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Phosphatidylinositol 3-KinasesPhosphatesPhosphatidylinositol PhosphatesPhosphatidylinositol 4,5-Diphosphate1-Phosphatidylinositol 4-KinasePhosphatidylinositolsPhosphorylationEnzyme ActivationPhosphotransferases (Alcohol Group Acceptor)SerineProtein-Serine-Threonine KinasesProto-Oncogene Proteins c-aktAndrostadienesChromonesTyrosinePhosphoproteinsSignal TransductionMolecular Sequence DataCell LinePhosphatidylinositol 3-KinaseAmino Acid SequenceMorpholinesEnzyme InhibitorsProtein KinasesKineticsCells, CulturedProtein-Tyrosine KinasesInositol PhosphatesProtein BindingSugar PhosphatesProtein Kinase CProto-Oncogene ProteinsPhosphoserinePhosphotransferasesPhosphoric Monoester HydrolasesThreonineOxidative PhosphorylationGlucose-6-PhosphateCalcium PhosphatesType C PhospholipasesMutationTransfectionPhosphotyrosineGlyceraldehyde-3-Phosphate DehydrogenasesMitogen-Activated Protein KinasesCalciumBlotting, WesternBinding SitesCell MembraneInositolCyclic AMP-Dependent Protein KinasesRecombinant ProteinsPhosphopeptidesProtein Structure, TertiaryIsoenzymesAdenosine TriphosphateIntracellular Signaling Peptides and ProteinsSubstrate SpecificityInsulin Receptor Substrate ProteinsPrecipitin TestsCarrier Proteinssrc-Family KinasesCDP-Diacylglycerol-Inositol 3-PhosphatidyltransferaseCOS CellsMitogen-Activated Protein Kinase 1Recombinant Fusion ProteinsModels, BiologicalInsulinPhospholipidsPhosphatidylinositol Diacylglycerol-LyaseCell Line, TumorPhosphorus RadioisotopesMAP Kinase Signaling SystemTime FactorsGlycogen Synthase Kinase 3ImmunoblottingMembrane ProteinsCalcium-Calmodulin-Dependent Protein Kinases3T3 CellsMitogen-Activated Protein Kinase 3Adaptor Proteins, Signal TransducingPhosphothreonineApoptosisProtein TransportProtein Processing, Post-TranslationalPeptide MappingExtracellular Signal-Regulated MAP KinasesMutagenesis, Site-DirectedProteinsDose-Response Relationship, DrugRibosomal Protein S6 KinasesElectrophoresis, Polyacrylamide GelTumor Cells, CulturedBase SequencePhosphoprotein PhosphatasesCasein Kinase IIGlucoseHeLa CellsCattleLysophospholipids
PI3KActivation of phosphatidylinositol-3-kinaSignal TransductionKinase-mediated phosphorylationDerivatives of phosphatidylinositolBiosynthesisPhosphorylate phosphatidylinositolTyrosine phosphorylationRegulatesGlucose-6-phosphaHydroxylPhosphoinositideNeuronalPtdInsLipidPathwaysEnzymeInositol-1,4,5-trisphosphateCatalyticKinasesEnzymesSubstancesPhospholipasePIP2EukaryoticCalciumPathwayInhibitsMembraneRolesTypeSecretionMetabolismHomologyPhoxGenesProteinsSpecificityMotifsGeneticReactionsRegulationEnablesActivityAdditionallyFunctionInhibitorPlays an important role
PI3K9
  • To address the possibility that activation of phosphatidylinositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR/FRAP), represents one of these pathways, we have examined the effect of simultaneous inhibition of the Ras-MAPK and PI3K-mTOR pathways on transformation of CEF by v-Src. (embl.de)
  • Similarly, inhibition of the PI3K-mTOR pathway by addition of the PI3K inhibitor 2-[4-morpholinyl]-8-phenyl-4H-1-benzopyran-4-one (LY294002) or the mTOR inhibitor rapamycin, although reducing several parameters of transformation, also failed to block transformation. (embl.de)
  • Lack of PTEN catalytic function results in de-repression from the phosphatidylinositol 3-kinase (PI3K)/AKT pathway and excitement of cell development and success pathways21,22. (health-ground.com)
  • Insulin-induced phosphatidylinositol 3-kinase (PI3K)/Akt signaling and interleukin-6 (IL-6)-instigated JAK/STAT3-signaling pathways in the liver inhibit the expression of gluconeogenic genes to decrease hepatic glucose output. (diabetesjournals.org)
  • The reduced hepatic glucose output coincided with decreased expression of the gluconeogenic genes G6pc and Pck1 and enhanced hepatic STAT3 phosphorylation and PI3K/Akt signaling in the fasted state. (diabetesjournals.org)
  • Insulin-induced IR-β-subunit Y1162/Y1163 phosphorylation and PI3K/Akt signaling and IL-6-induced STAT3 phosphorylation were also enhanced in isolated Ptpn2 +/− hepatocytes. (diabetesjournals.org)
  • a phosphatidylinositol 3-kinase (PI3K) to phosphorylate phosphatidylinositol 4,5-bisphosphate and produce phosphatidylinositol 3,4,5-trisphosphate, a major growth signal for activation of Akt kinase. (molcells.org)
  • Induction of canonical autophagy is mainly controlled by the AKT/mTOR and AMPK signaling pathways and relies on the activation and assembly of two macromolecular complexes, the ATG1/ULK1 and the Class III phosphatidylinositol 3-kinase (PI3K) complex (Figure 1 ) [ 5 ]. (hindawi.com)
  • It has previously been demonstrated that phosphatidylinositol‑3‑kinase (PI3K)/Akt and cleaved caspase‑3 serve critical roles in the apoptosis of cardiac myocytes following ischemia/reperfusion injury. (spandidos-publications.com)
Activation of phosphatidylinositol-3-kina1
Signal Transduction2
Kinase-mediated phosphorylation2
  • The results indicate that lipid kinase-mediated phosphorylation is an important basis for ATP use in the exocytotic pathway. (nih.gov)
  • The improved ICL level of sensitivity of PTEN-deficient cells can be caused, partly, by raised PLK1 kinase-mediated phosphorylation of FANCM, constitutive FANCM degradation and polyubiquitination, as well as the consequent inefficient set up from the FA primary complicated, FANCD2, and FANCI into DNA restoration foci. (health-ground.com)
Derivatives of phosphatidylinositol2
  • The recruitment of specific cytosolic proteins to intracellular membranes through binding phosphorylated derivatives of phosphatidylinositol (PtdIns) controls such processes as endocytosis, regulated exocytosis, cytoskeletal organization, and cell signaling. (embl.de)
  • Phosphorylated derivatives of phosphatidylinositol (PtdIns) regulate cytoskeletal functions, membrane trafficking, and receptor signaling by recruiting protein complexes to cell- and endosomal-membranes. (utsouthwestern.edu)
Biosynthesis3
  • Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. (molcells.org)
  • Biosynthesis of IP metabolites begins with the synthesis of inositol 1,4,5-trisphosphate (InsP 3 , IP3), which is produced by phospholipid-specific phospholipase C (PLC). (molcells.org)
  • After the degradation of damaged proteins and lipids, amino acids and fatty acids are released into the cytoplasm and recycled for new biosynthesis of cellular components or energy production [ 4 ]. (hindawi.com)
Phosphorylate phosphatidylinositol1
  • The long term goal of the proposed research is to purify the enzymes which phosphorylate phosphatidylinositol (PI) and characterize their structure, mechanism of action and regulation. (grantome.com)
Tyrosine phosphorylation1
Regulates2
  • The inositol-1,4,5-trisphosphate (IP3) which regulates free Ca2+ levels in the cytoplasm is derived from hydrolysis of phosphotidylinositol-4,5-bisphosphate (PIP2). (grantome.com)
  • Ypk1, in turn, regulates (via its phosphorylation of multiple substrates) maintenance of sphingolipid and glycerolipid homeostasis and bilayer lipid organization in the plasma membrane. (berkeley.edu)
Glucose-6-phospha1
  • The phosphopentose pathway (PPP), which converts glucose-6-phosphate to ribose-5-phosphate for synthesis of nucleotides and NADPH to reduce DNA damage caused by ROS was reported to be activated in DDR 2 . (nature.com)
Hydroxyl3
  • PI4KA is a kinase, which phosphorylates a hydroxyl group of phosphatidylinositol in its inositol-ring at position four. (wikipedia.org)
  • Phosphatidylinositol (PI) is a substance that inositol is bound as a phosphate ester to a remaining hydroxyl group of diacylglycerol. (justia.com)
  • Hydroxyl groups in the inositol moiety of PI may further be phosphorylated, and inositol phospholipids in which 3-position, 4-position or 5-position or two or more of these positions is/are phosphorylated are also known. (justia.com)
Phosphoinositide3
  • The roles of PEP3/PtdInsTP and PEP1/PtdInsP5K in sequential phosphoinositide recruitment and phosphorylation explains their synergistic activity in ATP-dependent priming. (nih.gov)
  • The cellular phosphoinositide signaling system, a complicated network of enzymes and phospholipid messengers, is a crucial regulator for many cellular processes [ 4 ]. (biomedcentral.com)
  • Srivastava R., Ratheesh A., Rajiv K. Gude, R.K., Rao K.V.K ., Panda D and Subrahmanyam G . (2005) Resveratrol inhibits type II phosphatidylinositol 4-kinase: A key component in pathways of phosphoinositide turn over Biochemical Pharmacology, 70, 1048-1055 . (iitb.ac.in)
Neuronal2
  • Type II PtdIns 4-kinases have also been shown to play a role in microbial pathogenicity and neuronal signaling. (iitb.ac.in)
  • Distribution and neuronal expression of phosphatidylinositol phosphate kinase IIgamma in the mouse brain. (neurotree.org)
PtdIns10
  • Moreover, inhibition of Ca(2+)-activated secretion by PtdIns(4,5)P2-specific antibodies and phospholipase C implies that 5-phosphorylated inositides play a novel, necessary role in the regulated secretory pathway. (nih.gov)
  • Protein modules such as FVYE domains and PH domains that bind specifically to PtdIns 3-phosphate (PtdIns-3-P) and polyphosphoinositides, respectively, can direct such membrane targeting. (embl.de)
  • The PX domain of Vam7p selectively binds PtdIns-3-P, while the PX domain of the CPK PI-3 kinase selectively binds PtdIns-4,5-P(2). (embl.de)
  • Taken together, these findings provide strong evidence that the generation of PtdIns(4)P is sufficient to trigger forward transport from the Golgi to the plasma membrane and that Sac1p is critically required for the termination of this signal. (embl.de)
  • Our studies have shown that a type II PtdIns 4-kinase activity is associated with CD3, CD4, CD7 and CD28 receptors in T cells and with FcRI in mast cells. (iitb.ac.in)
  • These studies suggest that type II PtdIns 4-kinases may generate a threshold of signals at plasma membrane that may regulate immune synapse formation, T cell adhesion and infiltration and inflammatory responses. (iitb.ac.in)
  • Understanding of type II PtdIns 4-kinases function and its regulators may help in development of rational drug design for immunomodulators and possibly in cancer metastasis. (iitb.ac.in)
  • Humans have multiple PtdIns proteins that differ by the degree and position of phosphorylation of the inositol ring. (utsouthwestern.edu)
  • also known as phosphatidylinositol-3-phosphate 5-kinase type III or PIPKIII) that phosphorylates the D-5 position in PtdIns and phosphatidylinositol-3-phosphate (PtdIns3P) to make PtdIns5P and PtdIns(3,5)biphosphate. (utsouthwestern.edu)
  • The D-5 position also can be phosphorylated by type I PtdIns4P-5-kinases (PIP5Ks) that are encoded by distinct genes and preferentially phosphorylate D-4 phosphorylated PtdIns. (utsouthwestern.edu)
Lipid2
  • The main catalytic function of PTEN would be to dephosphorylate the lipid second messenger phosphatidylinositol-3,4,5-triphosphate (PIP3), a powerful activator from the AKT kinases20. (health-ground.com)
  • Specific for lipid substrates, inactive towards water soluble inositol phosphates. (smpdb.ca)
Pathways1
  • In addition, new pathways involving phosphatidylinositol-5-phosphate 4-kinases, phosphatidylinositol-3-phosphate 5-kinases and phosphatidylinositol-3-phosphate 4-kinases have recently been described. (nih.gov)
Enzyme2
  • A previous screen of a human kinase and phosphatase shRNA library to select genes that mediate arsenite induction of spindle abnormalities resulted in the identification of phosphatidylinositol-5-phosphate 4-kinase type-2 gamma (PIP4KIIγ), a phosphatidylinositol 4,5-bisphosphate (PIP2)-synthesizing enzyme. (biomedcentral.com)
  • First, it remains on the membrane and serves as a scaffold for a variety of phosphorylation reactions for a phosphorylated enzyme and the like. (justia.com)
Inositol-1,4,5-trisphosphate3
  • These organelles are defined by the expression of receptors for the second messenger Inositol 1,4,5-trisphosphate. (rochester.edu)
  • An inside job: Annexin 1A-Inositol 1,4,5-trisphosphate receptor interaction conveys endoplasmic reticulum luminal Ca sensitivity. (rochester.edu)
  • Pivotal role of type-1 inositol 1,4,5-trisphosphate receptor for glucagon-induced gluconeogenesis. (rochester.edu)
Catalytic2
  • Orthologous to human PIK3C2A (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha). (nih.gov)
  • PF cells were found to express regulatory (p85) and catalytic (p110α and p110β) subunits of phosphatidylinositol 3′-kinase (PI3′-kinase). (jneurosci.org)
Kinases4
  • In eukaryotic cells, phosphatidylinositol can be phosphorylated on the inositol ring by a series of kinases to produce at least seven distinct phosphoinositides. (nih.gov)
  • However, progress has also been made in the characterization of phosphatidylinositol 4-kinases and phosphatidylinositol-4-phosphate 5-kinases. (nih.gov)
  • We have shown that Ypk1, a member of the AGC class of protein kinases conserved from yeast to humans, is the essential target of and activated via phosphorylation by the plasma membrane-associated TORC2 complex. (berkeley.edu)
  • IP6 can be further metabolized by the inositol-hexakisphosphate kinases (IP6Ks), which add a phosphate at the 5-position to produce 5-diphosphoinositol pentakisphosphate (5-PP-IP5,5-IP7). (molcells.org)
Enzymes2
  • The synthesis, chemical derivatization, and investigation of the inhibitory properties of novel cyclitol derivatives on the phosphatidylinositol 4-kinase enzymes PI4K55 and PI4K230 involved in the phosphatidylinositol cycle are reported. (embl.de)
  • The released inositol-1,4,5-triphosphate (IP3) binds to an IP 3 receptor (IP 3 R) residing on the surface of an endoplasmic reticulum of a cell and release Ca 2+ stored in endoplasmic reticula into the cytoplasm, thereby activating a variety of Ca 2+ dependent enzymes. (justia.com)
Substances2
  • The diagnosis of Fanconi syndrome is made based on tests that document the excessive loss of substances in the urine (eg, amino acids, glucose, phosphate, bicarbonate) in the absence of high plasma concentrations. (medscape.com)
  • Upon binding of substances such as hormones, cytokines and neurotransmitters on receptors of a cell, production of inositol-1,4,5-triphosphate (IP 3 ) is induced in the cell, and the IP 3 binds to inositol-1,4,5-triphosphate (IP 3 ) receptor (IP 3 R) residing on the surface of endoplasmic reticula of the cell. (justia.com)
Phospholipase1
  • Another important role of the PI(4,5)P 2 is that it is hydrolyzed by phospholipase C (PLC) into inositol-1,4,5-triphosphate (IP 3 ) and diacylglycerol (DAG) which are then released as second messengers. (justia.com)
PIP24
  • In addition, PIP2 binds to polo-like kinase (PLK1) and reduces PLK1-mediated phosphorylation of MCAK. (biomedcentral.com)
  • These results indicate that PIP4KIIγ and PIP2 may negatively regulate the MT depolymerization activity of MCAK by reducing PLK1-mediated phosphorylation of MCAK. (biomedcentral.com)
  • Phosphatidylinositol 4,5-bisphosphate (PI4,5P2, hereafter referred to as PIP2) either binds to intracellular proteins and directly modulates their subcellular localization and activity or acts as a precursor for the generation of other second messengers. (biomedcentral.com)
  • We have proposed that an increase in the rate of phosphorylation of PI to phosphatidylinositol-4-phosphate (PIP) and to phosphatidylinositol-4,5-bisphosphate (PIP2) could enhance responses to hormones by providing additional substrate for production of the second messengers. (grantome.com)
Eukaryotic1
  • ISRIB (integrated stress response inhibitor) as a drug, imparts resistance to the cells against the downstream effects of eukaryotic initiation factor 2 (eIF2)α phosphorylation such as activating transcription factor 4 (ATF4) and eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) induction. (sigmaaldrich.com)
Calcium1
  • More particularly, the present invention relates to a regulator for the activity of inositol-1,4,5-triphosphate (IP 3 ) receptor (IP 3 R) comprising carbonic anhydrase-related protein (CARP), a control agent for intracellular calcium release comprising carbonic anhydrase-related protein (CARP), and a method of control therewith. (justia.com)
Pathway1
Inhibits1
  • Inhibits MEK-1 and MEK-2 (IC 50 values of 0.07 and 0.06 μ M respectively) with little or no effect on the activities of PKC, Abl, Raf, MEKK, ERK, JNK, MKK-3, MKK-4/SEK, MKK-6, Cdk2 or Cdk4. (rndsystems.com)
Membrane3
  • This phosphorylation generates phosphatidylinositol 4-phosphate (PI4P), a docking site normally located at the Golgi membrane. (wikipedia.org)
  • Localization of phosphatidylinositol phosphate kinase IIgamma in kidney to a membrane trafficking compartment within specialized cells of the nephron. (neurotree.org)
  • PLCs are activated by external stimuli such as growth factors to cleave phosphatidylinositol 4,5-bisphosphate and produce IP3, which is then released from the cell membrane into the cytosol. (molcells.org)
Roles1
  • Phosphatidylinositol (PI) plays two major roles. (justia.com)
Type3
  • PEP3 was recently identified as phosphatidylinositol transfer protein (PtdInsTP), and here we report that PEP1 consists of the type I phosphatidylinositol-4-phosphate 5-kinase (PtdInsP5K). (nih.gov)
  • Sinha R.K and Subrahmanyam, G (2007) Type II Phosphatidylinositol 4-kinase(s) in Cell signaling cascades. (iitb.ac.in)
  • Srivastava,R., Sinha R.K and Subrahmanyam G. (2006) Type II phosphatidylinositol 4-kinase β associates with TCR-CD3 ζ chain in Jurkat cells Molecular Immunology, 43, 454-63. (iitb.ac.in)
Secretion1
  • We report here that Sac1p has a specific role in secretion and acts as an antagonist of the phosphatidylinositol 4-kinase Pik1p in Golgi trafficking. (embl.de)
Metabolism1
  • Under the scenario of a defective cellular energy metabolism, any process that results in a decrease in the level of ATP impairs the performance of secondary active transport mechanisms, such as those of glucose, phosphate, or amino acids. (medscape.com)
Homology2
Phox2
  • Phosphorylation of p47(phox), a cytoplasmic activator of the microbicidal phagocyte oxidase (phox), elicits interaction of p47(phox) with phoinositides. (embl.de)
  • The protein phosphorylation-driven conformational change of p47(phox) enables its PX domain to bind to phosphoinositides, the interaction of which plays a crucial role in recruitment of p47(phox) from the cytoplasm to membranes and subsequent activation of the phagocyte oxidase. (embl.de)
Genes1
Proteins1
  • PI(4,5)P 2 is able to bind to a variety of actin binding proteins, and serves to keep and change the shape of a cell by allowing rearrangement of actin in the cell. (justia.com)
Specificity1
  • encodes a dual specificity phosphatase with the capacity of eliminating phosphates from both protein and lipids19,20. (health-ground.com)
Motifs1
Genetic1
  • Further studies with pharmacological and genetic approaches revealed that TIGAR regulated the phosphorylation of ATM, a key protein in DDR, through Cdk5. (nature.com)
Reactions1
  • Additionally, these reactions necessitate long-term treatment with medications such as for example corticosteroids, thalidomide, and immunosuppressive agents [4] that are connected with many unwanted effects and raising morbidity. (researchensemble.com)
Regulation1
  • In addition the regulation of these receptors by phosphorylation and the consequences this may have for Ca2+ signaling are also being studied. (rochester.edu)
Enables1
  • Enables 1-phosphatidylinositol-3-kinase activity. (nih.gov)
Activity1
  • Synthesis of new cyclitol compounds that influence the activity of phosphatidylinositol 4-kinase isoform, PI4K230. (embl.de)
Additionally1
Function1
  • Increases in knowledge have revealed that the common pathophysiological scenario, myocardial ischemia reperfusion injury, including ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R) forms of injury, results in depressed myocardial function and harmful morphological alterations, which may lead to heart failure ( 4 ). (spandidos-publications.com)
Inhibitor2
  • Furthermore, LY294002, a PI3-K inhibitor and a quercetin derivative, inhibited Ang II-induced JNK activation as well as Akt phosphorylation. (aspetjournals.org)
  • ISRIB is a potent inhibitor of PERK signaling, which potently reverses the effects of eIF2a phosphorylation and restores the cells translation capacity. (sigmaaldrich.com)
Plays an important role1
  • In particular, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ) in which 4-position and 5-position are phosphorylated not only forms an intermediate of phosphatidylinositol 3,4,5-triphosphate (PI (3,4,5) P 3 ) that plays a role in vesicular transport and signal transmission to a nucleus, but also plays an important role by itself. (justia.com)