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.
Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.
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.
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)
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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
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.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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.
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.
Agents that inhibit PROTEIN KINASES.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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)
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.
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.
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.
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.
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.
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 kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
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.
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.
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.
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
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).
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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3.
An enzyme that catalyzes the formation of PHOSPHATIDYLINOSITOL and CMP from CDP-DIACYLGLYCEROL and MYOINOSITOL.
The rate dynamics in chemical or physical systems.
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.
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.
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.
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.
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 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.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
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.
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).
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
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.
Proteins prepared by recombinant DNA technology.
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.
A cell line derived from cultured tumor cells.
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).
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.
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.
Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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.
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.
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.
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.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
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.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
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.
A group of phenyl benzopyrans named for having structures like FLAVONES.
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.
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.
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 enzymes
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
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.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
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).
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
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.
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.
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 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.
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.
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.
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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
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.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
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.
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.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
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.
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.
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.
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.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
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.
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.
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.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
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.
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.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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.
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.
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.
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.
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 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.
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.
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.
Four carbon unsaturated hydrocarbons containing two double bonds.
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.
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.
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.
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.
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.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
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.
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.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
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.
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)
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.
Unstable isotopes of phosphorus that decay or disintegrate emitting radiation. P atoms with atomic weights 28-34 except 31 are radioactive phosphorus isotopes.
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.
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.
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.
A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.
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.
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.
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.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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)
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
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.
The phosphoric acid ester of serine.
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.
Compounds containing carbohydrate or glycosyl groups linked to phosphatidylinositols. They anchor GPI-LINKED PROTEINS or polysaccharides to cell membranes.
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).
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.
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.
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.
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.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.
A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.

Vac1p coordinates Rab and phosphatidylinositol 3-kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome. (1/13288)

The vacuolar protein sorting (VPS) pathway of Saccharomyces cerevisiae mediates transport of vacuolar protein precursors from the late Golgi to the lysosome-like vacuole. Sorting of some vacuolar proteins occurs via a prevacuolar endosomal compartment and mutations in a subset of VPS genes (the class D VPS genes) interfere with the Golgi-to-endosome transport step. Several of the encoded proteins, including Pep12p/Vps6p (an endosomal target (t) SNARE) and Vps45p (a Sec1p homologue), bind each other directly [1]. Another of these proteins, Vac1p/Pep7p/Vps19p, associates with Pep12p and binds phosphatidylinositol 3-phosphate (PI(3)P), the product of the Vps34 phosphatidylinositol 3-kinase (PI 3-kinase) [1] [2]. Here, we demonstrate that Vac1p genetically and physically interacts with the activated, GTP-bound form of Vps21p, a Rab GTPase that functions in Golgi-to-endosome transport, and with Vps45p. These results implicate Vac1p as an effector of Vps21p and as a novel Sec1p-family-binding protein. We suggest that Vac1p functions as a multivalent adaptor protein that ensures the high fidelity of vesicle docking and fusion by integrating both phosphoinositide (Vps34p) and GTPase (Vps21p) signals, which are essential for Pep12p- and Vps45p-dependent targeting of Golgi-derived vesicles to the prevacuolar endosome.  (+info)

Concomitant activation of pathways downstream of Grb2 and PI 3-kinase is required for MET-mediated metastasis. (2/13288)

The Met tyrosine kinase - the HGF receptor - induces cell transformation and metastasis when constitutively activated. Met signaling is mediated by phosphorylation of two carboxy-terminal tyrosines which act as docking sites for a number of SH2-containing molecules. These include Grb2 and p85 which couple the receptor, respectively, with Ras and PI 3-kinase. We previously showed that a Met mutant designed to obtain preferential coupling with Grb2 (Met2xGrb2) is permissive for motility, increases transformation, but - surprisingly - is impaired in causing invasion and metastasis. In this work we used Met mutants optimized for binding either p85 alone (Met2xPI3K) or p85 and Grb2 (MetPI3K/Grb2) to evaluate the relative importance of Ras and PI 3-kinase as downstream effectors of Met. Met2xPI3K was competent in eliciting motility, but not transformation, invasion, or metastasis. Conversely, MetP13K/Grb2 induced motility, transformation, invasion and metastasis as efficiently as wild type Met. Furthermore, the expression of constitutively active PI 3-kinase in cells transformed by the Met2xGrb2 mutant, fully rescued their ability to invade and metastasize. These data point to a central role for PI 3-kinase in Met-mediated invasiveness, and indicate that simultaneous activation of Ras and PI 3-kinase is required to unleash the Met metastatic potential.  (+info)

Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing. (3/13288)

Amyloid fibrils are assemblies of misfolded proteins and are associated with pathological conditions such as Alzheimer's disease and the spongiform encephalopathies. In the amyloid diseases, a diverse group of normally soluble proteins self-assemble to form insoluble fibrils. X-ray fibre diffraction studies have shown that the protofilament cores of fibrils formed from the various proteins all contain a cross-beta-scaffold, with beta-strands perpendicular and beta-sheets parallel to the fibre axis. We have determined the threedimensional structure of an amyloid fibril, formed by the SH3 domain of phosphatidylinositol-3'-kinase, using cryo-electron microscopy and image processing at 25 A resolution. The structure is a double helix of two protofilament pairs wound around a hollow core, with a helical crossover repeat of approximately 600 A and an axial subunit repeat of approximately 27 A. The native SH3 domain is too compact to fit into the fibril density, and must unfold to adopt a longer, thinner shape in the amyloid form. The 20x40-A protofilaments can only accommodate one pair of flat beta-sheets stacked against each other, with very little inter-strand twist. We propose a model for the polypeptide packing as a basis for understanding the structure of amyloid fibrils in general.  (+info)

Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. (4/13288)

Interaction between integrin alphavbeta3 and extracellular matrix is crucial for endothelial cells sprouting from capillaries and for angiogenesis. Furthermore, integrin-mediated outside-in signals co-operate with growth factor receptors to promote cell proliferation and motility. To determine a potential regulation of angiogenic inducer receptors by the integrin system, we investigated the interaction between alphavbeta3 integrin and tyrosine kinase vascular endothelial growth factor receptor-2 (VEGFR-2) in human endothelial cells. We report that tyrosine-phosphorylated VEGFR-2 co-immunoprecipitated with beta3 integrin subunit, but not with beta1 or beta5, from cells stimulated with VEGF-A165. VEGFR-2 phosphorylation and mitogenicity induced by VEGF-A165 were enhanced in cells plated on the alphavbeta3 ligand, vitronectin, compared with cells plated on the alpha5beta1 ligand, fibronectin or the alpha2beta1 ligand, collagen. BV4 anti-beta3 integrin mAb, which does not interfere with endothelial cell adhesion to vitronectin, reduced (i) the tyrosine phosphorylation of VEGFR-2; (ii) the activation of downstream transductor phosphoinositide 3-OH kinase; and (iii) biological effects triggered by VEGF-A165. These results indicate a new role for alphavbeta3 integrin in the activation of an in vitro angiogenic program in endothelial cells. Besides being the most important survival system for nascent vessels by regulating cell adhesion to matrix, alphavbeta3 integrin participates in the full activation of VEGFR-2 triggered by VEGF-A, which is an important angiogenic inducer in tumors, inflammation and tissue regeneration.  (+info)

The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase. (5/13288)

Stimulation of the hepatocyte growth factor (HGF) receptor tyrosine kinase, Met, induces mitogenesis, motility, invasion, and branching tubulogenesis of epithelial and endothelial cell lines in culture. We have previously shown that Gab1 is the major phosphorylated protein following stimulation of the Met receptor in epithelial cells that undergo a morphogenic program in response to HGF. Gab1 is a member of the family of IRS-1-like multisubstrate docking proteins and, like IRS-1, contains an amino-terminal pleckstrin homology domain, in addition to multiple tyrosine residues that are potential binding sites for proteins that contain SH2 or PTB domains. Following stimulation of epithelial cells with HGF, Gab1 associates with phosphatidylinositol 3-kinase and the tyrosine phosphatase SHP2. Met receptor mutants that are impaired in their association with Gab1 fail to induce branching tubulogenesis. Overexpression of Gab1 rescues the Met-dependent tubulogenic response in these cell lines. The ability of Gab1 to promote tubulogenesis is dependent on its pleckstrin homology domain. Whereas the wild-type Gab1 protein is localized to areas of cell-cell contact, a Gab1 protein lacking the pleckstrin homology domain is localized predominantly in the cytoplasm. Localization of Gab1 to areas of cell-cell contact is inhibited by LY294002, demonstrating that phosphatidylinositol 3-kinase activity is required. These data show that Gab1 is an important mediator of branching tubulogenesis downstream from the Met receptor and identify phosphatidylinositol 3-kinase and the Gab1 pleckstrin homology domain as crucial for subcellular localization of Gab1 and biological responses.  (+info)

Signals from the Ras, Rac, and Rho GTPases converge on the Pak protein kinase in Rat-1 fibroblasts. (6/13288)

Ras plays a key role in regulating cellular proliferation, differentiation, and transformation. Raf is the major effector of Ras in the Ras > Raf > Mek > extracellular signal-activated kinase (ERK) cascade. A second effector is phosphoinositide 3-OH kinase (PI 3-kinase), which, in turn, activates the small G protein Rac. Rac also has multiple effectors, one of which is the serine threonine kinase Pak (p65(Pak)). Here we show that Ras, but not Raf, activates Pak1 in cotransfection assays of Rat-1 cells but not NIH 3T3 cells. We tested agents that activate or block specific components downstream of Ras and demonstrate a Ras > PI 3-kinase > Rac/Cdc42 > Pak signal. Although these studies suggest that the signal from Ras through PI 3-kinase is sufficient to activate Pak, additional studies suggested that other effectors contribute to Pak activation. RasV12S35 and RasV12G37, two effector mutant proteins which fail to activate PI 3-kinase, did not activate Pak when tested alone but activated Pak when they were cotransfected. Similarly, RacV12H40, an effector mutant that does not bind Pak, and Rho both cooperated with Raf to activate Pak. A dominant negative Rho mutant also inhibited Ras activation of Pak. All combinations of Rac/Raf and Ras/Raf and Rho/Raf effector mutants that transform cells cooperatively stimulated ERK. Cooperation was Pak dependent, since all combinations were inhibited by kinase-deficient Pak mutants in both transformation assays and ERK activation assays. These data suggest that other Ras effectors can collaborate with PI 3-kinase and with each other to activate Pak. Furthermore, the strong correlation between Pak activation and cooperative transformation suggests that Pak activation is necessary, although not sufficient, for cooperative transformation of Rat-1 fibroblasts by Ras, Rac, and Rho.  (+info)

Salmonella typhimurium and lipopolysaccharide stimulate extracellularly regulated kinase activation in macrophages by a mechanism involving phosphatidylinositol 3-kinase and phospholipase D as novel intermediates. (7/13288)

Activation of the extracellularly regulated kinase (ERK) pathway is part of the early biochemical events that follow lipopolysaccharide (LPS) treatment of macrophages or their infection by virulent and attenuated Salmonella strains. Phagocytosis as well as the secretion of invasion-associated proteins is dispensable for ERK activation by the pathogen. Furthermore, the pathways used by Salmonella and LPS to stimulate ERK are identical, suggesting that kinase activation might be solely mediated by LPS. Both stimuli activate ERK by a mechanism involving herbimycin-dependent tyrosine kinase(s) and phosphatidylinositol 3-kinase. Phospholipase D activation and stimulation of protein kinase C appear to be intermediates in this novel pathway of MEK/ERK activation.  (+info)

Granulocyte-macrophage colony-stimulating factor-activated signaling pathways in human neutrophils. Involvement of Jak2 in the stimulation of phosphatidylinositol 3-kinase. (8/13288)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates many of the biological activities of human neutrophils. The signaling pathways via which these effects are mediated are not fully understood. We have shown previously that GM-CSF treatment of human neutrophils activates the Janus kinase/signal transducers and activators of transcription (Jak/STAT) pathway and, more specifically, Jak2, STAT3, and STAT5B in neutrophils. GM-CSF also stimulates the activity of the phosphatidylinositol 3-kinase (PI3-kinase) in a tyrosine kinase-dependent manner. Here we report that pretreating the cells with a Jak2 inhibitor (AG-490) abolishes tyrosine phosphorylation of the p85 subunit of PI3-kinase induced by GM-CSF. Furthermore, p85 was found to associate with Jak2, but not with Lyn, in stimulated cells in situ and with its autophosphorylated form in vitro; however, Jak2 did not bind to either of the two Src homology 2 (SH2) domains of the p85 subunit of PI3-kinase. Although STAT5B bound to the carboxyl-terminal SH2 domain of p85, it was absent from the complex containing PI3-kinase and Jak2. These results suggest that stimulation of the activity of PI3-kinase induced by GM-CSF is mediated by Jak2 and that the association between Jak2 and p85 depends on an adaptor protein yet to be identified.  (+info)

Murine D type cyclins associate with a catalytic subunit (p34PSK-J3) with properties distinct from known cyclin-dependent kinases (cdks). Mouse p34PSK-J3 shows less than 50% amino acid identity to p34cdc2, p33cdk2, and p36cdk3, lacks a PSTAIRE motif, and does not bind to p13suc1. Cyclin D1-p34PSK-J3 …
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 ...
[75 Pages Report] Check for Discount on Phosphatidylinositol 4,5 Bisphosphate 3 Kinase Catalytic Subunit Beta Isoform (Phosphatidylinositol 4,5 Bisphosphate 3 Kinase 110 kDa Catalytic Subunit Beta or PIK3CB or EC 2.7.1.153) - Pipeline Review, H2 2017 report by Global Markets Direct. Phosphatidylinositol 4,5 Bisphosphate 3 Kinase Catalytic Subunit Beta Isoform (...
TY - JOUR. T1 - Protein kinase B (c-Akt). T2 - A multifunctional mediator of phosphatidylinositol 3-kinase activation. AU - Coffer, Paul J.. AU - Jin, Jing. AU - Woodgett, James R.. PY - 1998/10/1. Y1 - 1998/10/1. N2 - While a plethora of extracellular molecules exist that modulate cellular functions via binding to membrane receptors inside the cell, their actions are mediated by relatively few signalling mechanisms. One of these is activation of phosphatidylinositol 3-kinase (PI-3K), which results in the generation of a membrane-restricted second messenger, polyphosphatidylinositides containing a 3-phosphate. How these molecules transduced the effects of agonists of PI-3K was unclear until the recent discovery that several protein kinases become activated upon exposure to 3-phosphorylated inositol lipids. These enzymes include protein kinase B (PKB)/AKT and PtdIns(3,4,5)P3-dependent kinases 1 and 2, the first two of which interact with 3-phosphorylated phosphoinositides via pleckstrin ...
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 ...
Lipid kinase activity of PI(3)K increased within 5 min of TNF stimulation and was maximal at 20 min. Probing Western blots of proteins from 293 cells with antibody to activated (phosphorylated) Akt revealed a temporal correlation with PI(3)K activity, an effect blocked by wortmannin. Dominant-negative PI(3)K transfection abrogated the 2.3-fold increase in Akt activity.. EMSA studies showed NF-?B activity in response to TNF stimulation and inhibition by wortmannin. Activity was enhanced by transient transfection with constitutively active PI(3)K or constitutively active Akt or NIK. Cotransfection of NIK with constitutively active Akt or PI(3)K produced an additive effect on NF-?B binding to DNA, while dominant negative PI(3)K inhibited NF-?B activation and dominant-negative NIK or wortmannin abrogated PI(3)K activation of NF-&?B. While constitutively active Akt alone promoted NF-?B binding to DNA, kinase-dead Akt inhibited it, showing Akt to be essential for NF-?B activation. However, ...
Beta-1 adrenergic receptor, Beta-2 adrenergic receptor, Beta-3 adrenergic receptor, Mitogen-activated protein kinase 1, Phosphatidylinositol 3-kinase regulatory subunit alpha, Phosphatidylinositol 3-kinase regulatory subunit beta, Phosphatidylinositol 3-kinase regulatory subunit gamma, CAMP ...
Order Anti-human phosphatidylinositol-3-phosphate phosphatidylinositol 5-kinase type III PAb 02012560599 at Gentaur phosphatidylinositol-3-phosphate/phosphatidylinositol 5-kinase, III PAb
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Phosphoinositide 3-kinase (PI3K) type IA is a heterodimer of a catalytic subunit, p110, and a regulatory subunit, p85. Here we show that p85 contains a GTPase-responsive domain and an inhibitory domain, which together form a molecular switch that regulates PI3K. H-Ras and Rac1 activate PI3K by targe …
The phosphoinositide 3-kinase (PI3K) family catalyses the addition of a phosphate group to the D-3 position of polyphosphoinositides (PPIn). Since the discovery in the late 80s that...
Inositol 5-phosphatase, which converts inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate. Also converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate and inositol 1,3,4,5-tetrakisphosphate to inositol 1,3,4-trisphosphate in vitro. May be involved in modulation of the function of inositol and phosphatidylinositol polyphosphate-binding proteins that are present at membranes ruffles (By similarity).
Mutations in the catalytic subunit of the phosphatidylinositol 3-kinase (PI3K, encoded by PIK3CA) are common in breast cancer. Drugs inhibiting PI3K show efficacy in a small proportion of patients; some tumors are intrinsically resistant, whereas others become resistant. Le et al. found that another kinase, proviral insertion site in murine leukemia virus (PIM), maintains the activity of downstream effectors of the PI3K pathway and that cotargeting PIM may be effective in patients that show resistance to PI3K inhibitors. A large gain-of-function screen in cultured PI3K-mutant, luminal A-type breast cancer cells identified genes encoding isoforms of PIM as promoting resistance to the PI3K inhibitor BYL719. Overexpression of PIM1 (more so than that of PIM2 or PIM3) decreased the potency of BYL719 and other PI3K pathway inhibitors in various types of breast cancer cells. Cultures of PI3K-mutant breast cancer cells that were resistant to BYL719 had greater abundance of all three PIM isoforms than ...
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Regulatory subunit of the PI3K gamma complex. Required for recruitment of the catalytic subunit to the plasma membrane via interaction with beta-gamma G protein dimers. Required for G protein-mediated activation of PIK3CG (By similarity).
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
TY - JOUR. T1 - Regulation of the PI3K pathway through a p85α monomer-homodimer equilibrium. AU - Cheung, Lydia W T. AU - Walkiewicz, Katarzyna Wiktoria. AU - Besong, Tabot M.D.. AU - Guo, Huifang. AU - Hawke, David H.. AU - Arold, Stefan T.. AU - Mills, Gordon B.. N1 - KAUST Repository Item: Exported on 2020-10-01. PY - 2015/7/29. Y1 - 2015/7/29. N2 - The canonical action of the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI3K) is to associate with the p110α catalytic subunit to allow stimuli-dependent activation of the PI3K pathway. We elucidate a p110α-independent role of homodimerized p85α in the positive regulation of PTEN stability and activity. p110α-free p85α homodimerizes via two intermolecular interactions (SH3:proline-rich region and BH:BH) to selectively bind unphosphorylated activated PTEN. As a consequence, homodimeric but not monomeric p85α suppresses the PI3K pathway by protecting PTEN from E3 ligase WWP2-mediated proteasomal degradation. Further, the p85α ...
Insulin-like growth factor-1 prevents Abeta[25-35]/(H2O2)- induced apoptosis in lymphocytes by reciprocal NF-kappaB activation and p53 inhibition via PI3K-dependent pathway ...
OriGene offers comprehensive product solutions for studying human protein kinases. Our functional kinome cDNA collection was featured in a Cell publication in 2008.
Epidermal-mesenchymal transition (EMT) confers an advantage to cancer cells by improving their invasive capacity and metastatic potential. Therefore hRad50 the concentrations of PTX were set as 1 nM 2.5 nM and 5 nM for the subsequent experiments. In the morphological investigation the CCKS-1 cells changed into a spindle morphology and became separated by the administration … Read more Epidermal-mesenchymal transition (EMT) confers an advantage to cancer cells by improving. Read More ...
Weve investigated the ability of anti-CD28 antibody costimulation to induce resistance to macrophage (M)-tropic strains of human immunodeficiency computer virus type 1 (HIV-1) in vitro. cells were passaged constantly on freshly coated plates. If the beads were removed after initial stimulation, p24 production increased over time and produced a result intermediate to the other forms … Read more Weve investigated the ability of anti-CD28 antibody costimulation to induce resistance. Read More ...
In contrast to what has been reported regarding PDGFR (Joly et al., 1994), our results indicate that the intracellular trafficking of EGFR does not require EGF‐stimulated PI3K activity. Among the three classes of PI3Ks, only class I p85/p110 PI3Ks are activated by EGFR and PDGFR (Hu et al., 1992; Rodriguez‐Viciana et al., 1994). To completely inhibit EGF‐stimulated PI3K activity, SKBR‐3 and 293T cells were transfected with the kinase‐deficient p110α subunit p110Δkin (Hu and Schlessinger, 1994). We showed that transfection of cells with p110Δkin had no effect on the EGF‐stimulated lysosomal targeting and degradation of EGFR (Figure 1). It has been reported that microinjection of inhibitory anti‐p110α antibodies did not block the transit of internalized PDGFR to perinuclear compartments (Siddhanta et al., 1998).. In addition, we showed that inhibition of PI3K activity by 100 nM or 20 μM LY294002 does not block the EGF‐induced lysosomal targeting and degradation of EGFR ...
Regeneron Pharmaceuticals Licenses OriGene TrueClone Collection. We believe that full-length cDNAs isolated from cDNA libraries are the most reliable source of authentic coding regions for our critical applications. said Drew Murphy, Vice President of Target Discovery for Regeneron. The OriGene True Clone collection has proven to be an excellent source of full-length human cDNAs for use in Regenerons protein expression and target validation platforms.. ...
Sigma-Aldrich offers abstracts and full-text articles by [Aashiq Hussain, Asif Khurshid Qazi, Nagaraju Mupparapu, Santosh Kumar Guru, Ashok Kumar, Parduman Raj Sharma, Shashank Kumar Singh, Paramjit Singh, Mohd Jamal Dar, Sandip B Bharate, Mohmmad Afzal Zargar, Qazi Naveed Ahmed, Shashi Bhushan, Ram A Vishwakarma, Abid Hamid].
We report the feasibility of screening for the presence of common oncogenic PIK3CA mutations in patients with breast cancer by a simple blood test using BEAMing. Overall, ctDNA was isolated from 109 patient blood samples and a PIK3CA mutation was identified in 28.4%. Of critical importance, testing done in the prospective cohort clearly exemplified the current challenges of locating quality archival tissue samples for biomarker testing. In this case, sufficient tissue was available for only 51 of 60 prospectively enrolled patients (85%). In contrast, BEAMing on ctDNA was successful in the blood samples from all 60 enrolled patients, with a PIK3CA mutation frequency similar to that previously reported (Table 2; refs. 6, 7, 20, 21). Of interest, BEAMing of plasma samples from 2 patients showed 2 separate PIK3CA mutations in each of exons 9 and 20; this is a rare phenomenon but has been previously described (22).. Most critical and with implications for both clinical trial design and clinical ...
PIK-93 is a potent PI3K inhibitor. PIK93 selectively inhibits the type III PI 4-kinase beta enzyme, and small interfering RNA-mediated down-regulation of the individual PI 4-kinase enzymes, revealed that PI 4-kinase beta has a dominant role in ceramide transport between the ER and Golgi.
MSC2360844 is a potent, orally active and selective PI3Kδ inhibitor, with an IC50 of 145 nM. MSC2360844 shows highly selective against a panel of 278 additional kinases. - Mechanism of Action & Protocol.
Overexpression of a dominant-negative PI3Kinase (DP110) resulted in mutants that have impaired regeneration of the intestinal epithelium and are short lived ...
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
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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.
PI 3-Kinase p110 beta/PIK3CB products available through Novus Biologicals. Browse our PI 3-Kinase p110 beta/PIK3CB product catalog backed by our Guarantee+.
Easy-to-use kits for performing kinase selectivity profiling that rely on the ADP-Glo Kinase Assay technology. Each system includes kinase and substrate pairs in an easy-to-use 8-tube strip format optimized for fast and simple kinase profiling reactions.
Easy-to-use kits for performing kinase selectivity profiling that rely on the ADP-Glo Kinase Assay technology. Each system includes kinase and substrate pairs in an easy-to-use 8-tube strip format optimized for fast and simple kinase profiling reactions.
Onconova therapeutics is developing selective inhibitors of phosphatidylinositol-3-kinase (PI3K) alpha/delta isoforms, called the ON 146 series, for the
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PI 3 Kinase p85 alpha + Gamma兔多克隆抗体(ab74136)可与小鼠, 大鼠, 人样本反应并经WB, ELISA, IHC, ICC/IF实验严格验证,被3篇文献引用并得到2个独立的用户反馈。
Patients who have breast cancers with double PIK3CA mutations seem to have a more robust response to PI3Kα inhibitors than those with a single PIK3CA mutation, based on an analysis of the phase III SA.... ...
The Akt/PKB signaling pathway is a pathway in cell signaling. Proteins involved include AKT (also known as protein kinase B) and phosphoinositide 3-kinase.
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高い抗原親和性、特異性と安定した品質を兼ね備えたアブカムのウサギ・モノクローナル抗体 RabMAb® ab79422 交差種: Hu 適用: WB
Phosphatidylinositol 4,5 Bisphosphate 3 Kinase Catalytic Subunit Alpha Isoform (Phosphatidylinositol 4,5 Bisphosphate 3 Kinase 110 kDa Catalytic Subunit Alpha or Phosphoinositide 3 Kinase Catalytic Alpha Polypeptide or Serine/Threonine Protein Kinase PIK3CA or PIK3CA or EC 2.7.11.1 or EC 2.7.1.153) - The phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha also called p110α is a protein encoded by the PIK3CA gene. It is involved in cell growth, survival, proliferation, motility and morphology. It participates in cellular signaling in response to various growth factors. It is involved in the activation of AKT1 and signaling via insulin receptor substrate (IRS) proteins. It is essential in endothelial cell migration during vascular development through VEGFA signaling. It is required for lymphatic vasculature development.. Phosphatidylinositol 4,5 Bisphosphate 3 Kinase Catalytic Subunit Alpha Isoform (Phosphatidylinositol 4,5 Bisphosphate 3 Kinase 110 kDa Catalytic Subunit Alpha ...
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.
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 ...
TY - JOUR. T1 - High-Resolution Structure of the Pleckstrin Homology Domain of Protein Kinase B/Akt Bound to Phosphatidylinositol (3,4,5)-Trisphosphate. AU - Thomas, Christine C.. AU - Deak, Maria. AU - Alessi, Dario R.. AU - van Aalten, Daan M. F.. PY - 2002/7/23. Y1 - 2002/7/23. N2 - The products of PI 3-kinase activation, PtdIns(3,4,5)P3 and its immediate breakdown product PtdIns(3,4)P2, trigger physiological processes, by interacting with proteins possessing pleckstrin homology (PH) domains [1, 2]. One of the best characterized PtdIns(3,4,5)P3/PtdIns(3,4)P2 effector proteins is protein kinase B (PKB), also known as Akt [3-5]. PKB possesses a PH domain located at its N terminus, and this domain binds specifically to PtdIns(3,4,5)P3 and PtdIns(3,4)P2 with similar affinity [6, 7]. Following activation of PI 3-kinase, PKB is recruited to the plasma membrane by virtue of its interaction with PtdIns(3,4,5)P3/PtdIns(3,4)P2 [8-10]. PKB is then activated by the 3-phosphoinositide-dependent pro-tein ...
The PI3K plays a major role in many aspects of cellular biology and is often hyperactivated in human cancers (1, 4). The PI3K family of enzymes has multifunctional roles regulating cellular growth, proliferation, differentiation, motility, intracellular trafficking, and metabolism (4). Three distinct classes of PI3K (class I, II, and III) have been characterized and grouped according to their structure and function. The class IA PI3Ks, which have been implicated in many human cancers, are activated downstream of receptor tyrosine kinases and G protein-coupled receptors (GPCRs) and via interaction with the activated RAS or RHO family of GTPases. Class IA PI3Ks are heterodimers, and each consists of a regulatory subunit p85 (p85α, p55α, or p50α isoforms encoded by PIK3R1, PIK3R2, or PIK3R3, respectively) and a catalytic subunit p110 (p110α, p110β, or p110δ isoforms encoded by PIK3CA, PIK3CB, or PIK3CD, respectively; refs. 1, 4). Class IB comprises a single catalytic subunit, p110δ, that ...
Phosphatidylinositol 3-kinase (PI 3-kinase) is stimulated by insulin and a variety of growth factors, but its exact role in signal transduction remains unclear. We have used a novel, highly specific inhibitor of PT 3-kinase to dissect the role of this enzyme in insulin action. Treatment of intact 3T3-L1 adipocytes with LY294002 produced a dose-dependent inhibition of insulin-stimulated PI 3-kinase (50% inhibitory concentration, 6 microM) with , 95% reduction in the levels of phosphatidylinositol-3,4,5-trisphosphate without changes in the levels of phosphatidylinositol-4-monophosphate or its derivatives. In parallel, there was a complete inhibition of insulin-stimulated phosphorylation and activation of pp70 S6 kinase. Inhibition of PI 3-kinase also effectively blocked insulin- and serum-stimulated DNA synthesis and insulin-stimulated glucose uptake by inhibiting translocation of GLUT 4 glucose transporters to the plasma membrane. By contrast, LY294002 had no effect on insulin stimulation of ...
The PI3K/mTOR pathway is one of the most commonly activated signaling pathway in human cancer. Many players in the PI3K pathway are either amplified, have undergone LOH, or are targeted by somatic or germline alterations (4). These observations led to the development of rapamycin and rapalogs, which are allosteric, irreversible inhibitors of mTORC1, for cancer treatment. Temsirolimus was approved for metastatic renal cell carcinoma in 2007, serving to validate the PI3K/mTOR pathway as a therapeutic target in cancer (17). Despite some success in selected tumor types, rapalogs generally showed very limited anticancer efficacy as single agents and mostly lead to cytostatic effects (18). Negative feedback loops involving S6K have been described to have dramatic effects on drug responses for mTORC1 inhibitors (19). Activated mTORC1 initiates a negative feedback cascade via S6K to downregulate PI3K activity. Treating tumors with rapalogs can result in increased PI3K/Akt activity leading to an enhanced ...
TY - JOUR. T1 - Phosphatidylinositol 3-kinase is a central mediator of NMDA receptor signalling to MAP kinase (Erk1/2), Akt/PKB and CREB in striatal neurones. AU - Perkinton, Michael S. AU - Ip, James K. AU - Wood, Gemma L. AU - Crossthwaite, Andrew J. AU - Williams, Robert J. PY - 2002. Y1 - 2002. N2 - Ca2+ influx through NMDA receptors can initiate molecular changes in neurones which may underlie synaptic plasticity, neuronal development, survival and excitotoxicity. Signalling through the MAP kinase (Erk1/2) cascade may be central to these processes. We previously demonstrated that Ca2+-permeable AMPA receptors activate Erkl/2 through a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent mechanism. We now report that NMDA receptor activation of Erk1/2 was also blocked by inhibitors of PI 3-kinase (LY 294002, wortmannin). In addition, pre-treatment of neurones with pertussis toxin inhibited NMDA-induced Erk1/2 activation, indicating a role for heterotrimeric Gi/o proteins. PI 3-kinase ...
Phosphatidylinositol (PI) 3-kinase mediates multiple pathways that regulate many aspects of the cell including rate of metabolism, survival, migration, and proliferation. apoptosis, suggesting that FLII itself is also a survival element. These findings support the model that CISK phosphorylates FLII and activates nuclear receptor transcription and suggest a new cell survival signaling pathway mediated by PI 3-kinase and CISK. Cell death and survival are tightly controlled throughout development, through the action of numerous factors and pathways (1C6). Of these, PI2 3-kinase and its own downstream effectors are being among the most studied widely. PI 3-kinase pathway is vital for success and proliferation of mammalian cells and continues to be implicated in cancers (7C10). Through the legislation of D3-phosphoinositol amounts in cells, PI 3-kinases control the experience of 3-phosphoinositide-dependent kinase and associates from the AGC (cAMP-dependent proteins kinase/proteins kinase G/proteins ...
Service of the PI3K/AKT signal pathway is a known driving force for the progression to castration-recurrent prostate cancer (CR-CaP), which constitutes the major lethal phenotype of CaP. RUNX2 binding to the PIP promoter is increased in FOXO4-KD cells. Indeed, the forced expression of FOXO4 reversed the increased invasiveness of LNCaP/shFOXO4 Rabbit Polyclonal to DECR2 cells; the forced expression of FOXO4 did not alter RUNX2 protein levels, yet it decreased RUNX2 binding to the PIP promoter, resulting in PIP downregulation. Finally, there was a correlation between FOXO4, but not FOXO1 or FOXO3, downregulation and decreased metastasis-free survival in human CaP patients. Our data strongly recommend that improved PI3E/AKT-mediated metastatic invasiveness in Cover can be connected with FOXO4 reduction, and that systems to induce FOXO4 re-expression might suppress Cover metastatic aggressiveness. Intro Prostate tumor (Cover) continues to be the most diagnosed non-cutaneous tumor and the second ...
We recently identified a novel adaptor protein, termed dual adaptor for phosphotyrosine and 3-phosphoinositides (DAPP1), that possesses a Src homology (SH2) domain and a pleckstrin homology (PH) domain. DAPP1 exhibits a high-affinity interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2, which bind to the PH domain. In the present study we show that when DAPP1 is expressed in HEK-293 cells, the agonists insulin, insulin-like growth factor-1 and epidermal growth factor induce the phosphorylation of DAPP1 at Tyr139. Treatment of cells with phosphoinositide 3-kinase (PI 3-kinase) inhibitors or expression of a dominant-negative PI 3-kinase prevent phosphorylation of DAPP1 at Tyr139, and a PH-domain mutant of DAPP1, which does not interact with PtdIns(3,4,5)P3 or PtdIns(3,4)P2, is not phosphorylated at Tyr139 following agonist stimulation of cells. Overexpression of a constitutively active form of PI 3-kinase induced the phosphorylation of DAPP1 in unstimulated cells. We demonstrated that Tyr139 of ...
The project aims to understand the molecular and structural mechanism of activation and inhibition of class I phosphoinositide 3 kinases. These lipid kinases are the key signaling element in a diverse array of cellular functions such as cell growth, motility, and, and a validated targets for pharmacological intervention. Deregulation of PI3K pathway is implicated in a variety of diseases including thromboembolism, inflammation, autoimmune diseases and cancer. We determined the structure of PI3Ka in heterodimeric form showing all five domains of p110a in complex with the nSH2 and iSH2 domains of the p85a. We determined the structure of the somatic p110a H1047R/niSH2 mutant alone and in complex with the inhibitor wortmannin. The PI3K enzyme, as the hub of the PI3K/AKT/ mTOR pathway, presents an opportunity where structural biology, enzymology, and inhibitor design converge to both elucidate mechanisms of action and provide initial hits for targeted therapies.. Isoprenoid Pathway as a target of ...
Leucettines, a family of pharmacological inhibitors of DYRKs (dual-specificity tyrosine phosphorylation regulated kinases) and CLKs (cdc2-like kinases), are currently under investigation for their potential therapeutic application to Down syndrome and Alzheimers disease. We here report that Leucettine L41 triggers bona fide autophagy in osteosarcoma U-2 OS cells and immortalized mouse hippocampal HT22 cells, characterized by LC3 membrane translocation and foci formation. Leucettine L41-triggered autophagy requires the ULK1 (Unc-51-like kinase) kinase and is sensitive to the PI3K (phosphatidylinositol 3-kinase) inhibitors wortmannin and 3-methyladenine, suggesting that it acts through the mTOR/PI3K-dependent pathway. Leucettine L41 does not act by modifying the autophagic flux of vesicles. Leucettine L41-induced autophagy correlates best with inhibition of CLKs. Leucettine L41 modestly inhibited PIKfyve (phosphatidylinositol-3-phosphate 5-kinase) activity as tested both in vitro and in vivo, ...
Order Recombinant Mouse Phosphatidylinositol 4 5-bisphosphate 3-kinase catalytic subunit beta isoform Pik3cb partial 01016103582 at Gentaur Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (Pik3cb) partial
Although interleukin 1 (IL-1) functions have been extensively characterized, the mechanisms by which IL-1 signals are transduced from the plasma membrane to the nucleus are less known. Recent evidence indicates that phosphatidylinositol 3-kinase (PI3-kinase) could be activated by a direct association with the activated IL-1 receptor. In this study we analyzed the effects of IL-1 on the intracellular distribution of PI3-kinase in wild-type Saos-2 human osteosarcoma cells, and in cell clones overexpressing type I IL-1 receptor (IL-1RI). PI3-kinase intracellular distribution displays two distinct patterns. In quiescent cells, PI3-kinase is distributed through the cytoplasm, although a portion is present in the nucleus; following stimulation with IL-1, PI3-kinase is redistributed, increasing in the nuclear compartment. Both immunoblotting and immunofluorescence data indicate that IL-1 causes a rapid and transient translocation of PI3-kinase from the cytoplasm to the nucleus. This phenomenon is ...
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 ...
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 ...
The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. This gene may play a role in several diseases, including type II diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014 ...
The phosphoinositide 3-kinase (PI3K) pathway is believed to be of key importance in pediatric glioblastoma. in protein appearance levels of regulatory digestive enzymes involved in glucose and choline rate of metabolism including GLUT1, HK2, LDHA and CHKA. Our results display that by using NMR we can detect unique biomarkers following PI3E pathway inhibition compared to treatment with the DNA-damaging anti-cancer agent TMZ. This is definitely the 1st study reporting that lactate 590-46-5 IC50 590-46-5 IC50 and choline metabolites are potential non-invasive biomarkers for monitoring response to PI3E pathway inhibitors in pediatric glioblastoma. Intro Approximately 40% of all pediatric mind tumors are astrocytomas (gliomas), and of these some 15C20% are malignant gliomas, i.elizabeth. high-grade (WHO grade III and IV) tumors [1], [2]. High-grade gliomas (HGGs) are very aggressive tumors and are one of the leading causes of cancer-related deaths in children with a median survival of just 12C15 ...
Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is extensively explored in cancers. It functions as an important regulator of cell growth, survival and metabolism. Activation of this pathway also predicts poor prognosis in numerous human malignancies. Drugs targeting this signaling pathway have been developed and have shown preliminary clinical activity. Accumulating evidence has highlighted the important role of PI3K in non-Hodgkin lymphoma (NHL), especially in the disease initiation and progression. Therapeutic functions of PI3K inhibitors in NHL have been demonstrated both in vivo and in vitro. This review will summarize recent advances in the activation of PI3K signaling in different types of NHL and the applications of PI3K inhibitors in NHL treatment.
LY3023414 is a small molecule that has been shown in vitro to be a selective ATP-competitive inhibitor of PI3Kα and mTOR, DNA-PK, and other class I PI3K family members. In vitro, LY3023414 has demonstrated inhibitory activity against PI3K and mTOR in tumor cells, as well as antiproliferative activity and cell cycle effects. In addition, in vitro, LY3023414 inhibits the ability of PI3K and mTOR to phosphorylate substrates in the PI3K/mTOR pathway. LY3023414 is being investigated in a phase I clinical trial.
Background:. Esophageal cancer (EC) is an aggressive malignancy with increasing incidence and poor outcome (1). New therapeutic strategies are urgently required. The phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway has been documented as a central hub for the malignant behaviors of cancer cells (2). However, the functional role and therapeutic effect of PI3K/AKT inhibitors in esophageal cancer metastasis is underappreciated.. Aim:. We aim to study the clinical significance of PI3K/AKT signaling pathway in EC metastasis and evaluate the therapeutic effect of PI3K/AKT-targeted therapy.. Methods:. A highly invasive cancer cell line (KYSE410-I3) was established by serial selection of the EC cells invading through the matrigel-coated Boyden chamber. Cell migration and invasion were determined using Boyden chamber migration and invasion assays. Western blot and immunohistochemistry were used to detect protein expressions in cell lysates and in a tissue microarray containing 40 pairs of ...
Phosphatidylinositol 3-kinase regulatory subunit beta is an enzyme that in humans is encoded by the PIK3R2 gene. PIK3R2 has been shown to interact with: CRKL Cbl gene, Epidermal growth factor, FYN, HER2/neu, Macrophage colony-stimulating factor, and PIK3CD. PIK3R2 mutations were recently shown to be associated with polymicrogyria. GRCh38: Ensembl release 89: ENSG00000105647 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Volinia S, Patracchini P, Otsu M, Hiles I, Gout I, Calzolari E, Bernardi F, Rooke L, Waterfield MD (Apr 1992). Chromosomal localization of human p85 alpha, a subunit of phosphatidylinositol 3-kinase, and its homologue p85 beta. Oncogene. 7 (4): 789-93. PMID 1314371. Entrez Gene: PIK3R2 phosphoinositide-3-kinase, regulatory subunit 2 (p85 beta). Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV, Griffin JD (Apr 1997). Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, ...
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The phosphatidylinositol 3 -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, translation, proliferation, growth, and survival. The binding of growth factors to their receptor tyrosine kinase (RTK) or G protein-coupled receptors (GPCR) stimulates class Ia and Ib PI3K isoforms, respectively. PI3K catalyzes the production of phosphatidylinositol-3,4,5-triphosphate (PIP3) at the cell membrane. PIP3 in turn serves as a second messenger that helps to activate Akt. Once active, Akt can control key cellular processes by phosphorylating substrates involved in apoptosis, protein synthesis, metabolism, and cell cycle ...
The phosphatidylinositol 3 -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, translation, proliferation, growth, and survival. The binding of growth factors to their receptor tyrosine kinase (RTK) or G protein-coupled receptors (GPCR) stimulates class Ia and Ib PI3K isoforms, respectively. PI3K catalyzes the production of phosphatidylinositol-3,4,5-triphosphate (PIP3) at the cell membrane. PIP3 in turn serves as a second messenger that helps to activate Akt. Once active, Akt can control key cellular processes by phosphorylating substrates involved in apoptosis, protein synthesis, metabolism, and cell cycle ...
The phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a key member of the phosphoinositide family. PI4P defines the membranes of Golgi and trans-Golgi network (TGN) and regulates trafficking to and from the Golgi.. In mammals there are four different PI4K enzymes, two type II enzymes (PI4KIIα and PI4KIIβ) and two type III enzymes (PI4KIIIα and PI4KIIIβ). PI4KIIIβ plays key roles in mediating lipid transport, cytokinesis, maintaining lysosomal identity, and in tandem with Rab GTPases plays key roles in regulating membrane trafficking. PI4KIIIβ is critical for mediating viral replication of a number of RNA viruses through the generation of PI4P enriched viral replication platforms. Small molecule inhibitors of PI4KIIIβ are potent anti-viral agents. Development of PI4KIIIβ as an effective drug target for anti-viral therapeutics requires the generation of highly potent and specific inhibitors.. ...
BACKGROUND: Exposure to intermittent hypoxia (IH) may enhance cardiac function and protects heart against ischemia-reperfusion (I/R) injury. To elucidate the underlying mechanisms, we developed a cardioprotective IH model that was characterized at hemodynamic, biochemical and molecular levels. METHODS: Mice were exposed to 4 daily IH cycles (each composed of 2-min at 6-8% O2 followed by 3-min reoxygenation for 5 times) for 14 days, with normoxic mice as controls. Mice were then anesthetized and subdivided in various subgroups for analysis of contractility (pressure-volume loop), morphology, biochemistry or resistance to I/R (30-min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion and measurement of the area at risk and infarct size). In some mice, the phosphatidylinositide 3-kinase (PI3K) inhibitor wortmannin was administered (24 µg/kg ip) 15 min before LAD. RESULTS: We found that IH did not induce myocardial hypertrophy; rather both contractility and ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. This gene may play a role in several diseases, including type II diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014 ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. This gene may play a role in several diseases, including type II diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014 ...
Introduction: This study describes the development of a novel dual specificity kinase inhibitor, ON 123300, which exhibits potent activity against Mantle Cell Lymphomas (MCLs) both in vitro and in vivo. Mantle cell lymphoma is genetically characterized by the t(11;14)(q13;q32) chromosomal translocation which results in constitutive overexpression of cyclin D1. In addition, MCLs also activate other pathways, including aberrant B-Cell Receptor and PI3K/AKT/mTOR signaling. As a result, MCL has a poor clinical outcome with a median survival of 4-5 years. In this study, we show that ON123300, which inhibits both CDK4/6 and PI3K-α (the predominant PI3K catalytic subunit expressed in MCL cells), is a superior inducer of apoptosis of MCL cells when compared to PD0332991, a selective inhibitor of CDK4/6 kinases.. Experimental Procedures: We examined the effects of PD 0332991 and ON123300 on cell cycle progression, modulation of the Rb and PI3K/AKT pathways, and the induction of apoptosis in the Granta ...
CNTRL-FGFR1 induces AML and T-cell lymphoma in murine and individual progenitor cells. to successfully treating this almost invariably lethal disease. Intro Constitutive activation of FGFR1 kinase in hematopoietic stem cells (HSC) resulting from chromosome translocations including 8p11 prospects to myeloproliferative neoplasms (MPN) that inevitably progress to acute myeloid leukemia (AML) and is frequently accompanied by T- and B-cell lymphomas. Overall survival is definitely poor due to resistance to current restorative regimens. The hallmark of FGFR1-related neoplasms is definitely bilineage disease, GX15-070 in which tumor cells from both lineages harbor the chimeric FGFR1 fusion gene, suggesting a common stem/progenitor source. fuses to more than 11 partner genes,1 such as ZMYM2-FGFR1, BCR-FGFR1, and CNTRL-FGFR1. Constitutive activation of FGFR1 is definitely believed to be the primary initiation event that drives disease development, although its oligoclonal nature suggests other genetic ...
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Background In mouse the cytokine interleukin-7 (IL-7) is necessary for generation of B lymphocytes, but human IL-7 does not appear to have this function. amino acid identity and are expressed in cell lines and main hematopoietic lineage cells differentially. Genes Selumetinib for FIGLER homologs had been discovered in macaque, orangutan, chimpanzee, mouse, rat, pup, rooster, toad, and puffer seafood databases. The nonhuman FIGLER homologs talk about 38C99% general amino acid identification with their individual counterpart. Bottom line The extracellular domains structure and lack of recognizable cytoplasmic signaling motifs in associates from the extremely conserved FIGLER gene family members recommend a trophic or cell adhesion function for these substances. History Interleukin-7 (IL-7) is normally a nonredundant cytokine necessary for the era of B and T lineage cells in mice [1-5]. Although Selumetinib IL-7 is vital for T cell advancement in humans, individual B cell advancement is unaffected ...
The protein encoded by this gene catalyzes the phosphorylation of phosphatidylinositol-5-phosphate on the fourth hydroxyl of the myo-inositol ring to form phosphatidylinositol-5,4-bisphosphate. This gene is a member of the phosphatidylinositol-5-phosphate 4-kinase family. The encoded protein sequence does not show similarity to other kinases, but the protein does exhibit kinase activity. Additionally, the encoded protein interacts with p55 TNF receptor. [provided by RefSeq, Jul 2008 ...
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
Our data reveal a novel PS1 function by which this protein stimulates PI3K/Akt signaling and promotes cell survival. This conclusion is supported by the following observations: (1) absence of PS1 results in low levels of phosphorylated Akt and increased apoptosis; (2) exogenous PS1 stimulates Akt phosphorylation and rescues PS1 null cells from apoptosis; (3) a constitutively active PI3K restores Akt activation and suppresses apoptosis induced by the absence of PS1; (4) pharmacological inhibition of either PI3K or Akt prevents the PS1‐dependent Akt phosphorylation and caspase‐3 inactivation, indicating that the PI3K/Akt pathway mediates the anti‐apoptotic effects of PS1.. Cadherin-cadherin interactions initiate a cascade of signaling events that result in increased cadherin/PI3K association, activation of PI3K/Akt signaling and increased cell survival (Pece et al, 1999; Peluso et al, 2001; Kovacs et al, 2002; Tran et al, 2002; Yap and Kovacs, 2003). Our data that cadherin overexpression ...
... phosphatidylinositol 4-kinase beta (PI4KB) phosphatidylinositol 4-kinase 2-alpha (PI4K2A) phosphatidylinositol 4-kinase 2-beta ... Phosphatidylinositol 4-kinases are evolutionary conserved among eukaryotes and include four human isoforms phosphatidylinositol ... This gene encodes a phosphatidylinositol 4-kinase which catalyzes phosphorylation of phosphatidylinositol at the D-4 position, ... "Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase IIIbeta at the ...
"OMIM: PHOSPHATIDYLINOSITOL 3-KINASE, CATALYTIC, DELTA; PIK3CD". OMIM. Johns Hopkins University. Retrieved December 8, 2018. CS1 ... Specific p110δ mutants cause stronger binding to membranes and relieve inhibition of the kinase by regulatory proteins. These ... PASLI disease is caused by gain-of-function mutations in the gene PIK3CD, which stands for phosphatidylinositol 3-kinase, ... and a kinase domain. Mutations have been identified in multiple domains, although there seems to be a recurrent transition ...
Yamaki N, Negishi M, Katoh H (August 2007). "RhoG regulates anoikis through a phosphatidylinositol 3-kinase-dependent mechanism ... Phospholipase D1 and the MAP Kinase activator MLK3. RhoG has been shown to interact with KTN1. GRCh38: Ensembl release 89: ... 22 (3): 330-42. doi:10.1038/sj.onc.1206116. PMID 12545154. Katoh H, Yasui H, Yamaguchi Y, Aoki J, Fujita H, Mori K, Negishi M ( ... Zalcman G, Closson V, Camonis J, Honoré N, Rousseau-Merck MF, Tavitian A, Olofsson B (November 1996). "RhoGDI-3 is a new GDP ...
Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2 is a protein that in humans is encoded by the PREX2 ... "Entrez Gene: Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2". Retrieved 2012-05-11. CS1 maint: ... 572 (1-3): 167-71. doi:10.1016/j.febslet.2004.06.097. PMID 15304342. S2CID 35668920. Berger MF, Hodis E, Heffernan TP, Deribe ... 572 (1-3): 172-6. doi:10.1016/j.febslet.2004.06.096. PMID 15304343. S2CID 31436247. Hernández-Negrete I, Carretero-Ortega J, ...
"DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene ... "Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit". J. Biol. Chem. 272 ( ... "Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex". J. ... DNA-dependent protein kinase, catalytic subunit, also known as DNA-PKcs, is an enzyme that in humans is encoded by the gene ...
Metjian A, Roll RL, Ma AD, Abrams CS (1999). "Agonists cause nuclear translocation of phosphatidylinositol 3-kinase gamma. A ... Phosphoinositide 3-kinase regulatory subunit 5 is an enzyme that in humans is encoded by the PIK3R5 gene. PIK3R5 has been shown ... 2005). "p84, a new Gbetagamma-activated regulatory subunit of the type IB phosphoinositide 3-kinase p110gamma". Curr. Biol. 15 ... "Entrez Gene: PIK3R5 phosphoinositide-3-kinase, regulatory subunit 5, p101". CS1 maint: discouraged parameter (link) Johnson C, ...
1995). "The activation of phosphatidylinositol 3-kinase by Ras". Curr. Biol. 4 (9): 798-806. doi:10.1016/S0960-9822(00)00177-9 ... 48 (4): 950-3. PMID 3276402. Hirai H, Kobayashi Y, Mano H, et al. (1987). "A point mutation at codon 13 of the N-ras oncogene ... 5 (3): 582-5. doi:10.1128/mcb.5.3.582. PMC 366752. PMID 3887133. Brown R, Marshall CJ, Pennie SG, Hall A (1984). "Mechanism of ... 299 (5879): 171-3. Bibcode:1982Natur.299..171M. doi:10.1038/299171a0. PMID 6287287. S2CID 4342747. Shimizu K, Goldfarb M, ...
Sidorenko SP, Law CL, Chandran KA, Clark EA (1995). "Human spleen tyrosine kinase p72Syk associates with the Src-family kinase ... "Thymocyte activation induces the association of phosphatidylinositol 3-kinase and pp120 with CD5". Eur. J. Immunol. 27 (3): 679 ... Jordan P, Heid H, Kinzel V, Kübler D (1995). "Major cell surface-located protein substrates of an ecto-protein kinase are ... 425 (3): 401-6. doi:10.1016/S0014-5793(98)00269-5. PMID 9563502. Matsui M, Breau WC, Iwasaki S, Hagiwara S, Tamai Y, Mori C, ...
Polo-like kinase phosphosites 1 (Plk1) at positions 336-342 aa and 351-357 aa. Ser/Thr residues are phosphorylated by the ... Phosphatidylinositol 3-kinase related kinase (PIKK) phosphorylation site at position 238-244 aa. Casein kinase (CK1) ... Ser/Thr residues are phosphorylated by the kinase. Two NEK2 phosphorylation sites at positions 415-420 bp and 423-428 aa. Table ... Glycogen synthase kinase-3 (GSK3) phosphorylation site at position 234-241 aa. ...
... also known as PI3-kinase regulatory subunit 4 or PI3-kinase p150 subunit or phosphoinositide 3-kinase adaptor protein, or VPS15 ... Substrate presentation by phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase complex". J. Biol. Chem. 272 (4): ... an adaptor protein for the human phosphatidylinositol (PtdIns) 3-kinase. ... "PIK3R4 phosphoinositide-3-kinase regulatory subunit 4 [ Homo sapiens (human) ]". Panaretou C, Domin J, Cockcroft S, Waterfield ...
... a cyclin-dependent kinase-activating kinase complex ring finger factor, and regulates estrogen receptor transactivation ... Interaction of estrogen receptor alpha with phosphatidylinositol 3-OH kinase". Steroids. 67 (12): 935-9. doi:10.1016/S0039-128X ... Fes tyrosine kinase, heat shock transcription factor Hsf1, and the aryl hydrocarbon receptor". Cell Stress Chaperones. 1 (4): ... monophosphate-dependent protein kinase". Endocrinology. 149 (9): 4336-45. doi:10.1210/en.2008-0037. PMID 18499756. Wong CW, ...
The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an ... Izuhara K, Harada N (1997). "Interleukin-4 activates two distinct pathways of phosphatidylinositol-3 kinase in the same cells ... Potential role of JAK kinases". J. Biol. Chem. 270 (48): 28527-30. doi:10.1074/jbc.270.48.28527. PMID 7499365. Patti ME, Sun XJ ... and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. ...
... a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase ... "Involvement of phosphatidylinositol 3-kinase, but not RalGDS, in TC21/R-Ras2-mediated transformation". J. Biol. Chem. 277 (12 ... Li W, Han M, Guan KL (April 2000). "The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex ... Ramírez de Molina A, Penalva V, Lucas L, Lacal JC (2002). "Regulation of choline kinase activity by Ras proteins involves Ral- ...
2005). "Distinct roles of the receptor tyrosine kinases Tie1 and Tie2 in blood vessel formation". Cell. 123 (2): 291-304. doi: ... Kumar, P; Amin, MA; Harlow, LA; Polverini, PJ; Koch, AE (2003). "Src and phosphatidylinositol 3-kinase mediate soluble E- ... 1995). "Distinct roles of the receptor tyrosine kinases Tie1 and Tie2 in blood vessel formation". Nature. 376 (6535): 70-74. ... and modulate the activity of focal adhesion kinase (FAK). Endostatin is a 20 kDa fragment of collagen XVIII. The major role of ...
"Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and ... It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a ... Chan TO, Rittenhouse SE, Tsichlis PN (2000). "AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by ... "Complex formation and cooperation of protein kinase C theta and Akt1/protein kinase B alpha in the NF-kappa B transactivation ...
... some phosphatidylinositol 4-kinases, myosin light chain kinase (MLCK) and mitogen-activated protein kinase (MAPK) at high ... Mizuno M, Yamada K, Takei N, Tran MH, He J, Nakajima A, Nawa H, Nabeshima T (February 2003). "Phosphatidylinositol 3-kinase: a ... Liu Y, Jiang N, Wu J, Dai W, Rosenblum JS (January 2007). "Polo-like kinases inhibited by wortmannin. Labeling site and ... Howes AL, Chiang GG, Lang ES, Ho CB, Powis G, Vuori K, Abraham RT (September 2007). "The phosphatidylinositol 3-kinase ...
... kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment ... ATR belongs to the phosphatidylinositol 3-kinase-related kinase protein family. ATR is activated in response to single strand ... Serine/threonine-protein kinase ATR also known as ataxia telangiectasia and Rad3-related protein (ATR) or FRAP-related protein ... Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J (Apr 2005). "Rheb binds and regulates the mTOR kinase". Current Biology. 15 ( ...
Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T (April 2001). "Beclin-phosphatidylinositol 3-kinase complex functions at the trans- ... April 2004). "Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1". The ... April 2009). "Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3- ... kinase complex". Nature Cell Biology. 11 (4): 468-76. doi:10.1038/ncb1854. PMC 2664389. PMID 19270693. Valente G, Morani F, ...
"PIP5K1A phosphatidylinositol-4-phosphate 5-kinase, type I, alpha [Homo sapiens (human)". Entrez Gene. PSD4 pleckstrin and Sec7 ... PIK3R2 and PIP5K1A are two kinases that phosphorylate Phosphatidylinositol (PIP) providing PSD4 with substrates for its GTP ... PIK3R2 and PIP5K1A are two kinases that create substrates for PSD4. PSD4 (Pleckstrin and Sec7 Domain containing 4) is a GEF ( ... MHC class II is also expressed on group 3 innate lymphoid cells. Having MHC class II molecules present proper peptides that are ...
"Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein". J ... Serine/threonine-protein kinase SMG1 is an enzyme that in humans is encoded by the SMG1 gene. SMG1 belongs to the ... The protein has kinase activity and is thought to function in NMD by phosphorylating the regulator of nonsense transcripts 1 ... Sanchez P, De Carcer G, Sandoval IV, Moscat J, Diaz-Meco MT (1998). "Localization of atypical protein kinase C isoforms into ...
... acts as a negative regulator of mTOR, a serine/threonine kinase that regulates a variety of cellular functions such as ... "REDD1 integrates hypoxia-mediated survival signaling downstream of phosphatidylinositol 3-kinase". Oncogene. 24 (7): 1138-49. ... 1 (3): 287-92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614. Kim JR, Lee SR, Chung HJ, Kim S, Baek SH, Kim JH, ... 11 (3): 422-35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166. Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann ...
"PI3 Kinase Disease , NIH: National Institute of Allergy and Infectious Diseases". www.niaid.nih.gov. Retrieved 2017-06-10. " ... "PIK3CD phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [Homo sapiens (human)] - Gene - NCBI". www.ncbi. ... a mutation in phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform is the reason for this condition ( ...
"The West Nile Virus Capsid Protein Blocks Apoptosis through a Phosphatidylinositol 3-Kinase-Dependent Mechanism". Journal of ... 20 (3): 326-7. PMID 15532939. "General Questions About West Nile Virus". www.cdc.gov. 19 October 2017. Archived from the ... 3 (1): 13-22. doi:10.1038/nrmicro1067. PMID 15608696. S2CID 4150641. Suthar, Mehul S.; Diamond, Michael S.; Jr, Michael Gale ( ... 3 October 2017. Retrieved 28 March 2019. "Vertebrate Ecology". West Nile Virus. Division of Vector-Borne Diseases, CDC. 30 ...
The age-1 gene encodes the catalytic subunit of class-I phosphatidylinositol 3-kinase (PI3K). A decade after Johnson's ... and tyrosine kinase-related pathways. They then used drugs known to target the identified pathways and showed these drugs kill ... 22 (3-4): 279-286. doi:10.1016/0047-6374(83)90082-9. PMID 6632998. S2CID 6870538. Friedman DB, Johnson TE (1988). "A mutation ... Bibcode:2020NatCo..11.3570T. doi:10.1038/s41467-020-17312-3. ISSN 2041-1723. PMC 7366647. PMID 32678081. Text and images are ...
"Protein kinase C alpha phosphorylates and negatively regulates diacylglycerol kinase zeta". The Journal of Biological Chemistry ... The phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (the HUGO-approved official symbol = PIK3CA; HGNC ... Li W, Han M, Guan KL (April 2000). "The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex ... Prasad KV, Kapeller R, Janssen O, Repke H, Duke-Cohan JS, Cantley LC, Rudd CE (December 1993). "Phosphatidylinositol (PI) 3- ...
It codes for an isozyme of pyruvate dehydrogenase kinase. This gene is a member of the PDK/BCKDK protein kinase family and ... This is done through a proposed phosphatidylinositol 3-kinase (PI3K)-dependent pathway. In fact, even when cells are exposed to ... Kwon HS, Huang B, Unterman TG, Harris RA (Apr 2004). "Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 ... Pyruvate dehydrogenase lipoamide kinase isozyme 4, mitochondrial is an enzyme that in humans is encoded by the PDK4 gene. ...
CT10 regulator of kinase (Crk) is also known as the breast cancer anti-oestrogen resistance protein. It plays a role in both ... Boudot C, Kadri Z, Petitfrère E, Lambert E, Chrétien S, Mayeux P, Haye B, Billat C (October 2002). "Phosphatidylinositol 3- ... This leads to the activation of c-Jun N-terminal kinase(JNK) as part of the JNK signaling pathway. Upon stimulation by growth ... It mediates the interaction between receptor tyrosine kinases (RTKs) and non-RTK receptors serving as the gateway into the cell ...
2003). "Phosphatidylinositol 3-kinases in carcinoembryonic antigen-related cellular adhesion molecule-mediated internalization ... 49 (3): 623-37. doi:10.1046/j.1365-2958.2003.03591.x. PMID 12864848. S2CID 12071872. Schmitter T, Agerer F, Peterson L, et al ... 158 (3): 996-1004. CiteSeerX 10.1.1.657.2780. doi:10.1016/0006-291X(89)92821-0. PMID 2537643. Watt SM, Fawcett J, Murdoch SJ, ... Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) also known as CD66d (Cluster of Differentiation 66d), is a ...
"Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity". J. Biol. Chem. 269 ( ... Pratt RL, Kinch MS (October 2002). "Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade". ... "Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity". J. Biol. Chem. 269 ( ... an epithelial cell receptor protein-tyrosine kinase in the eph/elk family of protein kinases". Mol. Cell. Biol. 10 (12): 6316- ...
... can inhibit the MAPK/ERK mitogenic pathway and the Akt/protein kinase B (PKB) survival pathway. Aside from these plasma-level ... "Anti-cancer alkyl-lysophospholipids inhibit the phosphatidylinositol 3-kinase-Akt/PKB survival pathway". Anti-Cancer Drugs. 14 ... by blocking ERK1/2 and p38 mitogenactivated protein kinases as potential targets" (PDF). 2008. Archived from the original (PDF ... 15 (3): 157-223. doi:10.1002/med.2610150302. PMID 7658750. Munder, PG; Ferber E; Modolell M; Fischer H. (1969). "The influence ...
Insulin Augmentation of 17α-Hydroxylase Activity Is Mediated by Phosphatidyl Inositol 3-Kinase But Not Extracellular Signal- ... Regulated Kinase-1/2 in Human Ovarian Theca Cells. Endocrinology. January 2004, 145 (1): 175-183. doi:10.1210/en.2003-0329.. ... 原始内容存档于3 March 2015).. *^ 4.0 4.1 4.2 4.3 4.4 4.5 Polycystic Ovary Syndrome (PCOS): Condition Information. US Department of ... 2013, 19 (3): 268-88. PMID 23303572. doi:10.1093/humupd/dms059.. *^ Kelly CJ, Stenton SR, Lashen H. Insulin-like growth factor ...
"PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3- ... Tropomyosin receptor kinase B § Agonists. References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000176697 - Ensembl, May ... positive regulation of non-membrane spanning protein tyrosine kinase activity. • transmembrane receptor protein tyrosine kinase ... The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and ...
Once active, VPS34 phosphorylates the lipid phosphatidylinositol to generate phosphatidylinositol 3-phosphate (PtdIns(3)P) on ... These two kinases regulate autophagy through inhibitory phosphorylation of the Unc-51-like kinases ULK1 and ULK2 (mammalian ... The autophagy-inducible Beclin-1 complex[40] contains the proteins p150, Atg14L and the class III phosphatidylinositol 3- ... E. Itakura, C. Kishi, K. Inoue, and N. Mizushima, 'Beclin 1 Forms Two Distinct Phosphatidylinositol 3-Kinase Complexes with ...
The ligands interact with the two tyrosine kinase receptor monomers, PDGFRα (PDGFRA) and -Rβ (PDGFRB).[6] The PDGF family also ... "Embryonic mesoderm cells spread in response to platelet-derived growth factor and signaling by phosphatidylinositol 3-kinase". ... The receptor for PDGF, PDGFR is classified as a receptor tyrosine kinase (RTK), a type of cell surface receptor. Two types of ... receptor tyrosine kinases". EMBO J. 15 (2): 290-298. doi:10.1002/j.1460-2075.1996.tb00359.x. PMC 449944. PMID 8617204.. ...
Once active, VPS34 phosphorylates the lipid phosphatidylinositol to generate phosphatidylinositol 3-phosphate (PtdIns(3)P) on ... These two kinases regulate autophagy through inhibitory phosphorylation of the Unc-51-like kinases ULK1 and ULK2 (mammalian ... The autophagy-inducible Beclin-1 complex[48] contains the proteins p150, Atg14L and the class III phosphatidylinositol 3- ... 1 (3): 131-40. doi:10.4161/auto.1.3.2017. PMID 16874025.. *^ a b c Tavassoly I (2015). Dynamics of Cell Fate Decision Mediated ...
protein serine/threonine kinase activator activity. • receptor ligand activity. Cellular component. • extracellular region. • ... insulin receptor signaling pathway via phosphatidylinositol 3-kinase. • positive regulation of multicellular organism growth. • ... positive regulation of protein kinase B signaling. • regulation of transcription, DNA-templated. • ossification. • platelet ... positive regulation of protein serine/threonine kinase activity. • carbohydrate metabolic process. • regulation of receptor ...
"Phosphatidic acid is a specific activator of phosphatidylinositol-4-phosphate kinase". J. Biol. Chem. 267 (11): 7207-10. PMID ... October 2004). "Sphingosine kinase 1 is an intracellular effector of phosphatidic acid". J. Biol. Chem. 279 (43): 44763-74. doi ... This will show whether the phosphate group is newly derived from the kinase activity or whether it originates from the PC.[18] ... Olivera A, Rosenthal J, Spiegel S (March 1996). "Effect of acidic phospholipids on sphingosine kinase". J. Cell. Biochem. 60 (4 ...
Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate". Nature. 332: 644-646 ... 1-phosphatidylinositol+4-kinase на US National Library of Medicine Medical Subject Headings (MeSH) ... Kai, M., White, G.L. and Hawthorne, J.N. (1966). „The phosphatidylinositol kinase of rat brain". Biochem. J. 101: 328-337. PMID ... Walker, D.H., Dougherty, N. and Pike, L.J. (1988). „Purification and characterization of a phosphatidylinositol kinase from ...
positive regulation of phosphatidylinositol 3-kinase signaling. • inflammatory response. • calcium-mediated signaling using ... 3 (2): 99-114. doi:10.1007/BF00047657. PMID 6386144.. *^ Monzavi-Karbassi B, Stanley JS, Hennings L, Jousheghany F, Artaud C, ... 12 (3): 315-9. doi:10.1165/ajrcmb.12.3.7532979. PMID 7532979.. *^ Köhler S, Ullrich S, Richter U, Schumacher U (February 2010 ... This page was last edited on 3 May 2018, at 12:15 (UTC). ... 1999 February; 126(3): 537-550. at page 538 doi:10.1038/sj.bjp. ...
Fyn and Lyn kinase. It also activates phosphatidylinositol 3-kinase (PI3K) and AKT signaling pathway and induce expression of ... kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) and Syk (spleen tyrosine kinase) ... kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) and Syk (spleen tyrosine kinase) ... Upon binding IL-15β subunit activates Janus kinase 1 (Jak1) and γc subunit Janus kinase 3 (Jak3), which leads to ...
Excessive eryptosis is observed in red blood cells lacking the cGMP-dependent protein kinase type I or the AMP-activated ... Both PS and phosphatidylinositol-4,5-bisphosphate (PIP2) can regulate membrane mechanical function, due to their interactions ... 135 (1-3): 14-8. doi:10.1016/j.bpc.2008.02.015. PMID 18394774.. CS1 maint: Uses authors parameter (link). ... 141 (3): 367-75. doi:10.1111/j.1365-2141.2008.07091.x. PMID 18341630.. CS1 maint: Uses authors parameter (link). ...
... phosphatidyl inositol-3 kinase, Phosphoinositide 3-kinases, PI3K) merupakan enzim kinase lipid yang berperan dalam perkembangan ... 21 (FVII · FIX · FX · FXI · FXII · FD · PROC · Trombin) · .22 · .23 · .24 (.1 ALA · .7 MMP-1 · .17 MMP-3/MMP-6 · .19 BMP-1 · . ... Enzim ini memiliki koenzim (PKB/c-Akt/Rac) yang menghambat enzim glikogen sintase kinase 3 dan mengaktivasi serina kinase yang ... "Potential role of protein kinase B in insulin-induced glucose transport, glycogen synthesis, and protein synthesis". Third ...
protein tyrosine kinase activity. • Ras guanyl-nucleotide exchange factor activity. • phosphatidylinositol-4,5-bisphosphate 3- ... positive regulation of phosphatidylinositol 3-kinase signaling. • regulation of p38MAPK cascade. • cell proliferation. • ... phosphatidylinositol phosphorylation. • mitotic cell cycle. • regulation of receptor activity. • positive regulation of protein ... regulation of tau-protein kinase activity. • proteolysis. • positive chemotaxis. • MAPK cascade. • peptidyl-tyrosine ...
These events promote many signaling cascades (such as the MAP kinase pathway) that generate responses like chemotaxis, ... PLC cleaves a molecule called phosphatidylinositol (4,5)-bisphosphate (PIP2) into two second messenger molecules known as ... DAG activates another enzyme called protein kinase C (PKC), and IP3 triggers the release of calcium from intracellular stores. ... CX3C chemokinesEdit. A fourth group has also been discovered and members have three amino acids between the two cysteines and ...
1993). „IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase.". Science. 260 (5115): 1808-10. ... 2000). „Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines.". ... the receptor is crucial for kinase activation". Biochem. J. England. 361 (Pt 1): 105-11. ISSN 0264-6021. PMC 1222284 . PMID ... Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase". J. Immunol. UNITED STATES. 158 (9): 4097-103. ISSN 0022 ...
PLC cleaves Phosphatidylinositol (4,5)-bisphosphate (PIP2) to form two second messenger molecules called inositol triphosphate ... At the same time, the G-protein subunit Gα directly activates an enzyme called protein tyrosine kinase (PTK), which ... IP3) and diacylglycerol (DAG); DAG activates another enzyme called protein kinase C (PKC), and IP3 triggers the release of ... The initiated MAP kinase pathway activates specific cellular mechanisms involved in chemotaxis, degranulation, release of ...
"PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3- ... protein kinase activity. • JUN kinase binding. • non-membrane spanning protein tyrosine kinase activity. • transferase activity ... FAK(focal adhesion kinase、フォーカルアドヒージョンキナーゼ、焦点接着キナーゼ、接着斑キナーゼ)またはPTK2(protein tyrosine kinase 2)は、ヒトではPTK2遺伝子にコードされるタンパク質である[4]。 ... "Janus kinases and focal adhesion kinases play in the 4.1
protein kinase activator activity. • 1-phosphatidylinositol-4-phosphate 3-kinase activity. • protein serine/threonine kinase ... kinase activity. • phosphatidylinositol 3-kinase activity. • phosphatidylinositol-3,4-bisphosphate 5-kinase activity. ... positive regulation of protein kinase B signaling. • phosphatidylinositol 3-kinase signaling. • cytokine-mediated signaling ... phosphatidylinositol-mediated signaling. • leukocyte migration. • ERBB2 signaling pathway. • phosphatidylinositol-3-phosphate ...
Protein kinase C activation[edit]. PIP2 cleavage to IP3 and DAG initiates intracellular calcium release and PKC activation. ... and is a product of the hydrolysis of the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) by the enzyme phospholipase ... Diacylglycerol can be phosphorylated to phosphatidic acid by diacylglycerol kinase. Insulin resistance[edit]. Activation of PKC ... whereas DAG is a physiological activator of protein kinase C (PKC). The production of DAG in the membrane facilitates ...
protein kinase B signaling. • regulation of multicellular organism growth. • positive regulation of cell migration. • platelet ... phosphatidylinositol 3-kinase signaling. • positive regulation of DNA binding. • Ras protein signal transduction. • cell ... activation of protein kinase B activity. • insulin-like growth factor receptor signaling pathway. • negative regulation of ... positive regulation of phosphatidylinositol 3-kinase signaling. • myoblast differentiation. • glycolate metabolic process. • ...
Mauceri D, Cattabeni F, Di Luca M, Gardoni F (May 2004). "Calcium/calmodulin-dependent protein kinase II phosphorylation drives ... permeable AMPA receptors induce phosphorylation of cAMP response element-binding protein through a phosphatidylinositol 3- ... kinase-dependent stimulation of the mitogen-activated protein kinase signaling cascade in neurons". The Journal of Neuroscience ... S818 is phosphorylated by protein kinase C, and is necessary for long-term potentiation (LTP; for GluA1's role in LTP, see ...
phosphatidylinositol phosphorylation. • positive regulation of protein kinase B signaling. • توصيل الإشارة. • negative ... protein tyrosine kinase activity. • phosphatidylinositol-4,5-bisphosphate 3-kinase activity. • Ras guanyl-nucleotide exchange ... positive regulation of protein kinase activity. • ERBB2 signaling pathway. • regulation of cell motility. • epidermal growth ... 1 (3): 201-7. PMC 3375599. . PMID 19138957. doi:10.1158/1940-6207.CAPR-08-0014. الوسيط ,السنة=. تم تجاهله (مساعدة); الوسيط , ...
positive regulation of I-kappaB kinase/NF-kappaB signaling. • positive regulation of cytosolic calcium ion concentration ... "Interferon-γ activates transglutaminase 2 via a phosphatidylinositol-3-kinase-dependent pathway: implications for celiac sprue ... Mishra S, Murphy LJ (June 2004). "Tissue transglutaminase has intrinsic kinase activity: identification of transglutaminase 2 ... tTG is proposed to also act as kinase,[30] and protein disulfide isomerase,[31] and deamidase.[32] This latter activity is ...
"Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate". Nature. 332 (6165): ... Whitman M, Kaplan DR, Schaffhausen B, Cantley L, Roberts TM (1985). "Association of phosphatidylinositol kinase activity with ... This approach was used to characterize the substrate specificity of a large number of protein kinases. The kinase specificity ... "The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress" ...
Firstly, it binds with high affinity to Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), found on the inner surface of the ... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase" ... "Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a Tat-dependent mechanism". J. Immunol. 169 ... III-3-III-18 *^ Kim JB, Sharp PA (April 2001). "Positive transcription elongation factor B ...
protein tyrosine kinase activity. • Ras guanyl-nucleotide exchange factor activity. • phosphatidylinositol-4,5-bisphosphate 3- ... phosphatidylinositol phosphorylation. • positive regulation of protein tyrosine kinase activity. • activation of transmembrane ... positive regulation of protein kinase B signaling. • negative regulation of Notch signaling pathway. • regulation of JAK-STAT ... positive regulation of MAP kinase activity. • epidermal growth factor receptor signaling pathway. • regulation of protein ...
... has been shown to interact with Protein kinase D1,[10] BAT2,[11] PRKCD,[10] PKC alpha[10] and Protein kinase Mζ.[10] ... phosphatidylinositol 3-kinase signaling. • innate immune system. • viral process. • positive regulation of dendritic cell ... protein kinase C binding. • complement component C1q binding. • adrenergic receptor binding. • translation activator activity. ... 2000). "Protein kinase C [micro] is regulated by the multifunctional chaperon protein p32". J. Biol. Chem. 275 (32): 24601-7. ...
mitogen-activated protein kinase kinase kinase binding. • protein binding. • thioesterase binding. • protein kinase binding. • ... positive regulation of phosphatidylinositol 3-kinase activity. • cellular protein localization. • positive regulation of ... "The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily ... regulation of protein kinase activity. • regulation of attachment of spindle microtubules to kinetochore. • regulation of small ...
negative regulation of protein kinase B signaling. • cell differentiation. • immune system process. • negative regulation of ... positive regulation of phosphatidylinositol 3-kinase signaling. • positive regulation of apoptotic process. • intracellular ... The protein binds estradiol, resulting in intracellular calcium mobilization and synthesis of phosphatidylinositol (3,4,5)- ... doi:10.1007/s00213-011-2599-3. PMC 3350630. PMID 22143579.. *^ a b Choleris E (11 April 2013). Oxytocin, Vasopressin and ...
... a role for phosphatidylinositol 3'-kinase". Cancer Research. 62 (15): 4469-77. PMID 12154057.. ... 3: 45-55. PMC 2688355 . PMID 19578493.. *^ Li J, Zhang G, Wang X, Li XF (2015). "Is carbonic anhydrase IX a validated target ... 33 (3): 480-7. doi:10.1006/geno.1996.0223. PMID 8661007.. *^ Nakagawa Y, Uemura H, Hirao Y, Yoshida K, Saga S, Yoshikawa K (Oct ... 21 (3): 473-82. doi:10.1200/JCO.2003.11.132. PMID 12560438.. *. Bui MH, Seligson D, Han KR, Pantuck AJ, Dorey FJ, Huang Y, ...
Association of p21ras with phosphatidylinositol 3-kinase. A Sjölander, K Yamamoto, B E Huber, and E G Lapetina ... the signaling pathways of several growth factors have been reported to involve phosphatidylinositol (PtdIns) 3-kinase. In the ... These data indicate that PtdIns 3-kinase activity is an important step in the cascade of reactions in p21ras signal ... The PtdIns 3-kinase activity was also immunoprecipitated in these experiments by the anti-Ras monoclonal antibody Y13-259. The ...
Phosphatidylinositol 4-kinase (PI4-kinase) (EC:2.7.1.67) [PMID: 8194527] is an enzyme that acts on phosphatidylinositol (PI) in ... Short name: PI3/4_kinase_CS Description. Phosphatidylinositol 3-kinase (PI3-kinase) (EC:2.7.1.137) [PMID: 1322797] is an enzyme ... PIK1, an essential phosphatidylinositol 4-kinase associated with the yeast nucleus.. EMBO J. 13 2352-61 1994 ... Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression.. Cell 73 ...
In enzymology, a phosphatidylinositol-4-phosphate 3-kinase (EC 2.7.1.154) is an enzyme that catalyzes the chemical reaction ATP ... This enzyme participates in phosphatidylinositol signaling system. As of late 2007, 3 structures have been solved for this ... The systematic name of this enzyme class is ATP:1-phosphatidyl-1D-myo-inositol-4-phosphate 3-phosphotransferase. Other names in ... PC, Woscholski R, Parker PJ, Waterfield MD (2001). "Synthesis and function of 3-phosphorylated inositol lipids". Annu. Rev. ...
... are a family of Ser/Thr-protein kinases with sequence similarity to phosphatidylinositol-3 kinases (PI3Ks). The human PIKK ... Pfam PF02259 kinase domain (KD; PI3_PI4_kinase), PIKK- regulatory domain (PRD), and C-terminus FAT-C-terminal (FATC) domain ... Kinase Family PIKK at WikiKinome. Biology portal v t e. ...
Mutant PI3-Kinase Proteins Display Enhanced Lipid Kinase Activity. PI3-kinase is a lipid kinase that catalyzes the ... Mutant PI3-Kinase Induces Constitutive Activation of Akt Signaling in CEF. One of the downstream targets of PI3-kinase is Akt, ... PI3-Kinase Assay. In vitro PI3-kinase activity was analyzed as described (16), with minor modifications. Briefly, the immune ... An important downstream target of PI3-kinase is the serinethreonine kinase Akt (18, 19). Binding of Akt to the product of PI3- ...
The phosphatidylinositol 3-Kinase AKT pathway in human cancer.. Vivanco I1, Sawyers CL. ...
... elevated lipid kinase activity and constitutive signaling through the kinases Akt and TOR. The location of the mutations on a ... Cancer-specific mutations in phosphatidylinositol 3-kinase.. Vogt PK1, Kang S, Elsliger MA, Gymnopoulos M. ... Cancer-specific mutations in the catalytic subunit of phosphatidylinositol 3-kinase (PI3K) p110 alpha occur in diverse tumors ...
... Biochem Biophys Res Commun. 1998 Nov 18;252(2):313-7. ... One of these proteins was immunologically identified as the p85 regulatory subunit of the phosphatidylinositol 3-kinase, a key ... Immunoprecipitation of the p110 catalytic subunit of the phosphatidylinositol 3-kinase co-immunoprecipitated p85 in control ...
They have been shown to express different membranous growth factor receptors, many of them signaling via intracellular kinase ... Phosphatidylinositol-3-kinase/AKT signaling is essential in synovial sarcoma Int J Cancer. 2011 Oct 1;129(7):1564-75. doi: ... They have been shown to express different membranous growth factor receptors, many of them signaling via intracellular kinase ... Most tumors showed significant expression levels of p-AKT, p-GSK-3β and p-mTOR, indicating activation of the PI3K/AKT signaling ...
The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/Akt in fibrogenesis of human lung fibroblasts ... Phosphatidylinositol-3-Kinase/Akt regulates bleomycin-induced fibroblast proliferation and collagen production.. ... The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/Akt in fibrogenesis of human lung fibroblasts ...
Interacts with HIV-1 Nef to activate the Nef associated p21-activated kinase (PAK). This interaction depends on the C-terminus ... Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the ...
Insulin Activation of Phosphatidylinositol 3-Kinase in the Hypothalamic Arcuate Nucleus. Kevin D. Niswender, Christopher D. ... Insulin Activation of Phosphatidylinositol 3-Kinase in the Hypothalamic Arcuate Nucleus. Kevin D. Niswender, Christopher D. ... Insulin Activation of Phosphatidylinositol 3-Kinase in the Hypothalamic Arcuate Nucleus Message Subject (Your Name) has ... Insulin Activation of Phosphatidylinositol 3-Kinase in the Hypothalamic Arcuate Nucleus. A Key Mediator of Insulin-Induced ...
... a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5- ... Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the ... a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5- ... Phosphatidylinositol 3-kinase regulatory subunit betaAdd BLAST. 722. Amino acid modifications. Feature key. Position(s). ...
A wortmannin-sensitive phosphatidylinositol 4-kinase that regulates hormone-sensitive pools of inositolphospholipids. Proc. ... Involvement of protein tyrosine kinase p72syk and phosphatidylinositol 3-kinase in CD2-mediated granular exocytosis in the ... Activation of phosphatidylinositol-3-kinase in Jurkat T cells depends on the presence of the p56lck tyrosine kinase. Eur. J. ... Phosphatidylinositol 3-Kinase-Dependent and -Independent Cytolytic Effector Functions. Claudette L. Fuller, Kodimangalam S. ...
A novel gene, STT4, encodes a phosphatidylinositol 4-kinase in the PKC1 protein kinase pathway of Saccharomyces cerevisiae. ... Receptor-mediated protein sorting to the vacuole in yeast: roles for a protein kinase, a lipid kinase and GTP-binding proteins. ... Phosphatidylinositol 4-kinase: gene structure and requirement for yeast cell viability. Flanagan, C.A., Schnieders, E.A., ... Vps34p required for yeast vacuolar protein sorting is a multiple specificity kinase that exhibits both protein kinase and ...
Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are ... IPR011009. Kinase-like_dom_sf. IPR000403. PI3/4_kinase_cat_dom. IPR036940. PI3/4_kinase_cat_sf. IPR018936. PI3/4_kinase_CS. ... IPR011009. Kinase-like_dom_sf. IPR000403. PI3/4_kinase_cat_dom. IPR036940. PI3/4_kinase_cat_sf. IPR018936. PI3/4_kinase_CS. ... PS00915. PI3_4_KINASE_1. 1 hit. PS00916. PI3_4_KINASE_2. 1 hit. PS50290. PI3_4_KINASE_3. 1 hit. PS51547. PI3K_C2. 1 hit. ...
tags: phosphatidylinositol (PI) 3-kinase x disease/medicine x The Scientist. » phosphatidylinositol (PI) 3-kinase and disease/ ...
IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was also measured in muscle biopsy samples obtained from ... Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. ... Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. ... Insulin stimulation, during the glycerol infusion, resulted in a fourfold increase in PI 3-kinase activity over basal that was ...
... kinase/Akt signaling. Taken together, we demonstrated that inhibition of PI3-kinase/Akt signaling promoted Fas-induced ... Inhibition of phosphatidylinositol 3-kinase/Akt signaling promotes Fas-induced apoptosis in cholangiocarcinoma. Yabing Chen, ... Inhibition of phosphatidylinositol 3-kinase/Akt signaling promotes Fas-induced apoptosis in cholangiocarcinoma ... Inhibition of phosphatidylinositol 3-kinase/Akt signaling promotes Fas-induced apoptosis in cholangiocarcinoma ...
Phosphatidylinositol (Pl)-3 kinase is one of many enzymes stimulated by growth factors. A constitutively activated mutant, p110 ... Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase ... Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase ... Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase ...
... phosphatidylinositol 3-kinase catalytic subunit type 3), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol ... ARM-type_fold C2_domain_sf Kinase-like_dom_sf PI3/4_kinase_cat_dom PI3/4_kinase_cat_sf PI3/4_kinase_CS PI3K_C2_dom PI3K_Vps34 ... PI3_4_KINASE_1 (PS00915) PI3_4_KINASE_2 (PS00916) PI3_4_KINASE_3 (PS50290) PI3K_C2 (PS51547) PIK_HELICAL (PS51545) ... autophagosome assembly phagophore assembly site protein kinase activity protein binding ATP binding cytoplasm endosome late ...
Phosphatidylinositol 3-kinase (PI3K) signaling pathway was also examined. ,i,Materials and Methods,/i,. Cultured endothelial ... believed that hyperpermeability induced by H2O2 was caused by activation of mitogen-activated protein kinase through ... P. Sheth, S. Basuroy, C. Li, A. P. Naren, and R. K. Rao, "Role of phosphatidylinositol 3-kinase in oxidative stress-induced ... To measure PI3K activity, a TLC-based assay was employed by using phosphatidylinositol 4-5-biphosphate (PIP2) as a substrate. ...
P3K stands for phosphatidylinositol 3-kinase. P3K is defined as phosphatidylinositol 3-kinase rarely. ... 602839 - phosphatidylinositol 3-kinase, catalytic, delta; pik3cd - phosphatidylinositol 3-kinase, catalytic, 110-kd, delta;; ... 171834 - phosphatidylinositol 3-kinase, catalytic, alpha; pik3ca - phosphatidylinositol 3-kinase, catalytic, 110-kd, alpha;; ... Phosphatidylinositol 3-kinase inhibitor(LY294002) induces apoptosis of human nasopharyngeal carcinoma in vitro and in vivo ...
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma. Kind. protein. Organism. Humans. Protein. Name. ... Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma. Details. Name. ... Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma. O75747. Details. ...
Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J. Biol. Chem. 273:3963-3966. doi:10.1074/jbc.273.7. ... Atg1 kinase and its regulators, the PI3-kinase complex, the Atg9 vesicle, the Atg2-Atg18 complex, and two ubiquitin-like ... PI3-kinase complex I (Vps34, Vps15, Vps30/Atg6, and Atg14), which functions in autophagy, and PI3-kinase complex II (Vps34, ... A novel protein kinase homolog essential for protein sorting to the yeast lysosome-like vacuole. Cell. 64:425-437. doi:10.1016/ ...
Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) plays a critical role in the pathogenesis of cancer including ... Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) plays a critical role in the pathogenesis of cancer including ... Oncogenic activation of the PI3-kinase p110beta isoform via the tumor-derived PIK3Cbeta(D1067V) kinase domain mutation. ... The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet (2006) 7:606-19. doi: ...
IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain. IPR036940 Phosphatidylinositol 3-/4-kinase, catalytic domain ... PIK3C2G, phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma. Orthology source: HomoloGene, HGNC ... PR:000012717 phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma ... IPR001263 Phosphoinositide 3-kinase, accessory (PIK) domain. IPR042236 Phosphoinositide 3-kinase, accessory (PIK) domain ...
Enhanced insulin-stimulated activation of phosphatidylinositol 3-kinase in the liver of high-fat-fed rats.. ... Enhanced insulin-stimulated activation of phosphatidylinositol 3-kinase in the liver of high-fat-fed rats. ... Insulin receptor substrate (IRS)-1 and IRS-2, which mediate phosphatidylinositol (PI) 3-kinase activation, play essential roles ... Enhanced insulin-stimulated activation of phosphatidylinositol 3-kinase in the liver of high-fat-fed rats. ...
Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci U S A 2005; 102: 802-7. ... Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science 1997; 277: 567-70. ... The phosphatidylinositol 3′-kinases (PI3K) activate Akt and a wide range of downstream effectors to regulate multiple cellular ... Class I PI3Ks are activated by receptor tyrosine kinases and comprise one of several signaling activities induced by activated ...
... in Middle-Aged Female Mice Requires Dorsal Hippocampal Extracellular Signal-Regulated Kinase and Phosphatidylinositol 3-Kinase ... we recently demonstrated that activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/ ... 2005) PI3 kinase signaling is required for retrieval and extinction of contextual memory. Nat Neurosci 8:925-931. ... 2003) Effects of estrogen, age, and calpain on MAP kinase and NMDA receptors in female rat brain. Neurobiol Aging 24:977-983. ...
  • The catalytic domain of PI3K has the typical bilobal structure that is seen in other ATP-dependent kinases, with a small N-terminal lobe and a large C-terminal lobe. (ebi.ac.uk)
  • In contrast to protein kinases, the PI3K loop which interacts with the phosphates of the ATP and is known as the glycine-rich or P-loop, contains no glycine residues. (ebi.ac.uk)
  • Phosphorylation of AKT, GSK-3β and mTOR was assessed, and cellular proliferation and apoptosis were analyzed to functionally characterize the effects of PI3K inhibition. (nih.gov)
  • In vitro, PI3K inhibition diminished synovial sarcoma cell growth accompanied by reduced phosphorylation of AKT, GSK-3β and mTOR. (nih.gov)
  • The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/Akt in fibrogenesis of human lung fibroblasts and its regulation by reactive oxygen species (ROS). (cdc.gov)
  • In peripheral tissues, insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. (diabetesjournals.org)
  • Here, we report that insulin induces tyrosine phosphorylation of the insulin receptor and IRS-1 and -2, increases binding of activated IRS-1 and -2 to the regulatory subunit of PI3K, and activates protein kinase B/Akt, a downstream target of PI3K. (diabetesjournals.org)
  • Using an immunohistochemical technique to detect PI 3,4,5-triphosphate, the main product of PI3K activity, we further demonstrate that in the arcuate nucleus, insulin-induced PI3K activity occurs preferentially within cells that contain IRS-2. (diabetesjournals.org)
  • This is a phase II, exploratory, open-label, single arm study of BYL719 monotherapy, a selective phosphatidylinositol 3-kinase (PI3K) alpha inhibitor, in adult patients with advanced metastatic breast cancer progressing after first line therapy. (clinicaltrials.gov)
  • Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). (uniprot.org)
  • Here, we discuss experimental evidence that argues for a critical role of the PI3K-phosphoinositide-dependent protein kinase (PDK1)-protein kinase B (PKB) signaling pathway in the development of both normal and malignant thymocytes, and we highlight molecules that can potentially be targeted therapeutically. (sciencemag.org)
  • Phosphatidylinositol 3-kinase (PI3K) signaling pathway was also examined. (hindawi.com)
  • Due to the involvement in the regulation of ZO-1, phosphatidylinositol 3-kinase (PI3K) signaling pathway was also examined. (hindawi.com)
  • Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) plays a critical role in the pathogenesis of cancer including glioblastoma, the most common and aggressive form of brain cancer. (frontiersin.org)
  • Deregulated signaling through the phosphatidylinositol 3′-kinase (PI3K) pathway is common in many types of cancer, including glioblastoma. (aacrjournals.org)
  • These results provide the first dissection of the PI3K pathway in glioblastoma in vivo and suggest an approach to stratifying patients for targeted kinase inhibitor therapy. (aacrjournals.org)
  • PI3K 4 is a lipid kinase that promotes diverse biological functions including cellular proliferation, survival, and motility. (aacrjournals.org)
  • Here, we asked whether E 2 has similar memory-enhancing effects in middle-aged and aged ovariectomized mice, and whether these effects depend on ERK and phosphatidylinositol 3-kinase (PI3K)/Akt activation. (jneurosci.org)
  • Phosphatidylinositol 3-kinase (PI3K) is activated by p185(erbB-2) /erbB-3 heterodimers in cells stimulated by HRG, and PI3K is constitutively activated by p185(erbB-2) /erbB-3 in breast carcinoma cells that overexpress c-erbB-2. (unboundmedicine.com)
  • To better understand the relative abilities of HRGs, epidermal growth factor (EGF), or insulin to activate PI3K under normal physiological conditions, we compared the levels of recruitment of the 85-kDa regulatory subunit of PI3K when activated by the type I (erbB) or type II [insulin-like growth factor (IGF)] receptor tyrosine kinases in two different nontransformed human mammary epithelial cell lines. (unboundmedicine.com)
  • Furthermore, erbB-3 principally mediated the direct recruitment of p85 in cells stimulated by HRG or EGF, indicating that, in addition to the high-level activation of PI3K by p185(erbB-2) / erbB-3, EGFR/erbB-3 heterodimer interaction is essential for the weak but significant level of PI3K activated by EGF in cells that express normal EGFR levels. (unboundmedicine.com)
  • 8 Ras has emerged as a convergent molecular switch that integrates and propagates extracellular signals to downstream cascades, the best characterized of which are the phosphatidylinositol-3-kinase (PI3K) and the mitogen-activated protein kinase (MAPK) pathways. (ahajournals.org)
  • The phosphatidylinositol 3-kinase δ (PI3Kδ) pathway regulates AID by suppressing its expression in B cells. (selleckchem.com)
  • In summary, we show that PI3Kδ or Bruton's tyrosine kinase inhibitors increase genomic instability in normal and neoplastic B cells by an AID-dependent mechanism. (selleckchem.com)
  • Phosphatidylinositol-3-kinase (PI3K) signalling was simultaneously induced at this time point. (sigmaaldrich.com)
  • The phosphatidylinositol 3-kinase (PI3K) catalytic subunit is amplified in cervical cancers, implicating PI3K in cervical carcinogenesis. (aacrjournals.org)
  • The phosphatidylinositol 3-kinase (PI3K) family of enzymes is well characterized with respect to promotion of cellular growth, survival, and suppression of apoptosis in cancer cells ( 4 - 6 ). (aacrjournals.org)
  • An inhibitor of all major subclasses of PI3K and PI3K-like kinases (ATM, ATR, and DNA-PK), LY294002 has been evaluated in various cell lines showing increased apoptosis ( 19 , 20 ). (aacrjournals.org)
  • Levels of Bcl-2, PI3K, p-GSK-3β/GSK-3β, and p-Akt were decreased in the DCM group, while the levels of Bax and Caspase-3 were obviously increased. (unboundmedicine.com)
  • The phosphatidylinositol 3-kinase (PI3K) signaling pathway is deregulated in many human diseases including: cancer, diabetes, obesity and autoimmunity. (pubmedcentralcanada.ca)
  • The p110-PI3K enzyme generates the key signaling lipid phosphatidylinositol 3,4,5-trisphosphate, which is dephosphorylated by the PI3-phosphatase PTEN. (pubmedcentralcanada.ca)
  • PTEN dephosphorylates the D3 position of phosphatidylinositol 3,4,5-trisphosphate (PI3,4,5P 3 ), the product of activated phosphatidylinositol 3-kinase (PI3K). (pubmedcentralcanada.ca)
  • PI3K consists of a p110 catalytic subunit and a p85α regulatory subunit, and is activated in response to receptor tyrosine kinases, including the platelet-derived growth factor (PDGF) receptor (PDGFR) and epidermal growth factor (EGF) receptor (EGFR). (pubmedcentralcanada.ca)
  • The PI3K pathway provides proliferative and anti-apoptotic signals and is frequently deregulated and/or activated in human cancers ( 1 - 3 ). (pubmedcentralcanada.ca)
  • The PI3K pathway also plays a central role in mediating insulin responses via the insulin receptor, a receptor tyrosine kinase that phosphorylates insulin receptor substrate proteins (e.g. (pubmedcentralcanada.ca)
  • In this report we demonstrate that p85α can directly bind and enhance the lipid phosphatase activity of PTEN, making it a dual regulatory protein for both the p110-PI3-kinase and the PTEN-PI3-phosphatase, performing a critical regulatory function in maintaining the balance of PI3K/PTEN signaling. (pubmedcentralcanada.ca)
  • Antiproliferative Activity of Carnosic Acid is Mediated via Inhibition of Cell Migration and Invasion, and Suppression of Phosphatidylinositol 3-Kinases (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Signaling Pathway. (medworm.com)
  • We showed here that PV simultaneously activates the phosphatidylinositol 3-kinase (PI3K)/Akt survival signaling pathway in these cells, limiting the extent of JNK activation and thereby cell death. (asm.org)
  • JNK inhibition is associated with PI3K-dependent negative regulation of the apoptosis signal-regulating kinase 1, which acts upstream from JNK in PV-infected IMR5 cells. (asm.org)
  • The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays a crucial role in the transmission of survival signals in various cell types ( 14 , 26 ), including neurons ( 16 ). (asm.org)
  • PI3K activates its downstream effector, the serine/threonine kinase Akt (also known as protein kinase B, PKB) by promoting its phosphorylation at the residues Thr308 and Ser473. (asm.org)
  • The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin inhibitor (mTOR) pathway is often constitutively activated in human tumor cells, providing unique opportunities for anticancer therapeutic intervention. (aacrjournals.org)
  • NVP-BEZ235 is an imidazo[4,5- c ]quinoline derivative that inhibits PI3K and mTOR kinase activity by binding to the ATP-binding cleft of these enzymes. (aacrjournals.org)
  • Phosphatidylinositol 3-kinase (PI3K) and its downstream effector Akt are frequently deregulated in human cancers ( 1 ). (aacrjournals.org)
  • Under some circumstances, the Ras oncogene or activated receptor tyrosine kinases have also been shown to mediate their transforming potential through aberrant PI3K signaling ( 16 ). (aacrjournals.org)
  • We show that cells lacking two Dictyostelium class I phosphatidylinositol (PI) 3′ kinases (PI3K and pi3k1/2 -null cells) or wild-type cells treated with the PI3K inhibitor LY294002 are unable to properly polarize, are very defective in the temporal, spatial, and quantitative regulation of chemoattractant-mediated filamentous (F)-actin polymerization, and chemotax very slowly. (rupress.org)
  • Activation of PI3K produces the membrane-soluble products PI 3,4,5-triphosphate (PI[3,4,5]P 3 ) and PI 3,4-bisphosphate (PI[3,4]P 2 ), resulting in the membrane localization and activation of downstream effectors. (rupress.org)
  • The phosphatidylinositol 3-kinase (PI3K) signalling pathway is one of the most frequently genetically altered pathways in human cancers (Samuels et al. (auckland.ac.nz)
  • 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. (auckland.ac.nz)
  • Our aim was to investigate whether rh-EPO augments neovascularization in the neonatal rat model of premature brain damage through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. (pubmedcentralcanada.ca)
  • Some in vitro experiments suggest that EPO enhances vascular endothelial growth factor (VEGF) secretion in neural progenitor cells through the activation of phosphatidylinositol 3 kinase (PI3K)/Akt signaling pathway. (pubmedcentralcanada.ca)
  • Using kinase inhibitors, we showed that 4E-BP phosphorylation was dependent on phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR) activation but did not require MAPKs. (asm.org)
  • PI3K and Akt activation led to the phosphorylation and inactivation of the positive cytokine regulator glycogen synthase kinase 3α/β (GSK-3α/β). (asm.org)
  • PI3K, Akt, and mTOR inhibitors and small interfering RNA knockdown of Akt expression all increased, whereas a GSK-3α/β inhibitor decreased, Stx1-induced soluble tumor necrosis factor alpha and interleukin-1β production. (asm.org)
  • Overall, these findings suggest that despite transient activation of 4E-BP, the PI3K/Akt/mTOR pathway negatively influences cytokine induction by inactivating the positive regulator GSK-3α/β. (asm.org)
  • Involvement of phosphatidylinositol 3-kinase (PI3K) in autophagy was also tested using wortmannin, a PI3K inhibitor. (deepdyve.com)
  • S )-1-{4-[2-(2-Amino-pyrimidin-5-yl)-7-methyl-4-morpholin-4-yl-thieno[3,2- d ]pyrimidin-6-ylmethyl]-piperazin-1-yl}-2-hydroxy-propan-1-one (GDC-0980) is a potent and selective inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin, two key components of the PI3K pathway, the deregulation of which is associated with the development of many cancers. (aspetjournals.org)
  • The phosphatidylinositol 3-kinase (PI3K) pathway is a major determinant of cell cycling and proliferation. (aspetjournals.org)
  • 2-(1 H -Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2- d ]pyrimidine (GDC-0941) is a novel small molecule inhibitor of PI3K currently being evaluated in the clinic as an anticancer agent. (aspetjournals.org)
  • As part of this pathway, the PI3K family of lipid kinases catalyzes the phosphorylation of the 3′-hydroxyl group of phosphatidylinositols, leading to the activation of the serine/threonine protein kinase Akt and further downstream effectors, such as PRAS40, part of the mTOR complex 1, and S6 kinases ( Engelman, 2009 ). (aspetjournals.org)
  • Xie, Zhixun 2014-08-01 00:00:00 We have previously reported that inhibition of phosphatidylinositol 3-kinase (PI3K) reduces porcine reproductive and respiratory syndrome (PRRSV) replication. (deepdyve.com)
  • Here, we further investigate the mechanism by which PI3K inhibition affects virus replication and the role of Akt1 kinase in virus replication. (deepdyve.com)
  • We investigated the effect of 2-methyl-2-{4-[3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydro-1 H -imidazo[4,5- c ]quinolin-1-yl]phenyl} propanenitrile (NVP-BEZ235) (Novartis, Basel Switzerland), a dual phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor currently being tested in phase I clinical trials, in radiosensitization. (aspetjournals.org)
  • A Rho inhibitor, ML141, LY294002, and an Akt1/2 inhibitor diminished K. pneumoniae invasion in a dose-dependent manner, indicating that Rho family GTPases and phosphatidylinositol 3-kinase (PI3K)/Akt signaling were required. (asm.org)
  • In addition, we discuss relatively novel chemical genetic studies of zebrafish vascular development that have provided evidence that a crosstalk between 2 ubiquitous signaling pathways, the phosphoinositide 3-kinase (PI3K) and the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathways, plays a central antagonistic role in artery-vein specification during vasculogenesis. (ahajournals.org)
  • A novel phosphatidylinositol 3-kinase (PI3K) inhibitor directs a potent FOXO-dependent, p53-independent cell cycle arrest phenotype characterized by the differential induction of a subset of FOXO-regulated genes. (ualg.pt)
  • The activation of the phosphoinositide 3-kinase (PI3K)/AKT signalling pathway is one the most frequent genetic events in breast cancer, consequently the development of PI3K inhibitors has attracted much attention. (ualg.pt)
  • Infection of C. jejuni SC11 was able to activate phosphatidylinositol 3-kinase (PI3K)/Akt pathway and induce pro-inflammatory interleukin-8(IL-8) as well as anti-inflammatory cytokine IL-10 in human intestinal epithelial cell line Colo 205. (dtu.dk)
  • The signalling pathways PI3K/Akt and mitogen-activated protein (MAP)kinases ERK and p38 were involved in C. jejuni-induced IL-8 and IL-10 expression. (dtu.dk)
  • To elucidate the mechanisms underlying the mechanical activation of chondrocytes, intracellular signaling pathways through the Ras/mitogen-activated protein kinase (MAPK) and the integrin/phosphatidylinositol 3 kinase (PI3K)/Akt pathways as well as proteins involved in proliferation of chondrocytes were examined in LIPUS-treated chondrocytes. (biomedcentral.com)
  • Among these growth factors, hepatocyte growth factor (HGF), also named as scatter factor, acts by recruiting the phosphatidylinositol 3-kinase (PI3K)-Akt signal transduction pathway, linked to cardioprotection, at the time of myocardial infarction and myocardial reperfusion. (elsevier.com)
  • Aberrantly triggered PI3K pathway promotes carcinogenesis and tumor angiogenesis [3 10 For instance around 30% of breasts cancers proven activating missense mutations of respectively whereas the regulatory p85 subunit- p85 p55 and PP121 p50 isoforms - are encoded by and genes respectively [26 27 Course IB PI3Ks also contain catalytic p110? (immune-source.com)
  • Course II PI3K enzymes also can be found in 3 isoforms (PI3KC2? (immune-source.com)
  • The central area can be made up of the C2 PI3K-type and PIK helical domains whereas the C-terminus provides the catalytic equipment (PI3K/PI4K kinase domain). (immune-source.com)
  • In course II enzymes nevertheless the central area can be made-up of four domains (PI3K-RBD C2 PI3K-type PIK helical PI3K/PI4K kinase) as well as the C-terminal series made up of the C2 and PX domains. (immune-source.com)
  • also acts as main binding site for clathrin trimers and therefore individually modulating clathrin distribution and function [32 33 Course III catalytic enzyme hVps34 can be seen as a an N-terminal C2 PP121 PI3K-type site a located PIK helical site and a C-terminus PI3K/PI4K kinase site [34]. (immune-source.com)
  • Since some RTKs act through Ras and phosphatidylinositol 3-kinase (PI3K), we investigated the role of these pathways in ARIA signaling. (rupress.org)
  • Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit. (ebi.ac.uk)
  • PIK3CA , which encodes for the catalytic subunit p110α of class IA PI3-kinase, is amplified and overexpressed in some cases of ovarian cancer ( 1 ). (pnas.org)
  • Mutations in the regulatory subunit p85 of PI3-kinase have been identified in ovarian and colon tumors ( 2 ). (pnas.org)
  • the catalytic subunit p110α of PI3-kinase is the cellular counterpart of the product of v- p3k , a viral oncogene found in the avian sarcoma virus 16 that induces hemangiosarcomas in chickens ( 10 ). (pnas.org)
  • One of these proteins was immunologically identified as the p85 regulatory subunit of the phosphatidylinositol 3-kinase, a key enzyme involved in the signal transduction cascade initiated by many agonists including growth factors. (nih.gov)
  • Immunoprecipitation of the p110 catalytic subunit of the phosphatidylinositol 3-kinase co-immunoprecipitated p85 in control lysates. (nih.gov)
  • Here we identify and characterize Atg38 as a stably associated subunit of complex I. In atg38Δ cells, autophagic activity was significantly reduced and PI3-kinase complex I dissociated into the Vps15-Vps34 and Atg14-Vps30 subcomplexes. (rupress.org)
  • In the liver of high-fat-fed rats, insulin increased the PI 3-kinase regulatory subunit p85alpha and the PI 3-kinase activities associated with IRS-1 3.6- and 2.4-fold, and with IRS-2, 4.7- and 3.0-fold, respectively, compared with those in control rats. (diabetesjournals.org)
  • BCR-induced glucose utilization is dependent upon phosphatidylinositol 3-kinase (PI-3K) activity as evidenced by inhibition of glucose uptake and glycolysis with LY294002 treatment of normal B cells and impaired glucose utilization in B cells deficient in the PI-3K regulatory subunit p85α. (bloodjournal.org)
  • Phosphatidylinositol 4,5 Bisphosphate 3 Kinase Catalytic Subunit Beta Isoform (Phosphatidylinositol 4,5 Bisphosphate 3 Kinase 110 kDa Catalytic Subunit Beta or PIK3CB or EC 2.7.1.153) pipeline Target constitutes close to 13 molecules. (medindia.net)
  • Phosphatidylinositol 4,5 Bisphosphate 3 Kinase Catalytic Subunit Beta Isoform (Phosphatidylinositol 4,5 Bisphosphate 3 Kinase 110 kDa Catalytic Subunit Beta or PIK3CB or EC 2.7.1.153) - Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit beta isoform is an enzyme encoded by the PIK3CB gene. (medindia.net)
  • It also reviews key players involved in Phosphatidylinositol 4,5 Bisphosphate 3 Kinase Catalytic Subunit Beta Isoform (Phosphatidylinositol 4,5 Bisphosphate 3 Kinase 110 kDa Catalytic Subunit Beta or PIK3CB or EC 2.7.1.153) targeted therapeutics development with respective active and dormant or discontinued projects. (medindia.net)
  • Among the proteins involved in complex formation is phosphatidylinositol (PI) 3-kinase, a heterodimeric enzyme composed of 85 kDa and 110 kDa subunits, which binds to receptor (and non-receptor) phosphotyrosine residues through the two SH2 domains in the p85 subunit. (royalsocietypublishing.org)
  • p85 acts as an adaptor protein and possibly a regulator of the p110 catalytic subunit that phosphorylates phosphoinositides at the D-3 position of the inositol ring. (royalsocietypublishing.org)
  • Phosphatidylinositol 4,5 Bisphosphate 3 Kinase Catalytic Subunit Alpha Isoform (Phosphatidylinositol 4,5 Bisphosphate 3 Kinase 110 kDa Catalytic Subunit Alpha or Phosphoinositide 3 Kinase Catalytic Alpha Polypeptide or Serine/Threonine Protein Kinase PIK3CA or PIK3CA or EC 2.7.11.1 or EC 2.7.1.153) - The phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha also called p110α is a protein encoded by the PIK3CA gene. (giiresearch.com)
  • Phosphatidylinositol 4,5 Bisphosphate 3 Kinase Catalytic Subunit Alpha Isoform (Phosphatidylinositol 4,5 Bisphosphate 3 Kinase 110 kDa Catalytic Subunit Alpha or Phosphoinositide 3 Kinase Catalytic Alpha Polypeptide or Serine/Threonine Protein Kinase PIK3CA or PIK3CA or EC 2.7.11.1 or EC 2.7.1.153) pipeline Target constitutes close to 26 molecules. (giiresearch.com)
  • Toxin A subunits mediate protein synthesis inhibition by depurination of a single adenine residue located on a stem-loop structure near the 3′ end of 28S rRNA of the 60S ribosomal subunit ( 11 , 41 ). (asm.org)
  • NVP-BEZ235 abrogated the radiation-induced phosphorylation of both DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and ataxia telangiectasia mutated. (aspetjournals.org)
  • ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) have been shown to have sequences homologous to the catalytic domains of mammalian phosphatidylinositol 3-kinase (PI3-kinase). (nii.ac.jp)
  • ARIA/HRG regulates AChR epsilon subunit gene expression at the neuromuscular synapse via activation of phosphatidylinositol 3-kinase and Ras/MAPK pathway. (rupress.org)
  • This domain is also present in a wide range of protein kinases, involved in diverse cellular functions, such as control of cell growth, regulation of cell cycle progression, a DNA damage checkpoint, recombination, and maintenance of telomere length. (ebi.ac.uk)
  • this domain seems to be distantly related to the catalytic domain of protein kinases [ PMID: 8387896 , PMID: 12151228 ]. (ebi.ac.uk)
  • The mutant-transformed cells show constitutive phosphorylation of Akt, of p70 S6 kinase, and of the 4E-binding protein 1. (pnas.org)
  • Phosphorylation of S6 kinase and of 4E-binding protein 1 is regulated by the target of rapamycin (TOR) kinase and affects rates of protein synthesis. (pnas.org)
  • When expressed in cultured cells, the H1047R mutant protein displayed higher lipid kinase activity as compared with wild-type (wt) p110α ( 13 ), suggesting a gain of function caused by the mutation. (pnas.org)
  • Phosphatidylinositol 3-kinase-related kinases (PIKKs) are a family of Ser/Thr-protein kinases with sequence similarity to phosphatidylinositol-3 kinases (PI3Ks). (wikipedia.org)
  • A class III phosphatidylinositol 3-kinase complex that is involved in vacuolar protein sorting (VPS) via endosomes. (yeastgenome.org)
  • Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. (rcsb.org)
  • PKB, protein kinase B. (diabetesjournals.org)
  • The p110 protein exhibited high specific activity as a Pl-3 kinase and as a protein kinase. (sciencemag.org)
  • The product, phosphatidylinositol 3-phosphate (PI3P), is essential not only for autophagosome formation but also for the vacuolar protein sorting (VPS) pathway in yeast ( Backer, 2008 ). (rupress.org)
  • We used rat sympathetic neurons maintained in vitro to characterize the potential survival signals mediated by PI 3-kinase and to test whether the Akt protein kinase, a putative effector of PI 3-kinase, functions during nerve growth factor (NGF)-mediated survival. (jneurosci.org)
  • Treatment of neurons with NGF activates endogenous Akt protein kinase, and LY294002 or wortmannin blocks this activation. (jneurosci.org)
  • The consequences of TrkA activation include Shc/Grb2/Sos-dependent activation of Ras and the subsequent activation of mitogen-activated protein (MAP) kinases, phospholipase C-γ-mediated production of diacylglycerol and inositol trisphosphate, and PI 3-kinase-mediated production of 3′-phosphorylated phosphoinositides ( Kaplan and Stephens, 1994 ). (jneurosci.org)
  • How these molecules transduced the effects of agonists of PI-3K was unclear until the recent discovery that several protein kinases become activated upon exposure to 3´-phosphorylated inositol lipids. (portlandpress.com)
  • These enzymes include protein kinase B (PKB)/AKT and PtdIns(3,4,5) P 3 -dependent kinases 1 and 2, the first two of which interact with 3´-phosphorylated phosphoinositides via pleckstrin homology domains. (portlandpress.com)
  • The generation of effective transdominant mutants, coupled with genetic analysis of the protein kinase in simpler organisms, should help in elucidating outstanding questions in the functions, targets and regulation of this important mediator of PI-3K signalling. (portlandpress.com)
  • Phosphatidylinositol 3-kinase was the upstream activator of protein kinase B (Akt), which was responsible for phosphorylation of the rat endothelial isoform of NO synthase at S1176 and thereby promoted the increase in NO production. (ahajournals.org)
  • 18,19 In particular, NOS3 can serve as a substrate for protein kinase B (Akt), which promotes serine phosphorylation at residue 1176 in the carboxyl terminal portion of NOS3 and increases NOS3 sensitivity to calcium/calmodulin and enzyme activity. (ahajournals.org)
  • 21 Pyk2 (also designated FAK2, CAK-ß, CADTK, or RAFTK) is a member of the focal adhesion protein tyrosine kinase family. (ahajournals.org)
  • 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)
  • 22,24 Pyk2 has multiple binding partners that include c-Src, the 60-kDa protein of c-src (also known as pp60 c-src ), phosphatidylinositol 3-kinase (PI3-kinase), and Grb2. (ahajournals.org)
  • Ligand stimulation of growth factor receptors with intrinsic protein-tyrosine kinase activity initiates the assembly of multienzyme signalling complexes. (royalsocietypublishing.org)
  • PTEN is a tumor suppressor protein lost or mutated in as many as 30% of human cancers ( 1 - 3 ). (pubmedcentralcanada.ca)
  • Davidson, 1995 ), suggesting that PtdIns 3‐kinase is involved in lysosomal protein transport. (embopress.org)
  • PEP005 (ingenol-3-angelate) is a novel anticancer agent extracted from Euphorbia peplus that was previously shown to modulate protein kinase C (PKC), resulting in antiproliferative and proapoptotic effects in several human cancer cell lines. (aacrjournals.org)
  • In Colo205 cells exposed to PEP005, a variety of signaling pathways were activated as shown by increased phosphorylation of PKCδ, Raf1, extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (MAPK), c-Jun NH 2 -terminal kinase, p38 MAPK, and PTEN. (aacrjournals.org)
  • Interestingly, PEP005 treatment also resulted in reduced expression of PKCα and reduced levels of phosphorylated active form of AKT/protein kinase B. These data suggest that PEP005-induced activation of PKCδ and reduced expression of PKCα resulted in apoptosis by mechanisms mediated by activation of Ras/Raf/MAPK and inhibition of the phosphatidylinositol 3-kinase/AKT signaling pathways. (aacrjournals.org)
  • The identity of the kinase responsible for the S473 phosphorylation (PDK2) has been a matter of debate as many candidates, including Akt itself, ILK, PDK1, or DNA protein kinase (DNA-PK), have been proposed ( 2 ). (aacrjournals.org)
  • Steatosis was associated with increased expression of microsomal triglyceride transfer protein (MTTP) mRNA and increased ALT release with over expression of ALT mRNA, all of which were completely prevented by inhibition of PI3-kinase (LY294002). (physiology.org)
  • Cells lacking one of these proteins, phdA -null cells, exhibit defects in the level and kinetics of actin polymerization at the leading edge and have chemotaxis phenotypes that are distinct from those described previously for protein kinase B (PKB) ( pkbA )-null cells. (rupress.org)
  • There was no correlation between protection from apoptosis and activation of mitogen-activated protein kinase, p38/HOG1, or p70S6 kinase. (asm.org)
  • Because Akt/PKB is believed to be a downstream effector for PI3 kinase, we also examined the role of this serine/threonine protein kinase in antiapoptotic signalling. (asm.org)
  • Recombinant PIP5K3 protein was catalytically active and converted phosphatidylinositol-4-phosphate to phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P 2 ]. (plantcell.org)
  • Increased cytokine production is partly due to activation of the translation initiation factor eIF4E through a mitogen-activated protein kinase (MAPK)- and Mnk1-dependent pathway. (asm.org)
  • In addition to protein synthesis inhibition, it has become clear that Stxs also activate host cell signaling pathways involved in the induction of cytokine and chemokine expression ( 3 , 5 , 20 , 34 , 51 ). (asm.org)
  • Increases in intracellular C18:2 CoA and DAG concentration were associated with protein kinase C (PKC)-theta activation and a reduction in both insulin-stimulated IRS-1 tyrosine phosphorylation and IRS-1 associated PI3-kinase activity, which were associated with an increase in IRS-1 Ser(307) phosphorylation. (garvan.org.au)
  • Using evanescent wave microscopy and a green fluorescent protein-tagged PIP 3 -binding protein domain for real-time monitoring of plasma membrane PIP 3 concentration in single MIN6 β-cells, we now demonstrate that glucose stimulation of insulin secretion results in pronounced PIP 3 oscillations via autocrine stimulation of insulin receptors. (diva-portal.org)
  • Protein kinase A (PKA) was important for promoting concomitant initial elevations of [cAMP] pm and [Ca 2+ ] i , and PKA inhibitors diminished the PIP 3 response when applied before glucose stimulation, but did not affect already manifested PIP 3 oscillations. (diva-portal.org)
  • IGF-I also caused a concentration-dependent and long-lasting activation of protein kinase B (PKB/Akt). (ahajournals.org)
  • 9 10 These molecules then interact with downstream signal transducers and effectors, resulting in activation of the mitogen-activated protein kinase (MAPK, also known as ERK, extracellular signal-regulated kinase) pathway and phosphatidylinositol 3-kinase (PI3 kinase) signaling pathways. (ahajournals.org)
  • Activation of the MAPK pathway is considered to be critical for cell proliferation, whereas the PI3 kinase pathway is important for mediating the metabolic and antiapoptotic signals of IGF-I. Although these "model" systems are ideal for demonstrating protein-protein interactions, they are less suited for elucidating the physiological outcomes of the activation of these signaling pathways. (ahajournals.org)
  • Recently, a chemical genetic approach has revealed evidence that artery-vein specification is governed by cross talk between phosphoinositide 3-kinase and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in artery-vein specification. (ahajournals.org)
  • Phosphoinositide 3-kinase (PI3-K) and the downstream serine/threonine kinase Akt/protein kinase B have a central role in modulating neutrophil function, including respiratory burst, chemotaxis, and apoptosis. (eurekamag.com)
  • DNA-dependent protein kinase (DNA-PK) activity was suppressed by wortmannin to 45-65% of the control values in all of the cells except SCF, in which DNA-PK activity was not detected. (nii.ac.jp)
  • The time courses for activation of phosphatidylinositol 3-kinase and its downstream target, protein kinase B, by IL-3 were consistent with a role in IL-3-induced transporter translocation and enhanced glucose uptake. (lancs.ac.uk)
  • The effects of vibration on chondrocytes were previously examined in this system, and the involvement of a mechano-transduction pathway via the integrin/mitogen-activated protein kinase (MAPK) pathway and of another signaling pathway via β-catenin was evaluated. (biomedcentral.com)
  • To validate coexisting mutations within epidermal growth factor receptor (EGFR), mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways. (elsevier.com)
  • The inhibitor of TOR, rapamycin, strongly interferes with cellular transformation induced by the PI3-kinase mutants, suggesting that the TOR and its downstream targets are essential components of the transformation process. (pnas.org)
  • PD98059 (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-1), a MEK inhibitor, was from Tocris. (ahajournals.org)
  • Compelling evidence have emerged recently that indicate that the rapamycin-insensitive mammalian target of rapamycin inhibitor mTORC2 complex (mTOR in complex with rictor, Sin1, and mLst8) is PDK2 ( 3 - 7 ). (aacrjournals.org)
  • Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-d, as therapy for previously treated indolent non-Hodgkin lymphoma. (harvard.edu)
  • 2011) Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer. (guidetopharmacology.org)
  • Histamine secretion was influenced 100-fold more by wortmannin than by KT7692.2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), a structurally different PI3-kinase inhibitor from wortmannin, inhibited PI3-kinase with an IC50 of 2 microM but had little effect on MLCK activity in this concentration range. (biochemj.org)
  • Effect of a phosphatidylinositol 3-kinase inhibitor wortmannin on radiation and bleomycin sensitivities. (nii.ac.jp)
  • Publications] Yoshio Hosoi: 'A phosphatidylinositol 3-kinase inhibitor wortmannin induces radioresistant DNA synthesis and sensitizes cells to bleomycin and ionizing radiation' International Journal of Cancer. (nii.ac.jp)
  • In contrast with the liver, tyrosine phosphorylation levels and associated PI 3-kinase proteins and activities were decreased in the muscle and adipose tissue of high-fat-fed rats. (diabetesjournals.org)
  • Phospholipase C-gamma (PLC-gamma) isoforms are thought to be activated by both tyrosine phosphorylation and phosphatidylinositol 3,4,5 trisphosphate (PtdIns 3,4,5 P(3)), the product of phosphatidylinositol 3-kinase (PtdIns 3-kinase). (lu.se)
  • These data indicate that PtdIns 3-kinase is critical for the translocation but not for the tyrosine phosphorylation of PLC-gamma 2 in mouse macrophages and that the latter may be insufficient for enzyme activation. (lu.se)
  • Bax activation was mediated by c-Jun NH2-terminal kinase (JNK) phosphorylation after PV infection ( 6 ). (asm.org)
  • The upstream kinase responsible for the T308 site phosphorylation is PDK1. (aacrjournals.org)
  • PTEN-inactivated tumor cells exhibit elevated Akt kinase activity due to uncontrolled phosphorylation of T308 and S473. (aacrjournals.org)
  • This in turn leads to decreased IRS-1 tyrosine phosphorylation and decreased activation of IRS-1-associated PI3-kinase activity resulting in decreased insulin-stimulated glucose transport activity. (garvan.org.au)
  • Inhibition of glycogen synthase kinase-3β by Angelica sinensis extract decreases β-amyloid-induced neurotoxicity and tau phosphorylation in cultured cortical neurons. (semanticscholar.org)
  • We used wortmannin, an irreversible antagonist of phosphatidylinositol 3-kinase (PI3-K) activity, to investigate the role of PI3-K in influenza-specific CD8 + CTL cytolytic effector function. (jimmunol.org)
  • Two PI 3-kinase inhibitors, LY294002 and wortmannin, block NGF-mediated survival of sympathetic neurons. (jneurosci.org)
  • Using the PI 3-kinase inhibitors wortmannin and LY294002, Yao and Cooper (1995) reported that the inhibition of PI 3-kinase activity induces apoptosis in PC12 cells in the presence of NGF. (jneurosci.org)
  • Zymosan stimulation also induced translocation to membrane and cytoskeleton fractions, which was inhibited by the PtdIns 3-kinase inhibitors wortmannin and LY 294002. (lu.se)
  • On the other hand, protection by any of the tyrosine kinases against UV-induced apoptosis was blocked by wortmannin, implying a role for phosphatidylinositol 3-kinase (PI3 kinase). (asm.org)
  • Time-lapse imaging exposed effective depletion of PtdIns3within 10 moments of wortmannin addition, using the FYVE-EEA1 probe, and a concomitant swelling of the Rab5-positive compartment, which comes from the stalling of PI 3-kinase-dependent trafficking at the early endosome [40,41]. (exposed-skin-care.net)
  • We found that integrins activated both NF-(κ)B and MAPK in a PI 3-K-dependent manner, as wortmannin and LY294002 blocked these responses. (biologists.org)
  • tert -Butylhydroquinone ( t -BHQ) caused Nrf2 to translocate into the nucleus in H4IIE cells, which was prevented by pretreatment of the cells with PI3-kinase inhibitors (wortmannin/LY294002). (aspetjournals.org)
  • Wortmannin inhibited phosphatidylinositol 3-kinase (P13-kinase) and Fc epsilon RI-mediated histamine secretion in RBL-2H3 cells to a similar degree, with IC50 values of 3 and 2 nM, respectively. (biochemj.org)
  • In the present study we synthesized a unique derivative of wortmannin, O-acetyl-delta 16-wortmannin-17-ol (KT7692), that has an inhibitory potency against PI3-kinase one-hundredth that of wortmannin, but retains a similar potency to wortmannin against MLCK. (biochemj.org)
  • Furthermore KT7692 in combination with wortmannin and LY294002 would be a powerful tool for clarifying the involvement of PI3-kinase as distinct from that of MLCK in signal transduction systems of various cellular responses. (biochemj.org)
  • Both IL-3 stimulation of transport and GLUT1 translocation were also prevented by the phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002. (lancs.ac.uk)
  • Phg2, a serine/threonine-specific kinase, mediates Rap1-regulated cell-substrate adhesion, but not cell polarity or chemotaxis. (rug.nl)
  • The involvement of MAPK and PI 3-K on nuclear factor (κ)B (NF-(κ)B) activation was then analyzed. (biologists.org)
  • One uses PI 3-K and Rac to activate NF-(κ)B, while the other uses PI 3-K, MEK, and MAPK to activate other nuclear factors, such as Elk-1. (biologists.org)
  • In addition, the anabolic LIPUS signal transduction to the nucleus via the integrin/phosphatidylinositol 3-OH kinase/Akt pathway rather than the integrin/MAPK pathway was generally associated with cell proliferation. (biomedcentral.com)
  • Taken together, we demonstrated that inhibition of PI3-kinase/Akt signaling promoted Fas-induced apoptosis in cholangiocarcinoma independent of Fas expression. (aacrjournals.org)
  • Decreased activation of FLIP, ERK and NFκB, and increased activation of caspase-3, 8 and 9 were responsible for the increased sensitivity of cells to Fas-induced apoptosis. (aacrjournals.org)
  • Conversely, expression of dominant negative forms of PI 3-kinase or Akt induces apoptosis in the presence of NGF. (jneurosci.org)
  • These kinases can be activated from a cell surface growth factor receptor (such as epidermal growth factor receptor) and are known to play a critical role in regulating the balance between cell survival and apoptosis. (aacrjournals.org)
  • Requirement for phosphatidylinositol 3'-kinase to protect hemopoietic progenitors against apoptosis depends upon the extracellular survival factor. (jimmunol.org)
  • Antiapoptotic signalling by the IGF-I receptor depended on receptor kinase activity, as cells overexpressing kinase-defective receptor mutants could not be protected by IGF-I. Overexpression of a kinase-defective receptor which contained a mutation in the ATP binding loop functioned as a dominant negative and sensitized cells to apoptosis. (asm.org)
  • To test this, we transiently expressed constitutively active or kinase-dead PI3 kinase and found that overexpression of activated phosphatidylinositol 3-kinase (PI3 kinase) was sufficient to provide protection against apoptosis. (asm.org)
  • We found that membrane-targeted Akt was sufficient to protect against apoptosis but that kinase-dead Akt was not. (asm.org)
  • The effects of Dox and AD198 on cell apoptosis were determined by caspase 3/7 assay, generation of reactive oxygen species (ROS), and Western Blotting (WB) analysis. (biomedcentral.com)
  • Intro Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that play central part in rules of cell routine apoptosis DNA restoration senescence angiogenesis mobile rate of metabolism and motility [1]. (immune-source.com)
  • however, the signaling pathways of several growth factors have been reported to involve phosphatidylinositol (PtdIns) 3-kinase. (pnas.org)
  • In the present study of a Ha-ras-transformed epithelial cell line, we demonstrated increased PtdIns 3-kinase activity in anti-phosphotyrosine and anti-receptor (insulin and hybrid insulin-like growth factor I) immunoprecipitates of cells that had been stimulated with insulin or insulin-like growth factor I. The PtdIns 3-kinase activity was also immunoprecipitated in these experiments by the anti-Ras monoclonal antibody Y13-259. (pnas.org)
  • The specificity of this association with p21ras was ascertained by the neutralizing effect of the antigen peptide and the absence of PtdIns 3-kinase activity in Y13-259 immunoprecipitates from cells in which the ras gene was turned off. (pnas.org)
  • These data indicate that PtdIns 3-kinase activity is an important step in the cascade of reactions in p21ras signal transduction, suggesting that the alterations of the cytoskeleton and growth in ras-transformed cells could be mediated by PtdIns 3-kinase activity. (pnas.org)
  • In this study, we showed that Beclin was co‐immunoprecipitated with phosphatidylinositol (PtdIns) 3‐kinase, which is also required for autophagy, suggesting that Beclin is a component of the PtdIns 3‐kinase complex. (embopress.org)
  • Quantitative analyses using a cross‐linker showed that all Beclin forms a complex with PtdIns 3‐kinase, whereas ∼50% of PtdIns 3‐kinase remains free from Beclin. (embopress.org)
  • Indirect immunofluorescence microscopy demonstrated that the majority of Beclin and PtdIns 3‐kinase localize to the trans ‐Golgi network (TGN). (embopress.org)
  • Some PtdIns 3‐kinase is also distributed in the late endosome. (embopress.org)
  • These results suggest that Beclin and PtdIns 3‐kinase control autophagy as a complex at the TGN. (embopress.org)
  • PI 3‐kinase is involved in several signal transduction pathways which regulate many diverse physiological functions, including adhesion, actin rearrangement, cell growth and cell survival by producing the signaling molecules phosphatidylinositol (PtdIns) 3,4,5‐triphosphate [PtdIns(3,4,5)P 3 ] and PtdIns(3,4)P 2 ( Toker and Cantley, 1997 ). (embopress.org)
  • However, the role of PtdIns(3)P, which is constitutively present, has long been unclear. (embopress.org)
  • revealed an essential role of PtdIns(3)P in vesicle‐mediated transport. (embopress.org)
  • We refer to the mammalian homolog of Vps34p as PtdIns 3‐kinase hereafter. (embopress.org)
  • We consequently wanted to confirm the specificity of the ML1Nx2 probes connection with PtdIns(3,5)[5], inhibition of PtdIns3synthesis would become expected to cause depletion of PtdIns(3,5)synthesis [39]. (exposed-skin-care.net)
  • Whereas manoeuvres that prevent PtdIns3synthesis possess been shown to prevent PtdIns(3,5)in localizing PIKfyve [42] and the truth that the PtdIns(3, 5)depletion could actually prevent PtdIns(3,5)and PtdIns(3,5)and PdIns(3,5) P 2. (exposed-skin-care.net)
  • The chemical substance was effective, generating the characteristic inflamed vacuole phenotype that results from PtdIns(3,5) P 2 inhibition [16]Cyet we observed no global decreases in GFP-ML1Nx2 labelling. (exposed-skin-care.net)
  • non-e the much less, the data obviously present no general lower in GFP-ML1Nx2 association with Light fixture1-positive walls after reduction of PtdIns(3,5) P 2 with YM201636. (exposed-skin-care.net)
  • Consequently, variations between cells in terms of appearance level and morphology may have accounted for the variations observed, rather than as a direct result of PtdIns(3,5) P 2 removal. (exposed-skin-care.net)
  • As a last check of the PtdIns(3,5) G 2-dependece of GFP-ML1Nx2 localization in cells, we transformed to our thoroughly characterized murine embryonic fibroblasts (MEF) null for PIKfyve, which are incapable to synthesize the lipid [17]. (exposed-skin-care.net)
  • The oncogenic transforming activity makes the mutated PI3-kinase proteins promising targets for small molecule inhibitors that could be developed into effective and highly specific anticancer drugs. (pnas.org)
  • In view of the fact that the signaling pathway of PI3-kinase controls microfilaments and translocation of actin-associated proteins, the current study was designed to investigate the PI3-kinase-mediated nuclear translocation of Nrf2 and the interaction of Nrf2 with actin. (aspetjournals.org)
  • Phosphatidylinositol 3-kinases (PI3Ks) play a critical role in thymocyte development, although not all of their downstream mediators have yet been identified. (sciencemag.org)
  • 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. (auckland.ac.nz)
  • The pivotal roles of phosphatidylinositol 3-kinases (PI3Ks) in human cancers have inspired active development of small substances to inhibit these lipid kinases. (immune-source.com)
  • Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that regulate diverse cellular procedures including PP121 proliferation adhesion success and motility. (immune-source.com)
  • Phosphatidylinositol 3-kinase (PI3-kinase) ( EC:2.7.1.137 ) [ PMID: 1322797 ] is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. (ebi.ac.uk)
  • Phosphatidylinositol 3-kinase (PI3-K), a phospholipid-modifying enzyme that phosphorylates phosphoinositols at the 3′ position of the inositol ring, has been implicated as a key player in the mediation of signals transduced through the TCR, CD28, and the IL-2R ( 10 , 11 , 12 ). (jimmunol.org)
  • Phosphatidylinositol 3 (PI3)-kinase , a phospholipid kinase that phosphorylates phosphatidylinositols at the 3-position of the inositol ring, is activated by receptor tyrosine kinases and forms complexes with phosphotyrosine sites in activated receptors. (aspetjournals.org)
  • Amplification or overexpression of Akt, a downstream effector of PI3-kinase, also has been detected in ovarian, breast, and thyroid cancers ( 7 , 8 ). (pnas.org)
  • Cytotoxic T lymphocytes exert short-term, cell-mediated cytolysis via two distinct effector mechanisms, perforin/granzyme exocytosis and CD95 ligand (CD95L) 3 /CD95-mediated cytolysis ( 1 , 2 , 3 ). (jimmunol.org)
  • Previous reports from our laboratory and others have suggested differential activation requirements for the induction of these two cytolytic effector functions following stimulation through the TCR ( 1 , 2 , 3 , 7 ). (jimmunol.org)
  • Therapies targeting essential survival pathways in glioblastoma [e.g., inhibitors of receptor tyrosine kinases (RTKs) or signaling molecules] have achieved modest, yet encouraging, therapeutic benefits in recurrent glioblastoma ( 11 - 22 ). (frontiersin.org)
  • Virdee and Tolkovsky, 1996 ), several recent reports suggest that PI 3-kinase functions in the survival pathways initiated by certain growth factors and survival-promoting agents. (jneurosci.org)
  • The results showed that the activation of phosphatidylinositol 3-kinase (PI3-K) and internal calcium pathways were crucial for alpha(IIb)beta3 outside-in signaling. (sigmaaldrich.com)
  • Mutations in genes that encode components of the phosphatidyl-inositol 3-kinase (PI3-kinase) signaling pathway are common in human cancer. (pnas.org)
  • We demonstrate that the transforming activity of the mutants is correlated with increased lipid kinase activity and activation of the Akt signaling pathway and depends on the target of rapamycin (TOR) kinase. (pnas.org)
  • The present study demonstrates that the PI3-kinase signaling pathway regulates rearrangement of actin microfilaments in response to oxidative stress and that depolymerization of actin causes a complex of Nrf2 bound with actin to translocate into nucleus. (aspetjournals.org)
  • Phosphatidylinositol 4-kinase (PI4-kinase) ( EC:2.7.1.67 ) [ PMID: 8194527 ] is an enzyme that acts on phosphatidylinositol (PI) in the first committed step in the production of the secondary messenger inositol-1'4'5'-trisphosphate. (ebi.ac.uk)
  • In enzymology, a phosphatidylinositol-4-phosphate 3-kinase (EC 2.7.1.154) is an enzyme that catalyzes the chemical reaction ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate ⇌ {\displaystyle \rightleftharpoons } ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate Thus, the two substrates of this enzyme are ATP and 1-phosphatidyl-1D-myo-inositol 4-phosphate, whereas its two products are ADP and 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate. (wikipedia.org)
  • The systematic name of this enzyme class is ATP:1-phosphatidyl-1D-myo-inositol-4-phosphate 3-phosphotransferase. (wikipedia.org)
  • This enzyme participates in phosphatidylinositol signaling system. (wikipedia.org)
  • Indeed, in cell clones stably transfected with Y479F receptor mutant, in which the binding of the enzyme to the activated receptor is blocked, IL-1-induced PI3-kinase translocation to the nucleus is completely prevented. (biologists.org)
  • In this study, we examined the role of phosphatidylinositol 3-kinase (PI3 kinase) in mediating the mitogenic and chemotactic signals of IGF-I. IGF-I treatment resulted in a significant increase in phosphotyrosine-associated PI3 kinase activity in cultured primary VSMCs. (ahajournals.org)
  • Recent studies have suggested a role for phosphatidylinositol (PI) 3-kinase in cell survival, including the survival of neurons. (jneurosci.org)
  • A novel recognition motif for phosphatidylinositol 3-kinase binding mediates its association with the hepatocyte growth factor/scatter factor receptor. (semanticscholar.org)
  • The pleiotropic effects (mitogenesis, motogenesis, and morphogenesis) elicited by hepatocyte growth factor/scatter factor (HGF/SF) are mediated by the activation of the tyrosine kinase receptor encoded by the MET proto-oncogene. (semanticscholar.org)
  • Hepatocyte growth factor-induced scatter of Madin-Darby canine kidney cells requires phosphatidylinositol 3-kinase. (semanticscholar.org)
  • Structural insight into substrate specificity and regulatory mechanisms of phosphoinositide 3-kinases. (ebi.ac.uk)
  • We have determined the growth-regulatory and signaling properties of the three most frequently observed PI3-kinase mutations: E542K, E545K, and H1047R. (pnas.org)
  • PI3_PI4_kinase), PIKK- regulatory domain (PRD), and C-terminus FAT-C-terminal (FATC) domain Pfam PF02260 Lempiäinen H, Halazonetis TD (October 2009). (wikipedia.org)
  • They have been shown to express different membranous growth factor receptors, many of them signaling via intracellular kinase cascades. (nih.gov)
  • 22,25-27 Binding to Pyk2 activates c-Src and PI3-kinase, and this signaling complex participates in a variety of intracellular processes. (ahajournals.org)
  • In this study we analyzed the effects of IL-1 on the intracellular distribution of PI3-kinase in wild-type Saos-2 human osteosarcoma cells, and in cell clones overexpressing type I IL-1 receptor (IL-1RI). (biologists.org)
  • PI3-kinase intracellular distribution displays two distinct patterns. (biologists.org)
  • Immunocytochemistry and photoaffinity labeling revealed that IL-3 caused translocation of intracellular GLUT1 transporters to the cell surface, whereas a second transporter isoform, GLUT3, remained predominantly intracellular. (lancs.ac.uk)
  • and increased activation of caspase-3, 8 and 9 were demonstrated in cells exposed to DIM and inhibitors of PI3- kinase/Akt signaling. (aacrjournals.org)
  • Enhanced insulin-stimulated activation of phosphatidylinositol 3-kinase in the liver of high-fat-fed rats. (diabetesjournals.org)
  • Insulin receptor substrate (IRS)-1 and IRS-2, which mediate phosphatidylinositol (PI) 3-kinase activation, play essential roles in insulin-induced translocation of GLUT4 and in glycogen synthesis. (diabetesjournals.org)
  • In this study, we investigated the process of PI 3-kinase activation via binding with IRS-1 and -2 in liver, muscle, and fat of high-fat-fed rats, a model of insulin-resistant diabetes. (diabetesjournals.org)
  • Thus, high-fat feeding appears to cause insulin resistance in the liver by a mechanism different from the impaired PI 3-kinase activation observed in muscle and adipose tissue. (diabetesjournals.org)
  • Taking into consideration that hepatic PI 3-kinase activation is severely impaired in obese diabetic models such as Zucker fatty rats, it is possible that the mechanism by which a high-fat diet causes insulin resistance is quite different from that associated with obesity and overeating due to abnormality in the leptin system. (diabetesjournals.org)
  • This is the first report to show increased PI 3-kinase activation by insulin in an insulin-resistant diabetic animal model. (diabetesjournals.org)
  • One of these is activation of phosphatidylinositol 3-kinase (PI-3K), which results in the generation of a membrane-restricted second messenger, polyphosphatidylinositides containing a 3´-phosphate. (portlandpress.com)
  • In the setting of a high-salt diet, proline-rich tyrosine kinase 2 served as the scaffold for c-Src-mediated phosphatidylinositol 3-kinase activation. (ahajournals.org)
  • MCD medium treatment also resulted in activation of PI3-kinase by 30 minutes and its downstream target p-Akt within 1hour of incubation. (physiology.org)
  • We conclude that the endogenous IGF-I receptor has a specific antiapoptotic signalling capacity, that overexpression of other tyrosine kinases can allow them also to be antiapoptotic, and that activation of PI3 kinase and Akt is sufficient for antiapoptotic signalling. (asm.org)
  • Recent studies have demonstrated that fatty acids induce insulin resistance in skeletal muscle by blocking insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-kinase). (garvan.org.au)
  • In insulin-secreting β-cells, activation of phosphatidylinositol 3′-OH-kinase with resulting formation of phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ) has been implicated in the regulation of ion channels, insulin secretion, and gene transcription as well as in cell growth and survival, but the kinetics of PIP 3 signals following physiological stimulation of insulin secretion is unknown. (diva-portal.org)
  • Glucose stimulation of insulin secretion resulted in pronounced oscillations of the membrane phospholipid PIP 3 caused by autocrine activation of insulin receptors. (diva-portal.org)
  • Pharmacological activation of Epac restored PIP 3 responses after adenylyl cyclase or PKA inhibition. (diva-portal.org)
  • These data suggest that PI3-kinase translocation to the nucleus upon IL-1R activation is an early event in IL-1 signaling mechanism, and may be involved in transcriptional activation. (biologists.org)
  • These results indicate that activation of PI3 kinase is required for both IGF-I-induced VSMC proliferation and migration. (ahajournals.org)
  • Phosphatidylinositol-3-kinase activation blocks amyloid beta-induced neurotoxicity. (semanticscholar.org)
  • 2011) Structural basis for activation and inhibition of class I phosphoinositide 3-kinases. (guidetopharmacology.org)
  • Both immunoblotting and immunofluorescence data indicate that IL-1 causes a rapid and transient translocation of PI3-kinase from the cytoplasm to the nucleus. (biologists.org)
  • This phenomenon is prevented by PI3-kinase inhibitors, suggesting that the maintenance of PI3-kinase activity is essential for IL-1-induced translocation. (biologists.org)
  • Interleukin-3-mediated Cell Survival Signals Include Phosphatidylinositol 3-Kinase-dependent Translocation of the Glucose Transporter GLUT1 to the Cell Surface. (lancs.ac.uk)
  • Autophagy is characterized by the formation of an autophagosome, for which Vps34-dervied phosphatidylinositol 3-phosphate (PI3P) is essential. (rupress.org)
  • Autophagy-related (ATG) 11, ATG9 and the phosphatidylinositol 3-kinase control ATG2-mediated. (deepdyve.com)
  • To assess the importance of this process in radiosensitization, we used the autophagy inhibitors 3-methyladenine and chloroquine and found that either drug increased cell killing after NVP-BEZ235 treatment and radiation. (aspetjournals.org)
  • These findings show that Pl-3 kinase can stimulate diverse Ras-dependent cellular processes, including oocyte maturation and fos transcription. (sciencemag.org)
  • Zonula occludens-1 (ZO-1) plays an important role in binding occludin to cytoarchitecture [ 2 ] and regulating cellular permeability [ 3 ]. (hindawi.com)
  • Recent studies show that dietary salt intake activates proline-rich tyrosine kinase 2 (Pyk2). (ahajournals.org)
  • Despite significant homology to lipid kinases, no lipid kinase activity has been demonstrated for any of the PIK-related kinases [ PMID: 12456783 ]. (ebi.ac.uk)
  • This transforming ability is correlated with elevated catalytic activity in in vitro kinase assays. (pnas.org)
  • PTEN, a lipid phosphatase that counteracts the kinase activity of PI3-kinase, is frequently mutated in various tumors including those of prostate, glioblastoma, melanoma, and endometrial carcinoma ( 3 - 6 ). (pnas.org)
  • IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was also measured in muscle biopsy samples obtained from seven additional subjects before and after an identical protocol. (jci.org)
  • Insulin stimulation, during the glycerol infusion, resulted in a fourfold increase in PI 3-kinase activity over basal that was abolished during the lipid infusion. (jci.org)
  • this may be a consequence of decreased IRS-1-associated PI 3-kinase activity. (jci.org)
  • IRS-1-associated PI 3-kinase activity in muscle biopsies obtained before the glycerol/lipid infusions (basal) and after 30 min of the hyperinsulinemic-euglycemic clamp following 5 h of glycerol or lipid infusion. (jci.org)
  • Peroxidase activity was quenched with 3% hydrogen peroxide in water. (aacrjournals.org)
  • 1 , 2 Treatment of B cells with inhibitors of phosphatidylinositol 3-kinase (PI-3K) activity in early G 1 phase of the cell cycle blunts the ongoing increase in cell size, suggesting that failure of anti-Ig-stimulated B cells to commit to genome replication in the absence of PI-3K activity results from a block at a critical growth checkpoint. (bloodjournal.org)
  • To determine whether insulin receptor substrate (IRS)-1, -2, or both are involved in IGF-I signaling in VSMCs, cell lysates were immunoprecipitated with either an anti-IRS-1 or an anti-IRS-2 antibody, and the associated PI3 kinase activity was determined. (ahajournals.org)
  • IGF-I stimulation resulted in a significant increase in IRS-1- but not IRS-2-associated PI3 kinase activity, suggesting that IGF-I primarily utilizes IRS-1 to transmit its signal in VSMCs. (ahajournals.org)
  • The IGF-I-induced increase in IRS-I-associated PI3 kinase activity was concentration dependent. (ahajournals.org)
  • AChR-inducing activity (ARIA)/heregulin, a ligand for erbB receptor tyrosine kinases (RTKs), is likely to be one nerve-supplied signal that induces expression of acetylcholine receptor (AChR) genes at the developing neuromuscular junction. (rupress.org)
  • Immunohistochemical stainings of (Ser473)-phosphorylated (p)-AKT, its targets p-(Ser9)-GSK-3β and p-(Ser2448)-mTOR and the cell cycle regulators Cyclin D1 and p27(KIP1) were performed in 36 synovial sarcomas. (nih.gov)
  • The high incidence of these nonrandom PI3-kinase mutations detected across different types of tumors strongly suggests a functional significance in tumorigenesis. (pnas.org)
  • In this article, we show that PI3-kinase carrying one of the three "hot-spot" mutations (E542K, E545K, or H1047R) is able to induce transformation in cultures of chicken embryo fibroblasts (CEF). (pnas.org)
  • EGFR mutations did not coexist with BRAF mutations, neither kinase-activated nor kinase-impaired mutations. (elsevier.com)
  • Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. (ebi.ac.uk)
  • NGF affects neuronal survival and differentiation by binding to and activating the TrkA tyrosine kinase receptor ( Barbacid, 1994 ). (jneurosci.org)
  • These phosphatidylinositol 3-kinase related enzymes play critical roles in DNA repair, V(D)J recombination and cell-cycle checkpoints, and their dysfunction leads to clinical manifestations ranging from immunodeficiency to cancer. (nih.gov)
  • As of late 2007, 3 structures have been solved for this class of enzymes, with PDB accession codes 2AR5, 2B3R, and 2IWL. (wikipedia.org)
  • Phosphatidylinositol (Pl)-3 kinase is one of many enzymes stimulated by growth factors. (sciencemag.org)
  • Both Akt and PI3-kinase can function as retroviral oncoproteins, inducing rapid oncogenic transformation in vivo and in vitro . (pnas.org)
  • Following autophosphorylation, the receptor associates with the p85/110 phosphatidylinositol (PI) 3-kinase complex in vivo and in vitro. (semanticscholar.org)
  • A constitutively activated mutant, p110, that functions independently of growth factor stimulation was constructed to determine the specific responses regulated by Pl-3 kinase. (sciencemag.org)
  • Expression of constitutively active Akt or PI 3-kinase in neurons efficiently prevents death after NGF withdrawal. (jneurosci.org)
  • We used a range of methodologies that include in silico compound analysis, in vitro kinase assays, cell invasion assays, proliferation assays, genome-wide transcription studies (Agilent Technologies full genome arrays), gene set enrichment analysis, quantitative real-time PCR, immunoblotting in addition to chromatin immunoprecipitation. (ualg.pt)
  • Phosphatidylinositol-3-Kinase/Akt regulates bleomycin-induced fibroblast proliferation and collagen production. (cdc.gov)
  • These results provide further evidence that PI3-kinase is involved in the signal transduction pathway responsible for histamine secretion after stimulation of Fc epsilon RI. (biochemj.org)