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Information on EC 2.7.1.137 - phosphatidylinositol 3-kinase and Organism(s) Rattus norvegicus and UniProt Accession O70173
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2.7.1.137 phosphatidylinositol 3-kinaseIUBMB Comments
One mammalian isoform is known.
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Word Map
- 2.7.1.137
- wortmannin
- mapks
- mtor
- rapamycin
- erk
- endothelial
- pten
-
signal-regulated
- pkc
- metastasis
- bcl-2
- sirna
- caspase-3
- agonist
- glycogen
- leukemia
- actin
- pik3ca
- phospholipase
-
insulin-like
-
mitogen
- cyclins
- integrins
- tumorigenesis
- irs-1
-
tensin
- tnf
-
neuroprotective
- c-jun
- pi3-kinase
-
dominant-negative
- adipocytes
- nf-kappab
-
anti-apoptotic
-
insulin-stimulated
- gtpases
-
insulin-induced
- akt1
-
transwell
-
platelet-derived
- rac1
- kinase-3
- igf-i
- sh2
- substrate-1
-
pleckstrin
- grb2
-
egf-induced
-
everolimus
-
tyrosine-phosphorylated
- drug development
- medicine
- pharmacology
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
pi3k, phosphatidylinositol 3-kinase, pi3 kinase, vps34, phosphoinositide-3-kinase, phosphatidylinositol 3 kinase, ptdins 3-kinase, pik3c3, phosphatidylinositide 3-kinase, hvps34, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
kinase (phosphorylating), phosphatidylinositol 3-
-
-
-
-
kinase, phosphatidylinositol 3- (phosphorylating)
-
-
-
-
p85/p110 phosphoinositide 3-kinase
-
-
-
-
phosphatidylinositol 3'-kinase
-
-
-
-
phosphatidylinositol 3-kinase
phosphoinositide 3'-kinase
-
-
-
-
phosphoinositide 3-kinase
-
-
-
-
PI 3-kinase
PI3K
PtdIns 3'-kinase
-
-
-
-
phosphatidylinositol 3-kinase
-
-
-
-
PI 3-kinase
-
-
-
-
PI3K
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase
One mammalian isoform is known.
CAS REGISTRY NUMBER
COMMENTARY
115926-52-8
-
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-phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
-
-
-
?
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
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
substrate from bovine liver
-
-
?
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 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
-
-
?
ATP + phosphatidylinositol 4,5-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
-
-
-
?
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)
-
-
?
NATURAL SUBSTRATE
NATURAL 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-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
-
-
-
?
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
-
-
-
-
?
phosphatidylinositol-4,5-bisphosphate + ATP
?
-
involved in signalling pathways leading to mitosis and differentiation
-
-
?
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
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mn2+
-
can partially replace Mg2+ in activation, about 10% of the activity with Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ethanol
-
dose-dependent inhibition of insulin receptor substrate-1-associated PI3K activity in skeletal muscle, but not in adipose tissue, ethanol-induced diabetic rats
LY303511
-
the inhibitor potently, reversibly blocks voltage-dependent K+ channel currents via a direct mechanism, IC50 is 0.065 mM
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
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
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
adenosine
-
adenosine activates PI3K and induces Akt phosphorylation leading to induction of hemeoxygenase-1, HO-1, expression in microglia. Adenosine acts as an endogenous regulator of brain inflammation via modulation of microglial reactive oxygen species production, mechanism, overview
cAMP
-
PI 3-kinase is activated in response to cAMP or IGF-I, the PI 3-kinase activity bound to its p85 regulatory subunit increases by 1.7fold. cAMP-dependent PI 3-kinase activation plays an important role in the increase in cyclin D1 translation. In contrast, IGF-I-dependent PI 3-kinase activation is required for the increase in cyclin D1 mRNA levels and degradation of p27Kip1
IGF-I
-
PI 3-kinase is activated in response to cAMP or IGF-I. cAMP-dependent PI 3-kinase activation plays an important role in the increase in cyclin D1 translation. In contrast, IGF-I-dependent PI 3-kinase activation is required for the increase in cyclin D1 mRNA levels and degradation of p27Kip1
-
Phosphotyrosine peptides
-
high-affinity activation of the enzyme requires the simultaneous binding of two phosphorylated YMXM motifs on insulin receptor substrate 1 to the two SH2 domains of the phosphatidylinositol 3'-kinase
-
leptin
-
1-5 nmol/L stimulates insulin receptor substrate-2 by 280-954% and its associated phosphatidylinositol-3 kinase activity 122-621%. 0.5-25 nmol/L inhibits IRS-1 pY and its associated phosphatidylinositol-3 kinase activity by 20-89%
-
leptin
-
increases the activity by 183% in liver at 90 ng/ml, livers and enzymes of rats with diet-induced obesity are resistant to leptin
-
additional information
-
in cells loaded with protein-tyrosine phosphatase antibody, phosphatidylinositol 3'-kinase activity is increased by 38%, respectively, compared with control cells loaded with preimmune IgG
-
additional information
-
epidermal growth factor induces activation of phosphatidylinositol 3-kinase in rat hepatocyte primary culture
-
additional information
-
stimulation of beta1-adrenergic receptor increases the enzyme activity in cardiomyocyte via the PKA-dependent mechanism involving Gbetagamma
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.03
ATP
-
with phosphatidylinositol 4-phosphate or phosphatidylinositol 4,5-bisphosphate as cosubstrate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.009
LY294002
Rattus norvegicus
-
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
0.065
LY303511
Rattus norvegicus
-
the inhibitor potently, reversibly blocks voltage-dependent K+ channel currents via a direct mechanism, IC50 is 0.065 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 9
-
pH 6.5: about 80% of maximal activity, pH 9.0: about 40% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
expression increases during liver regeneration after partial hepatectomy with maximal expression after the growth period, PI3K-IIgamma may function mainly in highly differentiated hepatic cells
-
shell and core. Cocaine sensitization decreases PI3K activity in nuclear accumbens core. The changes are not normalized following the reversal of cocaine-sensitization. Cocaine-sensitized animals exhibited increased PI3K activity in the nuclear accumbens shell, and this increase is reversed by combined pergolide/ondansetron treatment. Selective enhancement of the PI3K activity in the NAc shell may be one of key alterations underlying the long-term cocaine sensitization
-
inhibition of PI3-kinase induces apoptotic cell death, which is mediated by inactivation of Akt pathway in rat osteoblasts
-
cocaine sensitization increases PI3K activity. The changes are not normalized following the reversal of cocaine-sensitization
-
during differentiation of 3T3-L1 cells into adipocytes, isoform p110b is up-regulated approximately 10-fold, expression of p110a is unaltered
-
activation of the prosurvival phosphatidylinositol 3-kinase-Akt pathway is involved in the protective action of poly(ADP-ribose) polymerase 1 inhibition in a model of donor heart procurement and hypothermic storage
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
the enzyme translocates onto liver endoplasmic reticulum
-
insulin-triggered mechanism of translocation of PI3K onto microsomes occurs in the liver of rats during refeeding
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
physiological function
metabolism
-
phosphatidylinositol 3-kinase is closely associated with TGFbeta3 production/secretion in astrocytes. Microglia-derived plasminogen or plasmin facilitates the production/secretion of TGFbeta3 in astrocytes through both PAR-1 and the subsequent signaling cascade including PI3K and Akt
metabolism
-
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
-
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
-
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
-
PI 3-kinase activated in response to cAMP or IGF-I stimulus plays important roles in increasing the translation rate or mRNA levels of cyclin D1, respectively. Activation of PI 3-kinase in response to cAMP or IGF-I are essential for marked increases in G1 CDK activities and DNA synthesis. cAMP-dependent PI 3-kinase activation plays an important role in the increase in cyclin D1 translation. In contrast, IGF-I-dependent PI 3-kinase activation is required for the increase in cyclin D1 mRNA levels and degradation of p27Kip1
physiological function
-
PI-3-K and the PI-3-K signaling pathway, besides the MAPK signaling pathway, are involved in the signaling mechanism underlying the neuroprotection of brain-derived neurotrophic factor against hypoxic insult, molecular mechanisms, overview. ERK but not PI-3-K pathway induce CREB phosphorylation
physiological function
-
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
-
insulin-like growth factor-I stimulation leads to prolonged association of phosphatidylinositol 3-kinase with insulin-like growth factor-I receptor. Phosphatidylinositol 3-kinase activity is present in this complex in thyrocytes and fibroblasts. Insulin-like growth factor-I withdrawal in mid-G1 phase impairs the association of phosphatidylinositol 3-kinase with insulin-like growth factor-I receptor and suppresses DNA synthesis the same as when phosphatidylinositol 3-kinase inhibitor is added. Residues Tyr1316-X-X-Met of insulin-like growth factor-I receptor function as a phosphatidylinositol 3-kinase binding sequence when this tyrosine is phosphorylated. In cells expressing exogenous mutant insulin-like growth factor-I receptor in which Tyr1316 is substituted with Phe, insulin-like growth factor-I stimulation induces tyrosine phosphorylation of insulin-like growth factor-I receptor and insulin receptor substrates-1/2, but mutated insulin-like growth factor-IR fails to bind phosphatidylinositol 3-kinase and to induce maximal phosphorylation of GSK3 and cell proliferation in response to insulin-like growth factor-I. Phosphatidylinositol 3-kinase activity bound to insulin-like growth factor-I receptor, which is continuously sustained by insulin-like growth factor-I stimulation, is required for insulin-like growth factor-I-induced cell proliferation
physiological function
-
intracerebroventricular injection of leptin significantly increases phosphodiesterase 3B activity by twofold in the hypothalamus. Previous administration of wortmannin, a specific PI3K inhibitor, completely reverses the stimulatory effect of leptin on phosphodiesterase 3B activity in the hypothalamus. PI3K but not Akt acts as an upstream regulator of the PDE3B pathway of leptin signalling in the rat hypothalamus
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). P3C2G_RAT
1505
0
170975
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
heterodimer
-
a p110alpha/beta-subunit binds to a p85 regulatory subunit, and this heterodimer is recruited to the membrane through the association with phosphotyrosyl proteins, leading to production of phosphatidylinositol 3,4,5-triphosphate, PIP3, followed by activation of downstream signal pathway(s)
additional information
-
isoforms of the p110 catalytic subunit: p110a or p110b
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
-
p85 subunit is rapidly phosphorylated in response to insulin
phosphoprotein
-
PI3-K is activated by phosphorylation through serine/threonine protein kinases
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Herbst, J.J.; Andrews, G.; Contillo, L.; Lamphere, L.; Gardner, J.; Lienhard, G.E.; Gibbs, E.M.
Potent activation of phosphatidylinositol 3-kinase by simple phosphotyrosine peptides derived from insulin receptor substrate 1 containing two YMXM motifs for binding SH2 domains
Biochemistry
33
9376-9381
1994
Rattus norvegicus
Carpenter, C.L.; Duckworth, B.C.; Auger, K.R.; Cohen, B.; Schaffhausen, B.S.; Cantley, L.C.
Purification and characterization of phosphoinositide 3-kinase from rat liver
J. Biol. Chem.
265
19704-19711
1990
Rattus norvegicus
Baxter, R.M.; Bramham, J.; Thomason, P.A.; Downes, C.P.; Carter, A.N.
Characterisation of phosphatidylinositol 3-kinase in PC12 cell extracts and isolation of the enzyme from rat brain extracts
Biochem. Soc. Trans.
21
359S
1993
Rattus norvegicus
Ahmad, F.; Li, P.M.; Meyerovitch, J.; Goldstein, B.J.
Osmotic loading of neutralizing antibodies demonstrates a role of protein-tyrosine phosphatase 1B in negative regulation of the insulin action pathway
J. Biol. Chem.
270
20503-20508
1995
Rattus norvegicus
Anderwald, C.; Muller, G.; Koca, G.; Furnsinn, C.; Waldhausl, W.; Roden, M.
Short-term leptin-dependent inhibition of hepatic gluconeogenesis is mediated by insulin receptor substrate-2
Mol. Endocrinol.
16
1612-1628
2002
Rattus norvegicus
Asano, T.; Kanda, A.; Katagiri, H.; Nawano, M.; Ogihara, T.; Inukai, K.; Anai, M.; Fukushima, Y.; Yazaki, Y.; Kikuchi, M.; Hooshmand-Rad, R.; Heldin, C.H.; Oka, Y.; Funaki, M.
p110b is up-regulated during differentiation of 3T3-L1 cells and contributes to the highly insulin-responsive glucose transport activity
J. Biol. Chem.
275
17671-17676
2000
Rattus norvegicus
Bezerra, R.M.N.; Ueno, M.; Silva, M.S.; Tavares, D.Q.; Carvalho, C.R.O.; Saad, M.J.A.
A high fructose diet affects the early steps of insulin action in muscle and liver of rats
J. Nutr.
130
1531-1535
2000
Rattus norvegicus
Blondeau, F.; Laporte, J.; Bodin, S.; Superti-Furga, G.; Payrastre, B.; Mandel, J.L.
Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway
Hum. Mol. Genet.
9
2223-2229
2000
Homo sapiens, Rattus norvegicus
Carrillo, J.J.; Ibares, B.; Esteban-Gamboa, A.; Feliu, J.E.
Involvement of both phosphatidylinositol 3-kinase and p44/p42 mitogen-activated protein kinase pathways in the short-term regulation of pyruvate kinase L by insulin
Endocrinology
142
1057-1064
2001
Rattus norvegicus
Daniele, N.; Rajas, F.; Payrastre, B.; Mauco, G.; Zitoun, C.; Mithieux, G.
Phosphatidylinositol 3-kinase translocates onto liver endoplasmic reticulum and may account for the inhibition of glucose-6-phosphatase during refeeding
J. Biol. Chem.
274
3597-3601
1999
Rattus norvegicus
Fujioka, T.; Ui, M.
Involvement of insulin receptor substrates in epidermal growth factor induced activation of phosphatidylinositol 3-kinase in rat hepatocyte primary culture
Eur. J. Biochem.
268
25-34
2001
Rattus norvegicus
Kessler, A.; Uphues, I.; Ouwens, D.M.; Till, M.; Eckel, J.
Diversification of cardiac insulin signaling involves the p85a/b subunits of phosphatidylinositol 3-kinase
Am. J. Physiol.
280
E65-E74
2001
Rattus norvegicus
Marandi, S.; De Keyser, N.; Saliez, A.; Maernoudt, A.S.; Sokal, E.M.; Stilmant, C.; Rider, M.H.; Buts, J.P.
Insulin signal transduction in rat small intestine: role of MAP kinases in expression of mucosal hydrolases
Am. J. Physiol.
280
G229-G240
2001
Rattus norvegicus
Muller, G.; Wied, S.; Piossek, C.; Bauer, A.; Bauer, J.; Frick, W.
Convergence and divergence of the signaling pathways for insulin and phosphoinositolglycans
Mol. Med.
4
299-323
1998
Rattus norvegicus
Ogihara, T.; Asano, T.; Ando, K.; Chiba, Y.; Sekine, N.; Sakoda, H.; Anai, M.; Onishi, Y.; Fujishiro, M.; Ono, H.; Shojima, N.; Inukai, K.; Fukushima, Y.; Kikuchi, M.; Fujita, T.
Insulin resistance with enhanced insulin signaling in high-salt diet-fed rats
Diabetes
50
573-583
2001
Rattus norvegicus
Okada, T.; Kawano, Y.; Sakakibara, T.; Hazeki, O.; Ui, M.
Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin
J. Biol. Chem.
269
3568-3573
1994
Rattus norvegicus
Saad, M.J.A.; Folli, F.; Kahn, C.R.
Insulin and dexamethasone regulate insulin receptors, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in Fao hepatoma cells
Endocrinology
136
1579-1588
1995
Rattus norvegicus
Sato, M.; Bryant, H.U.; Dodge, J.A.; Davis, H.; Matter, W.F.; Vlahos, C.J.
Effects of wortmannin analogs on bone in vitro and in vivo
J. Pharmacol. Exp. Ther.
277
543-550
1996
Bos taurus, Gallus gallus, Rattus norvegicus
Tremblay, F.; Lavigne, C.; Jacques, H.; Marette, A.
Defective insulin-induced GLUT4 translocation in skeletal muscle of high fat-fed rats is associated with alterations in both Akt/protein kinase B and atypical protein kinase C (z/l) activities
Diabetes
50
1901-1910
2001
Rattus norvegicus
Velloso, L.A.; Carvalho, C.R.O.; Rojas, F.A.; Folli, F.; Saad, M.J.A.
Insulin signaling in heart involves insulin receptor substrates-1 and -2, activation of phosphatidylinositol 3-kinase and the JAK 2-growth related pathway
Cardiovasc. Res.
40
96-102
1998
Rattus norvegicus
Ono, F.; Nakagawa, T.; Saito, S.; Owada, Y.; Sakagami, H.; Goto, K.; Suzuki, M.; Matsuno, S.; Kondo, H.
A novel class II phosphoinositide 3-kinase predominantly expressed in the liver and its enhanced expression during liver regeneration
J. Biol. Chem.
273
7731-7736
1998
Rattus norvegicus (O70173)
Leblais, V.; Jo, S.H.; Chakir, K.; Maltsev, V.; Zheng, M.; Crow, M.T.; Wang, W.; Lakatta, E.G.; Xiao, R.P.
Phosphatidylinositol 3-kinase offsets cAMP-mediated positive inotropic effect via inhibiting Ca2+ influx in cardiomyocytes
Circ. Res.
95
1183-1190
2004
Rattus norvegicus
El-Kholy, W.; Macdonald, P.E.; Lin, J.H.; Wang, J.; Fox, J.M.; Light, P.E.; Wang, Q.; Tsushima, R.G.; Wheeler, M.B.
The phosphatidylinositol 3-kinase inhibitor LY294002 potently blocks K(V) currents via a direct mechanism
FASEB J.
17
720-722
2003
Mus musculus, Rattus norvegicus
Huang, W.; Dedousis, N.; Bhatt, B.A.; O'Doherty, R.M.
Impaired activation of phosphatidylinositol 3-kinase by leptin is a novel mechanism of hepatic leptin resistance in diet-induced obesity
J. Biol. Chem.
279
21695-21700
2004
Rattus norvegicus
Clarke, C.J.; Ohanian, V.; Ohanian, J.
Norepinephrine and endothelin activate diacylglycerol kinases in caveolae/rafts of rat mesenteric arteries: agonist-specific role of PI3-kinase
Am. J. Physiol. Heart Circ. Physiol.
292
H2248-H2256
2007
Rattus norvegicus
Zhang, X.; Mi, J.; Wetsel, W.C.; Davidson, C.; Xiong, X.; Chen, Q.; Ellinwood, E.H.; Lee, T.H.
PI3 kinase is involved in cocaine behavioral sensitization and its reversal with brain area specificity
Biochem. Biophys. Res. Commun.
340
1144-1150
2006
Homo sapiens, Rattus norvegicus
Zhang, Y.; Zhang, L.; Yan, M.; Zheng, X.
Inhibition of phosphatidylinositol 3-kinase causes cell death in rat osteoblasts through inactivation of Akt
Biomed. Pharmacother.
61
277-284
2007
Rattus norvegicus
Wu, Z.L.; OKane, T.M.; Connors, T.J.; Marino, M.J.; Schaffhauser, H.
The phosphatidylinositol 3-kinase inhibitor LY 294002 inhibits GlyT1-mediated glycine uptake
Brain Res.
1227
42-51
2008
Rattus norvegicus
Good, D.W.; George, T.; Watts, B.A.
Nerve growth factor inhibits Na+/H+ exchange and formula absorption through parallel phosphatidylinositol 3-kinase-mTOR and ERK pathways in thick ascending limb
J. Biol. Chem.
283
26602-26611
2008
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Gao, L.; Kwan, J.C.; Macdonald, P.S.; Yang, L.; Preiss, T.; Hicks, M.
Improved poststorage cardiac function by poly (ADP-ribose) polymerase inhibition: role of phosphatidylinositol 3-kinase Akt pathway
Transplantation
84
380-386
2007
Rattus norvegicus
Li, X.; Xu, B.
HMG-CoA reductase inhibitor regulates endothelial progenitor function through the phosphatidylinositol 3-kinase/AKT signal transduction pathway
Appl. Biochem. Biotechnol.
157
545-553
2008
Rattus norvegicus, Rattus norvegicus Wistar
Zhao, L.N.; Hao, L.P.; Yang, X.F.; Ying, C.J.; Yu, D.; Sun, X.F.
The diabetogenic effects of excessive ethanol: reducing beta-cell mass, decreasing phosphatidylinositol 3-kinase activity and GLUT-4 expression in rats
Br. J. Nutr.
101
1467-1473
2009
Rattus norvegicus
Maeda, S.; Nakajima, K.; Tohyama, Y.; Kohsaka, S.
Characteristic response of astrocytes to plasminogen/plasmin to upregulate transforming growth factor beta 3 (TGFbeta3) production/secretion through proteinase-activated receptor-1 (PAR-1) and the downstream phosphatidylinositol 3-kinase (PI3K)-Akt/PKB si
Brain Res.
1305
1-13
2009
Rattus norvegicus
Fukushima, T.; Nedachi, T.; Akizawa, H.; Akahori, M.; Hakuno, F.; Takahashi, S.
Distinct modes of activation of phosphatidylinositol 3-kinase in response to cyclic adenosine 3',5'-monophosphate or insulin-like growth factor I play different roles in regulation of cyclin D1 and p27Kip1 in FRTL-5 cells
Endocrinology
149
3729-3742
2008
Rattus norvegicus
Min, K.J.; Kim, J.H.; Jou, I.; Joe, E.H.
Adenosine induces hemeoxygenase-1 expression in microglia through the activation of phosphatidylinositol 3-kinase and nuclear factor E2-related factor 2
Glia
56
1028-1037
2008
Rattus norvegicus
Sun, X.; Zhou, H.; Luo, X.; Li, S.; Yu, D.; Hua, J.; Mu, D.; Mao, M.
Neuroprotection of brain-derived neurotrophic factor against hypoxic injury in vitro requires activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase
Int. J. Dev. Neurosci.
26
363-370
2008
Rattus norvegicus
Hai, J.; Lin, Q.; Lu, Y.
Phosphatidylinositol 3-kinase activity is required for the induction of differentiation in C6 glioma cells by panaxydol
J. Clin. Neurosci.
16
444-448
2009
Rattus norvegicus
Pezet, S.; Marchand, F.; DMello, R.; Grist, J.; Clark, A.K.; Malcangio, M.; Dickenson, A.H.; Williams, R.J.; McMahon, S.B.
Phosphatidylinositol 3-kinase is a key mediator of central sensitization in painful inflammatory conditions
J. Neurosci.
28
4261-4270
2008
Rattus norvegicus
Chae, C.H.; Kim, H.T.
Forced, moderate-intensity treadmill exercise suppresses apoptosis by increasing the level of NGF and stimulating phosphatidylinositol 3-kinase signaling in the hippocampus of induced aging rats
Neurochem. Int.
55
208-213
2009
Rattus norvegicus
Fukushima, T.; Nakamura, Y.; Yamanaka, D.; Shibano, T.; Chida, K.; Minami, S.; Asano, T.; Hakuno, F.; Takahashi, S.
Phosphatidylinositol 3-kinase (PI3K) activity bound to insulin-like growth factor-I (IGF-I) receptor, which is continuously sustained by IGF-I stimulation, is required for IGF-I-induced cell proliferation
J. Biol. Chem.
287
29713-29721
2012
Rattus norvegicus
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