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Enzyme Nomenclature
Information on EC 2.7.1.137 - phosphatidylinositol 3-kinase
for references in articles please use BRENDA:EC2.7.1.137
Word Map on EC 2.7.1.137
- 2.7.1.137
- wortmannin
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mapks
-
mitogen-activated
- rapamycin
- endothelial
- vascular
- carcinoma
- breast
-
signal-regulated
- injury
- inflammatory
- adhesion
- inflammation
- diabetes
-
insulin-like
- glycogen
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angiogenesis
- actin
- metastasis
-
insulin-stimulated
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mitogen
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autophagy
-
blockade
- caspase-3
-
nf-kappab
-
cyclins
- adipocytes
-
gtpases
-
dominant-negative
- pi3-kinase
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integrins
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xenograft
-
tensin
-
anti-apoptotic
-
neuroprotective
- pik3ca
-
phosphatidylinositol-3-kinase
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platelet-derived
-
insulin-induced
- sh2
-
tyrosine-phosphorylated
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phosphatidylinositol-3
-
substrate-1
- pertussis
-
mtorc1
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insulin-mediated
-
egf-induced
- gsk-3beta
-
pleckstrin
-
everolimus
- pharmacology
- medicine
- drug development
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The enzyme appears in viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
2.7.1.137
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RECOMMENDED NAME
GeneOntology No.
phosphatidylinositol 3-kinase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
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-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase
One mammalian isoform is known.
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CAS REGISTRY NUMBER
COMMENTARY
115926-52-8
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
class I isozymes, 2 subgroups Ia and Ib, subgroup Ia contains 3 isozymes alpha, beta, and gamma, different splicing variants of subunits
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640864, 640866, 640868, 640869, 640872, 640876, 640877, 640880, 640885, 640886, 640887, 640893, 640894, 640896, 640899, 640909, 640910, 640911, 640916, 640922, 640927, 640928, 640929, 661041, 661766, 662576, 671736, 675011, 675786, 677231, 684123, 684792, 684937, 685788, 685816, 685959, 685960, 685961, 686034, 686138, 687177, 687179, 687233, 687266, 687561, 687700, 687707, 688155, 688217, 688453, 688596, 688925, 688930, 688952, 688967, 690219, 694255, 707040, 707454, 707617, 707915, 707969, 707976, 708040, 708417, 708568, 708681, 709003, 709207, 709341, 709342, 709478, 709772, 709870, 709906, 710515, 710598, 710681, 721731, 722666, 739217
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Atg14; Vps34, p150, Beclin 1, Atg14, and UVRAG form two distinct class III phosphatidylinositol 3-kinase complexes
UniProt
UVRAG; Vps34, p150, Beclin 1, Atg14, and UVRAG form two distinct class III phosphatidylinositol 3-kinase complexes
UniProt
Vps34, p150, Beclin 1, Atg14, and UVRAG form two distinct class III phosphatidylinositol 3-kinase complexes
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640859, 640865, 640870, 640874, 640876, 640881, 640889, 640890, 640892, 640897, 640900, 640901, 640902, 640921, 640923, 640924, 640926, 661681, 674741, 675210, 675211, 685969, 686889, 688768, 688988, 689299, 708644, 709478, 709772, 710354, 722666
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
PI3K type III is the only type of PI3K identified in plants
malfunction
metabolism
physiological function
additional information
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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
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
-
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
-
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
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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
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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
inhibition of TcVps34 with specific PI3K inhibitors, such as wortmannin and LY294000, result in reduced regulatory volume decrease after hyposmotic stress
malfunction
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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
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deletion of a key endosomal trafficking regulator, the class 3 phosphatidylinositol (PtdIns) 3-kinase vacuolar protein sorting 34 (Vps34), in podocytes results in aberrant endosomal membrane morphology and podocyte dysfunction. The vacuolation phenotype in cultured Vps34-deficient podocytes is caused by the absence of a substrate for the Vps34 downstream effector PtdIns 3-phosphate 5-kinase, which phosphorylates Vps34-generated PtdIns(3)P to produce PtdIns (3,5)P2
malfunction
enzyme mutations are involved in bilateral perisylvian polymicrogyria (BPP), the most common form of regional polymicrogyria, that causes the congenital bilateral perisylvian syndrome, featuring oromotor dysfunction, cognitive impairment, and epilepsy. Constitutional and mosaic mutations in the PIK3R2 gene are associated with developmental brain disorders ranging from BPP with a normal head size to the MPPH syndrome. They occur primarily in the caucasian white genotype, phenotypes, overview
malfunction
treatment with PI3K inhibitors or downregulation of AtVPS34 gene expression further suppressed V-ATPase activation in methyl jasmonate-induced leaf senescence. Downregulation of PI3K activity accelerates methyl jasmonate-induced leaf senescence. Vacuolar pH and the stomatal aperture also increased in the pi3k mutant and in treatments with PI3K inhibitors
malfunction
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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
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malfunction
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inhibition of TcVps34 with specific PI3K inhibitors, such as wortmannin and LY294000, result in reduced regulatory volume decrease after hyposmotic stress
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metabolism
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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
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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
metabolism
-
the enzyme is part of the phosphatidylinositol 3-kinase/Akt signaling pathway
metabolism
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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
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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
mammalian cells have at least two distinct class III PI3-kinase complexes, which may function in different membrane trafficking pathways; mammalian cells have at least two distinct class III PI3-kinase complexes, which may function in different membrane trafficking pathways; mammalian cells have at least two distinct class III PI3-kinase complexes, which may function in different membrane trafficking pathways
metabolism
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a signaling network regulates interleukin-8 production in response to proteasome activation or inactivation also involving PI3K, detailed overview
metabolism
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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
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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
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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
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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
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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
-
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
-
the thiazolidinedione pioglitazone acutely stimulates adiponectin secretion from mouse and human adipocytes via activation of the phosphatidylinositol 3-kinase
physiological function
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the thiazolidinedione pioglitazone acutely stimulates adiponectin secretion from mouse and human adipocytes via activation of the phosphatidylinositol 3-kinase
physiological function
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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 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
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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
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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
phosphatidylinositol 3-kinase is essential for normal growth and is essential for vacuole reorganization and nuclear division during pollen development
physiological function
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PI3K is involved in regulation of actin polymerization and cell movement
physiological function
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Vps34 appears to be important in endocytosis and vesicular trafficking, and is also implicated in Toll-like receptor signalling
physiological function
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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
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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
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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
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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
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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
enzyme PIK3C3 plays a role, such as endocytic trafficking, in synapses
physiological function
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enzyme PI3K can modify the PI3K-related kinases (PIKKs) in response to radiation. PIKKs interact with PI3K and contribute to radioresistance in thyroid-carcinomas
physiological function
phosphatidylinositol 3-kinase, PI3K, binds to VHA-B2 and promotes the activation of V-ATPase, resulting in vacuolar acidification and stomatal closure, thereby delaying methyl jasmonate-induced leaf senescence. PI3K is involved in the regulation of dark-induced senescence but does not function through the regulation of V-ATPase activity. PI3K regulates the activity of V-ATPase in MeJA-induced leaf senescence but not in dark-induced leaf senescence
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; 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
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physiological function
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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
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physiological function
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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
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 1,2-dibutanoylphosphatidylinositol 4,5-diphosphate
ADP + 1,2-dibutanoylphosphatidylinositol 3,4,5-trisphosphate
-
-
-
-
?
ATP + 1,2-dioctanoylphosphatidylinositol 4,5-diphosphate
ADP + 1,2-dioctanoylphosphatidylinositol 3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
phosphatidylinositol-4,5-bisphosphate + ATP
?
-
involved in signalling pathways leading to mitosis and differentiation
-
-
?
ATP + 1-O-octadecyl-2-O-methyl-rac-3-glycerophospho-myo-inositol
ADP + ?
-
-
-
-
?
ATP + 1-O-octadecyl-2-O-methyl-rac-3-glycerophospho-myo-inositol
ADP + ?
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
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
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
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
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
-
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
substrate from bovine liver
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
TcVps34 specifically phosphorylates phosphatidylinositol to produce phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
TcVps34 specifically phosphorylates phosphatidylinositol to produce phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
Chlamydomonas sp.
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
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
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
Q8NJ23
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + Akt1
ADP + Akt1 phosphate
-
phosphorylation at Ser473, a step in PI3K/Akt signaling
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
class I enzyme, preferred substrate of the class III enzyme
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
class I enzyme
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
weak activity
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
no activity
-
-
-
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
no activity
-
-
-
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
class I enzyme, preferred substrate in vivo, physiologic regulation and mode of action
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
class I enzyme, preferred substrate of the class I enzyme
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
class I enzyme, preferred substrate in vivo
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
class I enzyme
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
-
-
-
-
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
-
weak activity
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
-
no activity
-
-
-
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
-
class I enzyme, preferred substrate of the class II enzyme
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
-
class I enzyme
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
class Ia isozyme
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
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
-
from rat liver and bovine erythrocyte and brain, substrate specificities, free or membrane anchored, phosphorylated phosphatidylinositol is poorer substrate than nonphosphorlyated, overview
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
-
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
-
-
-
-
?
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
-
-
-
-
?
additional information
?
-
PI3K binds to the V-ATPase subunit B2 (VHA-B2) in vitro and in vivo
-
-
-
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
?
-
-
PI 3-kinase activity is a necessary step in the regulation of bone resorption
-
-
-
additional information
?
-
-
enzyme plays an important role in the signaling of cell growth
-
-
-
additional information
?
-
-
receptor linked enzyme may generate a second-messenger signal
-
-
-
additional information
?
-
regulating longevity and diapause
-
-
-
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
?
-
-
enzyme is involved in formyl peptide-induced stimulation of neutrophils
-
-
-
additional information
?
-
-
the level of insulin receptor tyrosine kinase activity modulates the activities of phosphatidylinositol 3-kinase
-
-
-
additional information
?
-
role for Dp110 in growth control during Drosophila development
-
-
-
additional information
?
-
-
PI 3-kinase activity is a necessary step in the regulation of bone resorption
-
-
-
additional information
?
-
-
enzyme is induced during soybean nodule organogenesis and plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
enzyme is induced during soybean nodule organogenesis and plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
enzyme is induced during soybean nodule organogenesis and plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
-
PI3K plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
PI3K plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
PI3K plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
-
TAPP1 and TAPP2 are direct targets of PI3K signaling
-
-
-
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
?
-
-
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
?
-
-
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
?
-
-
phosphatidylinositol 3-kinase-mediated signaling in the immune system
-
-
-
additional information
?
-
-
IL-10 inhibits apoptosis of promyeloid cells by activating insulin receptor substrate-2 and phosphatidylinositol 3'-kinase
-
-
-
additional information
?
-
-
plays a central part in the mediation of insulin-stimulated glucose disposal
-
-
-
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
?
-
-
myotubularin, a phosphatase deficient in myotubular myopathy, may decrease PI3P levels by down-regulating PI3K activity and by directly degrading PI3P
-
-
-
additional information
?
-
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
?
-
-
enzyme is involved in the signaling pathways regulating cell growth by virtue of its activation in response to various mitogenic stimuli
-
-
-
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 cytokin-stimulated cell migration
-
-
-
additional information
?
-
-
the enzyme interacts with other proteins and substrates via the pleckstrin homology PH domain
-
-
-
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
?
-
-
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
-
-
-
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
-
-
-
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
?
-
-
mTOR inhibition increases eIF4E phosphorylation through a PI3K-dependent and Mnk-mediated mechanism
-
-
-
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
?
-
-
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
?
-
-
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
-
-
-
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 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
?
-
-
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
?
-
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
?
-
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
?
-
-
PI3-kinase activity is not required for starvation-induced Atg14 puncta formation
-
-
-
additional information
?
-
PI3-kinase activity is not required for starvation-induced Atg14 puncta formation
-
-
-
additional information
?
-
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
-
-
-
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
-
-
-
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
?
-
-
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 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
?
-
-
PI-3-kinase might be involved in the induction of erythroid differentiation, possibly engaging a protein kinase C z as downstream effector
-
-
-
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
?
-
may play a role in phosphatidylinositol 3-kinase-mediated signaling in the immune system
-
-
-
additional information
?
-
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
?
-
-
insulin stimulation of fatty acid synthase promoter is mediated by the PI 3-kinase pathway
-
-
-
additional information
?
-
-
enzyme might contribute to the antiproliferative activity of the antitumor ether lipid analogs
-
-
-
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
?
-
-
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
?
-
-
enzyme could be involved in stimulated glucose transport in muscle
-
-
-
additional information
?
-
-
the isozyme gamma stimulates the protein kinases Erk, JNK, and PKB and thus plays a role in cellular signaling, overview
-
-
-
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 shows both lipid and protein kinase activity
-
-
-
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
?
-
-
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
?
-
-
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
?
-
-
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
?
-
-
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
?
-
-
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
?
-
-
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
?
-
-
isoform p110b of the catalytic subunit plays a crucial role in cellular activities evoked acutely by insulin
-
-
-
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
?
-
-
PI 3-K pathways is involved in the short-term activation of pyruvate kinase L by insulin in rat hepatocytes
-
-
-
additional information
?
-
-
insulin signaling in heart involves insulin receptor substrate-1 and insulin receptor substrate-2, activation of phosphatidylinositol 3-kinase
-
-
-
additional information
?
-
-
signaling pathways for phosphoinositolglycan-peptide and insulin to glucose transport and metabolism converge at the level of PI 3-kinase
-
-
-
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
?
-
-
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
?
-
-
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
?
-
-
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 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 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
?
-
-
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
?
-
-
HMG-CoA reductase inhibitor regulates endothelial progenitor function through the phosphatidylinositol 3-kinase/AKT signal transduction pathway
-
-
-
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
?
-
-
activation of PI3K by adenosine leads to induction of hemeoxygenase-1, HO-1, expression in microglia
-
-
-
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
?
-
-
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)
-
-
-
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
?
-
-
HMG-CoA reductase inhibitor regulates endothelial progenitor function through the phosphatidylinositol 3-kinase/AKT signal transduction pathway
-
-
-
additional information
?
-
enzyme is required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae
-
-
-
additional information
?
-
-
enzyme is required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae
-
-
-
additional information
?
-
-
the enzyme is essential for protein sorting
-
-
-
additional information
?
-
-
essential for normal cell growth and vacuole morphology
-
-
-
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
?
-
-
generation of phosphatidyl 3,4,5-triphosphate by phosphatidylinositol 3-kinase is necessary for insulin-induced germinal vesicle breakdown in Xenopus oocytes
-
-
-
additional information
?
-
-
lysophosphatidic acid stimulates glucose transport in Xenopus oocytes via a phosphatidylinositol 3'-kinase
-
-
-
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
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 1-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
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
-
phosphorylation at Ser473, a step in PI3K/Akt signaling
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
phosphatidylinositol-4,5-bisphosphate + ATP
?
-
involved in signalling pathways leading to mitosis and differentiation
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
P42339
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
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
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
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
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
A9QWR8
TcVps34 specifically phosphorylates phosphatidylinositol to produce phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
A9QWR8
TcVps34 specifically phosphorylates phosphatidylinositol to produce phosphatidylinositol 3-phosphate
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
-
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
class I enzyme, preferred substrate in vivo, physiologic regulation and mode of action
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
class I enzyme, preferred substrate in vivo
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
class Ia isozyme
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
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
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
-
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
-
-
-
-
?
ATP + phosphatidylinositol-4-phosphate
ADP + phosphatidylinositol-3,4-bisphosphate
-
-
-
-
?
additional information
?
-
P42339
PI3K binds to the V-ATPase subunit B2 (VHA-B2) in vitro and in vivo
-
-
-
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
?
-
-
PI 3-kinase activity is a necessary step in the regulation of bone resorption
-
-
-
additional information
?
-
-
enzyme plays an important role in the signaling of cell growth
-
-
-
additional information
?
-
-
receptor linked enzyme may generate a second-messenger signal
-
-
-
additional information
?
-
Q94125
regulating longevity and diapause
-
-
-
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
?
-
-
enzyme is involved in formyl peptide-induced stimulation of neutrophils
-
-
-
additional information
?
-
-
the level of insulin receptor tyrosine kinase activity modulates the activities of phosphatidylinositol 3-kinase
-
-
-
additional information
?
-
P91634
role for Dp110 in growth control during Drosophila development
-
-
-
additional information
?
-
-
PI 3-kinase activity is a necessary step in the regulation of bone resorption
-
-
-
additional information
?
-
-
enzyme is induced during soybean nodule organogenesis and plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
P42347
enzyme is induced during soybean nodule organogenesis and plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
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
?
-
-
PI3K plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
P42347
PI3K plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
P42348
PI3K plays a pivotal role in development of the peribacteroid membrane forming a subcellular compartment
-
-
-
additional information
?
-
-
TAPP1 and TAPP2 are direct targets of PI3K signaling
-
-
-
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
?
-
-
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
?
-
-
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
?
-
-
phosphatidylinositol 3-kinase-mediated signaling in the immune system
-
-
-
additional information
?
-
-
IL-10 inhibits apoptosis of promyeloid cells by activating insulin receptor substrate-2 and phosphatidylinositol 3'-kinase
-
-
-
additional information
?
-
-
plays a central part in the mediation of insulin-stimulated glucose disposal
-
-
-
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
?
-
-
myotubularin, a phosphatase deficient in myotubular myopathy, may decrease PI3P levels by down-regulating PI3K activity and by directly degrading PI3P
-
-
-
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
?
-
-
enzyme is involved in the signaling pathways regulating cell growth by virtue of its activation in response to various mitogenic stimuli
-
-
-
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 cytokin-stimulated cell migration
-
-
-
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
?
-
-
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
-
-
-
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
-
-
-
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
?
-
-
mTOR inhibition increases eIF4E phosphorylation through a PI3K-dependent and Mnk-mediated mechanism
-
-
-
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
?
-
-
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
?
-
-
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 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
?
-
-
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
?
-
Q6ZNE5
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
?
-
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
?
-
-
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
?
-
-
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
?
-
-
PI-3-kinase might be involved in the induction of erythroid differentiation, possibly engaging a protein kinase C z as downstream effector
-
-
-
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
?
-
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
?
-
-
insulin stimulation of fatty acid synthase promoter is mediated by the PI 3-kinase pathway
-
-
-
additional information
?
-
-
enzyme might contribute to the antiproliferative activity of the antitumor ether lipid analogs
-
-
-
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
?
-
-
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
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additional information
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enzyme could be involved in stimulated glucose transport in muscle
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additional information
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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
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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
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additional information
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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
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additional information
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lutein inhibits NF-kappaB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-kappaB-inducing kinase pathways
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additional information
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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
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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
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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
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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
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additional information
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isoform p110b of the catalytic subunit plays a crucial role in cellular activities evoked acutely by insulin
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additional information
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PI 3-kinase is the first step of the insulin signaling pathway to be impaired by high-fat feeding
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additional information
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essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes
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additional information
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PI 3-K pathways is involved in the short-term activation of pyruvate kinase L by insulin in rat hepatocytes
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additional information
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insulin signaling in heart involves insulin receptor substrate-1 and insulin receptor substrate-2, activation of phosphatidylinositol 3-kinase
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additional information
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signaling pathways for phosphoinositolglycan-peptide and insulin to glucose transport and metabolism converge at the level of PI 3-kinase
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additional information
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PI 3-kinase activity appears to be an important component of ovariectomy-stimulated bone loss in rats
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additional information
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insulin and dexamethasone regulate phosphatidylinositol 3-kinase in Fao hepatoma cells
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additional information
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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
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additional information
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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
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additional information
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multiple defects of PI 3-kinase activation, involving both the p85a and the p85b adaptor subunits, may contribute to cardiac insulin resistance
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additional information
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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
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additional information
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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
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additional information
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PI3-kinase-dependent activation of diacylglycerol kinase and production of phosphatidic acid in caveolae/rafts in response to norepinephrine but not endothelin-1
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additional information
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HMG-CoA reductase inhibitor regulates endothelial progenitor function through the phosphatidylinositol 3-kinase/AKT signal transduction pathway
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additional information
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nerve growth factor inhibits Na+/H+ exchange and formula absorption through parallel phosphatidylinositol 3-kinase-mTOR and ERK pathways in thick ascending limb
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additional information
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activation of PI3K by adenosine leads to induction of hemeoxygenase-1, HO-1, expression in microglia
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additional information
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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
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nerve growth factor inhibits Na+/H+ exchange and formula absorption through parallel phosphatidylinositol 3-kinase-mTOR and ERK pathways in thick ascending limb
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additional information
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HMG-CoA reductase inhibitor regulates endothelial progenitor function through the phosphatidylinositol 3-kinase/AKT signal transduction pathway
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additional information
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P22543
enzyme is required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae
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additional information
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enzyme is required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae
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additional information
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the enzyme is essential for protein sorting
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additional information
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essential for normal cell growth and vacuole morphology
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additional information
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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
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generation of phosphatidyl 3,4,5-triphosphate by phosphatidylinositol 3-kinase is necessary for insulin-induced germinal vesicle breakdown in Xenopus oocytes
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additional information
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lysophosphatidic acid stimulates glucose transport in Xenopus oocytes via a phosphatidylinositol 3'-kinase
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additional information
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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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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
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
Mn2+
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
Mn2+
-
can partially replace Mg2+ in activation, about 10% of the activity with Mg2+
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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
-
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(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
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1-((3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)methyl)guanidine
i.e. idelalisib
2-morpholin-4-yl-3-phenylchromen-4-one
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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
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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
apocynin
-
specific PI3K inhibitor, restores vasorelaxation and hyperpolarization in response to an ATP-sensitive K+ channel opener levcromakalim
ethanol
-
dose-dependent inhibition of insulin receptor substrate-1-associated PI3K activity in skeletal muscle, but not in adipose tissue, ethanol-induced diabetic rats
GDC-0941
-
enzyme PI3K-inhibition via GDC-0941 and PTEN-reconstitution into PTEN-null follicular thyroid carcinomas FTC-133s. GDC-0941 inhibits radiation-induced activation of Ataxia-telangiectasia mutated (ATM), ATM-and Rad3-related (ATR) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Under anoxia, radiation-induced PI3K-related kinase activation is markedly inhibited by GDC-0941. Inhibition of ATM and DNA-protein kinase catalytic subunits is PI3K-dependent
Gö6976
inhibitor directly targets phosphatidylinositol 3-kinase and confers profound inhibition of autophagic flux by inhibiting the formation of autophagosomes. It does not inhibit the cell survival promoting class I phosphoinositide 3-kinase-Akt signaling at the concentrations required for effective autophagy inhibition
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
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
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
LY303511
-
the inhibitor potently, reversibly blocks voltage-dependent K+ channel currents via a direct mechanism, IC50 is 0.065 mM
peptide N24
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a peptide inhibitor derived from p55PIK phosphatidylinositol 3-kinase, N24, regulatory subunit acts as inhibitor in cancer therapy, it blocks cell proliferation and induces cell cycle arrest in all cancer cell lines tested. Modeling of mechanisms of Rb-dependent and Rb-independent cell cycle arrest by N24 peptide, overview
-
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
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
(+/-)-2-[hydroxy[tetrahydro-2-(octadecyloxy)methylfuran-2-yl]methoxyl]phosphinyloxy-N,N,N-trimethylethaniminium hydroxide
-
-
(+/-)-2-[hydroxy[tetrahydro-2-(octadecyloxy)methylfuran-2-yl]methoxyl]phosphinyloxy-N,N,N-trimethylethaniminium hydroxide
-
-
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
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
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
competes with ATP and binds to Lys residues in the ATP-binding pocket of PI3Ks
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
-
IC50 is 0.0011 mM for the recombinant wild-type enzyme and for the recombinant mutant C838V/I848A
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 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
-
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
-
specific PI3K inhibtor, effects of LY294002 on Kv1.5 channels, wild-type and mutant, are independent of the effects on PI3K activity, overview
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
-
specific PI3K inhibitor, restores vasorelaxation and hyperpolarization in response to an ATP-sensitive K+ channel opener levcromakalim
LY294002
-
-
LY294002
inhibits wild-type activity in vitro almost as efficiently as KU55933, but is required at much higher concentrations for efficient inhibition of autophagy
LY294002
-
preclinical evidence for the in vivo efficacy for LY294002 in the treatment of follicular thyroid cancer
LY294002
-
significantly inhibits retinal neovascularization in a mouse model of retinal neovascularization
LY294002
-
application inhibits rice seed germination and the expression of NADPK oxidase
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
-
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
-
a specific inhibitor of PI3K, effectively suppresses the microglia-derived plasminogen-dependent phosphorylation of Akt
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
-
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
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
phosphatidylcholine
-
strong inhibition of enzyme form PI3KII, weak inhibition of enzyme form PI3KI
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
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
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
-
inhibition of PI 3-kinase I and II; PI 3-kinase I and PI 3-kinase II, non-competitive
Wortmannin
-
inhibition is of a noncompetitive type with regard to ATP, observed with phosphatidylinositol, phosphatidylinositol monophosphate, or phosphatidylinositol bisphosphate as substrate
Wortmannin
-
phosphoinositide 3-kinase with a C2 domain displays reduced sensitivity to the inhibitor wortmannin
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
-
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
-
specific irreversible inhibition, binds covalently to the active site, mixed type inhibition, IC50 is 12 nM
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
-
application inhibits rice seed germination and the expression of NADPK oxidase
Wortmannin
-
specific inhibition, no blockage of whole-cell outward K+ currents
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
additional information
-
LY303511, i.e. 2-(4-Piperazinyl)-8-phenyl-4H-1-benzopyran-4-one, is an inactive analogue of LY294002
-
additional information
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no inhibition by resveratrol, i.e. 3,4',5-trihydroxystilbene, which is an inhibitor of type II phosphatidylinositol 4-kinase
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additional information
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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
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additional information
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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
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additional information
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drug design and synthesis, 17-hydroxywortmannin analogues conjugated to rapamycin analogues via a prodrug linker , inhibitory potency, overview
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additional information
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the PI3K-related kinase proteins share significant sequence homology with PI3K, therefore drugs targeting PI3K may also inhibit PI3K-related kinase, PIKK, activity
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additional information
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downstream lipid products affect the enzyme activity via effectors
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additional information
inhibition of TcVps34 with specific PI3K inhibitors, such as wortmannin and LY294000, result in reduced regulatory volume decrease after hyposmotic stress
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
activated PDGFRbeta
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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
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adenosine
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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
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PAS localization, along with that of the other components of PI3K complex I, requires Atg14
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Atg6
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in the absence of PpAtg6, PpUvrag-GFP as well as PpAtg8 fully mislocalized to the cytosol
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betagamma subunit of heterotrimeric G-proteins
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direct activation, acts synergistically with Ras
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bone morphogenetic protein-2
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activates Akt phopshorylation by PI3K. Cell treatment with BMP-2 exhibits dramatic changes in cell morphology, from a cuboid, epithelial-like shape to a spindle, fibroblastic-like appearance, consistent with epithelial-mesenchymal transition, EMT, overview
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cAMP
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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
IGF-I
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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
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insulin-like growth factor-I
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strongly stimulates insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity about 54fold and total phosphatidylinositol 3-kinase activity abozut 6fold
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low density lipoprotein receptor-related protein 1
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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
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monosodium urate
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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
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morphine
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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
p38 mitogen-activated protein kinase
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activates PI3K, and proteasome inactivation promotes p38 mitogen-activated protein kinase-dependent phosphatidylinositol 3-kinase activation in retinal piment epithelial cells
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phosphatidic acid
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enhances activity more markedly for PI 3-kinase II than for PI 3-kinase I
Phosphotyrosine peptides
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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
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Ron kinase
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Ron plays an essential role in maintaining malignant phenotypes of colon cancer cells through regulating mutant PI3K activity
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Syk
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protein kinase Syk associates with clathrin and mediates phosphatidylinositol 3-kinase activation during human rhinovirus internalization in leukocytes
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Vps38
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the endosomal localization of Atg6 and the other components of PI3K complex II requires Vps38
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leptin
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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%
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leptin
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increases the activity by 183% in liver at 90 ng/ml, livers and enzymes of rats with diet-induced obesity are resistant to leptin
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pioglitazone
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a thiazolidinedione, activates PI3K 2-2.5fold at 0.002-0.010 mM, activates adiponectin secretion from adipocytes in vivo
pioglitazone
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a thiazolidinedione, activates PI3K 2-2.5fold at 0.002-0.010 mM, activates adiponectin secretion from adipocytes in vivo
additional information
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insulin and IGF-I treatment increases phosphatidylinositol 3-kinase activity 4.5fold in aPY20 immunoprecipitation from whole cell lysates
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additional information
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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
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additional information
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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
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additional information
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both anti-IgM and anti-IgD stimulation results in an increase in the anti-phosphotyrosine-precipitable PI3K activity
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additional information
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EGF stimulates phosphatidylinositol 3-kinase in human airway smooth muscle cells
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additional information
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insulin differentially stimulates phosphatidylinositol 3-kinase activity
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additional information
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
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additional information
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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
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additional information
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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
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additional information
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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
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additional information
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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
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additional information
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binding to the platelet-derived growth factor receptor transiently activates the p85a-p110a phosphoinositide 3-kinase complex in vivo
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additional information
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Fyn may be directly involved in the activation of the downstream signaling enzyme, PI3-kinase, in IL-2-stimulated T cells
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additional information
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PI3-kinase is activated by insulin and IGF-I in a rapid and transient manner in incubated soleus muscles
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additional information
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thrombopoietin induces phosphoinositol 3-kinase activation through SHP2, Gab, and insulin receptor substrate proteins in BAF3 cells and primary murine megakaryocytes
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additional information
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enzyme induction in cell culture by platelet-derived growth factor PGDF and starvation via the G-protein-coupled fMLP receptor
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additional information
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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
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additional information
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epidermal growth factor induces activation of phosphatidylinositol 3-kinase in rat hepatocyte primary culture
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additional information
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stimulation of beta1-adrenergic receptor increases the enzyme activity in cardiomyocyte via the PKA-dependent mechanism involving Gbetagamma
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
1,2-dioctanoylphosphatidylinositol 4,5-diphosphate
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pH 7.4, recombinant enzyme
0.004 - 15
phosphatidylinositol 4,5-bisphosphate