Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Phosphatidylinositol Phosphates: Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.1-Phosphatidylinositol 4-Kinase: An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.Phosphatidylinositol 4,5-Diphosphate: A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994)Phosphatidylinositols: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.ChromonesAndrostadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Phosphatidylinositol 3-Kinase: A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.MorpholinesProto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Ribosomal Protein S6 Kinases: A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.Mitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).p21-Activated Kinases: A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.PhosphoproteinsIsoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3.CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase: An enzyme that catalyzes the formation of PHOSPHATIDYLINOSITOL and CMP from CDP-DIACYLGLYCEROL and MYOINOSITOL.Kinetics: The rate dynamics in chemical or physical systems.Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Phosphatidylinositol Diacylglycerol-Lyase: A phosphorus-oxygen lyase found primarily in BACTERIA. The enzyme catalyzes the cleavage of a phosphoester linkage in 1-phosphatidyl-1D-myo-inositol to form 1D-myo-inositol 1,2-cyclic phosphate and diacylglycerol. The enzyme was formerly classified as a phosphoric diester hydrolase (EC 3.1.4.10) and is often referred to as a TYPE C PHOSPHOLIPASES. However it is now known that a cyclic phosphate is the final product of this enzyme and that water does not enter into the reaction.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.MAP Kinase Kinase Kinases: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.MAP Kinase Kinase 1: An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.Creatine Kinase: A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.Casein Kinases: A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.eIF-2 Kinase: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.TOR Serine-Threonine Kinases: A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Phosphotransferases: A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Insulin Receptor Substrate Proteins: A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.Diacylglycerol Kinase: An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Recombinant Proteins: Proteins prepared by recombinant DNA technology.MAP Kinase Kinase 4: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.Cell Line, Tumor: A cell line derived from cultured tumor cells.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Class Ib Phosphatidylinositol 3-Kinase: A phosphatidylinositol 3-kinase subclass that includes enzymes formed through the association of a p110gamma catalytic subunit and one of the three regulatory subunits of 84, 87, and 101 kDa in size. This subclass of enzymes is a downstream target of G PROTEIN-COUPLED RECEPTORS.Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.Inositol Phosphates: Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Protein Kinase C-alpha: A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.I-kappa B Kinase: A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.Phospholipid Transfer Proteins: A ubiquitous family of proteins that transport PHOSPHOLIPIDS such as PHOSPHATIDYLINOSITOL and PHOSPHATIDYLCHOLINE between membranes. They play an important role in phospholipid metabolism during vesicular transport and SIGNAL TRANSDUCTION.DiglyceridesBinding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.CDC2-CDC28 Kinases: A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.Protein Kinase C-delta: A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.Focal Adhesion Kinase 1: A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Class III Phosphatidylinositol 3-Kinases: A phosphatidylinositol 3-kinase subclass that includes enzymes whose specificity is limited to 1-phosphatidylinositol. Members of this class play a role in vesicular transport and in the regulation of TOR KINASES.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesBase Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Ribosomal Protein S6 Kinases, 70-kDa: A family of ribosomal protein S6 kinases that are considered the major physiological kinases for RIBOSOMAL PROTEIN S6. Unlike RIBOSOMAL PROTEIN S6 KINASES, 90KDa the proteins in this family are sensitive to the inhibitory effects of RAPAMYCIN and contain a single kinase domain. They are referred to as 70kDa proteins, however ALTERNATIVE SPLICING of mRNAs for proteins in this class also results in 85kDa variants being formed.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.3-Phosphoinositide-Dependent Protein Kinases: Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).PTEN Phosphohydrolase: A lipid phosphatase that acts on phosphatidylinositol-3,4,5-trisphosphate to regulate various SIGNAL TRANSDUCTION PATHWAYS. It modulates CELL GROWTH PROCESSES; CELL MIGRATION; and APOPTOSIS. Mutations in PTEN are associated with COWDEN DISEASE and PROTEUS SYNDROME as well as NEOPLASTIC CELL TRANSFORMATION.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Aurora Kinases: A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.Phosphatidic Acids: Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups.src Homology Domains: Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.AMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Janus Kinase 2: A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.Phosphoinositide Phospholipase C: A type C phospholipase with specificity towards PHOSPHATIDYLINOSITOLS that contain INOSITOL 1,4,5-TRISPHOSPHATE. Many of the enzymes listed under this classification are involved in intracellular signaling.Oncogene Protein v-akt: A viral oncoprotein originally isolated from a murine T CELL LYMPHOMA infected with the acutely transforming retrovirus AKT8. v-akt protein is the viral homologue of PROTO-ONCOGENE PROTEINS C-AKT.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Epidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.MAP Kinase Kinase 2: A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Ribosomal Protein S6 Kinases, 90-kDa: A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.Phospholipase D: An enzyme found mostly in plant tissue. It hydrolyzes glycerophosphatidates with the formation of a phosphatidic acid and a nitrogenous base such as choline. This enzyme also catalyzes transphosphatidylation reactions. EC 3.1.4.4.Phospholipase C gamma: A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.Protein Kinase C-epsilon: A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.MAP Kinase Kinase Kinase 1: A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.Protein Kinase C beta: PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Myosin-Light-Chain Kinase: An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Receptor, Insulin: A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Class Ia Phosphatidylinositol 3-Kinase: A phosphatidylinositol 3-kinase subclass that includes enzymes formed through the heterodimerization of a p110 catalytic and a p85, p55, or p50 regulatory subunit. This subclass of enzymes is a downstream target of TYROSINE KINASE RECEPTORS and G PROTEIN-COUPLED RECEPTORS.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Calcium-Calmodulin-Dependent Protein Kinase Type 2: A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Class I Phosphatidylinositol 3-Kinases: A phosphatidylinositol 3-kinase subclass that includes enzymes with a specificity for 1-phosphatidylinositol, 1-phosphatidylinositol 4-phosphate, and 1-phosphatidylinositol 4,5-bisphosphate. Members of this enzyme subclass are activated by cell surface receptors and occur as heterodimers of enzymatic and regulatory subunits.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.Glycogen Synthase Kinases: A class of protein-serine-threonine kinases that was originally found as one of the three types of kinases that phosphorylate GLYCOGEN SYNTHASE. Glycogen synthase kinases along with CA(2+)-CALMODULIN DEPENDENT PROTEIN KINASES and CYCLIC AMP-DEPENDENT PROTEIN KINASES regulate glycogen synthase activity.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Cyclin-Dependent Kinase 2: A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.Butadienes: Four carbon unsaturated hydrocarbons containing two double bonds.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.Phospholipase C delta: A phosphoinositide phospholipase C subtype that is structurally defined by the presence of an N-terminal pleckstrin-homology and EF-hand domains, a central catalytic domain, and a C-terminal calcium-dependent membrane-binding domain.Receptor, Epidermal Growth Factor: A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Focal Adhesion Kinase 2: A non-receptor protein-tyrosine kinase that is expressed primarily in the BRAIN; OSTEOBLASTS; and LYMPHOID CELLS. In the CENTRAL NERVOUS SYSTEM focal adhesion kinase 2 modulates ION CHANNEL function and MITOGEN-ACTIVATED PROTEIN KINASES activity.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Mitogen-Activated Protein Kinase 8: A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Proto-Oncogene Proteins pp60(c-src): Membrane-associated tyrosine-specific kinases encoded by the c-src genes. They have an important role in cellular growth control. Truncation of carboxy-terminal residues in pp60(c-src) leads to PP60(V-SRC) which has the ability to transform cells. This kinase pp60 c-src should not be confused with csk, also known as c-src kinase.Phosphorus Radioisotopes: Unstable isotopes of phosphorus that decay or disintegrate emitting radiation. P atoms with atomic weights 28-34 except 31 are radioactive phosphorus isotopes.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.PC12 Cells: A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.MAP Kinase Kinase 6: A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Cyclin-Dependent Kinase 5: A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Subcellular Fractions: Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.MAP Kinase Kinase 3: A mitogen-activated protein kinase kinase with specificity for a subset of P38 MITOGEN-ACTIVATED PROTEIN KINASES that includes MITOGEN-ACTIVATED PROTEIN KINASE 12; MITOGEN-ACTIVATED PROTEIN KINASE 13; and MITOGEN-ACTIVATED PROTEIN KINASE 14.Phosphoserine: The phosphoric acid ester of serine.Phosphatidylserines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.Glycosylphosphatidylinositols: Compounds containing carbohydrate or glycosyl groups linked to phosphatidylinositols. They anchor GPI-LINKED PROTEINS or polysaccharides to cell membranes.GRB2 Adaptor Protein: A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Phosphoglycerate Kinase: An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.raf Kinases: A family of closely-related serine-threonine kinases that were originally identified as the cellular homologs of the retrovirus-derived V-RAF KINASES. They are MAP kinase kinase kinases that play important roles in SIGNAL TRANSDUCTION.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Phosphoric Diester Hydrolases: A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.

A plant 126-kDa phosphatidylinositol 4-kinase with a novel repeat structure. Cloning and functional expression in baculovirus-infected insect cells. (1/398)

Phosphatidylinositol metabolism plays a central role in signaling pathways in animals and is also believed to be of importance in signal transduction in higher plants. We report here the molecular cloning of a cDNA encoding a previously unidentified 126-kDa phosphatidylinositol (PI) 4-kinase (AtPI4Kbeta) from the higher plant Arabidopsis thaliana. The novel protein possesses the conserved domains present in animal and yeast PI 4-kinases, namely a lipid kinase unique domain and a catalytic domain. An additional domain, approximately 300 amino acids long, containing a high percentage (46%) of charged amino acids is specific to this plant enzyme. Recombinant AtPI4Kbeta expressed in baculovirus-infected insect (Spodoptera frugiperda) cells phosphorylated phosphatidylinositol exclusively at the D4 position of the inositol ring. Recombinant protein was maximally activated by 0.6% Triton X-100 but was inhibited by adenosine with an IC50 of approximately 200 microM. Wortmannin at a concentration of 10 microM inhibited AtPI4Kbeta activity by approximately 90%. AtPI4Kbeta transcript levels were similar in all tissues analyzed. Light or treatment with hormones or salts did not change AtPI4Kbeta transcript levels to a great extent, indicating constitutive expression of the AtPI4Kbeta gene.  (+info)

Functional expression and characterisation of a new human phosphatidylinositol 4-kinase PI4K230. (2/398)

By constructing DNA probes we have identified and cloned a human PtdIns 4-kinase, PI4K230, corresponding to a mRNA of 7.0 kb. The cDNA encodes a protein of 2044 amino acids. The C-terminal part of ca. 260 amino acids represents the catalytic domain which is highly conserved in all recently cloned PtdIns 4-kinases. N-terminal motifs indicate multiple heterologous protein interactions. Human PtdIns 4-kinase PI4K230 expressed in vitro exhibits a specific activity of 58 micromol mg-1min-1. The enzyme expressed in Sf9 cells is essentially not inhibited by adenosine, it shows a high Km for ATP of about 300 microM and it is half-maximally inactivated by approximately 200 nM wortmannin. These data classify this enzyme as type 3 PtdIns 4-kinase. Antibodies raised against the N-terminal part moderately activate and those raised against the C-terminal catalytic domain inhibit the enzymatic activity. The coexistence of two different type 3 PtdIns 4-kinases, PI4K92 and PI4K230, in several human tissues, including brain, suggests that these enzymes are involved in distinct basic cellular functions.  (+info)

G-protein-stimulated phospholipase D activity is inhibited by lethal toxin from Clostridium sordellii in HL-60 cells. (3/398)

Lethal toxin (LT) from Clostridium sordellii has been shown in HeLa cells to glucosylate and inactivate Ras and Rac and, hence, to disorganize the actin cytoskeleton. In the present work, we demonstrate that LT treatment provokes the same effects in HL-60 cells. We show that guanosine 5'-O-(3-thiotriphosphate)-stimulated phospholipase D (PLD) activity is inhibited in a time- and dose-dependent manner after an overnight treatment with LT. A similar dose response to the toxin was found when PLD activity was stimulated by phorbol 12-myristate 13-acetate via the protein kinase C pathway. The toxin effect on actin organization seemed unlikely to account directly for PLD inhibition as cytochalasin D and iota toxin from Clostridium perfringens E disorganize the actin cytoskeleton without modifying PLD activity. However, the enzyme inhibition and actin cytoskeleton disorganization could both be related to a major decrease observed in phosphatidylinositol 4,5-bisphosphate (PtdIns(4, 5)P2). Likely in a relationship with this decrease, recombinant ADP-ribosylation factor, RhoA, Rac, and RalA were not able to reconstitute PLD activity in LT-treated cells permeabilized and depleted of cytosol. Studies of phosphoinositide kinase activities did not allow us to attribute the decrease in PtdIns(4,5)P2 to inactivation of PtdIns4P 5-kinase. LT was also found to provoke a major inhibition in phosphatidylinositol 3-kinase that could not account for the inhibition of PLD activity because wortmannin, at doses that fully inhibit phosphatidylinositol 3-kinase, had no effect on the phospholipase activity. Among the three small G-proteins, Ras, Rac, and RalA, inactivated by LT and involved in PLD regulation, inactivation of Ral proteins appeared to be responsible for PLD inhibition as LT toxin (strain 9048) unable to glucosylate Ral proteins did not modify PLD activity. In HL-60 cells, LT treatment appeared also to modify cytosol components in relationship with PLD inhibition as a cytosol prepared from LT-treated cells was less efficient than one from control HL-60 cells in stimulating PLD activity. Phosphatidylinositol transfer proteins involved in the regulation of polyphosphoinositides and ADP-ribosylation factor, a major cytosolic PLD activator in HL-60 cells, were unchanged, whereas the level of cytosolic protein kinase Calpha was decreased after LT treatment. We conclude that in HL-60 cells, lethal toxin from C. sordellii, in inactivating small G-proteins involved in PLD regulation, provokes major modifications at the membrane and the cytosol levels that participate in the inhibition of PLD activity. Although Ral appeared to play an essential role in PLD activity, we discuss the role of other small G-proteins inactivated by LT in the different modifications observed in HL-60 cells.  (+info)

Coupled inositide phosphorylation and phospholipase D activation initiates clathrin-coat assembly on lysosomes. (4/398)

Adaptors appear to control clathrin-coat assembly by determining the site of lattice polymerization but the nucleating events that target soluble adaptors to an appropriate membrane are poorly understood. Using an in vitro model system that allows AP-2-containing clathrin coats to assemble on lysosomes, we show that adaptor recruitment and coat initiation requires phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) synthesis. PtdIns(4,5)P2 is generated on lysosomes by the sequential action of a lysosome-associated type II phosphatidylinositol 4-kinase and a soluble type I phosphatidylinositol 4-phosphate 5-kinase. Phosphatidic acid, which potently stimulates type I phosphatidylinositol 4-phosphate 5-kinase activity, is generated on the bilayer by a phospholipase D1-like enzyme located on the lysosomal surface. Quenching phosphatidic acid function with primary alcohols prevents the synthesis of PtdIns(4, 5)P2 and blocks coat assembly. Generating phosphatidic acid directly on lysosomes with exogenous bacterial phospholipase D in the absence of ATP still drives adaptor recruitment and limited coat assembly, indicating that PtdIns(4,5)P2 functions, at least in part, to activate the PtdIns(4,5)P2-dependent phospholipase D1. These results provide the first direct evidence for the involvement of anionic phospholipids in clathrin-coat assembly on membranes and define the enzymes responsible for the production of these important lipid mediators.  (+info)

Involvement of PITPnm, a mammalian homologue of Drosophila rdgB, in phosphoinositide synthesis on Golgi membranes. (5/398)

Phosphatidylinositol transfer protein (PITP) is involved in phospholipase C-mediated signaling and membrane trafficking. We previously reported cloning and characterization of a gene encoding for membrane-bound PITP, named PITPnm, that is a mammalian homologue of the Drosophila retinal degeneration B (rdgB) gene (Aikawa, Y., Hara, H., and Watanabe, T. (1997) Biochem. Biophys. Res. Commun. 236, 559-564). Here we report the subcellular localization of PITPnm protein and provide evidence for its involvement in phosphatidylinositol 4-phosphate (PtdIns 4-P) synthesis. PITPnm is an integral membrane protein that largely localized in close association with membranes of Golgi vacuoles and the endoplasmic reticulum (ER). The amino terminus region of PITPnm was exposed to cytoplasmic side. Interaction with various phosphoinositides was observed in the amino terminus region spanning from 196 amino acids to 257 amino acids of PITPnm. At the amino terminus regions of 1-372 amino acids, PITPnm formed a complex with type III PtdIns 4-kinase. The transmembrane and carboxyl-terminal portions (residues 418-1242) functioned to retain the PITPnm in the Golgi vacuole. These results suggest that PITPnm plays a role in phosphoinositide synthesis on the Golgi vacuoles and possibly in the PtdIns signaling pathway in mammalian cells.  (+info)

p85/p110-type phosphatidylinositol kinase phosphorylates not only the D-3, but also the D-4 position of the inositol ring. (6/398)

Activation of p85/p110-type phosphatidylinositol (PI) kinase has been implicated in various cellular activities. This PI kinase phosphorylates the D-4 position with a similar or higher efficiency than the D-3 position when trichloroacetic acid-treated cell membrane is used as a substrate, although it phosphorylates almost exclusively the D-3 position of the inositol ring in phosphoinositides when purified PI is used as a substrate. Furthermore, the lipid kinase activities of p110 for both the D-3 and D-4 positions were completely abolished by introducing kinase-dead point mutations in their lipid kinase domains (DeltaKinalpha and DeltaKinbeta, respectively). In addition, both PI 3- and PI 4-kinase activities of p110alpha and p110beta immunoprecipitates were similarly inhibited by either wortmannin or LY294002, specific inhibitors of p110. Insulin induced phosphorylation of not only the D-3 position, but also the D-4 position. Indeed, overexpression of p110 in Sf9 or 3T3-L1 cells induced marked phosphorylation of the D-4 position to a level comparable to or much greater than that of D-3, whereas inhibition of endogenous p85/p110-type PI kinase via overexpression of dominant-negative p85alpha (Deltap85alpha) in 3T3-L1 adipocytes abolished insulin-induced synthesis of both. Thus, p85/p110-type PI kinase phosphorylates the D-4 position of phosphoinositides more efficiently than the D-3 position in vivo, and each of the D-3- or D-4-phosphorylated phosphoinositides may transmit signals downstream.  (+info)

Identification of a mating type-like locus in the asexual pathogenic yeast Candida albicans. (7/398)

Candida albicans, the most prevalent fungal pathogen in humans, is thought to lack a sexual cycle. A set of C. albicans genes has been identified that corresponds to the master sexual cycle regulators a1, alpha1, and alpha2 of the Saccharomyces cerevisiae mating-type (MAT) locus. The C. albicans genes are arranged in a way that suggests that these genes are part of a mating type-like locus that is similar to the mating-type loci of other fungi. In addition to the transcriptional regulators a1, alpha1, and alpha2, the C. albicans mating type-like locus contains several genes not seen in other fungal MAT loci, including those encoding proteins similar to poly(A) polymerases, oxysterol binding proteins, and phosphatidylinositol kinases.  (+info)

Receptor-mediated signaling pathways: potential targets of modulation by dietary fatty acids. (8/398)

Extracellular signals are transmitted to intracellular targets through many signal-transduction pathways. Each signaling pathway is composed of a network of interacting signaling molecules that regulate diverse cellular responses. A modulation of the functional activities of these signaling molecules as a result of altered nutritional status could lead to qualitative and quantitative changes in cellular responses to extracellular signals. Growing evidence now suggests that fatty acids can directly and indirectly modulate signaling pathways at multiple levels. Elucidating the mechanism of this modulation could help us to understand how different types of dietary fat modify the risks of many chronic diseases.  (+info)

Type II phosphatidylinositol (PtdIns) 4-kinases produce PtdIns 4-phosphate, an early key signaling molecule in phosphatidylinositol cycle, which is indispensable for T cell activation. Type II PtdIns 4-kinase alpha and beta have similar biochemical properties. To distinguish these isoforms Epigallocatechin gallate (EGCG) has been evaluated as a specific inhibitor. EGCG is the major active catechin in green tea having anti-inflammatory, antiatherogenic and cancer chemopreventive properties. The precise mechanism of actions and molecular targets of EGCG in early signaling cascades are not well understood. In the present study, we have shown that EGCG inhibits type II PtdIns 4-kinases (alpha and beta isoforms) and PtdIns 3-kinase activity in vitro. EGCG directly bind to both alpha and beta isoforms of type II PtdIns 4-kinases with a Kd of 2.62 mu M and 1.02 mu M, respectively. Type II PtdIns 4-kinase-EGCG complex have different binding pattern at its excited state. Both isoforms showed significant ...
Recent evidence suggests that concanavalin A modulates tyrosyl phosphorylation and activation of a type II PtdIns 4-kinase in rat splenic lymphocytes. However, the regulatory protein tyrosine kinase(s) remain to be elusive. The present manuscript provides evidence that a type II PtdIns 4-kinase associates with p56(lck) in Con A stimulated rat splenic lymphocytes. In vitro phosphorylation studies suggest that p561(lck) regulates phosphorylation and activation of type II PtdIns 4-kinase. Inhibition of p561(lck) activity in vivo has shown to reduce tyrosyl phosphorylation and activation of PtdIns 4-kinase by Con A. These results suggest that p56(lck) may be the physiological regulator of type II PtdIns 4-kinase ...
The IUPHAR/BPS Guide to Pharmacology. phosphoinositide-3-kinase regulatory subunit 1 - Phosphatidylinositol kinases. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
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One challenge in studying the second messenger inositol(1,4,5)-trisphosphate (InsP3) is that it is present in very low amounts and increases only transiently in response to stimuli. To identify events downstream of InsP3, we generated transgenic plants constitutively expressing the high specific activity, human phosphatidylinositol 4-phosphate 5-kinase Iα (HsPIPKIα). PIP5K is the enzyme that synthesizes phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2); this reaction is flux limiting in InsP3 biosynthesis in plants. Plasma membranes from transgenic Arabidopsis expressing HsPIPKIα had 2-3 fold higher PIP5K specific activity, and basal InsP3 levels in seedlings and leaves were |2-fold higher than wild type. Although there was no significant difference in photosynthetic electron transport, HsPIPKIα plants had significantly higher starch (2-4 fold) and 20% higher anthocyanin compared to controls. Starch content was higher both during the day and at the end of dark period. In addition, transcripts
Oncogenic mutations in PIK3CA lead to an increase in instrinsic phosphoinositide kinase activity, but it is thought that increased access of PI3Kα to its plasma membrane localised substrate is also required for increased levels of downstream PIP3/Ak
Mutations in phosphatidylinositol 3-kinase (PIK3CA), encoding the p110α catalytic subunit of the class I PI3K, have been implicated in colon, lung, ovarian and breast cancer.
Mutations in phosphatidylinositol 3-kinase (PIK3R1), encoding the regulatory subunit of p85, have been implicated in colon, lung, ovarian and breast cancer.
In a phase 1 trial, idelalisib (GS-1101, CAL-101), a selective inhibitor of the lipid kinase PI3K delta, was evaluated in 54 patients with relapsed/refractory ...
Seema Verma, the Indiana health care consultant who has been tapped to head the Centers for Medicare and Medicaid Services, will face senators questions Thursday on how she would approach the job if confirmed.
Lenti ORF particles, PIGP (Myc-DDK tagged) - Human phosphatidylinositol glycan anchor biosynthesis, class P (PIGP), transcript variant 2 , 200 uL, |10^7 TU/mL, 200 µl.
Page 1 of 5 - [WIP] Grand Theft Auto III Beta Version - posted in GTA III, VC & SA: AboutThis mod simply plans to bring back different features seen in different early stages of gta3 mixed together to make it more fun enjoyable to play.ChecklistWhats been done so far: - the police car has been restored to its pre-9/11 look; - all cars have their beta names; - Esparanto now has Hydraulics; - The first mission have been modified to make it as in the original concept (8ball doesnt...
In a series of studies spanning several years, Cantley and colleagues demonstrated that a kinase activity associated with the middle T oncoprotein is a phosphoinositide kinase,[7] that it is a novel type of phosphoinositide kinase that phosphorylates the 3 position on the inositol ring,[8] and that this phosphatidylinositol-3-kinase (PI-3-kinase) is activated by growth factors to produce novel 3-phosphorylated phosphoinositides, in particularly PtdIns(3,4,5)P3 [9] that had previously been identified in physiologically stimulated human neutrophils.[10] In subsequent years Cantley and colleagues identified critical aspects of the regulation of PI-3-kinase by growth factor receptors. Specifically, they discovered that the catalytic subunit p110 dimerizes with the regulatory subunit p85,[11] and that the SH2 domain of p85 specifically recognized phosphotyrosines[12] on growth factor receptors or adaptor proteins via the pY-X-X-M motif.[13][14]. The Cantley lab has also made seminal contributions ...
PI-3 kinase subunit gamma antibody for detecting human phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform. Validated on up to 12 cell lysates for western blotting. Try a trial size today.
Two cases of successful molecular replacement using NMR trial models are presented. One is the crystal structure of the E. coli colicin immunity protein Im7; the other is the previously unreported crystal structure of the carboxy-terminal SH2 domain from the p85α subunit of human phosphatidylinositol 3-OH kinase complexed to a PDGF receptor-derived specificity peptide ...
The beta keys have been bought from dedicated players whove earned their beta keys doing various things in-game (Diablo). We have also been handed a few extra ones from our fellow community members as a thank you for everything that we have given away during the last months ...
KIN Raiders Heroic Spine of Deathwing Video Now that Stars has defeated Heroic Spine of Deathwing 25, KIN Raiders has released their video of the kill. |iframe width=853 height=480 src=http://www.youtube.com/embed/gZHeTNr7xzM?rel=0&hd=1 frameborder=0 allowfullscreen||/iframe| KIN Raiders Raid Composition / Damage Meters KIN Raiders defeated Heroic Spine of Deathwing 25 utilizing lots of high burst DPS classes. You can see their damage meters from the Spine fight (only the
Neuronal calcium sensor-1 (NCS-1) also known as frequenin homolog (Drosophila) (freq) is a protein that is encoded by the FREQ gene in humans. NCS-1 is a member of the neuronal calcium sensor family, a class of EF hand containing calcium-myristoyl-switch proteins. NCS-1 regulates synaptic transmission, helps control the dynamics of nerve terminal growth, is critical for some forms of learning and memory in C. elegans and mammals, regulates corticohippocampal plasticity; and enhancing levels of NCS-1 in the mouse dentate gyrus increases spontaneous exploration of safe environments, potentially linking NCS-1 to curiosity. NCS-1 is a calcium sensor, not a calcium buffer (chelator); thus it is a high-affinity, low-capacity, calcium-binding protein. Frq can substitute for calmodulin in some situations. It is thought to be associated with neuronal secretory vesicles and regulate neurosecretion. It is the Ca2+-sensing subunit of the yeast phosphatidylinositol (PtdIns)-4-OH kinase, PIK1 It binds to many ...
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PI-273 is a first reversibly and specific phosphatidylinositol 4-kinase (PI4KIIα) inhibitor with an IC50 of 0.47 μM. PI-273 can inhibit breast cancer cell proliferation, block the cell cycle and induce cell apoptosis. - Mechanism of Action & Protocol.
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Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of PtdIns(4,5)P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a variety of cellular processes such as vesicle mediated transport, cell adhesion, cell polarization and cell migration. Together with PIP5K1A is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport. Controls the plasma membrane pool of ...
The phosphatidylinositol 3-kinase (PI3K) signalling pathway is one of the most frequently genetically altered pathways in human cancers (Samuels et al., 2004). Class I PI3Ks are lipid kinases that bind to the cell membrane and phosphorylate the lipid substrate, phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2), in order to produce the second messenger, PIP3. In turn, this regulates several biological signalling pathways involved in cell growth, proliferation, differentiation, and survival (Qiu et al., 1998; Roche, Koegl, & Courtneidge, 1994; Yao & Cooper, 1995). The work in this thesis explores how different PI(4,5)P2 fatty acyl chain arrangements and specific PI3K amino acids can affect membrane binding interactions and catalysis events for both wild-type (WT) and oncogenic class I PI3Ks. Firstly, the effects of different PI(4,5)P2 lipid species were investigated on PI3K lipid kinase activity using biochemical methods, and on PI3K membrane binding using biophysical methods. The influences of ...
Order Anti-human phosphatidylinositol-3-phosphate phosphatidylinositol 5-kinase type III PAb 02012560599 at Gentaur phosphatidylinositol-3-phosphate/phosphatidylinositol 5-kinase, III PAb
Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. May also phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165).
ProQinase offers off-the-shelf a significant panel of lipid kinases, active recombinant lipid kinases which can be used for biochemical enzyme assays
The p85 subunit of phosphatidylinositol 3-kinase interacts with the phosphodomain of TARP.a) Binding of CMTPX-labeled C. trachomatis L2 EBs to cells expressing
Online Cover This week features a Research Article that identifies ARAP3 as the downstream effector of phosphoinositide 3-kinase (PI3K) in the regulation of sprouting angiogenesis during development. The image shows a wild-type mouse embryo stained for a marker of vascular endothelial cells. [Image: Laure Gambardella, Inositide Laboratory, The Babraham Institute] ...
The STT3A gene currently has no well-established disease association; however, there is preliminary evidence supporting a correlation with autosomal recessive STT3A-congenital disorder of glycosylation (CDG-Iw) (PMID: 23842455).
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The family of PI3Ks (phosphatidylinositol 3-kinases) was discovered several decades ago, but until now most attention has been given to class I PI3Ks, mainly due to their previously established role in human disorders such as cancer and metabolic diseases. Class II PI3K has therefore been a bit in the shadow of the more intensively studied other families. Nevertheless, the number of reports about class II has started to increase over the past few years and we are now beginning to gain a clearer picture about the role of class II enzymes in different cellular functions and their involvement in human diseases. The fact that class II PI3K generates different second messengers (phosphoinositides) than the other PI3K family members, gives an indication that these enzymes might play a specific role in the regulation of distinct cellular functions. However, there is still a lot to be learned about the molecular mechanism of activation, the cellular function and the physiological and pathological role ...
Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) has long been recognized as an important source of second messengers. Hydrolysis of PtdIns(4,5)P2 by phospholipase C yields diacylglycerol, a potent activator of most protein kinase C isoforms and other enzymes bearing C1 domains, and inositol 1,4,5-trisphosphate, which induces release of calcium stored in the endoplasmic reticulum (Taylor, 2002). In addition, phosphorylation of PtdIns(4,5)P2 by class I phosphatidylinositol 3-kinases generates phosphatidylinositol 3,4,5-trisphosphate, a ligand and activator of various effectors that contain pleckstrin homology (PH) domains (Vanhaesebroeck et al., 2001; Lemmon, 2003). Not only are its metabolites critical for signal transduction, but PtdIns(4,5)P2 itself serves multiple regulatory functions in the cell. It affects several stages of actin microfilament assembly and remodeling, including uncapping of barbed ends, severing and bundling of filaments, and de novo nucleation (Hilpela et al., 2004; ...
TY - JOUR. T1 - Phosphatidylinositol 3-kinase activation is required for stress protocol-induced modification of hippocampal synaptic plasticity. AU - Yang, Ping Chun. AU - Yang, Chih Hao. AU - Huang, Chiung Chun. AU - Hsu, Kuei Sen. PY - 2008/2/1. Y1 - 2008/2/1. N2 - Stress dramatically affects the induction of hippocampal synaptic plasticity; however, the molecular details of how it does so remain unclear. Phosphatidylinositol 3-kinase (PI3K) signaling plays a crucial role in promoting neuronal survival and neuroplasticity, but its role, if any, in stress-induced alterations of long term potentiation (LTP) and long term depression (LTD) is unknown. We found here that inhibitors of PI3K signaling blocked the effects of acute restraint-tail shock stress protocol on LTP and LTD. Therefore, the purpose of the present study is to explore the signaling events involving PI3K in terms of its role in mediating stress protocol-induced alterations of LTP and LTD. We found that stress protocol-induced ...
Order GDP-mannose-dependent alpha- 1-6 -phosphatidylinositol dimannoside mannosyltransferase-E coli 01022698370 at Gentaur GDP-mannose-dependent alpha (1-6) phosphatidylinositol dimannoside mannosyltransferase
Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Activates JNK1 via CDC42 but not RAC1. Binds to phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 5-monophosphate, phosphatidylinositol 4-monophosphate and phosphatidylinositol 3-monophosphate (By similarity).
Ito, K., Caramori, G. and Adcock, I.M. (2007) Therapeu tic potential of phosphatidylinositol 3-kinase inhibitors in inflammatory respiratory disease. The Journal of Phar macology and Experimental Therapeutics, 321, 1-8. Epub 4 October 2006. doi10.1124/jpet.106.111674
In this esp32 tutorial, we will check how we can get humidity measurements from a DHT22 sensor, with the Arduino core running on the ESP32.
http://www.india-forums.com/tellybuzz/wassup/8079-sharmi-fails-in-the-pavitrata-test-in-ganga-kii-dheej.htm Sharmi fails the Pavitara Test in Ganga Ki Dheej... Tuesday, November 16, 2010 | 6:09:52 PM IST (+05:30 GMT) 29 Comments Tonights episode of Sahara Ones Ganga Kii dheej ... | Page: 2 | 1568176 | Ganga Kii Dheej Forum
PIPKIβ knockdown inhibits dHL60 cell polarization and chemotaxis. (A) PIPKIβ knockdown in dHL60 cells 48 h after transfection with 50 nM control or PIPKIβ-specific siRNA, as determined by quantitative RT-PCR (see Materials and methods). The results are normalized to the relative PIPKIβ mRNA levels in cells transfected with control siRNA (representative of five experiments). (B) Crude lysates (80 μg/lane) from cells as in A were analyzed by immunoblot with anti-PIPKIβ and anti-actin antibodies. The graph represents mean ± SEM of densitometry values for the PIPKIβ band from three independent experiments, taking the band in siRNA control cells as 100%. (C) Cell polarity depends on PIPKIβ. Uniformly stimulated dHL60 cells transfected with control or two PIPKIβ-specific siRNA were stained with phalloidin (red) and phospho-ERM proteins (green) as leading edge and uropod markers, respectively. Only cells showing clear segregation of phalloidin and phospho-ERM proteins were scored as ...
The IUPHAR/BPS Guide to Pharmacology. phosphatidylinositol-5-phosphate 4-kinase type 2 beta - Phosphatidylinositol phosphate kinases. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
PIK3CA [ENSP00000263967]. Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4- phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5- bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature ...
BEZ235 showed modest clinical activity and an unfavourable toxicity profile in patients with advanced and pretreated TCC; however, a minority of patients experienced a clinical benefit, suggesting that a complete blockade of the PI3K/mTOR axis could improve outcome in some specific patients. Further …
Signaling via G-protein-coupled receptors undergoes desensitization after prolonged agonist exposure. Here we investigated the role of phosphoinositide 3-kinase (PI3K) and its downstream pathways in desensitization of micro-opioid inhibition of neuro
On Wed, Apr 30, 2003 at 12:16:14AM -0700, Chris Waters wrote: , On Wed, Apr 30, 2003 at 04:48:29PM +1000, Anthony Towns wrote: , , Isnt this whole thread about our users demanding it? , If thats your interpretation of the thread (and its not mine), then , hadnt you better get cracking at implementing whatever the missing , pieces might be? Actions speak louder than words, yknow! :p ;) http://people.debian.org/~ajt/lsb/patches/ deb http://people.debian.org/~ajt/lsb woody lsb/main These were enough to get woody to support LSB 1.2 late last year; unfortunately weve left it so late that its not possible to get certified for that, and LSB 1.3 has some additional requirements that I expect we dont meet. AFAIK, we still have bugs like #142072 blocking unstable from complying with LSB 1.2 too. , Personally, I dont think that one person asking a question qualifies , as our users are demanding it. Id rather not set the bar any higher than that, personally. What are the alternatives? Having ...
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Class I phosphoinositide 3-kinases (PI3Ks) are bifunctional enzymes possessing lipid kinase activity and the capacity to phosphorylate their catalytic and/or regulatory subunits. In this study, in vitro autophosphorylation of the G protein-sensitive p85-coupled class I(A) PI3K beta and p101-coupled class I(B) PI3K gamma was examined. Autophosphorylation sites of both PI3K isoforms were mapped to C-terminal serine residues of the catalytic p110 subunit (i.e. serine 1070 of p110 beta and serine 1101 of p110 gamma). Like other class I(A) PI3K isoforms, autophosphorylation of p110 beta resulted in down-regulated PI3K beta lipid kinase activity. However, no inhibitory effect of p110 gamma autophosphorylation on PI3K gamma lipid kinase activity was observed. Moreover, PI3K beta and PI3K gamma differed in the regulation of their autophosphorylation. Whereas p110 beta autophosphorylation was stimulated neither by G beta gamma complexes nor by a phosphotyrosyl peptide derived from the platelet-derived ...
Rab5 and phosphatidylinositol 3-kinase (PI3K) have been proposed to co-regulate receptor endocytosis by controlling early endosome fusion. However, in this report we demonstrate that inhibition of epidermal growth factor (EGF)-stimulated PI3K activity by expression of the kinase-deficient PI3K p110 …
Phosphatidylinositol 3-kinase (PI3K) phosphorylates phosphatidylinositol and similar compounds, which then serve as second messengers in growth signaling pathways. PI3K is composed of a catalytic and a regulatory subunit. The protein encoded by this gene represents a regulatory subunit of PI3K. The encoded protein contains two SH2 domains through which it binds activated protein tyrosine kinases to regulate their activity. [provided by RefSeq, Jun 2016 ...
Phosphatidylinositol 4-kinase type 2-beta is an enzyme that in humans is encoded by the PI4K2B gene. GRCm38: Ensembl release 89 ... "Entrez Gene: PI4K2B phosphatidylinositol 4-kinase type 2 beta". Griffioen M, van der Meijden ED, Slager EH, et al. (2008). " ... 2003). "Type II phosphatidylinositol 4-kinase beta is a cytosolic and peripheral membrane protein that is recruited to the ... Srivastava R, Sinha RK, Subrahmanyam G (2006). "Type II phosphatidylinositol 4-kinase beta associates with TCR-CD3 zeta chain ...
"Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphate synthesis by AP-2mu-cargo ... 2007). "Type Igamma phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct ... 2006). "Type Igamma661 phosphatidylinositol phosphate kinase directly interacts with AP2 and regulates endocytosis". J. Biol. ... 2002). "Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin". Nature. ...
"Entrez Gene: PIP5K1B phosphatidylinositol-4-phosphate 5-kinase, type I, beta". Bayot A, Reichman S, Lebon S, Csaba Z, Aubry L, ... 2004). "Identification and characterization of a phosphoinositide phosphate kinase homolog". J. Biol. Chem. 279 (12): 11672-9. ... Phosphatidylinositol-4-phosphate 5-kinase type-1 beta is an enzyme that in humans is encoded by the PIP5K1B gene. Abnormal ... Loijens JC, Anderson RA (1997). "Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid ...
2003). "Membrane ruffling requires coordination between type Ialpha phosphatidylinositol phosphate kinase and Rac signaling". J ... Phosphatidylinositol-4-phosphate 5-kinase type-1 alpha is an enzyme that in humans is encoded by the PIP5K1A gene. GRCh38: ... "Entrez Gene: PIP5K1A phosphatidylinositol-4-phosphate 5-kinase, type I, alpha". Honda A, Nogami M, Yokozeki T, et al. (1999). " ... 2000). "Type I phosphatidylinositol 4-phosphate 5-kinase directly interacts with ADP-ribosylation factor 1 and is responsible ...
1994). "Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI ... 2013). "The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A ... "The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A". PLoS ... Phosphatidylinositol 4-kinase alpha is an enzyme that in humans is encoded by the PI4KA gene. This gene encodes a 1- ...
... map kinase kinase kinases MeSH D08.811.913.696.620.682.700.559.100 --- map kinase kinase kinase 1 MeSH D08.811.913.696.620.682. ... phosphatidylinositol diacylglycerol-lyase MeSH D08.811.277.352.640.700.700.750 --- phospholipase c gamma MeSH D08.811.277.352. ... map kinase kinase kinase 2 MeSH D08.811.913.696.620.682.700.559.300 --- map kinase kinase kinase 3 MeSH D08.811.913.696.620.682 ... map kinase kinase 2 MeSH D08.811.913.696.620.682.700.565.300 --- map kinase kinase 3 MeSH D08.811.913.696.620.682.700.565.400 ...
Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV (1996). "TNF-dependent recruitment of the protein kinase RIP to the TNF receptor ... "A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4- ... phosphate 5-kinase". J. Biol. Chem. 272 (9): 5861-70. doi:10.1074/jbc.272.9.5861. PMID 9038203. Boldin MP, Mett IL, Wallach D ( ... 367 (1): 39-44. doi:10.1016/0014-5793(95)00534-G. PMID 7601280. Dunbar JD, Song HY, Guo D, Wu LW, Donner DB (1997). "Two-hybrid ...
... kinase domain can be divided into N-terminal and C-terminal lobes with the ATP binding groove and putative phosphatidylinositol ... Phosphatidylinositol 4-kinase 2-alpha is an enzyme that in humans is encoded by the PI4K2A gene. This gene encodes a ... "Entrez Gene: PI4KII phosphatidylinositol 4-kinase type II". Balla, A; Tuymetova, G; Barshishat, M; Geiszt, M; Balla, T (31 May ... PI4K2A is composed of a proline-rich N-terminal region and a kinase domain located C-terminally. The proline-rich N-terminal ...
"Centaurin-alpha1 is a phosphatidylinositol 3-kinase-dependent activator of ERK1/2 mitogen-activated protein kinases". The ... "Casein kinase I associates with members of the centaurin-alpha family of phosphatidylinositol 3,4,5-trisphosphate-binding ... "Casein kinase I associates with members of the centaurin-alpha family of phosphatidylinositol 3,4,5-trisphosphate-binding ... Protein kinase D1, and Protein kinase Mζ. Model organisms have been used in the study of ADAP1 function. A conditional knockout ...
... phosphatidylinositol kinase, type II phosphatidylinositol kinase, PI kinase, and PI 4-kinase. This enzyme participates in ... Other names in common use include phosphatidylinositol kinase (phosphorylating), phosphatidylinositol 4-kinase, ... "Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate". Nature. 332 (6165): ... Kai M, White GL, Hawthorne JN (1966). "The phosphatidylinositol kinase of rat brain". Biochem. J. 101 (2): 328-37. PMC 1270113 ...
Ling K, Doughman RL, Firestone AJ, Bunce MW, Anderson RA (Nov 2002). "Type I gamma phosphatidylinositol phosphate kinase ... coordinating phosphatidylinositol synthesis, and modulating actin dynamics through interactions with PIP kinase type 1γ, the ... "Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin". Nature. 420 ( ... Chen HC, Appeddu PA, Parsons JT, Hildebrand JD, Schaller MD, Guan JL (Jul 1995). "Interaction of focal adhesion kinase with ...
Other names in common use include diphosphoinositide kinase, PIP kinase, phosphatidylinositol 4-phosphate kinase, ... and type I PIP kinase. This enzyme participates in 3 metabolic pathways: inositol phosphate metabolism, phosphatidylinositol ... Kai M, Salway JG, Hawthorne JN (1968). "The diphosphoinositide kinase of rat brain". Biochem. J. 106 (4): 791-801. PMC 1198582 ... "A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate". Nature. 390 (6656): 192-6. doi:10.1038/36621. PMID ...
This enzyme is also called type II PIP kinase. This enzyme participates in 3 metabolic pathways: inositol phosphate metabolism ... Rameh LE, Tolias KF, Duckworth BC, Cantley LC (1997). "A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate". ... phosphatidylinositol signaling system, and regulation of actin cytoskeleton. ... In enzymology, a 1-phosphatidylinositol-5-phosphate 4-kinase (EC 2.7.1.149) is an enzyme that catalyzes the chemical reaction ...
It is the Ca2+-sensing subunit of the yeast phosphatidylinositol (PtdIns)-4-OH kinase, PIK1 It binds to many proteins, some in ... G-protein-coupled receptor kinase 2) D2 dopamine receptor IL1RAPL1 (interleukin-1 receptor accessory protein-like 1 protein) ... type III phosphatidylinositol 4-kinase β) IP3 receptor (this activity is inhibited by lithium - a drug used for the treatment ... 30 (1): 241-8. doi:10.1016/S0896-6273(01)00276-8. PMID 11343658. Saab BJ, Georgiou J, Nath A, Lee FJ, Wang M, Michalon A, Liu F ...
"Casein kinase I associates with members of the centaurin-alpha family of phosphatidylinositol 3,4,5-trisphosphate-binding ... Casein kinase I isoform alpha is an enzyme that in humans is encoded by the CSNK1A1 gene. Casein kinase 1, alpha 1 has been ... Zhang Y, Qiu WJ, Chan SC, Han J, He X, Lin SC (May 2002). "Casein kinase I and casein kinase II differentially regulate axin ... Casein kinase 1 GRCh38: Ensembl release 89: ENSG00000113712 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000024576 ...
Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T (Apr 2001). "Beclin-phosphatidylinositol 3-kinase complex functions at the trans- ... Zeng X, Overmeyer JH, Maltese WA (Jan 2006). "Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in ... "Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1". The Journal of ... Beclin-1 is a protein that in humans is encoded by the BECN1 gene. Beclin-1 is a mammalian ortholog of the yeast autophagy- ...
"Complementary DNA cloning and chromosomal mapping of a novel phosphatidylinositol kinase gene". DNA Research. 4 (4): 301-5. doi ... "Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase IIIbeta at the ... The kinase domain can be divided into N-terminal and C-terminal lobes with the ATP binding groove and putative ... Phosphatidylinositol 4-kinase beta is an enzyme that in humans is encoded by the PI4KB gene. This gene encodes a ...
"Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity". The Journal of ... Phosphatidylinositol 3-kinase regulatory subunit beta is an enzyme that in humans is encoded by the PIK3R2 gene. PIK3R2 has ... August A, Dupont B (May 1994). "CD28 of T lymphocytes associates with phosphatidylinositol 3-kinase". International Immunology ... a subunit of phosphatidylinositol 3-kinase, and its homologue p85 beta". Oncogene. 7 (4): 789-93. PMID 1314371. "Entrez Gene: ...
Lee DM, Patel DD, Pendergast AM, Haynes BF (August 1996). "Functional association of CD7 with phosphatidylinositol 3-kinase: ... "Functional association of CD7 with phosphatidylinositol 3-kinase: interaction via a YEDM motif". International Immunology. 8 (8 ... Subrahmanyam G, Rudd CE, Schneider H (January 2003). "Association of T cell antigen CD7 with type II phosphatidylinositol-4 ... 24 (1): 31-52. doi:10.1385/IR:24:1:31. PMID 11485208. Baker E, Sandrin MS, Garson OM, Sutherland GR, McKenzie IF, Webber LM ( ...
"The phosphatidylinositol 3' kinase pathway is required for the survival signal of leukocyte tyrosine kinase". Oncogene. 14 (25 ... Cook JA, August A, Henderson AJ (Jul 2002). "Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by ... The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling ... The PI3-kinase activity of this protein is sensitive to low nanomolar levels of the inhibitor wortmannin. The C2 domain of this ...
3-kinase. Substrate presentation by phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase complex". J. Biol. Chem. ... Phosphatidylinositol 3-kinase catalytic subunit type 3 is an enzyme that in humans is encoded by the PIK3C3 gene. GRCh38: ... Vogel LB, Fujita DJ (1994). "The SH3 domain of p56lck is involved in binding to phosphatidylinositol 3'-kinase from T ... Cook JA, August A, Henderson AJ (2002). "Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a ...
Cook JA, August A, Henderson AJ (2002). "Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a ... François F, Klotman ME (2003). "Phosphatidylinositol 3-Kinase Regulates Human Immunodeficiency Virus Type 1 Replication ... The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling ... production by primary human macrophages is mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein (MAP ...
Cook JA, August A, Henderson AJ (2002). "Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a ... 1997). "p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed ... François F, Klotman ME (2003). "Phosphatidylinositol 3-kinase regulates human immunodeficiency virus type 1 replication ... 1999). "Autophosphorylation of p110delta phosphoinositide 3-kinase: a new paradigm for the regulation of lipid kinases in vitro ...
This enzyme participates in inositol phosphate metabolism and phosphatidylinositol signaling system. Shears SB (1989). "The ... In enzymology, an inositol-tetrakisphosphate 5-kinase (EC 2.7.1.140) is an enzyme that catalyzes the chemical reaction ATP + 1D ... This enzyme is also called 1D-myo-inositol-tetrakisphosphate 5-kinase. ... 6-tetrakisphosphate 5-kinase". J. Biol. Chem. 264 (33): 19879-86. PMID 2584198. Stevenson-Paulik J, Odom AR, York JD (2002). " ...
AASDH: aminoadipate-semialdehyde dehydrogenase ACVR1: activin-like kinase 2 (ALK-2) ACOX3: encoding enzyme Peroxisomal acyl- ... Phosphatidylinositol 4-kinase type 2-beta PKD2: polycystic kidney disease 2 (autosomal dominant) PLK4: Serine/threonine-protein ... Kinase insert domain receptor (Vascular endothelial growth factor receptor 2) KIAA1530: UV stimulated scaffold protein A LCORL ... Chromosome 4 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 4 ...
... of 17α-Hydroxylase Activity Is Mediated by Phosphatidyl Inositol 3-Kinase But Not Extracellular Signal-Regulated Kinase-1/2 in ... 2007-02-22: 4 [29 March 2013]. ISBN 9781139462037.. *^ 18.00 18.01 18.02 18.03 18.04 18.05 18.06 18.07 18.08 18.09 18.10 18.11 ... 多囊性卵巢會受基因遺傳與環境因素影響[6][7]。其危險因子包含肥胖症、運動量不足或是有家族病史[8]。如果有以下三種症狀中的兩種便可診斷患者有多囊性卵巢:無排卵、雄性激素過高與卵
Type II phosphatidylinositol (PtdIns) 4-kinases produce PtdIns 4-phosphate, an early key signaling molecule in ... Epigallocatechin gallate (EGCG) inhibits type II phosphatidylinositol 4-kinases: A key component in pathways of ... and PtdIns 3-kinase activity in vitro. EGCG directly bind to both alpha and beta isoforms of type II PtdIns 4-kinases with a Kd ... phosphatidylinositol cycle, which is indispensable for T cell activation. Type II PtdIns 4-kinase alpha and beta have similar ...
Activation of the purified enzymes by phosphatidylinositol 4,5-bisphosphate, ADP-ribosylation factor, and Rho family monomeric ... GTP-binding proteins and protein kinase C-alpha. J. Biol. Chem., 272 (6): 3860-8. [PMID:9013646] ... 4. Scott SA, Selvy PE, Buck JR, Cho HP, Criswell TL, Thomas AL, Armstrong MD, Arteaga CL, Lindsley CW, Brown HA. (2009) Design ... ADP-ribosylation factor 1 (ARF1, P84077), PIP2, RhoA, PKC evoked phosphorylation, RalA [1-2] ...
... phosphatidylinositol kinase, type II phosphatidylinositol kinase, PI kinase, and PI 4-kinase. This enzyme participates in ... Other names in common use include phosphatidylinositol kinase (phosphorylating), phosphatidylinositol 4-kinase, ... "Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate". Nature. 332 (6165): ... Kai M, White GL, Hawthorne JN (1966). "The phosphatidylinositol kinase of rat brain". Biochem. J. 101 (2): 328-37. PMC 1270113 ...
Other names in common use include diphosphoinositide kinase, PIP kinase, phosphatidylinositol 4-phosphate kinase, ... and type I PIP kinase. This enzyme participates in 3 metabolic pathways: inositol phosphate metabolism, phosphatidylinositol ... Kai M, Salway JG, Hawthorne JN (1968). "The diphosphoinositide kinase of rat brain". Biochem. J. 106 (4): 791-801. PMC 1198582 ... "A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate". Nature. 390 (6656): 192-6. doi:10.1038/36621. PMID ...
Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. Mediates RAC1-dependent reorganization of actin ... 1,2-diacyl-sn-glycero-3-phospho-1D-myo-inositol 4-phosphate + ATP = a 1,2-diacyl-sn-glycero-3-phospho-1D-myo-inositol-4,5- ...
... phosphatidylinositol 4-kinase alpha pseudogene 1), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol. ... X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA PI4KAP1 (phosphatidylinositol 4-kinase alpha pseudogene 1). ... 1-phosphatidylinositol 4-kinase activity intracellular plasma membrane phosphatidylinositol phosphorylation ... phosphatidylinositol-mediated signaling Ontology : EGO-EBI. 1-phosphatidylinositol 4-kinase activity intracellular plasma ...
... to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and ... P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a ... Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis. Plays a role in ... is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of ...
Human phosphatidylinositol 4-kinase, catalytic, alpha (PI4KA), transcript variant 1 - 10 µg - RC218825 from OriGene ... PI4KA (Myc-DDK-tagged)-Human phosphatidylinositol 4-kinase, catalytic, alpha (PI4KA), transcript variant 1 - 10 µg ... PI4KA (Myc-DDK-tagged)-Human phosphatidylinositol 4-kinase, catalytic, alpha (PI4KA), transcript variant 1. ... RC218827: ZNF419 (Myc-DDK-tagged)-Human zinc finger protein 419 (ZNF419), transcript variant 1. Note: ORF is codon optimized ...
Mouse phosphatidylinositol-4-phosphate 5-kinase, type 1 beta (cDNA clone MGC:41200 IMAGE:3326897), (10ug), 10 µg. ... Home » cDNA » Mouse cDNA » Pip5k1b (untagged) - Mouse phosphatidylinositol-4-phosphate 5-kinase, type 1 beta (cDNA clone MGC: ... Properties for Pip5k1b (untagged) - Mouse phosphatidylinositol-4-phosphate 5-kinase, type 1 beta (cDNA clone MGC:41200 IMAGE: ... MC217732 Pip5k1b (untagged) - Mouse phosphatidylinositol-4-phosphate 5-kinase, type 1 beta (cDNA clone MGC:41200 IMAGE:3326897 ...
Other names in common use include diphosphoinositide kinase, PIP kinase, phosphatidylinositol 4-phosphate kinase, ... and type I PIP kinase. This enzyme participates in 3 metabolic pathways: inositol phosphate metabolism, phosphatidylinositol ... Kai M, Salway JG, Hawthorne JN (1968). "The diphosphoinositide kinase of rat brain". Biochem. J. 106: 791-801. PMID 4295336.. ... Rameh LE, Tolias KF, Duckworth BC, Cantley LC (1997). "A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate". ...
PIP5KL1 is a phosphoinositide kinase-like protein that lacks intrinsic lipid kinase activity but associates with type I PIPKs ( ... HCA RNA Cell Line for Phosphatidylinositol 4-phosphate 5-kinase-like protein 1. ... P 5-kinases to specific compartments within the cell, where they generate PI(4,5)P2 for actin nucleation, signaling and ... May act as a scaffold to localize and regulate type I PI(4) ... Brain - Spinal cord (cervical c-1) 17,973 Colon - Transverse ...
1) year after it arises, except to the extent such limitation is not enforceable. To the fullest extent permitted by law, each ...
... phosphate 5-kinase type-1 gamma PIP5K1C 01011393927 at Gentaur for Phosphatidylinositol-4-phosphate 5-kinase 1 gamma (PIP5K1C) ... Human Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (PIP5K1C) ELISA Kit is manufactured by highest quality antibodies ... Store and ship all of of the comptents of the EIA assay for Human Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma ( ... ELISA test for Human Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (PIP5K1C). * ...
... suggest that phosphatidylinositol kinase (PtdInsK) and phospholipase C (PLC) are elevated in this renal disorder. Therefore, ... suggest that phosphatidylinositol kinase (PtdInsK) and phospholipase C (PLC) are elevated in this renal disorder. Therefore, ... Overexpression of kidney phosphatidylinositol 4-kinasebeta and phospholipase C(gamma1) proteins in two rodent models of ... Disease-related increases in phosphatidylinositol 4-kinasebeta (PtdIns4Kbeta) and PLC(gamma1) levels were present in both ...
The generation of second messengers from the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdInsP2) by ... Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate Nature. 1988 Apr 14; ... The first step in the production of PtdInsP2 from phosphatidylinositol (PtdIns) is catalysed by PtdIns kinase. A PtdIns kinase ... We have now characterized the site on the inositol ring phosphorylated by type I PtdIns kinase, and find that this kinase ...
phosphatidylinositol-4-phosphate 5-kinase type 1 gamma. Enable Javascript to view the expand/collapse boxes.. Open All Close ... This locus encodes a type I phosphatidylinositol 4-phosphate 5-kinase. The encoded protein catalyzes phosphorylation of ... Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate ( ... producing phosphatidylinositol 4,5-bisphosphate. This enzyme is found at synapses and has been found to play roles in ...
Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,- ... Phosphatidylinositol 4-kinase betaAdd BLAST. 815. Amino acid modifications. Feature key. Position(s). DescriptionActions. ... kinase_CS. IPR015433 PI_Kinase. IPR001263 PInositide-3_kin_accessory_dom. ... kinase_CS. IPR015433 PI_Kinase. IPR001263 PInositide-3_kin_accessory_dom. ...
Thus, inositol phosphate analogues inter alia are shown for the first time to inhibit PI 3-kinase and may be useful tools for ... PI 3-kinase) activity immunoprecipitated from a leukemic T cell line by a p85 monoclonal antibody. A 3-position ring-modified ... did not inhibit PI 3-kinase activity under identical conditions. L-chiro-Ins(2,3,5)P3 closely resembles Ins(1,4,5)P3 and D-Ins( ... P3 did not inhibit PI 3-kinase activity, this suggests that the orientation of the two hydroxyl groups at the 2- and 3- ...
ENCODES a protein that exhibits 1-phosphatidylinositol-4-phosphate 3-kinase activity (ortholog); INVOLVED IN chemotaxis ( ... phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma. Orthologs:. Homo sapiens (human) : PIK3C2G ( ... phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma. Description:. ENCODES a protein that exhibits 1- ... Gene: PIK3C2G (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma) Pan paniscus. {{ watchLinkText }} ...
5 expression by protein kinase C. Lippoldt, Andrea; Liebner, Stefan; Andbjer, Beth; More ... 5 expression by protein kinase C. Lippoldt, Andrea; Liebner, Stefan; Andbjer, Beth; More ... 5 expression by protein kinase C. Lippoldt, Andrea; Liebner, Stefan; Andbjer, Beth; More ... 5 expression by protein kinase C. Lippoldt, Andrea; Liebner, Stefan; Andbjer, Beth; More ...
phosphatidylinositol kinase (phosphorylating);. phosphatidylinositol 4-kinase;. phosphatidylinositol kinase;. type II ... Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. ... A novel family of phosphatidylinositol 4-kinases conserved from yeast to humans. ... Pathway (7) KEGG PATHWAY (6) KEGG MODULE (1) Chemical substance (4) KEGG COMPOUND (4) Chemical reaction (3) KEGG REACTION (1) ...
kinase binding. PIP5K1A. IDA. Human. PMID:15157668. Molecular Function. GO:0005515. protein binding. PIP5K1A. IPI. UniProtKB: ... phosphatidylinositol metabolic process. Pip5k1a. IDA. Mouse. MGI:MGI:83079,PMID:8798574. Biological Process. GO:0008654. ... phosphatidylinositol biosynthetic process. Pip5k1a. IGI. MGI:MGI:1298224. Mouse. MGI:MGI:4844021,PMID:20622009. Biological ... 1-phosphatidylinositol-4-phosphate 5-kinase activity. Pip5k1a. IDA. Mouse. MGI:MGI:83079,PMID:8798574. Molecular Function. GO: ...
Phosphatidylinositol 4-Kinase Alpha Pseudogene 2, including: function, proteins, disorders, pathways, orthologs, and expression ... Putative phosphatidylinositol 4-kinase alpha-like protein P2. Protein Accession:. A4QPH2. Secondary Accessions: *Q6ICJ0 ... Gene Ontology (GO) annotations related to this gene include kinase activity and phosphotransferase activity, alcohol group as ... Phosphatidylinositol 4-Kinase, Catalytic, Alpha Pseudogene 2 2 3 * Phosphatidylinositol 4-Kinase, Catalytic, Alpha Polypeptide ...
phosphatidylinositol-4-phosphate 5-kinase, type 1 beta. 15. 4. 9. 22. ... pep:known chromosome:VEGA66:19:24294794:24555872:-1 gene:OTTMUSG00000031802 transcript:OTTMUST00000078826 gene_biotype:protein_ ... coding transcript_biotype:protein_coding gene_symbol:Pip5k1b description:phosphatidylinositol-4-phosphate 5-kinase, type 1 beta ...
Phosphatidylinositol 3 phosphate 5 kinase type III. *Phosphatidylinositol 3 phosphate/phosphatidylinositol 5 kinase type III ... The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5 ... to form phosphatidylinositol 3,5-bisphosphate. Required for endocytic-vacuolar pathway and nuclear migration. Plays a role in ... P2). Catalyzes the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, ...
  • A PtdIns kinase activity has been found to associate specifically with several oncogene products, as well as with the platelet-derived growth factor (PDGF) receptor. (nih.gov)
  • Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor. (nih.gov)
  • At a symposium at the 61st Scientific Sessions of the ADA in June 2001, the results of three recent diabetic nephropathy trials with angiotensin II subtype 1 receptor antagonists were presented. (diabetesjournals.org)
  • Castellino AM, Parker GJ, Boronenkov IV, Anderson RA, Chao MV. A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase. (springer.com)
  • 22 This nonreceptor tyrosine kinase is typically activated by extracellular stress signals, such as shear stress, 23 but also by G protein-coupled receptors, such as the angiotensin type 1 receptor. (ahajournals.org)
  • CBL is a negative regulator of activated receptor tyrosine kinases (RTK). (aacrjournals.org)
  • This phenotype resembles that seen with activated receptor tyrosine kinases. (aacrjournals.org)
  • CBL, a known negative regulator of activated receptor tyrosine kinases (RTK), is localized on human chromosome 11q23, a region frequently associated with chromosomal aberrations. (aacrjournals.org)
  • CBL-70Z deregulates the cellular tyrosine kinase machinery, as NIH3T3 serum-starved cells expressing CBL-70Z showed significantly increased endothelial growth factor receptor (EGFR) kinase activity after EGF stimulation ( 5 ). (aacrjournals.org)
  • Restoring STAT5 activity via a heterologous receptor rescued Shc-induced Akt/p70S6 kinase activity and cell proliferation with kinetics consistent with a transcriptional mechanism. (jimmunol.org)
  • Furthermore, expression of kinase dead AKT2(181 amino acid methionine [M]), and not kinase dead AKT1(179M) or AKT3(177M), was capable of blocking invasion induced by either human epidermal growth factor receptor-2 (HER-2) overexpression or by activation of PI3-K. Taken together, these data indicate that AKT2 mediates PI3-K-dependent effects on adhesion, motility, invasion, and metastasis in vivo . (aacrjournals.org)
  • GLP-1 and its long-acting receptor agonist, exendin-4 (ex-4) ( 6 , 7 ), increase the survival of immortalized rodent β-cell lines and purified rat β-cells when challenged with various pro-apoptotic stimuli, including the pro-inflammatory cytokine interleukin-1β (IL-1β) ( 8 - 13 ). (diabetesjournals.org)
  • Increased levels of IL-1β and reduction in IL-1β-receptor antagonist content have been observed in pancreatic islets of patients with type 2 diabetes ( 14 , 15 ). (diabetesjournals.org)
  • The GLP-1 promotes β-cell survival by interaction with GLP-1 receptor (GLP-1R), a member of the G s -protein-coupled receptor superfamily ( 16 ). (diabetesjournals.org)
  • Analysis of D2 receptors expressed in human embryonic kidney 293 cells indicates that NCS-1 attenuates agonist-induced receptor internalization via a mechanism that involves a reduction in D2 receptor phosphorylation. (jneurosci.org)
  • This effect of NCS-1 was accompanied by an increase in D2 receptor-mediated cAMP inhibition after dopamine stimulation. (jneurosci.org)
  • The ability of NCS-1 to modulate D2 receptor signaling was abolished after a single amino acid mutation in NCS-1 that has been shown to impair the calcium-binding properties of NCS-1. (jneurosci.org)
  • Coimmunoprecipitation experiments from striatal neurons reveal that NCS-1 is found in association with both the D2 receptor and G-protein-coupled receptor kinase 2, a regulator of D2 receptor desensitization. (jneurosci.org)
  • NCS-1-D2 receptor interaction may serve to couple dopamine and calcium signaling pathways, thereby providing a critical component in the regulation of dopaminergic signaling in normal and diseased brain. (jneurosci.org)
  • Although originally thought to mediate agonist-dependent (homologous) and agonist-independent (heterologous) forms of receptor desensitization, both GRKs and second messenger kinases are now believed to contribute to both forms of receptor desensitization in a more complex manner ( Ferguson, 2001 ). (jneurosci.org)
  • Therefore, it is likely that the mechanism underlying receptor desensitization, including the desensitization of subtypes of dopamine receptors, is modulated by the activity of proteins that can interact with both the receptor and its kinase. (jneurosci.org)
  • The elevated MCP-1 may alter adipocyte function because addition of MCP-1 to differentiated adipocytes in vitro decreases insulin-stimulated glucose uptake and the expression of several adipogenic genes ( LpL, adipsin, GLUT-4, aP2 , β3-adrenergic receptor, and peroxisome proliferator-activated receptor γ). (pnas.org)
  • Activated CD4 + T cells secrete IL-1, IFN-γ, and TNF-α, inducing the expression of TSH receptor and CD40 on the surface of orbital fibroblasts, which promote the secretion of IL-6, −8, fibronectin, type 1 collagen, and glycosaminoglycans. (arvojournals.org)
  • Expression of CBLΔexon8 and CBLΔexon8+9 in FLT3-WT-Ba/F3 cells induced growth factor-independent proliferation associated with autophosphorylation of FLT3 and activated the downstream targets signal transducer and activator of transcription 5 (STAT5) and protein kinase B (AKT). (aacrjournals.org)
  • PKB/Akt and serum and glucocorticoid-regulated kinase (SGK) family kinases are important downstream targets of phosphatidylinositol 3 (PI-3) kinase and have been shown to mediate a variety of cellular processes, including cell growth and survival. (rupress.org)
  • Intracellular signaling is mediated by IL-2Rβ and γ c , which undergo IL-2-induced heterodimerization followed by activation of the associated tyrosine kinases Jak1 and Jak3 ( 4 , 5 ). (jimmunol.org)
  • Thus, inositol phosphate analogues inter alia are shown for the first time to inhibit PI 3-kinase and may be useful tools for determining the function of PI 3-kinase and its substrate binding specificities. (ox.ac.uk)
  • Substrate specificities and identification of putative substrates of ATM kinase family members. (eu.org)
  • However till date the treatment of cancer is a major challenge for the reasons associated with the complexity of cell signalling pathways, heterogeneity of tumor cell, development of resistance to current therapy[ 4 ] and inevitable side effects[ 5 ]. (ijpsonline.com)
  • Interestingly, these studies also reveal that insulin-resistant (IR) adipocytes and mice remained sensitive to insulin in terms of PAI-1 gene expression, possibly because glucose homeostasis and PAI-1 gene expression are regulated by different insulin signaling pathways ( 13 ). (pnas.org)
  • The 5-year overall survival for glioblastoma is only about 5% even after aggressive treatments including maximal surgical removal of the tumor, ionizing radiation, and chemotherapy ( 1 - 6 ). (frontiersin.org)
  • Interleukin-2 is a potent cytokine used for the in vitro expansion of T cells and to treat diseases such as melanoma, renal cell carcinoma, and HIV/AIDS ( 1 , 2 , 3 ). (jimmunol.org)
  • In addition to class II molecules bearing the appropriate peptide, adhesive and costimulatory interactions are required to induce T cell proliferation and effector function ( 1 , 2 , 3 ). (jimmunol.org)