregulation of expression of the close homologue of adhesion molecule L1, CHL1, by reactive astrocytes in the glial scar requires the activation of PI3K/PKCdelta-dependent pathways reduces axonal regeneration and inhibits functional recovery after spinal cord injury, overview
-
metabolism
-
a signaling network regulates interleukin-8 production in response to proteasome activation or inactivation also involving PI3K, detailed overview
metabolism
-
mammalian cells have at least two distinct class III PI3-kinase complexes, which may function in different membrane trafficking pathways
metabolism
-
phosphatidylinositol 3-kinase is closely associated with TGFbeta3 production/secretion in astrocytes. Microglia-derived plasminogen or plasmin facilitates the production/secretion of TGFbeta3 in astrocytes through both PAR-1 and the subsequent signaling cascade including PI3K and Akt
metabolism
-
PI3K is part of the PI3K/Akt pathway, e.g. responsible for promoting motility and invasion of gastric cancer cells in epithelial-mesenchymal transition and metastasis, after activation and signaling by bone morphogenetic protein 2, BMP-2, with Snail induction, E-cadherin delocalization and down-regulation, and up-regulation of mesenchymal and invasiveness markers, overview
metabolism
-
the enzyme is part of the phosphatidylinositol 3-kinase-Akt pathway, which plays a role in the adenosine 5'-triphosphate-sensitive K+ channel function, overview
metabolism
-
the enzyme is part of the phosphatidylinositol 3-kinase/Akt signaling pathway
metabolism
-
the phosphatidylinositol 3'-kinase-Akt/protein kinase B axis is a pro-survival pathway which prevents apoptosis through defined anti-apoptotic mechanisms in a variety of cancer cells
physiological function
-
Atg6/Beclin 1, the phosphatidylinositol 3-kinase Vps34, and associated proteins Atg6 and Vps15 have direct or indirect roles in autophagic pathways. Roles of PI3K complex proteins and PpUvrag in autophagy, autophagy-related and the VPS pathways, overview. PpUvrag is required for the vacuolar sorting of PpCPY and in its absence PpCPY is mis-sorted
physiological function
-
differentiation in C6 cells by panaxydol, isolated from the lipophilic fractions of Tienchi ginseng, Panax notoginseng, might be mediated through a PI 3-K-dependent pathway. Treatment of C6 cells with panaxydol causes marked inhibition of growth that is abolished by wortmannin, a PI 3-K inhibitor
physiological function
-
involvement of PI 3-kinase in the Nrf2 pathway during muscle differentiation. Nrf2 is transcriptionally up-regulated and translocated to the nucleus during myogenesis, but does not affect the PI 3-kinase activity acting downstream of it, overview
physiological function
-
involvement of PI3K in all-trans-retinoic acid or Ro40-6055, a retinoic acid receptor alpha specific agonist, dependent granulocyte differentiation of NB4 cells, overview
physiological function
-
NF-kappaB and phosphatidylinositol 3-kinase activity mediate the human cytomegalovirus, HCMV, induced atypical M1/M2 polarization of monocytes, overview. PI3K activity is involved in the upregulation of about 12% of M1-associated genes following infection with HCMV. And the enzyme is involved increased motility of HCMV-infected native cells by about 5.5fold compared to uninfected cells treated with mock-infected cell supernatants
physiological function
-
phosphatidylinositol 3-kinase and xanthine oxidase regulate nitric oxide and reactive oxygen species productions by apoptotic lymphocyte microparticles in endothelial cells. PI3K inhibition reduces the effects of microparticles on endothelial NO synthase, but not on caveolin-1, whereas it enhances the effects of microparticles on reactive oxygen species production. Microparticles stimulated ERK1/2 phosphorylation via a PI3K-depedent mechanism
physiological function
-
phosphatidylinositol 3-kinase is a key mediator of central sensitization, induced by intraplantar formalin, the spinal cord phenomenon associated with persistent afferent inputs and contributing to chronic pain states, in painful inflammatory conditions
physiological function
P42339
phosphatidylinositol 3-kinase is essential for normal growth and is essential for vacuole reorganization and nuclear division during pollen development
physiological function
-
phosphatidylinositol 3-kinase is involved in sperm-induced tyrosine kinase signaling in Xenopus egg fertilization. Inhibition of sperm-induced activation of the tyrosine kinase Src and a transient increase in the intracellular concentration of Ca2+ at fertilization, overview. PIP3 acts as a positive regulator of the Src signaling pathway in Xenopus fertilization
physiological function
-
PI 3-kinase activated in response to cAMP or IGF-I stimulus plays important roles in increasing the translation rate or mRNA levels of cyclin D1, respectively. Activation of PI 3-kinase in response to cAMP or IGF-I are essential for marked increases in G1 CDK activities and DNA synthesis. cAMP-dependent PI 3-kinase activation plays an important role in the increase in cyclin D1 translation. In contrast, IGF-I-dependent PI 3-kinase activation is required for the increase in cyclin D1 mRNA levels and degradation of p27Kip1
physiological function
-
PI-3-K and the PI-3-K signaling pathway, besides the MAPK signaling pathway, are involved in the signaling mechanism underlying the neuroprotection of brain-derived neurotrophic factor against hypoxic insult, molecular mechanisms, overview. ERK but not PI-3-K pathway induce CREB phosphorylation
physiological function
-
PI3-K is involved in the intracellular signal transduction pathways in the regulation of fowl sperm motility, the calcium-regulated maintenance of flagellar movement, and in reversible temperature-dependent immobilization at 40°C, but PI3K is probably not involved in regulation of Ca2+ mobilization
physiological function
-
PI3K activity is involved in interleukin-8 production in retinal pigment epithelial cells, independent of 3-phosphoinositide-dependent protein kinase 1, PDK1, and Akt
physiological function
-
PI3K is involved in LPS-induced signaling in glial cells inducing the lipopolysaccharide-stimulated expression of adhesion molecule L1, CHL1. PI3K/PKCdelta-mediated nuclear translocation of NF-kappaB
physiological function
-
PI3K is involved in regulation of actin polymerization and cell movement
physiological function
-
PI3K isozymes play selective roles in ischemic preconditioning, a potent cellular protective mechanism whereby brief periods of sublethal ischemia protect the myocardium from prolonged ischemia-induced injury, overview
physiological function
-
PI3K plays a role in root hair growth
physiological function
-
PI3K specifically interacts with retinoblastoma protein through the unique NH2 terminus of its regulatory subunit p55PIK, N24, which is critical for cell proliferation and cell cycle progression
physiological function
-
PI3K-dependent phosphorylation of Akt1 activates it to phosphorylate p40phox and p40phox-p67phox complex, causing platelet-activating factor-mediated endosome formation required for the membrane translocation of p40phox and p67phox in neutrophils. Platelet-activating factor elicites an interaction between PI3K and p40phox and to a lesser extent between PI3K and phosphorylated p40phox, pathway overview
physiological function
-
protein kinase Syk associates with clathrin and mediates phosphatidylinositol 3-kinase activation during human rhinovirus internalization in leukocytes, PI3K activity is required for HRV internalization, regulation and signaling mechanism, overview
physiological function
-
role of crosstalk between phosphatidylinositol 3-kinase and extracellular signal-regulated kinase/mitogen-activated protein kinase pathways in artery-vein specification, mechanism of artery-vein specification during embryogenesis, the developmental process involves several protein factors, overview. PI3K is involved in the PI3K-ATK pathway, activated by the vascular endothelial growth factor, VEGF
physiological function
-
role of PI3K/AKT signaling in expression of the MOR gene in CEM x 174 cells. Phosphatidylinositol 3-kinase pathway mediated up-regulation of the mu opioid receptor in lymphocytes, mechanisms, overview
physiological function
-
the enzyme activates Akt signaling
physiological function
-
the PI3-K/Akt pathway plays a pivotal role in controlling the survival of neurons, although this activity declines during the aging process. NGF receptors and the PI3-K signaling pathway strongly influence cell survival
physiological function
-
the PI3K signaling pathway regulates several aspects of hepatic stellate cell activation in vitro, including collagen synthesis and cell proliferation, overview. Inhibition of PI3K decreases expression of alpha1(I)collagen in hepatic stellate cells mediated in part by inhibiting gene transcription, mechanism, overview
physiological function
-
the thiazolidinedione pioglitazone acutely stimulates adiponectin secretion from mouse and human adipocytes via activation of the phosphatidylinositol 3-kinase
physiological function
A9QWR8
the Trypanosoma cruzi phosphatidylinositol 3-kinase, TcVps34, is involved in osmoregulation and receptor-mediated endocytosis. TcVps34 participates in the endocytic pathway, fluid phase uptake of BSA and receptor-mediated endocytosis of transferrin. Multiple roles for TcVps34, schematic overview
physiological function
-
Tiam1-mediated Rac1 activation and E-cadherin-mediated cell-cell adhesion are dependent on PI3K activity, regulation, overview. The signaling hierarchy leads from PI3K to Tiam1 to Rac to the actin cytoskeleton resulting in adherens junction formation. PI3K is involved in E-cadherin-dependent regulation of epithelial cell differentiation and polarity
physiological function
-
Vps34 appears to be important in endocytosis and vesicular trafficking, and is also implicated in Toll-like receptor signalling
physiological function
-
epidermal growth factor and fibroblast growth factor inhibit insulin-like growth factor-I-stimulated tyrosine phosphorylation of insulin receptor substrate-1 and the subsequent insulin-like growth factor-I-induced phosphatidylinositol 3-kinase activity. These epidermal growth factor and fibroblast growth factor inhibitory effects are dependent on both phosphatidylinositol 3-kinase and protein kinase D1 signaling pathways. Specific inhibition of either phosphatidylinositol 3-kinase or protein kinase D1 totally impairs epidermal growth factor- or fibroblast growth factor-induced inhibition of insulin-like growth factor-I-stimulated insulin receptor substrate-1 tyrosine phosphorylation. The negative regulation of IRS-1 requires the coordinated action of phosphatidylinositol 3-kinase and protein kinase D1
physiological function
-
insulin-like growth factor-I stimulation leads to prolonged association of phosphatidylinositol 3-kinase with insulin-like growth factor-I receptor. Phosphatidylinositol 3-kinase activity is present in this complex in thyrocytes and fibroblasts. Insulin-like growth factor-I withdrawal in mid-G1 phase impairs the association of phosphatidylinositol 3-kinase with insulin-like growth factor-I receptor and suppresses DNA synthesis the same as when phosphatidylinositol 3-kinase inhibitor is added. Residues Tyr1316-X-X-Met of insulin-like growth factor-I receptor function as a phosphatidylinositol 3-kinase binding sequence when this tyrosine is phosphorylated. In cells expressing exogenous mutant insulin-like growth factor-I receptor in which Tyr1316 is substituted with Phe, insulin-like growth factor-I stimulation induces tyrosine phosphorylation of insulin-like growth factor-I receptor and insulin receptor substrates-1/2, but mutated insulin-like growth factor-IR fails to bind phosphatidylinositol 3-kinase and to induce maximal phosphorylation of GSK3 and cell proliferation in response to insulin-like growth factor-I. Phosphatidylinositol 3-kinase activity bound to insulin-like growth factor-I receptor, which is continuously sustained by insulin-like growth factor-I stimulation, is required for insulin-like growth factor-I-induced cell proliferation
physiological function
-
intracerebroventricular injection of leptin significantly increases phosphodiesterase 3B activity by twofold in the hypothalamus. Previous administration of wortmannin, a specific PI3K inhibitor, completely reverses the stimulatory effect of leptin on phosphodiesterase 3B activity in the hypothalamus. PI3K but not Akt acts as an upstream regulator of the PDE3B pathway of leptin signalling in the rat hypothalamus
physiological function
-
PI3K regulates NADPH oxidase activity through modulating the recruitment of Rac-1 to plasma membrane and accelerates the process of rice seed germination
physiological function
Trypanosoma cruzi CL Brener
-
the Trypanosoma cruzi phosphatidylinositol 3-kinase, TcVps34, is involved in osmoregulation and receptor-mediated endocytosis. TcVps34 participates in the endocytic pathway, fluid phase uptake of BSA and receptor-mediated endocytosis of transferrin. Multiple roles for TcVps34, schematic overview
-
physiological function
Mus musculus C57BL/6
-
PI3K isozymes play selective roles in ischemic preconditioning, a potent cellular protective mechanism whereby brief periods of sublethal ischemia protect the myocardium from prolonged ischemia-induced injury, overview, PI3K is involved in LPS-induced signaling in glial cells inducing the lipopolysaccharide-stimulated expression of adhesion molecule L1, CHL1. PI3K/PKCdelta-mediated nuclear translocation of NF-kappaB
-
metabolism
-
the PI3-K/Akt pathway plays a pivotal role in controlling the survival of neurons, although this activity declines during the aging process. NGF receptors and the PI3-K signaling pathway strongly influence cell survival
additional information
-
hyperactivation of the PI3K/AKT/mTOR signaling pathway is common in cancer, and PI3K and mTOR act synergistically in promoting tumor growth, survival, and resistance to chemotherapy
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 1,2-dibutanoylphosphatidylinositol 4,5-diphosphate
ADP + 1,2-dibutanoylphosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1,2-dioctanoylphosphatidylinositol 4,5-diphosphate
ADP + 1,2-dioctanoylphosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-O-octadecyl-2-O-methyl-rac-3-glycerophospho-myo-inositol
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 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-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 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-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 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-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
-
catalyzed by class I and III, and probably by class II enzymes, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
A9QWR8
TcVps34 specifically phosphorylates phosphatidylinositol to produce phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
-
substrate from bovine liver
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
Trypanosoma cruzi CL Brener
A9QWR8
TcVps34 specifically phosphorylates phosphatidylinositol to produce phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
Mus musculus C57BL/6
-
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
O35940
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
O00750
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P48736
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Q8NEB9
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P32871
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P42347, P42348
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Chlamydomonas sp.
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P35169
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
O00329
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Q92213
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P22543
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
O14356, P50520, Q9Y7K2
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P42337
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P32600
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P91634
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P91635
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Q9VTN5
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P42338
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
O70167
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Q94125
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
O70173
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Q8NJ23
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
O75747
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
O02696, O02697
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P42336
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P42339
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
P54673, P54674, P54675, P54676
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Q8NEB9
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 + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Homo sapiens PI3K-C2alpha
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Homo sapiens PI3K-C2alpha
-
-
-
?
ATP + Akt1
ADP + Akt1 phosphate
show the reaction diagram
-
phosphorylation at Ser473, phosphorylation at Ser473, a step in PI3K/Akt signaling
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
-
class I enzyme
-
-
?
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 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
-
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
O00750
no activity
-
-
-
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
no activity
-
-
-
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
weak activity
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
class I enzyme, preferred substrate in vivo
-
-
?
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
-
class I enzyme
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
class I enzyme, preferred substrate of the class I enzyme
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
O00750
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
Q9VTN5
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
-
no activity
-
-
-
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
-
weak activity
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
-
class I enzyme
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
-
class I enzyme, preferred substrate of the class II enzyme
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
-
class Ia isozyme
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
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
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
-
from rat liver and bovine erythrocyte and brain, substrate specificities, free or membrane anchored, phosphorylated phosphatidylinositol is poorer substrate than nonphosphorlyated, overview
-
-
?
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
show the reaction diagram
-
-
-
-
?
phosphatidylinositol-4,5-bisphosphate + ATP
?
show the reaction diagram
-
involved in signalling pathways leading to mitosis and differentiation
-
-
?
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
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
TAPP1 and TAPP2 are direct targets of PI3K signaling
-
-
-
additional information
?
-
-
isoform p110b of the catalytic subunit plays a crucial role in cellular activities evoked acutely by insulin
-
-
-
additional information
?
-
-
activation of phosphatidylinositol-3 kinase by ligation of the interleukin-7 receptor is dependent on protein tyrosine kinase activity, activation is dependent on the phosphorylation event of p85
-
-
-
additional information
?
-
-
PI-3-kinase might be involved in the induction of erythroid differentiation, possibly engaging a protein kinase C z as downstream effector
-
-
-
additional information
?
-
-
generation of phosphatidyl 3,4,5-triphosphate by phosphatidylinositol 3-kinase is necessary for insulin-induced germinal vesicle breakdown in Xenopus oocytes
-
-
-
additional information
?
-
-
the enzyme is implicated in the control of breast cancer cell growth by free fatty acids and may provide a link between fat and cancer
-
-
-
additional information
?
-
-
important functional role of phosphatidylinositol 3-kinase in motile responses of HL-60 cells
-
-
-
additional information
?
-
-
PI 3-kinase is the first step of the insulin signaling pathway to be impaired by high-fat feeding
-
-
-
additional information
?
-
-
essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes
-
-
-
additional information
?
-
-
monocytes respond to LPS with the rapid activation of PI 3-kinase, resulting in transient increases in levels of PtdIns 3,4,5-P3. This process is CD14 dependent and involves the physiological association of PI 3-kinase with activated p53/56lyn
-
-
-
additional information
?
-
-
role for phosphatidylinositol 3-kinase in the activation of Raf kinases in G protein-coupled receptor systems in human neutrophils
-
-
-
additional information
?
-
Q94125
regulating longevity and diapause
-
-
-
additional information
?
-
-
PI 3-K pathways is involved in the short-term activation of pyruvate kinase L by insulin in rat hepatocytes
-
-
-
additional information
?
-
-
the enzyme catalyzes the formation of 3'-phosphoinositides, which appear to promote cellular responses to growth factors and such membrane trafficking events as insulin-stimulated translocation of intracellular glucose transporters
-
-
-
additional information
?
-
O35940
may play a role in phosphatidylinositol 3-kinase-mediated signaling in the immune system
-
-
-
additional information
?
-
P42347, P42348
enzyme is induced during soybean nodule organogenesis and plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
-
phosphatidylinositol 3-kinase-mediated signaling in the immune system
-
-
-
additional information
?
-
O35940
phosphatidylinositol 3-kinase-mediated signaling in the immune system
-
-
-
additional information
?
-
-
phosphatidylinositol 3-kinase acts at an intracellular membrane site to enhance GLUT4 exocytosis in 3T3-L1 cells
-
-
-
additional information
?
-
-
enzyme is involved in formyl peptide-induced stimulation of neutrophils
-
-
-
additional information
?
-
-
IL-10 inhibits apoptosis of promyeloid cells by activating insulin receptor substrate-2 and phosphatidylinositol 3'-kinase
-
-
-
additional information
?
-
P22543
enzyme is required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae
-
-
-
additional information
?
-
P42347, P42348
PI3K plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
-
insulin stimulation of fatty acid synthase promoter is mediated by the PI 3-kinase pathway
-
-
-
additional information
?
-
-
plays a central part in the mediation of insulin-stimulated glucose disposal
-
-
-
additional information
?
-
P91634
role for Dp110 in growth control during Drosophila development
-
-
-
additional information
?
-
-
insulin signaling in heart involves insulin receptor substrate-1 and insulin receptor substrate-2, activation of phosphatidylinositol 3-kinase
-
-
-
additional information
?
-
-
activation of PI3K is a critical component of the anti-Ig-initiated signaling cascade that leads to growth inhibition of human B lymphoma cells
-
-
-
additional information
?
-
-
signaling pathways for phosphoinositolglycan-peptide and insulin to glucose transport and metabolism converge at the level of PI 3-kinase
-
-
-
additional information
?
-
-
the enzyme is essential for protein sorting
-
-
-
additional information
?
-
-
enzyme plays an important role in the signalling of cell growth
-
-
-
additional information
?
-
-
enzyme might contribute to the antiproliferative activity of the antitumor ether lipid analogs
-
-
-
additional information
?
-
-
myotubularin, a phosphatase deficient in myotubular myopathy, may decrease PI3P levels by down-regulating PI3K activity and by directly degrading PI3P
-
-
-
additional information
?
-
-
PI 3-kinase activity is a necessary step in the regulation of bone resorption
-
-
-
additional information
?
-
-
PI 3-kinase activity appears to be an important component of ovariectomy-stimulated bone loss in rats
-
-
-
additional information
?
-
-
insulin and dexamethasone regulate phosphatidylinositol 3-kinase in Fao hepatoma cells
-
-
-
additional information
?
-
-
enzyme plays an important role in the signaling of cell growth
-
-
-
additional information
?
-
-
insulin-stimulated IRS-1 association with PI 3-kinase is decreased to 84% in the liver and to 84% in the muscle in the fructose-fed group compared to controls
-
-
-
additional information
?
-
-
lysophosphatidic acid stimulates glucose transport in Xenopus oocytes via a phosphatidylinositol 3'-kinase
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-
-
additional information
?
-
-
differential regulation of insulin receptor substrate-1 and insulin receptor substrate-2 and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic mouse
-
-
-
additional information
?
-
-
the level of insulin receptor tyrosine kinase activity modulates the activities of phosphatidylinositol 3-kinase
-
-
-
additional information
?
-
-
insulin activates ATP-sensitive K+ channels in pancreatic B-cells through a phosphatidylinositol 3-kinase-dependent pathway
-
-
-
additional information
?
-
-
reduced expression of the murine p85a subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes
-
-
-
additional information
?
-
-
essential for normal cell growth and vacuole morphology
-
-
-
additional information
?
-
P42336
mitogenic signal transduction pathway mediated by P13K is dependent upon the enzymatic activity of the p110 alpha subunit of P13K
-
-
-
additional information
?
-
-
enzyme may represent a common pathway of integrin and adhesiveness regulation in leukocytes
-
-
-
additional information
?
-
-
class II PI3K enzymes may contribute to the generation of 3'-phosphoinositides following the activation of polypeptide growth factor receptors in vivo and thus mediate certain aspects of their biological activity
-
-
-
additional information
?
-
-
in both the liver and muscle of high salt-fed rats, intracellular insulin signaling leading to PI 3-kinase activation is enhanced and insulin action is attenuated
-
-
-
additional information
?
-
-
enzyme could be involved in stimulated glucose transport in muscle
-
-
-
additional information
?
-
-
receptor linked enzyme may generate a second-messenger signal
-
-
-
additional information
?
-
-
enzyme is involved in the signaling pathways regulating cell growth by virtue of its activation in response to various mitogenic stimuli
-
-
-
additional information
?
-
-
multiple defects of PI 3-kinase activation, involving both the p85a and the p85b adaptor subunits, may contribute to cardiac insulin resistance
-
-
-
additional information
?
-
-
the enzyme 3'-phosphorylates the inositol head group of membrane phosphoinositides, isozymes are subject to differential regulation and may play distinct roles in the cell, e.g. in cell survival, vesicle trafficking, cytoskeletal reorganization, and chemotaxis, the enzymeis involved in diverse signalling pathways, detailed schematic overview
-
-
-
additional information
?
-
-
the enzyme 3'-phosphorylates the inositol head group of membrane phosphoinositides, isozymes are subject to differential regulation and may play distinct roles in the cell, the enzyme is involved in many cellular responses important in pathogenesis of disease
-
-
-
additional information
?
-
-
the enzyme is involved in beta2-adrenergic receptor/G1-mediated compartmentation of the concurrent Gs-cAMP signaling, negating beta2-AR-induced phospholamban phosphorylation and the positive inotropic and lusitropic responses in cardiomyocytes, regulation of enzyme activity in cell signaling cascades, effects of enzyme inhibition on cellular processes, detailed overview
-
-
-
additional information
?
-
-
the enzyme is involved in cytokin-stimulated cell migration
-
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-
additional information
?
-
-
the isozyme gamma stimulates the protein kinases Erk, JNK, and PKB and thus plays a role in cellular signaling, overview
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-
-
additional information
?
-
-
the lipid-lowering effect of leptin on livers from lean rats is mediated by the enzyme, diet-induced obesity abolishes the effect of leptin on the enzyme and the lipid level and causes leptin resistance
-
-
-
additional information
?
-
-
phosphoinositide quantification via labeled and/or tagged ligands binding to the pleckstrin homology PH domain of the enzyme in competition with phosphoinositides, overview
-
-
-
additional information
?
-
-
the enzyme interacts with other proteins and substrates via the pleckstrin homology PH domain
-
-
-
additional information
?
-
-
the enzyme interacts with other proteins and substrates via the pleckstrin homology PH domain, class I isozyme subgroups Ia and Ib are divided due to their mode of action and structure
-
-
-
additional information
?
-
-
the enzyme shows both lipid and protein kinase activity
-
-
-
additional information
?
-
-
interaction between Beclin and hVps34 PI 3-kinase is essential for engagement of hVps34 in the process of macroautophagy, but is dispensable for the normal function of hVps34 in endocytic trafficking or lysosomal enzyme sorting
-
-
-
additional information
?
-
-
leptin activates leptin receptor and results in the actvation of insulin receptor substrate-1, phosphatidylinositol 3-kinase, Akt, NF-kappaB, and p300, leading to up-regulation of IL-6 expression
-
-
-
additional information
?
-
-
PI3-kinase-dependent activation of diacylglycerol kinase and production of phosphatidic acid in caveolae/rafts in response to norepinephrine but not endothelin-1
-
-
-
additional information
?
-
-
two populations of p27 use different kinetics to phosphorylate Ser-10 and Thr-187 via phosphatidylinositol 3-Kinase in response to fibroblast growth factor-2 stimulation
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-
-
additional information
?
-
-
type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3
-
-
-
additional information
?
-
-
AMP-activated protein kinase, activated by energy depletion, inhibits cell survival by binding to and phosphorylating insulin receptor substrate-1 at Ser-794. Phosphorylation of insulin receptor substrate-1 at this site inhibits phosphatidylinositol 3-kinase/Akt signaling, suppresses the mitochondrial membrane potential, and promotes apoptosis
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-
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additional information
?
-
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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
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-
-
additional information
?
-
-
HMG-CoA reductase inhibitor regulates endothelial progenitor function through the phosphatidylinositol 3-kinase/AKT signal transduction pathway
-
-
-
additional information
?
-
-
Hsp27 antagonizes Bax-mediated mitochondrial injury and apoptosis by promoting Akt activation via a PI3-kinase-dependent mechanism
-
-
-
additional information
?
-
-
IGF-I regulates the expression of FLIP in FRTL cells by activating the PI3K/NF-kB cascade
-
-
-
additional information
?
-
-
IL-2-induced PI3K activation limits IL-17RA gene expression. Blockade of the PI3K pathway but not p70S6K leads to up-regulation of IL-17RA
-
-
-
additional information
?
-
-
lutein inhibits NF-kappaB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-kappaB-inducing kinase pathways
-
-
-
additional information
?
-
-
mTOR inhibition increases eIF4E phosphorylation through a PI3K-dependent and Mnk-mediated mechanism
-
-
-
additional information
?
-
-
nerve growth factor inhibits Na+/H+ exchange and formula absorption through parallel phosphatidylinositol 3-kinase-mTOR and ERK pathways in thick ascending limb
-
-
-
additional information
?
-
-
overexpression of mkrn2 completely abrogates constitutively active PI3K- and Akt-induced, but not dominant negative glycogen synthase kinase-3beta-induced, neural cell adhesion molecule expression, indicating that mkrn2 acts downstream of PI3K and Akt and upstream of GSK-3beta. Important role of mkrn2 as a new player in PI3K/Akt-mediated neurogenesis during Xenopus embryonic development
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-
-
additional information
?
-
-
PI 3-kinase signaling in proliferating cells regulates a novel program of gene expression, which is distinct from that induced by growth factor stimulation of quiescent cells. The expression program controlled by continuous PI 3-kinase signaling in proliferating cells is enriched in genes that regulate cell survival and is mediated in large part by FOXO and RelB transcription factors
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additional information
?
-
-
raloxifene exerts its anti-inflammatory action in LPS-stimulated macrophages by blocking the PI 3-kinase-Akt-NF-kappaB signaling cascade, and eventually reduces expression of pro-inflammatory genes such as the nitric oxide synthase gene
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-
-
additional information
?
-
-
the phosphatidylinositol 3-kinase/Akt signaling pathway is required for regulation of tissue inhibitor of metalloproteinases-3 gene expression by TGF-beta in human chondrocytes
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-
-
additional information
?
-
-
two populations of p27 use differential kinetics to phosphorylate Ser-10 and Thr-187 via phosphatidylinositol 3-Kinase in response to fibroblast growth factor-2 stimulation
-
-
-
additional information
?
-
-
PI3K family plays a prominent role in various inflammatory cells by controlling cell growth, differentiation, survival, proliferation, migration, and mediator production (such as cytokines) through its downstream components
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-
-
additional information
?
-
-
activated PDGFRbeta interacts with PI3 kinase, which binds to the phosphorylated Tyr739 and Tyr750 residues, in the signaling cascade in vascular smooth muscle cells. disruption of PDGFRbeta-PI3K signaling in mice reduces atherosclerosis. PDGF-BB-induced chemotaxis is inhibited by blocking PI3K activation through PDGFRbeta
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-
-
additional information
?
-
-
activation of PI3K by adenosine leads to induction of hemeoxygenase-1, HO-1, expression in microglia
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-
-
additional information
?
-
-
class III PI3K Vps34p is associated with Vsp15
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-
-
additional information
?
-
-
effects of the specific PI3K inhibtor LY294002 on Kv1.5 channels, wild-type and mutant, are independent of the effects on PI3K activity, overview
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-
-
additional information
?
-
-
PI3K inhibits recombinantly expressed rat excitatory amino acid transporter 4 in oocytes, which is inhibited by the specific PI3K inhibitor wortmannin
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-
-
additional information
?
-
-
PI3K is implicated in the phosphorylation of ERK and CaMKII in spinal neurons, and of NR2B subunits of the NMDA receptor, as well as in the increased synthesis of c-Fos and the trafficking of AMPA-R GluR1 subunit, all after formalin injection
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-
-
additional information
?
-
-
PI3K signaling, overview
-
-
-
additional information
?
-
-
PI3K specifically interacts with retinoblastoma protein through the unique NH2 terminus of its regulatory subunit p55PIK, peptide N24. This interaction is critical for cell proliferation and cell cycle progression
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-
-
additional information
?
-
-
the enzyme is activated and associated to E-cadherin complexes, the assembly is mediated by docking proteins, e.g. beta-catenin, gamma-catenin, and Dlg, and involves c-SRC. Cell-cell adhesion induces c-SRC recruitment and E-cadherin complex assembly as well as activity of PI3K, regulatory and molecular mechanism, overview. PI3K, stimulated by E-cadherin adhesion, activates PKB/Akt
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-
-
additional information
?
-
Q6ZNE5, Q9P2Y5
Vps34, p150, Beclin 1, Atg14, and UVRAG form two distinct class III phosphatidylinositol 3-kinase complexes, overview. Atg14 interacts with Beclin 1 and Vps34 but not with UVRAG, the coiled-coil region of Atg14 required for binding with Vps34 and Beclin 1 is essential for autophagy
-
-
-
additional information
?
-
-
a p110alpha/beta-subunit binds to a p85 regulatory subunit, and this heterodimer is recruited to the membrane through the association with phosphotyrosyl proteins, leading to production of phosphatidylinositol 3,4,5-triphosphate, PIP3, followed by activation of downstream signal pathway(s)
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-
-
additional information
?
-
Q6ZNE5, Q9P2Y5
PI3-kinase activity is not required for starvation-induced Atg14 puncta formation
-
-
-
additional information
?
-
-
PI3K binds PD1 peptide, a 12-residue proline-rich peptide HSKRPLPPLPSL, and PD1R peptide, at the SH3 domain with type I ligand orientation of the bound peptide with an extended conformation where the central portion forms a left-handed type II polyproline, PPII, helix. The residue at anchor position P-3 is a tyrosine
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-
-
additional information
?
-
-
the enzyme also catalyzes the reactions of EC 2.7.1.68, 1-phosphatidylinositol-4-phosphate 5-kinase, and EC 2.7.1.67, 1-phosphatidylinositol 4-kinase
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-
-
additional information
?
-
Rattus norvegicus Sprague-Dawley
-
nerve growth factor inhibits Na+/H+ exchange and formula absorption through parallel phosphatidylinositol 3-kinase-mTOR and ERK pathways in thick ascending limb
-
-
-
additional information
?
-
Mus musculus C57BL/6
-
PI3K signaling, overview
-
-
-
additional information
?
-
Rattus norvegicus Wistar
-
HMG-CoA reductase inhibitor regulates endothelial progenitor function through the phosphatidylinositol 3-kinase/AKT signal transduction pathway
-
-
-
additional information
?
-
Homo sapiens PI3K-C2alpha
-
class II PI3K enzymes may contribute to the generation of 3'-phosphoinositides following the activation of polypeptide growth factor receptors in vivo and thus mediate certain aspects of their biological activity
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 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-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
-
catalyzed by class I and III, and probably by class II enzymes, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
Trypanosoma cruzi, Trypanosoma cruzi CL Brener
A9QWR8
TcVps34 specifically phosphorylates phosphatidylinositol to produce phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
show the reaction diagram
Mus musculus C57BL/6
-
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
show the reaction diagram
Q8NEB9
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 + Akt1
ADP + Akt1 phosphate
show the reaction diagram
-
phosphorylation at Ser473, a step in PI3K/Akt signaling
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
class I enzyme, preferred substrate in vivo
-
-
?
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-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
show the reaction diagram
-
class Ia isozyme
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
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
-
-
?
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
show the reaction diagram
-
-
-
-
?
phosphatidylinositol-4,5-bisphosphate + ATP
?
show the reaction diagram
-
involved in signalling pathways leading to mitosis and differentiation
-
-
?
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
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
TAPP1 and TAPP2 are direct targets of PI3K signaling
-
-
-
additional information
?
-
-
isoform p110b of the catalytic subunit plays a crucial role in cellular activities evoked acutely by insulin
-
-
-
additional information
?
-
-
activation of phosphatidylinositol-3 kinase by ligation of the interleukin-7 receptor is dependent on protein tyrosine kinase activity, activation is dependent on the phosphorylation event of p85
-
-
-
additional information
?
-
-
PI-3-kinase might be involved in the induction of erythroid differentiation, possibly engaging a protein kinase C z as downstream effector
-
-
-
additional information
?
-
-
generation of phosphatidyl 3,4,5-triphosphate by phosphatidylinositol 3-kinase is necessary for insulin-induced germinal vesicle breakdown in Xenopus oocytes
-
-
-
additional information
?
-
-
the enzyme is implicated in the control of breast cancer cell growth by free fatty acids and may provide a link between fat and cancer
-
-
-
additional information
?
-
-
important functional role of phosphatidylinositol 3-kinase in motile responses of HL-60 cells
-
-
-
additional information
?
-
-
PI 3-kinase is the first step of the insulin signaling pathway to be impaired by high-fat feeding
-
-
-
additional information
?
-
-
essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes
-
-
-
additional information
?
-
-
monocytes respond to LPS with the rapid activation of PI 3-kinase, resulting in transient increases in levels of PtdIns 3,4,5-P3. This process is CD14 dependent and involves the physiological association of PI 3-kinase with activated p53/56lyn
-
-
-
additional information
?
-
-
role for phosphatidylinositol 3-kinase in the activation of Raf kinases in G protein-coupled receptor systems in human neutrophils
-
-
-
additional information
?
-
Q94125
regulating longevity and diapause
-
-
-
additional information
?
-
-
PI 3-K pathways is involved in the short-term activation of pyruvate kinase L by insulin in rat hepatocytes
-
-
-
additional information
?
-
-
the enzyme catalyzes the formation of 3'-phosphoinositides, which appear to promote cellular responses to growth factors and such membrane trafficking events as insulin-stimulated translocation of intracellular glucose transporters
-
-
-
additional information
?
-
O35940
may play a role in phosphatidylinositol 3-kinase-mediated signaling in the immune system
-
-
-
additional information
?
-
P42347, P42348
enzyme is induced during soybean nodule organogenesis and plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
-
phosphatidylinositol 3-kinase-mediated signaling in the immune system
-
-
-
additional information
?
-
O35940
phosphatidylinositol 3-kinase-mediated signaling in the immune system
-
-
-
additional information
?
-
-
phosphatidylinositol 3-kinase acts at an intracellular membrane site to enhance GLUT4 exocytosis in 3T3-L1 cells
-
-
-
additional information
?
-
-
enzyme is involved in formyl peptide-induced stimulation of neutrophils
-
-
-
additional information
?
-
-
IL-10 inhibits apoptosis of promyeloid cells by activating insulin receptor substrate-2 and phosphatidylinositol 3'-kinase
-
-
-
additional information
?
-
P22543
enzyme is required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae
-
-
-
additional information
?
-
P42347, P42348
PI3K plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
-
insulin stimulation of fatty acid synthase promoter is mediated by the PI 3-kinase pathway
-
-
-
additional information
?
-
-
plays a central part in the mediation of insulin-stimulated glucose disposal
-
-
-
additional information
?
-
P91634
role for Dp110 in growth control during Drosophila development
-
-
-
additional information
?
-
-
insulin signaling in heart involves insulin receptor substrate-1 and insulin receptor substrate-2, activation of phosphatidylinositol 3-kinase
-
-
-
additional information
?
-
-
activation of PI3K is a critical component of the anti-Ig-initiated signaling cascade that leads to growth inhibition of human B lymphoma cells
-
-
-
additional information
?
-
-
signaling pathways for phosphoinositolglycan-peptide and insulin to glucose transport and metabolism converge at the level of PI 3-kinase
-
-
-
additional information
?
-
-
the enzyme is essential for protein sorting
-
-
-
additional information
?
-
-
enzyme plays an important role in the signalling of cell growth
-
-
-
additional information
?
-
-
enzyme might contribute to the antiproliferative activity of the antitumor ether lipid analogs
-
-
-
additional information
?
-
-
myotubularin, a phosphatase deficient in myotubular myopathy, may decrease PI3P levels by down-regulating PI3K activity and by directly degrading PI3P
-
-
-
additional information
?
-
-
PI 3-kinase activity is a necessary step in the regulation of bone resorption
-
-
-
additional information
?
-
-
PI 3-kinase activity appears to be an important component of ovariectomy-stimulated bone loss in rats
-
-
-
additional information
?
-
-
insulin and dexamethasone regulate phosphatidylinositol 3-kinase in Fao hepatoma cells
-
-
-
additional information
?
-
-
enzyme plays an important role in the signaling of cell growth
-
-
-
additional information
?
-
-
insulin-stimulated IRS-1 association with PI 3-kinase is decreased to 84% in the liver and to 84% in the muscle in the fructose-fed group compared to controls
-
-
-
additional information
?
-
-
lysophosphatidic acid stimulates glucose transport in Xenopus oocytes via a phosphatidylinositol 3'-kinase
-
-
-
additional information
?
-
-
differential regulation of insulin receptor substrate-1 and insulin receptor substrate-2 and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic mouse
-
-
-
additional information
?
-
-
the level of insulin receptor tyrosine kinase activity modulates the activities of phosphatidylinositol 3-kinase
-
-
-
additional information
?
-
-
insulin activates ATP-sensitive K+ channels in pancreatic B-cells through a phosphatidylinositol 3-kinase-dependent pathway
-
-
-
additional information
?
-
-
reduced expression of the murine p85a subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes
-
-
-
additional information
?
-
-
essential for normal cell growth and vacuole morphology
-
-
-
additional information
?
-
P42336
mitogenic signal transduction pathway mediated by P13K is dependent upon the enzymatic activity of the p110 alpha subunit of P13K
-
-
-
additional information
?
-
-
enzyme may represent a common pathway of integrin and adhesiveness regulation in leukocytes
-
-
-
additional information
?
-
-
class II PI3K enzymes may contribute to the generation of 3'-phosphoinositides following the activation of polypeptide growth factor receptors in vivo and thus mediate certain aspects of their biological activity
-
-
-
additional information
?
-
-
in both the liver and muscle of high salt-fed rats, intracellular insulin signaling leading to PI 3-kinase activation is enhanced and insulin action is attenuated
-
-
-
additional information
?
-
-
enzyme could be involved in stimulated glucose transport in muscle
-
-
-
additional information
?
-
-
receptor linked enzyme may generate a second-messenger signal
-
-
-
additional information
?
-
-
enzyme is involved in the signaling pathways regulating cell growth by virtue of its activation in response to various mitogenic stimuli
-
-
-
additional information
?
-
-
multiple defects of PI 3-kinase activation, involving both the p85a and the p85b adaptor subunits, may contribute to cardiac insulin resistance
-
-
-
additional information
?
-
-
the enzyme 3'-phosphorylates the inositol head group of membrane phosphoinositides, isozymes are subject to differential regulation and may play distinct roles in the cell, e.g. in cell survival, vesicle trafficking, cytoskeletal reorganization, and chemotaxis, the enzymeis involved in diverse signalling pathways, detailed schematic overview
-
-
-
additional information
?
-
-
the enzyme 3'-phosphorylates the inositol head group of membrane phosphoinositides, isozymes are subject to differential regulation and may play distinct roles in the cell, the enzyme is involved in many cellular responses important in pathogenesis of disease
-
-
-
additional information
?
-
-
the enzyme is involved in beta2-adrenergic receptor/G1-mediated compartmentation of the concurrent Gs-cAMP signaling, negating beta2-AR-induced phospholamban phosphorylation and the positive inotropic and lusitropic responses in cardiomyocytes, regulation of enzyme activity in cell signaling cascades, effects of enzyme inhibition on cellular processes, detailed overview
-
-
-
additional information
?
-
-
the enzyme is involved in cytokin-stimulated cell migration
-
-
-
additional information
?
-
-
the isozyme gamma stimulates the protein kinases Erk, JNK, and PKB and thus plays a role in cellular signaling, overview
-
-
-
additional information
?
-
-
the lipid-lowering effect of leptin on livers from lean rats is mediated by the enzyme, diet-induced obesity abolishes the effect of leptin on the enzyme and the lipid level and causes leptin resistance
-
-
-
additional information
?
-
-
interaction between Beclin and hVps34 PI 3-kinase is essential for engagement of hVps34 in the process of macroautophagy, but is dispensable for the normal function of hVps34 in endocytic trafficking or lysosomal enzyme sorting
-
-
-
additional information
?
-
-
leptin activates leptin receptor and results in the actvation of insulin receptor substrate-1, phosphatidylinositol 3-kinase, Akt, NF-kappaB, and p300, leading to up-regulation of IL-6 expression
-
-
-
additional information
?
-
-
PI3-kinase-dependent activation of diacylglycerol kinase and production of phosphatidic acid in caveolae/rafts in response to norepinephrine but not endothelin-1
-
-
-
additional information
?
-
-
two populations of p27 use different kinetics to phosphorylate Ser-10 and Thr-187 via phosphatidylinositol 3-Kinase in response to fibroblast growth factor-2 stimulation
-
-
-
additional information
?
-
-
type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3
-
-
-
additional information
?
-
-
AMP-activated protein kinase, activated by energy depletion, inhibits cell survival by binding to and phosphorylating insulin receptor substrate-1 at Ser-794. Phosphorylation of insulin receptor substrate-1 at this site inhibits phosphatidylinositol 3-kinase/Akt signaling, suppresses the mitochondrial membrane potential, and promotes apoptosis
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-
-
additional information
?
-
-
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
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-
-
additional information
?
-
-
HMG-CoA reductase inhibitor regulates endothelial progenitor function through the phosphatidylinositol 3-kinase/AKT signal transduction pathway
-
-
-
additional information
?
-
-
Hsp27 antagonizes Bax-mediated mitochondrial injury and apoptosis by promoting Akt activation via a PI3-kinase-dependent mechanism
-
-
-
additional information
?
-
-
IGF-I regulates the expression of FLIP in FRTL cells by activating the PI3K/NF-kB cascade
-
-
-
additional information
?
-
-
IL-2-induced PI3K activation limits IL-17RA gene expression. Blockade of the PI3K pathway but not p70S6K leads to up-regulation of IL-17RA
-
-
-
additional information
?
-
-
lutein inhibits NF-kappaB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-kappaB-inducing kinase pathways
-
-
-
additional information
?
-
-
mTOR inhibition increases eIF4E phosphorylation through a PI3K-dependent and Mnk-mediated mechanism
-
-
-
additional information
?
-
-
nerve growth factor inhibits Na+/H+ exchange and formula absorption through parallel phosphatidylinositol 3-kinase-mTOR and ERK pathways in thick ascending limb
-
-
-
additional information
?
-
-
overexpression of mkrn2 completely abrogates constitutively active PI3K- and Akt-induced, but not dominant negative glycogen synthase kinase-3beta-induced, neural cell adhesion molecule expression, indicating that mkrn2 acts downstream of PI3K and Akt and upstream of GSK-3beta. Important role of mkrn2 as a new player in PI3K/Akt-mediated neurogenesis during Xenopus embryonic development
-
-
-
additional information
?
-
-
PI 3-kinase signaling in proliferating cells regulates a novel program of gene expression, which is distinct from that induced by growth factor stimulation of quiescent cells. The expression program controlled by continuous PI 3-kinase signaling in proliferating cells is enriched in genes that regulate cell survival and is mediated in large part by FOXO and RelB transcription factors
-
-
-
additional information
?
-
-
raloxifene exerts its anti-inflammatory action in LPS-stimulated macrophages by blocking the PI 3-kinase-Akt-NF-kappaB signaling cascade, and eventually reduces expression of pro-inflammatory genes such as the nitric oxide synthase gene
-
-
-
additional information
?
-
-
the phosphatidylinositol 3-kinase/Akt signaling pathway is required for regulation of tissue inhibitor of metalloproteinases-3 gene expression by TGF-beta in human chondrocytes
-
-
-
additional information
?
-
-
two populations of p27 use differential kinetics to phosphorylate Ser-10 and Thr-187 via phosphatidylinositol 3-Kinase in response to fibroblast growth factor-2 stimulation
-
-
-
additional information
?
-
-
activated PDGFRbeta interacts with PI3 kinase, which binds to the phosphorylated Tyr739 and Tyr750 residues, in the signaling cascade in vascular smooth muscle cells. disruption of PDGFRbeta-PI3K signaling in mice reduces atherosclerosis. PDGF-BB-induced chemotaxis is inhibited by blocking PI3K activation through PDGFRbeta
-
-
-
additional information
?
-
-
activation of PI3K by adenosine leads to induction of hemeoxygenase-1, HO-1, expression in microglia
-
-
-
additional information
?
-
-
class III PI3K Vps34p is associated with Vsp15
-
-
-
additional information
?
-
-
effects of the specific PI3K inhibtor LY294002 on Kv1.5 channels, wild-type and mutant, are independent of the effects on PI3K activity, overview
-
-
-
additional information
?
-
-
PI3K inhibits recombinantly expressed rat excitatory amino acid transporter 4 in oocytes, which is inhibited by the specific PI3K inhibitor wortmannin
-
-
-
additional information
?
-
-
PI3K is implicated in the phosphorylation of ERK and CaMKII in spinal neurons, and of NR2B subunits of the NMDA receptor, as well as in the increased synthesis of c-Fos and the trafficking of AMPA-R GluR1 subunit, all after formalin injection
-
-
-
additional information
?
-
-
PI3K signaling, overview
-
-
-
additional information
?
-
-
PI3K specifically interacts with retinoblastoma protein through the unique NH2 terminus of its regulatory subunit p55PIK, peptide N24. This interaction is critical for cell proliferation and cell cycle progression
-
-
-
additional information
?
-
-
the enzyme is activated and associated to E-cadherin complexes, the assembly is mediated by docking proteins, e.g. beta-catenin, gamma-catenin, and Dlg, and involves c-SRC. Cell-cell adhesion induces c-SRC recruitment and E-cadherin complex assembly as well as activity of PI3K, regulatory and molecular mechanism, overview. PI3K, stimulated by E-cadherin adhesion, activates PKB/Akt
-
-
-
additional information
?
-
Q6ZNE5, Q9P2Y5
Vps34, p150, Beclin 1, Atg14, and UVRAG form two distinct class III phosphatidylinositol 3-kinase complexes, overview. Atg14 interacts with Beclin 1 and Vps34 but not with UVRAG, the coiled-coil region of Atg14 required for binding with Vps34 and Beclin 1 is essential for autophagy
-
-
-
additional information
?
-
Rattus norvegicus Sprague-Dawley
-
nerve growth factor inhibits Na+/H+ exchange and formula absorption through parallel phosphatidylinositol 3-kinase-mTOR and ERK pathways in thick ascending limb
-
-
-
additional information
?
-
Mus musculus C57BL/6
-
PI3K signaling, overview
-
-
-
additional information
?
-
Rattus norvegicus Wistar
-
HMG-CoA reductase inhibitor regulates endothelial progenitor function through the phosphatidylinositol 3-kinase/AKT signal transduction pathway
-
-
-
additional information
?
-
Homo sapiens PI3K-C2alpha
-
class II PI3K enzymes may contribute to the generation of 3'-phosphoinositides following the activation of polypeptide growth factor receptors in vivo and thus mediate certain aspects of their biological activity
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
binding site structure, a single conserved residue 884, termed the gatekeeper, controls the sensitivity to a wide range of small molecule inhibitors, inhibitor resistance is conferred by a large resiude at this position, e.g. isoleucine, whereas a small amino acid at this position like alanine, glycine, or threonine renders the enzyme sensitive for inhibition by small molecule drugs, the effect can be reversed by mutation of residue C838 to valine or isoleucine
ATP
-
binding site structure, a single conserved residue I670 of VPS34 and L2129 of PI3-K-related protein MEC1, termed the gatekeeper, controls the sensitivity to a wide range of small molecule inhibitors, inhibitor resistance id conferred by a large resiude at this position, e.g. isoleucine, whereas a small amino acid at this position like alanine, glycine, or threonine renders the enzyme sensitive for inhibition by small molecule drugs
ATP
-
as MgATP2-
ATP
-
-
ATP
A9QWR8
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
CaCl2 stimulates enzyme forms PI3KI and PI3KII in absence of MnCl2. Half-maximal activation of PI3KI at 0.1 mM Ca2+, maximal activity at 1 mM, in presence of 10 mM MgCl2 further 2fold activation by 2 mM Ca2+. For PI3KII maximal activity is obtained in presence of 2 mM Ca2+, 1.6fold higher than that obtained in presence of 10 mM MgCl2
Ca2+
-
no effect at physiological concentrations
Ca2+
-
essential divalent cation in lipid kinase assays
Ca2+
-
can use either MgATP2- or CaATP2-
Mg2+
-
activation; maximal activation at 5 mM
Mg2+
-
activation; Km: 6.9 mM
Mg2+
-
maximal activation at 5 mM; required
Mg2+
-
can use either MgATP2- or CaATP2-
Mg2+
-
-
Mg2+
-
dependent on, optimal at 5 mM
Mg2+
-
as MgATP2-
Mn2+
-
scarcely activates
Mn2+
-
can partially replace Mg2+ in activation, about 10% of the activity with Mg2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(+/-)-2-[hydroxy[tetrahydro-2-(octadecyloxy)methylfuran-2-yl]methoxyl]phosphinyloxy-N,N,N-trimethylethaniminium hydroxide
-
-
(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]oxazacyclohentriaconti
-
-
-
(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
-
-
-
(1E,4S,4aR,5R,6aS,7S,9aR)-1-({[3-(dimethylamino)propyl](methyl)amino}methylidene)-7,11-dihydroxy-4-(methoxymethyl)-4a,6a,9a-trimethyl-2,10-dioxo-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydroindeno[4,5-h]isochromen-5-yl acetate
-
-
(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
-
-
(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-3-{(2R)-1-[(1S,3R)-3-hydroxycyclohexyl]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
-
-
1-O-octadecyl-2-O-methyl-rac-3-glycerophospho-myo-inositol
-
-
1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine
-
noncompetitive with ATP
17-hydroxywortmannin
-
-
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
-
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
-
treatment in full medium for a prolonged period of time leads to marked increases of the autophagic markers in cells. The increase of autophagic markers is the result of enhanced autophagic flux. The autophagy promotion activity is due to its differential temporal effects on class I and class III PI3K enzymes. 3-Methyladenine blocks class I PI3K persistently, whereas its suppressive effect on class III PI3K is transient. Treatment with 3-methyladenine in full medium significantly reduces the level of phosphatidylinositol 3-phosphate, the product of class III PI3K, at early time points, but almost completely blocks the product of phosphatidylinositol 3,4,5-trisphosphate up to 9 h
5'-p-fluorosulfonylbenzoyladenosine
-
-
adenosine
-
above 0.1 mM
ADP
-
above 0.1 mM
AMP
-
above 0.1 mM
apocynin
-
specific PI3K inhibitor, restores vasorelaxation and hyperpolarization in response to an ATP-sensitive K+ channel opener levcromakalim
Ca2+
-
0.1 mM, 60% inhibition, in presence of 10 mM MgCl2
cardiolipin
-
-
cardiolipin
-
-
Dodecyl sucrose
-
-
Ead125
-
-
EDTA
-
-
ethanol
-
dose-dependent inhibition of insulin receptor substrate-1-associated PI3K activity in skeletal muscle, but not in adipose tissue, ethanol-induced diabetic rats
Gö6976
Q8NEB9
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
hexadexylphosphocholine
-
-
-
IC87114
-
-
isoquercetin
-
PI 3-kinase I and PI 3-kinase II; strong inhibition of PI 3-kinase I and II, noncompetitive, apparent Ki value: 4 mM for PI 3-kinase I and 2.5 mM for PI 3-kinase II
KU55933
Q8NEB9
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
-
-
LY-294,002
A9QWR8
-
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
-
IC50 values: 2 mM
LY294002
-
specific inhibition
LY294002
-
IC50 is 0.0011 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
LY294002
-
specific inhibition
LY294002
-
the inhibitor potently, reversibly blocks voltage-dependent K+ channel currents via a direct mechanism, IC50 is 0.009 mM, potentiates glucose-stimulated insulin secretion from MIN6 cells in vivo
LY294002
-
specific inhibitor
LY294002
-
the inhibitor activates autophagy and induces apoptosis through p53 pathway in gastric cancer cell line SGC7901
LY294002
-
could suppress leukemia cell invasion and migration at least in part through up-regulation of Egr-1, independent of its PI3 K-Akt inhibitory activity
LY294002
-
inhibition of PI3-kinase induces apoptotic cell death, which is mediated by inactivation of Akt pathway in rat osteoblasts
LY294002
-
may modulate function of the glycine transporters GlyT1 independent of PI3 kinase inhibition
LY294002
-
inhibition of PI3K by LY294002 broadly sensitizes wild-type and mutant PTEN glioblastoma cells to both death receptor– and chemotherapy-induced apoptosis
LY294002
-
simultaneous inhibition of the mitogen-activated protein kinase kinase and phosphatidylinositol 3-kinase pathways enhances sensitivity to paclitaxel in ovarian carcinoma
LY294002
-
preclinical evidence for the in vivo efficacy for LY294002 in the treatment of follicular thyroid cancer
LY294002
-
the inhibitor markedly suppresses phosphorylation of Akt and accelerates TRAIL-mediated apoptosis in oral squamous cell carcinoma cell
LY294002
-
inhibition of PI 3-K enhances the susceptibility of oral squamous cell carcinoma cells to anticancer drug-mediated apoptosis through regulation of expression and post-translational modification of both pro- and antiapoptotic proteins
LY294002
-
the specific inhibitor of the phosphatidylinositol 3-kinase upregulates beta1,4-galactosyltransferase I and thus sensitizes SMMC-7721 human hepatocarcinoma cells to cycloheximide-induced apoptosis. PI3K inhibitors might have therapeutic potential when combined with cycloheximide in the treatment of hepatoma
LY294002
-
significantly inhibits retinal neovascularization in a mouse model of retinal neovascularization
LY294002
-
i.e. [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one]
LY294002
-
inhibits sperm-induced activation of the tyrosine kinase Src and a transient increase in the intracellular concentration of Ca2+ at fertilization. LY294002 also has an inhibitory effect on the Ca2+-dependent breakdown of the Mos protein kinase and cyclin B2 as well as dephosphorylation of mitogenactivated protein kinase
LY294002
-
specific PI3K inhibtor, effects of LY294002 on Kv1.5 channels, wild-type and mutant, are independent of the effects on PI3K activity, overview
LY294002
-
a specific inhibitor of PI3K, effectively suppresses the microglia-derived plasminogen-dependent phosphorylation of Akt
LY294002
-
acts synergistically with the leukotriene biosynthesis inhibitor MK591, overview
LY294002
-
a potent inhibitor of PI3-kinase, significantly inhibits phosphorylation of both p85 and ERK1/2 in vivo
LY294002
-
a PI3K antagonist
LY294002
-
specific PI3K inhibitor, restores vasorelaxation and hyperpolarization in response to an ATP-sensitive K+ channel opener levcromakalim
LY294002
-
i.e. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, a potent PI3K inhibitor, in vitro and vivo inhibition. Spinal application of LY294002 reduces the wind-up of deep dorsal WDR neurons and inhibits electrically evoked responses. Electrically evoked substance P release is not inhibited by LY294002
LY294002
-
i.e. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, a specific cell-permeable PI3-K inhibitor, inhibits spermatozoa motility at 40°C, not at 30°C, independent of and not reversable by Ca2+
LY294002
-
a PI3Kspecific inhibitor, inhibition in vivo: in LY294002-treated root hair cells, endocytosis at the stage of final fusion of the late endosomes to the tonoplast is inhibited and ROS level decreases in a dose-dependent manner, overview
LY294002
Q8NEB9
inhibits wild-type activity in vitro almost as efficiently as KU55933, but is required at much higher concentrations for efficient inhibition of autophagy
LY294002
-
application inhibits rice seed germination and the expression of NADPK oxidase
LY303511
-
the inhibitor potently, reversibly blocks voltage-dependent K+ channel currents via a direct mechanism, IC50 is 0.065 mM
lysophosphatidic acid
-
-
naloxone
-
-
noggin
-
-
-
Nonidet P40
-
-
Nonidet P40
-
-
Nonidet P40
P91635
-
NVP-BEZ235
-
the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin catalytic inhibitor, interferes with tumor growth likely by affecting tumor cells and their vasculature system
NVP-BEZ235
-
potency and selectivity for efficient P13K pathway blockade, potent in vivo antitumor activity
NVP-BEZ235
-
a mTOR/phosphatidylinositol 3-kinase inhibitor. Effector lapatinib and the PI3K inhibitor NVP-BEZ235 collaborate to suppress the PI3K-AKT-mTOR axis driven by loss-offunction PTEN mutations, overview
octylglucoside
-
-
palmitate
-
-
peptide N24
-
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
-
phosphatidic acid
-
-
phosphatidylcholine
-
-
phosphatidylcholine
-
strong inhibition of enzyme form PI3KII, weak inhibition of enzyme form PI3KI
PI3Kalpha inhibitor IV
-
-
-
PI3Kbeta inhibitor VI
-
i.e. TGX-221
-
PI3Kgamma inhibitor
-
-
-
PWT-458
-
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
-
potent inhibitor of cancer cell motility and growth in three-dimensional cultures
PX-866
-
i.e. acetic acid 4-diallylaminomethylene-6-hydroxy-1-alpha-methoxymethyl-10beta,13beta-dimethyl-3,7,17-trioxo-1,3,4,7,10,11beta,12,13,14alpha,15,16,17-dodecahydro-2-oxacyclopenta[a]phenanthren-11-yl ester
quercetin
-
5 mM, 70% inhibition
quercetin
-
inhibition of PI 3-kinase I and II; PI 3-kinase I and PI 3-kinase II, non-competitive
Sodium cholate
-
-
Sodium deoxycholate
-
-
staurosporine
-
-
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
Triton X-100
-
-
Wortmannin
-
PI3K-C2a is refractory to
Wortmannin
-
; at nanomolar levels
Wortmannin
-
phosphoinositide 3-kinase with a C2 domain displays reduced sensitivity to the inhibitor wortmannin
Wortmannin
-
inhibition is of a noncompetitive type with regard to ATP, observed with phosphatidylinositol, phosphatidylinositol monophosphate, or phosphatidylinositol bisphosphate as substrate
Wortmannin
-
-
Wortmannin
-
IC50: 10 nM
Wortmannin
P91635
IC50 10 nM
Wortmannin
-
specific irreversible inhibition, binds covalently to the active site, mixed type inhibition, IC50 is 12 nM
Wortmannin
-
specific inhibition, no blockage of whole-cell outward K+ currents
Wortmannin
-
specific inhibitor
Wortmannin
-
inhibition of the phosphatidylinositol 3-kinase/Akt pathway improves response of long-term estrogen-deprived breast cancer xenografts to antiestrogens
Wortmannin
-
the inhibitor markedly suppresses phosphorylation of Akt and accelerates TRAIL-mediated apoptosis in oral squamous cell carcinoma cell
Wortmannin
-
inhibition of PI 3-K enhances the susceptibility of oral squamous cell carcinoma cells to anticancer drug-mediated apoptosis through regulation of expression and post-translational modification of both pro- and antiapoptotic proteins
Wortmannin
-
the specific inhibitor of the phosphatidylinositol 3-kinase upregulates beta1,4-galactosyltransferase I and thus sensitizes SMMC-7721 human hepatocarcinoma cells to cycloheximide-induced apoptosis. PI3K inhibitors might have therapeutic potential when combined with cycloheximide in the treatment of hepatoma
Wortmannin
-
-
Wortmannin
-
-
Wortmannin
-
a PI3K antagonist
Wortmannin
A9QWR8
-
Wortmannin
-
a specific PI 3-K inhibitor
Wortmannin
-
an irreversible inhibitor with pan-PI3K activity
Wortmannin
-
treatment with wortmannin results in sustained reduction of phosphatidylinositol 3-phosphate and a transient effect on production of phosphatidylinositol 3,4,5-trisphosphate with recovery after 9 h
Wortmannin
-
intracerebroventricular injection of leptin significantly increases phosphodiesterase 3B activity by twofold in the hypothalamus. Previous administration of wortmannin, a specific PI3K inhibitor, completely reverses the stimulatory effect of leptin on phosphodiesterase 3B activity in the hypothalamus
Wortmannin
-
application inhibits rice seed germination and the expression of NADPK oxidase
ZSTK474
-
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
Mg2+
-
inhibition above 2.5 mM, activation below
additional information
-
no inhibition by resveratrol, i.e. 3,4',5-trihydroxystilbene, which is an inhibitor of type II phosphatidylinositol 4-kinase
-
additional information
-
no inhibition by 5,6-dichlorobenzimidazole
-
additional information
-
downstream lipid products affect the enzyme activity via effectors
-
additional information
-
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
-
additional information
-
chelation of intracellular Ca2+
-
additional information
-
MK591 does not inhibit PI3K
-
additional information
-
small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth. The inhibitors affect beta-catenin signaling by inhibition of GSK-3beta activity, resulting in cytoplasmic retention of beta-catenin and reduced expression of its target genes cyclin D1 and c-Myc
-
additional information
A9QWR8
inhibition of TcVps34 with specific PI3K inhibitors, such as wortmannin and LY294000, result in reduced regulatory volume decrease after hyposmotic stress
-
additional information
-
drug design and synthesis, 17-hydroxywortmannin analogues conjugated to rapamycin analogues via a prodrug linker , inhibitory potency, overview
-
additional information
-
LY303511, i.e. 2-(4-Piperazinyl)-8-phenyl-4H-1-benzopyran-4-one, is an inactive analogue of LY294002
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
activated PDGFRbeta
-
PI3K binding to the cytoplasmic domain of activated PDGFRbeta receptors requires phosphorylation at residues 739 and 750 and this interaction in turn activates the kinase
-
adenosine
-
adenosine activates PI3K and induces Akt phosphorylation leading to induction of hemeoxygenase-1, HO-1, expression in microglia. Adenosine acts as an endogenous regulator of brain inflammation via modulation of microglial reactive oxygen species production, mechanism, overview
Atg14
-
PAS localization, along with that of the other components of PI3K complex I, requires Atg14
-
Atg6
-
in the absence of PpAtg6, PpUvrag-GFP as well as PpAtg8 fully mislocalized to the cytosol
-
beta-catenin
-
tyrosine-phopshorylated
-
betagamma subunit of heterotrimeric G-proteins
-
direct activation, acts synergistically with Ras
-
bone morphogenetic protein-2
-
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
-
cAMP
-
PI 3-kinase is activated in response to cAMP or IGF-I, the PI 3-kinase activity bound to its p85 regulatory subunit increases by 1.7fold. cAMP-dependent PI 3-kinase activation plays an important role in the increase in cyclin D1 translation. In contrast, IGF-I-dependent PI 3-kinase activation is required for the increase in cyclin D1 mRNA levels and degradation of p27Kip1
Dlg
-
tyrosine-phopshorylated
-
forskolin
-
activates enzyme activity
G-protein betagamma subunits
-
betagamma subunits of heterotrimeric G-protein
-
IGF-1
-
stimulates
-
IGF-I
-
PI 3-kinase is activated in response to cAMP or IGF-I. cAMP-dependent PI 3-kinase activation plays an important role in the increase in cyclin D1 translation. In contrast, IGF-I-dependent PI 3-kinase activation is required for the increase in cyclin D1 mRNA levels and degradation of p27Kip1
-
Insulin
-
stimulates PI3K activity
-
insulin-like growth factor-I
-
strongly stimulates insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity about 54fold and total phosphatidylinositol 3-kinase activity abozut 6fold
-
leptin
-
1-5 nmol/L stimulates insulin receptor substrate-2 by 280-954% and its associated phosphatidylinositol-3 kinase activity 122-621%. 0.5-25 nmol/L inhibits IRS-1 pY and its associated phosphatidylinositol-3 kinase activity by 20-89%
-
leptin
-
increases the activity by 183% in liver at 90 ng/ml, livers and enzymes of rats with diet-induced obesity are resistant to leptin
-
low density lipoprotein receptor-related protein 1
-
LRP1, positively regulates PI3K activation. LRP1-deficient smooth muscle cells show disorganized actin in the form of membrane ruffling and enhanced cell migration, and show abnormal activation of TGFbeta signaling
-
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
nerve growth factor
-
activates the PI3-K/Akt signaling pathway
-
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
-
phosphatidic acid
-
enhances activity more markedly for PI 3-kinase II than for PI 3-kinase I
Phosphotyrosine peptides
-
high-affinity activation of the enzyme requires the simultaneous binding of two phosphorylated YMXM motifs on insulin receptor substrate 1 to the two SH2 domains of the phosphatidylinositol 3'-kinase
-
pioglitazone
-
a thiazolidinedione, activates PI3K 2-2.5fold at 0.002-0.010 mM, activates adiponectin secretion from adipocytes in vivo
Ras
-
acts synergistically with betagamma subunit of heterotrimeric G-proteins
-
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
-
Vps38
-
the endosomal localization of Atg6 and the other components of PI3K complex II requires Vps38
-
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
-
additional information
-
in cells loaded with protein-tyrosine phosphatase antibody, phosphatidylinositol 3'-kinase activity is increased by 38%, respectively, compared with control cells loaded with preimmune IgG
-
additional information
-
b2-integrins activate the tyrosine kinases p58c-fgr and p59/61hck and causes them to associate with the p85 subunit of PtdIns 3-kinase. Thus, even if PtdIns 3-kinase is not activated by p21ras, it can maintain full enzyme activity due to the interaction with p58c-fgr or p59/61hck
-
additional information
-
direct association with the activated IL-1 receptor
-
additional information
-
both anti-IgM and anti-IgD stimulation results in an increase in the anti-phosphotyrosine-precipitable PI3K activity
-
additional information
-
insulin and IGF-I treatment increases phosphatidylinositol 3-kinase activity 4.5fold in aPY20 immunoprecipitation from whole cell lysates
-
additional information
-
binding to the platelet-derived growth factor receptor transiently activates the p85a-p110a phosphoinositide 3-kinase complex in vivo
-
additional information
-
epidermal growth factor induces activation of phosphatidylinositol 3-kinase in rat hepatocyte primary culture
-
additional information
-
Fyn may be directly involved in the activation of the downstream signaling enzyme, PI3-kinase, in IL-2-stimulated T cells
-
additional information
-
EGF stimulates phosphatidylinositol 3-kinase in human airway smooth muscle cells
-
additional information
-
PI3-kinase is activated by insulin and IGF-I in a rapid and transient manner in incubated soleus muscles
-
additional information
-
IL-3 and IGF-I stimulate PI 3-kinase activity
-
additional information
-
thrombopoietin induces phosphoinositol 3-kinase activation through SHP2, Gab, and insulin receptor substrate proteins in BAF3 cells and primary murine megakaryocytes
-
additional information
-
insulin differentially stimulates phosphatidylinositol 3-kinase activity
-
additional information
P48736
p110 gamma enzyme is activated in vitro by both the alpha and beta gamma subunits of heterotrimeric guanosine triphosphate-binding proteins and does not interact with p85; phosphoinositide-3 kinase isotype p110g is activated in vitro by both the alpha and betagamma subunits of heterotrimeric GTP-binding proteins
-
additional information
-
vascular endothelial growth factor activates phosphatidylinositol 3-kinase in human umbilical vein endothelial cells. Activities of ERK, PI 3-kinase, and p70 S6 kinase are essential for vascular endothelial growth factor-induced human umbelical vein proliferation
-
additional information
-
enzyme induction in cell culture by platelet-derived growth factor PGDF and starvation via the G-protein-coupled fMLP receptor
-
additional information
-
stimulation of beta1-adrenergic receptor increases the enzyme activity in cardiomyocyte via the PKA-dependent mechanism involving Gbetagamma
-
additional information
-
insulin stimulates
-
additional information
-
downstream lipid products affect the enzyme activity via effectors, enzyme activation occurs via G-protein-coupled receptors, cell adhesion, and phosphorylation by tyrosine kinase, the subunits are differently sensitive, overview
-
additional information
-
microparticles, membrane vesicles released during cell activation and apoptosis, activate pathways related to NO and reactive oxygen species productions through PI3K, xanthine oxidase, and NF-kappaB pathways, overview
-
additional information
-
the enzyme is activated and associated to E-cadherin complexes, the assembly is mediated by docking proteins, e.g. beta-catenin, gamma-catenin, and Dlg, and involves c-SRC. Cell-cell adhesion induces c-SRC recruitment and E-cadherin complex assembly as well as activity of PI3K, regulatory and molecular mechanism, overview. Interaction of docking proteins via the p85 subunit of PI3K
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
1,2-dioctanoylphosphatidylinositol 4,5-diphosphate
-
pH 7.4, recombinant enzyme
0.03
ATP
-
with phosphatidylinositol 4-phosphate or phosphatidylinositol 4,5-bisphosphate as cosubstrate
0.035
ATP
-
pH 7.4, recombinant enzyme
0.06
ATP
-
with phosphatidylinositol as cosubstrate
0.067
ATP
-
-
25
ATP
-
reaction with phosphatidylinositol
37
ATP
-
reaction with phosphatidylinositol 4,5-diphosphate
44
ATP
-
reaction with phosphatidylinositol 4-phosphate
0.034
phosphatidylinositol
-
sonicated
0.06
phosphatidylinositol
-
-
64
phosphatidylinositol
-
-
0.004
phosphatidylinositol 4,5-bisphosphate
-
-
15
phosphatidylinositol 4,5-bisphosphate
-
-
0.009
phosphatidylinositol 4-phosphate
-
-
10
phosphatidylinositol 4-phosphate
-
-
0.011
phosphatidylinositol-4,5-bisphosphate
-
preferred free substrate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0038
staurosporine
-
pH 7.4, recombinant enzyme
0.0056
LY294002
-
pH 7.4, recombinant enzyme
additional information
additional information
-
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.2
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
0.0031
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
0.2
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
0.025
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
0.028
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
0.051
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
0.033
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
0.0026
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
0.0011
LY294002
-
IC50 is 0.0011 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
0.009
LY294002
-
the inhibitor potently, reversibly blocks voltage-dependent K+ channel currents via a direct mechanism, IC50 is 0.009 mM, potentiates glucose-stimulated insulin secretion from MIN6 cells in vivo
2
LY294002
-
IC50 values: 2 mM
0.065
LY303511
-
the inhibitor potently, reversibly blocks voltage-dependent K+ channel currents via a direct mechanism, IC50 is 0.065 mM
0.00001
Wortmannin
-
IC50: 10 nM
0.00001
Wortmannin
P91635
IC50 10 nM
0.000012
Wortmannin
-
specific irreversible inhibition, binds covalently to the active site, mixed type inhibition, IC50 is 12 nM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0016
-
purified recombinant isozyme gamma, at phosphatidylinositol-4,5-bisphosphate surface concentration of 10 mol%
0.0017
-
-
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%
0.05
-
dimeric enzyme form PI3KII
0.058
-
production of phosphatidylinositol 3,4-diphosphate
0.124
-
production of phosphatidylinositol 3-phosphate
0.214
-
production of phosphatidylinositol 3,4,5-triphosphate
0.25
-
monomeric enzyme form PI3KI
additional information
-
assay method development and optimization, phosphoinositide quantification via labeled and/or tagged ligands binding to the pleckstrin homology PH domain of the recombinant enzyme in competition with phosphoinositides, overview
additional information
-
-
additional information
-
optimization of substrate surface concentration in enzyme assays for each isozyme, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2 - 7.3
-
assay at
7.4
-
assay at
7.4
-
assay at
7.5
-
enzyme forms PI3KII and PI3KI
7.5
-
kinase assay at
7.5
-
assay at
7.5
-
assay at
7.5
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 9
-
pH 6.5: about 80% of maximal activity, pH 9.0: about 40% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
-
assay at room temperature
22
-
assay at room temperature
25
-
assay at
30 - 40
-
assay at
30
-
kinase assay at
37
-
assay at
37
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
,during differentiation of 3T3-L1 cells into adipocytes, isoform p110b is up-regulated approximately 10-fold, expression of p110a is unaltered
Manually annotated by BRENDA team
-
insulin-sensitive mouse 3T3-L1 adipocytes
Manually annotated by BRENDA team
-
primary, obtained from subcutaneous tissue biopsies performed on two lean non-diabetic male subjects
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
nuclear accumbens shell and core, prefrontal cortex
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
ER-positive breast cancer cells (UMB-1Ca) are grown as tumors in ovariectomized athymic nude mice
Manually annotated by BRENDA team
-
microglial cell
Manually annotated by BRENDA team
-
KRC-7 hepatoma cells
Manually annotated by BRENDA team
-
BAF3 cells and primary murine megakaryocyte
Manually annotated by BRENDA team
-
carcinoma-derived A431 cells
Manually annotated by BRENDA team
-
U937 monocyte
Manually annotated by BRENDA team
O70167
a N-terminal truncated form is found a certain hematopoietic cell line
Manually annotated by BRENDA team
-
U937 monocytes
Manually annotated by BRENDA team
-
osteosarcoma sensitive and multidrug-resistant Saos-2 cells
Manually annotated by BRENDA team
-
Fao hepatoma cells
Manually annotated by BRENDA team
-
T cell line CTLL-2
Manually annotated by BRENDA team
-
breast cancer cells
Manually annotated by BRENDA team
-
hepatocyte primary culture
Manually annotated by BRENDA team
-
Friend erythroleukemia cells
Manually annotated by BRENDA team
-
Swiss 3T3 fibroblast
Manually annotated by BRENDA team
-
B lymphoma cell line
Manually annotated by BRENDA team
-
osteosarcoma Saos-2 cells
Manually annotated by BRENDA team
-
of astrocytes from cerebral cortices
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
of astrocytes from cerebral cortices
-
Manually annotated by BRENDA team
Homo sapiens PI3K-C2alpha
-
carcinoma-derived A431 cells
-
Manually annotated by BRENDA team
-
colorectal tumors exhibit enhanced PI 3-kinase activity compared with normal colonic mucosa
Manually annotated by BRENDA team
-
colorectal tumors exhibit enhanced PI 3-kinase activity compared with normal colonic mucosa
Manually annotated by BRENDA team
Q3U6Q4
the regulatory subunit p87PIKAP and the catalytic subunit p101 are both expressed
Manually annotated by BRENDA team
-
fibroblasts
Manually annotated by BRENDA team
O35940
isoform P110d
Manually annotated by BRENDA team
-
umbilical vein endothelial cells
Manually annotated by BRENDA team
Trypanosoma cruzi CL Brener
-
-
-
Manually annotated by BRENDA team
-
airway, primary cells
Manually annotated by BRENDA team
-
Swiss 3T3 fibroblast
Manually annotated by BRENDA team
-
embryonic fibroblast cells
Manually annotated by BRENDA team
-
thyroid follicular cell line
Manually annotated by BRENDA team
-
primary tumor cell line
Manually annotated by BRENDA team
-
nodal metastasis cell line
Manually annotated by BRENDA team
-
,sympathetic superior cervical ganglia and sensory trigeminal ganglia. In cultured sympathetic superior cervical ganglia and dorsal root ganglia neurons, p110a, b, and g immunoreactivity is in the sympathetic superior cervical ganglia and DRG growth cones, and predominantly in puncta throughout the growth cone varicosity
Manually annotated by BRENDA team
-
primary glioblastoma
Manually annotated by BRENDA team
-
HCT-116 cells are heterozygous for gain of function mutant PIK3CA H1047R
Manually annotated by BRENDA team
-
chicken HD11 macrophage cell
Manually annotated by BRENDA team
Q3U6Q4
p87PIKAP is a regulatory subunit of phosphoinositide 3-kinase gamma that is highly expressed in heart and interacts with phosphodiesterase 3B
Manually annotated by BRENDA team
-
activation of the prosurvival phosphatidylinositol 3-kinase-Akt pathway is involved in the protective action of poly(ADP-ribose) polymerase 1 inhibition in a model of donor heart procurement and hypothermic storage
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
IL-3-dependent FDCP-1/Mac-1 murine hemopoietic progenitors
Manually annotated by BRENDA team
-
a primary cell type in the liver responsible for excess collagen deposition during fibrosis
Manually annotated by BRENDA team
-
Fao hepatoma cells
Manually annotated by BRENDA team
-
isoform P110d
Manually annotated by BRENDA team
-
p110delta is exclusively found in leukocytes
Manually annotated by BRENDA team
-
isozyme Ia gamma
Manually annotated by BRENDA team
-
of obese diabetic mouse
Manually annotated by BRENDA team
O70173
expression increases during liver regeneration after partial hepatectomy with maximal expression after the growth period, PI3K-IIgamma may function mainly in highly differentiated hepatic cells
Manually annotated by BRENDA team
O70167
a N-terminal truncated form is found in lung
Manually annotated by BRENDA team
Q3U6Q4
the regulatory subunit p87PIKAP and the catalytic subunit p101 are both expressed
Manually annotated by BRENDA team
-
insulinoma cell
Manually annotated by BRENDA team
-
skeletal muscle
Manually annotated by BRENDA team
-
of obese diabetic mouse
Manually annotated by BRENDA team
-
airway smooth muscle cells
Manually annotated by BRENDA team
-
isozyme phosphatidylinositol 3-kinase gamma
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
isozyme phosphatidylinositol 3-kinase gamma
-
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
-
cultured sympathetic superior cervical ganglia and dorsal root ganglion neurons
Manually annotated by BRENDA team
-
primary, cortical
Manually annotated by BRENDA team
Q3U6Q4
the regulatory subunit p87PIKAP and the catalytic subunit p101 are both expressed
Manually annotated by BRENDA team
-
short-term spikes of modest heat abrogate antineutrophil cytoplasmic autoantibody-induced activation of neutrophils via inhibition of PI 3-kinase/Akt signaling
Manually annotated by BRENDA team
-
shell and core. Cocaine sensitization decreases PI3K activity in nuclear accumbens core. The changes are not normalized following the reversal of cocaine-sensitization. Cocaine-sensitized animals exhibited increased PI3K activity in the nuclear accumbens shell, and this increase is reversed by combined pergolide/ondansetron treatment. Selective enhancement of the PI3K activity in the NAc shell may be one of key alterations underlying the long-term cocaine sensitization
Manually annotated by BRENDA team
-
inhibition of PI3-kinase induces apoptotic cell death, which is mediated by inactivation of Akt pathway in rat osteoblasts
Manually annotated by BRENDA team
-
the phosphatidylinositol 3-kinase-mediated production of interferon-beta is critical for the lipopolysaccharide inhibition of osteoclastogenesis
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
-
cocaine sensitization increases PI3K activity. The changes are not normalized following the reversal of cocaine-sensitization
Manually annotated by BRENDA team
-
of rat embryonic cortex
Manually annotated by BRENDA team
-
PI3K regulates NADPH oxidase activity through modulating the recruitment of Rac-1 to plasma membrane and accelerates the process of rice seed germination
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
-
T cell line CTLL-2
Manually annotated by BRENDA team
-
ATCC CRTL-1486
Manually annotated by BRENDA team
-
glioblastoma cell
Manually annotated by BRENDA team
-
activation of PI3K signaling is required for the inhibitory effect of Axl on mineral deposition
Manually annotated by BRENDA team
-
U937 monocyte
Manually annotated by BRENDA team
additional information
-
isozymes Ia alpha and beta are widely expressed in tissues
Manually annotated by BRENDA team
additional information
-
isozymes Ia alpha and Ia beta are widely expressed in tissues
Manually annotated by BRENDA team
additional information
-
the phosphatidylinositol 3-kinase, PI3K, family is a family of conserved lipid and protein kinases that are ubiquitously expressed in many cells, including the heart
Manually annotated by BRENDA team
additional information
Mus musculus C57BL/6
-
the phosphatidylinositol 3-kinase, PI3K, family is a family of conserved lipid and protein kinases that are ubiquitously expressed in many cells, including the heart
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
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
-
the enzyme translocates onto liver endoplasmic reticulum
Manually annotated by BRENDA team
-
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
-
in interchromatin domains, in stable association with inner nuclear matrix components
Manually annotated by BRENDA team
-
p110a is localized predominantly at the plasma membrane, while p110b and g is localized in the perinuclear region of the cells
-
Manually annotated by BRENDA team
-
PI3K complex localization during the elongation of the phagophor
-
Manually annotated by BRENDA team
-
p110a is localized predominantly at the plasma membrane, while p110b and g is localized in the perinuclear region of the cells
Manually annotated by BRENDA team
-
the enzyme binds to the plasma membrane to get access to its lipid substrate phosphatidylinositol-4,5-bisphosphate, membrane binding via the C-terminal CAAX domain
Manually annotated by BRENDA team
Trypanosoma cruzi CL Brener
-
-
-
Manually annotated by BRENDA team
-
insulin-triggered mechanism of translocation of PI3K onto microsomes occurs in the liver of rats during refeeding
-
Manually annotated by BRENDA team
additional information
-
actin filaments facilitate the insulin-mediated association of the p85-p110 PI 3-kinase with glucose-transporter-containing compartments
-
Manually annotated by BRENDA team
additional information
-
enzyme and free or anchored glycosylated substrate meet in the submembrane space
-
Manually annotated by BRENDA team
additional information
Q6ZNE5, Q9P2Y5
Atg14 is present on autophagic isolation membranes
-
Manually annotated by BRENDA team
additional information
-
PI3K associates with E-cadherin and part of the E-cadherin signaling complex, which is intergrated into the plasma membrane, complex formation, overview
-
Manually annotated by BRENDA team
additional information
Q6ZNE5, Q9P2Y5
UVRAG primarily associates with Rab9-positive endosomes
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
95000
-
-
640936
110000
-
monomeric form PI3KI, gel filtration
640848
118000
Q92213
calculation from nucleotide sequence
640934
190000
-
heterodimeric form PI3KII, gel filtration
640848
190000
-
gel filtration
640851
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 85000, SDS-PAGE
dimer
-
1 * 110000 + 1 * 85000, enzyme form PI3KII, SDS-PAGE
dimer
-
1 * 110000 + 1 * 85000, SDS-PAGE
dimer
-
1 * 110000 + 1 * 85000, SDS-PAGE
dimer
-
1 * 85000 + 1 * 110000
dimer
P42337
1 * 85000 + 1 * 110000
dimer
-
1 * 85000 + 1 * 110000
dimer
P32871
1 * 85000 + 1 * 124000, deduced from nucleotide sequence
dimer
-
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
dimer
-
1 * 85000, class IA regulatory/adaptor subunit, + 1 * 110000, class IB catalytic subunit
dimer
-
1 * 85000, regulatory/adaptor subunit, + 1 * 110000, catalytic subunit
dimer
-
1 * 85000, regulatory subunit, + 1 * 110000, catalytic subunit, SDS-PAGE
heterodimer
-
a p110alpha/beta-subunit binds to a p85 regulatory subunit, and this heterodimer is recruited to the membrane through the association with phosphotyrosyl proteins, leading to production of phosphatidylinositol 3,4,5-triphosphate, PIP3, followed by activation of downstream signal pathway(s)
heterodimer
-
PI3K is a heterodimer composed of a p85 regulatory subunit and a p110 catalytic subunit
heterodimer
-
the regulatory p85 subunit of PI3K stabilizes catalytic subunit p110, but also inhibits its lipid kinase activity
monomer
-
1 * 110000, enzyme form PI3KI, SDS-PAGE
additional information
-
the 110000 Da subunit contains an ATP-binding site
additional information
-
two types of PI 3-kinase a monomer form, PI 3-kinase I, and a heterodimeric form, PI 3-kinase II
additional information
-
isoforms of the p110 catalytic subunit: p110a or p110b
additional information
P42337
85000 Da subunit, previously thought to have only a linking role in localizing the p110 catalytic subunit, is an important component of the catalytic complex
additional information
-
different splicing variants of subunits, class I isozyme subgroups Ia and Ib are divided due to their mode of action and structure, the 110 kDa catalytic subunit contains at least 4 domains, the catalytic lipid kinase domain, a PI kinase domain, a C2 phospholipid binding domain, and a Ras-binding domain, the regulatory 85 kDa subunit contains a Src homology 3 SH3 domain, 2 Src homology 2 SH2 domains, a Bcr homologue, and a proline-rich region, domain organization and functions of class I-III enzymes, overview
additional information
-
PI3K contains a Src homology 3, SH3, domain, residues 1-83, overall structure, overview
additional information
Q6ZNE5, Q9P2Y5
Vps34 contains three distinct domains: the N-terminal C2 domain, central accessory domain and C-terminal catalytic domain
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
putative PI 3-kinase 85000 Da subunit is phosphorylated by pp60vscr
phosphoprotein
-
purified enzyme complex is highly phosphorylated on both subunits, dephosphorylation generates a deactivated complex, highly phosphorylated on both p85a and p110 subunits, and dephosphorylation generates a deactivated complex, indicating that phosphorylation is an important covalent modification of the complex and may modulate PtdIns 3-kinase activity
phosphoprotein
-
the enzyme may be tyrosine-phosphorylated
phosphoprotein
-
phosphorylation by tyrosine kinases activates the enzyme
phosphoprotein
-
IL-2 stimulation triggers tyrosine phosphorylation of the p85 subunit of PI3-kinase in murine T cell line CTLL-2
phosphoprotein
-
the enzyme performs autophosphorylation at Ser1039 of the catalytic p110delta subunit
phosphoprotein
-
p85 subunit is rapidly phosphorylated in response to insulin
phosphoprotein
-
PI3-K is activated by phosphorylation through serine/threonine protein kinases
additional information
-
no glycosylation
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
-
vapor diffusion hanging drop method. Crystal structure of the C2 domain
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
large scale
-
PI3KII, heterodimeric form; PI3KI, monomeric form
-
type I phosphatidylinositol kinase
-
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
-
recombinant GRP1 domain, comprising residues 263-380, from Escherichia coli by glutathione affinity chromatography
-
recombinant His-tagged TcVps34 from Escherichia coli strain BL21(DE3) by affinity chromatography
A9QWR8
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gene AtVPS34, genetic structure determination, sequence determination and genotyping, overview
P42339
expression of the 110000 Da subunit in Sf9 insect cells and in COS-1 cells; p110 expressed in insect cells possesses Pl3-kinase activity and associates with p85 alpha into an active p85 alpha-p110 complex that binds the activated colony-stimulating factor 1 receptor. p110 expressed in COS-1 cells is catalytically active only when complexed with p85 alpha
P32871
expression of the p85 subunit and a related p85beta protein by using baculovirus expression system
-
CaVPS34 gene under the control of its own promoter is not able to complement the temperature-sensitive growth of Saccharomyces cerevisiae vps34, overexpression of CaVPS34 is sufficient to rescue the temperature-sensitive vps34 phenotype, suggesting a functional conservation in Candida albicans
Q92213
expression of the complete coding sequence as a glutathione S-transferase fusion protein in Sf9 cells
P91635
;
P42347, P42348
; phosphoinositide-3 kinase isotype, p110 gamma
P48736
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, PI 3-kinase C2b, with a C2 domain is cloned from a U937 monocyte cDNA library and expressed in mammalian and insect cells; class II phosphoinositide 3-kinase with a C2 domain, cloned from a U937 monocyte cDNA library, expression 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
-
genotyping
-
PIK3C2G is mapped to chromosome 12
O75747
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
Q6ZNE5, Q9P2Y5
-
Q3U6Q4
cloning, structural organization, and chromosomal localization of the mouse PI3-kinase p110a gene
-
expression of the GRP1 domain, comprising residues 263-380, in Escherichia coli
-
expression of wild-type and mutant HA-tagged PI3K isozyme gamma and of subunit p110 in COS-7 cells, stimulation of the protein kinases Erk, JNK, and PKB
-
PI 3-kinase p170
-
PI3K-C2 gamma gene locus is mapped to the distal region of mouse chromosome 6 in a region of homology with human chromosome 12p
O70167
expression of wild-type VPS34 and PI3-K-related protein MEC1 in a enzyme-knockout mutant strain, functional complementation analysis, overview
-
DNA and amino acid sequence determination and analysis, recombinant expression of the His-tagged TcVps34 in Escherichia coli strain BL21(DE3) and complementation of an enzyme-deficient Saccharomyces cerevisiae knockout mutant strain
A9QWR8
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of PI3K in seed increases with the prolongation of imbibition time
-
ENGINEERING
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
D743N
Q8NEB9
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
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
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
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
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
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
P42339
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
L750M
Q8NEB9
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
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
-
cancer specific mutation of p110a
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
Q6ZNE5, Q9P2Y5
silencing by siRNA-mediated knockdown of Atg14 in HeLa cells suppresses autophagosome formation
additional information
Q6ZNE5, Q9P2Y5
silencing by siRNA-mediated knockdown of UVRAG in HeLa cells suppresses autophagosome formation
Y836T
-
site-directed mutagenesis, completely inactive p110alpha mutant
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
Mus musculus C57BL/6
-
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
-
L2129G
-
site-directed mutagenesis, functional complementation of a yeast enzyme-knockout mutant strain
additional information
A9QWR8
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
Trypanosoma cruzi CL Brener
-
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
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
-
the enzyme is a potential target for drug development, e.g. in cancer therapy, analysis of inhibitory potential of LY294002 inhibotr analogues
drug development
-
the enzyme is a target for drug design in cancer therapy. Combined targeting of PI3K and mTOR presents an opportunity for robust and synergistic anticancer efficacy
drug development
-
the PI3K/Akt signaling pathway is a therapeutic target in treatment of medulloblastoma disease, a primitive neuroectodermal tumor, and the most common malignant pediatric brain tumor
drug development
-
the regulatory subunit p55PIK of PI3K is a trget for inhibitor development in cancer therapy
medicine
-
p110a is a target for cancer therapies
medicine
-
selective enhancement of the PI3K activity in the nuclear accumbens shell may be one of key alterations underlying the long-term cocaine sensitization. To the extent cocaine sensitization is an important factor in human cocaine abuse, pharmacological interventions targeted toward the NAc shell PI3K alteration may be useful in cocaine abuse treatment
medicine
-
dual inhibition of the mTORC1 complex and the IGF-1/IGF-1R/PI3K/Akt pathway in acute myeloid leukemia may enhance the efficacy of mTOR inhibitors in treatment of this disease
medicine
-
inhibition of PI 3-K enhances the susceptibility of oral squamous cell carcinoma cells to anticancer drug-mediated apoptosis through regulation of expression and post-translational modification of both pro- and antiapoptotic proteins. These findings could potentially lead to new strategies for improving the efficacy of anticancer drugs in oral squamous cell carcinoma cells
medicine
-
inhibition of the class I PI3K signaling pathway is a potential strategy for managing gastric cancers
medicine
-
inhibitors of PI3K/Akt may prove to be useful novel therapies in the treatment of asthma and chronic obstructive pulmonary disease
medicine
-
PI 3-K inhibitors may represent a novel strategy for overcoming resistance to TRAIL-mediated apoptosis in oral squamous cell carcinoma cell
medicine
-
PI3K inhibitors might have therapeutic potential when combined with cycloheximide in the treatment of hepatoma
medicine
-
PI3K lipid kinase is an attractive target for the development of therapeutic agents to treat cancer and other related diseases
pharmacology
-
development of specific isozyme inhibitors may offer therapeutic benefit in a broad range of clinical settings related to cancer, inflammatory and immunological diseases
drug development
-
reduction of PI3K/PKCdelta activity represents a therapeutic target to downregulate adhesion molecule L1, CHL1, expression and thus benefit axonal regeneration after spinal cord injury
medicine
-
preclinical evidence for the in vivo efficacy for the phosphatidylinositol 3-kinase inhibitor LY294002 in the treatment of follicular thyroid cancer
drug development
Mus musculus C57BL/6
-
reduction of PI3K/PKCdelta activity represents a therapeutic target to downregulate adhesion molecule L1, CHL1, expression and thus benefit axonal regeneration after spinal cord injury
-