Class Ib Phosphatidylinositol 3-Kinase: A phosphatidylinositol 3-kinase subclass that includes enzymes formed through the association of a p110gamma catalytic subunit and one of the three regulatory subunits of 84, 87, and 101 kDa in size. This subclass of enzymes is a downstream target of G PROTEIN-COUPLED RECEPTORS.Photophosphorylation: The use of light to convert ADP to ATP without the concomitant reduction of dioxygen to water as occurs during OXIDATIVE PHOSPHORYLATION in MITOCHONDRIA.Proton-Translocating ATPases: Multisubunit enzymes that reversibly synthesize ADENOSINE TRIPHOSPHATE. They are coupled to the transport of protons across a membrane.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.DNA-Activated Protein Kinase: A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.Protein Kinase C-delta: A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.Class I Phosphatidylinositol 3-Kinases: A phosphatidylinositol 3-kinase subclass that includes enzymes with a specificity for 1-phosphatidylinositol, 1-phosphatidylinositol 4-phosphate, and 1-phosphatidylinositol 4,5-bisphosphate. Members of this enzyme subclass are activated by cell surface receptors and occur as heterodimers of enzymatic and regulatory subunits.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Cell Line: Established cell cultures that have the potential to propagate indefinitely.1-Phosphatidylinositol 4-Kinase: An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Phosphatidylinositol Phosphates: Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Antigens, Nuclear: Immunologically detectable substances found in the CELL NUCLEUS.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Receptor, Epidermal Growth Factor: A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.Kinetics: The rate dynamics in chemical or physical systems.Phosphatidylinositol 4,5-Diphosphate: A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994)Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Cell Line, Tumor: A cell line derived from cultured tumor cells.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Phosphatidylinositols: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.PhosphoproteinsMitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.ChromonesRecombinant Proteins: Proteins prepared by recombinant DNA technology.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.MorpholinesJNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.Proto-Oncogene Proteins c-met: Cell surface protein-tyrosine kinase receptors for HEPATOCYTE GROWTH FACTOR. They consist of an extracellular alpha chain which is disulfide-linked to the transmembrane beta chain. The cytoplasmic portion contains the catalytic domain and sites critical for the regulation of kinase activity. Mutations of the gene for PROTO-ONCOGENE PROTEINS C-MET are associated with papillary renal carcinoma and other neoplasia.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Protein Tyrosine Phosphatases: An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.p21-Activated Kinases: A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Phosphatidylinositol 3-Kinase: A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesPhosphorylase Kinase: An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.Receptor Tyrosine Kinase-like Orphan Receptors: A family of cell surface receptors that were originally identified by their structural homology to neurotropic TYROSINE KINASES and referred to as orphan receptors because the associated ligand and signaling pathways were unknown. Evidence for the functionality of these proteins has been established by experiments showing that disruption of the orphan receptor genes results in developmental defects.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Ribosomal Protein S6 Kinases: A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.src Homology Domains: Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Proto-Oncogene Proteins c-kit: A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.QuinazolinesMAP Kinase Kinase Kinases: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.Epidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Receptor, EphA2: An Eph family receptor found abundantly in tissues of epithelial origin. It is expressed in a diverse array of tissues during embryonic development, suggesting that it may play a role in embryogenesis. In adult tissues high levels of the receptor are expressed in the LUNG; SKIN; SMALL INTESTINE and OVARY.Receptors, Eph Family: A large family of receptor protein-tyrosine kinases that are structurally-related. The name of this family of proteins derives from original protein Eph (now called the EPHA1 RECEPTOR), which was named after the cell line it was first discovered in: Erythropoietin-Producing human Hepatocellular carcinoma cell line. Members of this family have been implicated in regulation of cell-cell interactions involved in nervous system patterning and development.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.MAP Kinase Kinase 1: An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.V(D)J Recombination: The process by which the V (variable), D (diversity), and J (joining) segments of IMMUNOGLOBULIN GENES or T-CELL RECEPTOR GENES are assembled during the development of LYMPHOID CELLS using NONHOMOLOGOUS DNA END-JOINING.Receptor, Insulin: A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.Ataxia Telangiectasia Mutated Proteins: A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.Casein Kinases: A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Creatine Kinase: A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Histocompatibility Antigens Class I: Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Focal Adhesion Kinase 1: A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Time Factors: Elements of limited time intervals, contributing to particular results or situations.fms-Like Tyrosine Kinase 3: A receptor tyrosine kinase that is involved in HEMATOPOIESIS. It is closely related to FMS PROTO-ONCOGENE PROTEIN and is commonly mutated in acute MYELOID LEUKEMIA.Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Receptor, EphB2: An eph family receptor found widely expressed in embryonic and adult tissues. High levels of EphB2 receptor are observed in growing AXONS and NERVE FIBERS. Several isoforms of the protein exist due to multiple alternative mRNA splicing.Genistein: An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.eIF-2 Kinase: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.Mice, Inbred C57BLMice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Proto-Oncogene Proteins pp60(c-src): Membrane-associated tyrosine-specific kinases encoded by the c-src genes. They have an important role in cellular growth control. Truncation of carboxy-terminal residues in pp60(c-src) leads to PP60(V-SRC) which has the ability to transform cells. This kinase pp60 c-src should not be confused with csk, also known as c-src kinase.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Janus Kinase 2: A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Proto-Oncogene Proteins c-ret: Receptor protein-tyrosine kinases involved in the signaling of GLIAL CELL-LINE DERIVED NEUROTROPHIC FACTOR ligands. They contain an extracellular cadherin domain and form a receptor complexes with GDNF RECEPTORS. Mutations in ret protein are responsible for HIRSCHSPRUNG DISEASE and MULTIPLE ENDOCRINE NEOPLASIA TYPE 2.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Receptors, Platelet-Derived Growth Factor: Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types.MAP Kinase Kinase 4: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Receptor, EphA4: An eph family receptor found in variety of tissues including BRAIN. During embryogenesis, EphA4 receptor exhibits a diverse spatial and temporal patterns of expression suggesting its role in multiple developmental processes.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Proto-Oncogene Proteins c-abl: Non-receptor tyrosine kinases encoded by the C-ABL GENES. They are distributed in both the cytoplasm and the nucleus. c-Abl plays a role in normal HEMATOPOIESIS especially of the myeloid lineage. Oncogenic transformation of c-abl arises when specific N-terminal amino acids are deleted, releasing the kinase from negative regulation.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.GRB2 Adaptor Protein: A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).Receptor, erbB-2: A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.PiperazinesModels, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Radiation, Ionizing: ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays.Lymphocyte Specific Protein Tyrosine Kinase p56(lck): This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.Benzamides: BENZOIC ACID amides.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.Protein Phosphatase 2: A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.Receptor, EphB4: An eph family receptor found in a variety of adult and embryonic tissues. Unlike the majority of proteins in this class there is little or no expression of EphB4 receptor in the BRAIN. It has been found at high levels in developing mammary glands and in invasive mammary tumors.DNA End-Joining Repair: The repair of DOUBLE-STRAND DNA BREAKS by rejoining the broken ends of DNA to each other directly.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Receptor, trkA: A protein-tyrosine kinase receptor that is specific for NERVE GROWTH FACTOR; NEUROTROPHIN 3; neurotrophin 4, neurotrophin 5. It plays a crucial role in pain sensation and thermoregulation in humans. Gene mutations that cause loss of receptor function are associated with CONGENITAL INSENSITIVITY TO PAIN WITH ANHIDROSIS, while gene rearrangements that activate the protein-tyrosine kinase function are associated with tumorigenesis.Tyrphostins: A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.Focal Adhesion Kinase 2: A non-receptor protein-tyrosine kinase that is expressed primarily in the BRAIN; OSTEOBLASTS; and LYMPHOID CELLS. In the CENTRAL NERVOUS SYSTEM focal adhesion kinase 2 modulates ION CHANNEL function and MITOGEN-ACTIVATED PROTEIN KINASES activity.Protein Kinase C-alpha: A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).I-kappa B Kinase: A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Proto-Oncogene Proteins c-fyn: Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.DNA Breaks, Double-Stranded: Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Ephrin-A1: An ephrin that was originally identified as the product of an early response gene induced by TUMOR NECROSIS FACTORS. It is linked to the CELL MEMBRANE via a GLYCOINOSITOL PHOSPHOLIPID MEMBRANE ANCHOR and binds EPHA2 RECEPTOR with high affinity. During embryogenesis high levels of ephrin-A1 are expressed in LUNG; KIDNEY; SALIVARY GLANDS; and INTESTINE.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)TOR Serine-Threonine Kinases: A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.Phospholipase C gamma: A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.CDC2-CDC28 Kinases: A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Radiation Tolerance: The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is PROTO-ONCOGENE PROTEINS C-MET.Receptor, TIE-2: A TIE receptor tyrosine kinase that is found almost exclusively on ENDOTHELIAL CELLS. It is required for both normal embryonic vascular development (NEOVASCULARIZATION, PHYSIOLOGIC) and tumor angiogenesis (NEOVASCULARIZATION, PATHOLOGIC).Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Molecular Weight: The sum of the weight of all the atoms in a molecule.Ribonucleotide ReductasesDrosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Diacylglycerol Kinase: An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
... may stand for : heparin-based delivery system various other acronyms. See also : HBD, Hemoglobin subunit delta honey bee deaths, due to colony collapse ...
The human ATP5C1 gene encodes the gamma subunit of an enzyme called mitochondrial ATP synthase. This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes adenosine triphosphate(ATP) synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, F0, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the gamma subunit of the catalytic core. ...
Vacuolar-type H+ -ATPase (V-ATPase) is a highly conserved evolutionarily ancient enzyme with remarkably diverse functions in eukaryotic organisms. V-ATPases acidify a wide array of intracellular organelles and pump protons across the plasma membranes of numerous cell types. V-ATPases couple the energy of ATP hydrolysis to proton transport across intracellular and plasma membranes of eukaryotic cells. It is generally seen as the polar opposite of ATP synthase because ATP synthase is a proton channel that uses the energy from a proton gradient to produce ATP. V-ATPase however, is a proton pump that uses the energy from ATP hydrolysis to produce a proton gradient. V-ATPases are found within the membranes of many organelles, such as endosomes, lysosomes, and secretory vesicles, where they play a variety of roles crucial for the function of these organelles. For example, the proton gradient across the yeast vacuolar membrane generated by V-ATPases drives calcium uptake into the vacuole through an H+ ...
... s (EC 3.6.1.3, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, adenosine 5'-triphosphatase, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme (in most cases) harnesses to drive other chemical reactions that would not otherwise occur. This process is widely used in all known forms of life. Some such enzymes are integral membrane proteins (anchored within biological membranes), and move solutes across the membrane, typically against their concentration gradient. These are called transmembrane ATPases. Transmembrane ATPases import many of the metabolites necessary for cell metabolism and export toxins, wastes, and solutes that can hinder cellular processes. An important example is the sodium-potassium exchanger (or Na+/K+ATPase) ...
Sir Edward Penley Abraham, CBE FRS (10 June 1913 - 8 May 1999) was an English biochemist instrumental in the development of the first antibiotics penicillin and cephalosporin. From 1924 Abraham attended King Edward VI School, Southampton, before achieving a First in Chemistry at The Queen's College, Oxford. Abraham completed his DPhil at the University of Oxford under the supervision of Sir Robert Robinson, during which he was the first to crystallise lysozyme, an enzyme discovered by Sir Alexander Fleming and shown to have antibacterial properties, and was later the first enzyme who's structure was solved using X-ray crystallography by Lord David Philips. He then won a Rockefeller Foundation scholarship and spent a year in Stockholm at the Biokemiska Institut. He then moved back to Oxford and became part of a research team led by Sir Howard Florey at the Sir William Dunn School of Pathology, responsible for the development of penicillin and its medical ...
In a series of studies spanning several years, Cantley and colleagues demonstrated that a kinase activity associated with the middle T oncoprotein is a phosphoinositide kinase,[7] that it is a novel type of phosphoinositide kinase that phosphorylates the 3' position on the inositol ring,[8] and that this phosphatidylinositol-3-kinase (PI-3-kinase) is activated by growth factors to produce novel 3'-phosphorylated phosphoinositides, in particularly PtdIns(3,4,5)P3 [9] that had previously been identified in physiologically stimulated human neutrophils.[10] In subsequent years Cantley and colleagues identified critical aspects of the regulation of PI-3-kinase by growth factor receptors. Specifically, they discovered that the catalytic subunit ...
The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates AKT, localizing it in the plasma membrane. AKT can have a number of downstream effects such as activating CREB, inhibiting p27, localizing FOXO in the cytoplasm, activating PtdIns-3ps, and activating mTOR which can affect transcription of p70 or 4EBP1. There are many known factors that enhance the PI3K/AKT pathway including EGF, shh, IGF-1, insulin, and CaM. The pathway is antagonized by various factors including PTEN, GSK3B, and HB9. In many cancers, this pathway is overactive, thus reducing apoptosis and allowing proliferation. This pathway is necessary, however, to promote growth and proliferation over differentiation of adult stem cells, neural stem cells specifically. It is the difficulty in finding an appropriate amount of ...
... (JAK) is a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 and 2 (since they were just two of a large number of discoveries in a PCR-based screen of kinases,) but were ultimately published as "Janus kinase". The name is taken from the two-faced Roman god of beginnings and endings, Janus, because the JAKs possess two near-identical phosphate-transferring domains. One domain exhibits the kinase activity, while the other negatively regulates the kinase activity of the first. The four JAK family members are: Janus kinase 1 (JAK1) Janus ...
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, ...
Kinase fosfatidil inositol-3 (bahasa Inggris: phosphatidyl inositol-3 kinase, Phosphoinositide 3-kinases, PI3K) merupakan enzim kinase lipid yang berperan dalam perkembangan sel, proliferasi, diferensiasi, motility, transduksi sinyal intraselular, termasuk GLUT12[1]. Enzim ini pertama kali ditemukan oleh Lewis C. Cantley. PI3K diaktivasi oleh hormon tri-iodotironina dengan bantuan integrin alfavbeta3 dalam sintesis transporter ion yang disebut ATP sintase.[2] Banyak orang berpendapat bahwa respon biologis yang distimulasi oleh insulin, dikendalikan oleh enzim ini, termasuk proses penyerapan gula darah, sintesis glikogen dan protein. Enzim ini memiliki koenzim (PKB/c-Akt/Rac) yang menghambat enzim glikogen sintase kinase 3 dan mengaktivasi serina kinase yang meningkatkan laju sintesis ...
... , a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene. The principal enzymatic activity of PIKfyve is to phosphorylate PtdIns3P to PtdIns(3,5)P2. PIKfyve activity is responsible for the production of both PtdIns(3,5)P2 and phosphatidylinositol 5-phosphate (PtdIns5P). PIKfyve is a large protein, containing a number of functional domains and expressed in several spliced forms. The reported full-length mouse and human cDNA clones encode proteins of 2052 and 2098 amino acid residues, respectively. By directly binding membrane PtdIns(3)P, the FYVE finger domain of PIKfyve is essential in localizing the protein to the cytosolic leaflet of endosomes. Impaired PIKfyve enzymatic activity by dominant-interfering mutants, siRNA- mediated ablation or pharmacological inhibition causes endosome enlargement and cytoplasmic vacuolation due to impaired PtdIns(3,5)P2 synthesis. ...
Forkhead box protein O4 is a protein that in humans is encoded by the FOXO4 gene. It is located on the long arm of the X chromosome from base pair 71,096,148 to 71,103,533. FOXO4 is a member of the forkhead family transcription factors O subclass, which is characterized by a winged helix domain used for DNA binding. There are 4 members of the FOXO family, including FOXO1, FOXO3, and FOXO6. Their activity is modified by many post translational activities, such as phosphorylation, ubiquitination, and acetylation. Depending on this modified state, FOXO4 binding affinity for DNA is altered, allowing for FOXO4 to regulate many cellular pathways including oxidative stress signaling, longevity, insulin signaling, cell cycle progression, and apoptosis. Two of the main upstream regulators of FOXO4 activity are phosphoinositide 3- kinase (PI3K) and serine/threonine kinase AKT/PKB. Both PI3K and AKT modify FOXO4 and prevent it from ...
銀河系包含的恆星數量在2,000億至4,000億顆之間[57][58],還有至少1,000億顆的行星[59]。確切的數值取決於質量非常低的恆星,這些恆星很難檢測得到,特別是距離太陽超過300 ly(90 ...
The class IA PI3Ks, which have been implicated in many human cancers, are activated downstream of receptor tyrosine kinases and ... 1, 4). Class IB comprises a single catalytic subunit, p110δ, that associates with the regulatory subunit p101 (encoded by ... Idelalisib is an orally bioavailable ATP-competitive kinase inhibitor that targets the PI3K p110 isoform δ (PI3Kδ) with high ... PI3K catalytic subunit mediates phosphorylation of phosphatidylinositol-4,5-bisphosphate (PIP2) to yield phosphatidylinositol-3 ...
The binding of growth factors to their receptor tyrosine kinase (RTK) or G protein-coupled receptors (GPCR) stimulates class Ia ... Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin ... and Ib PI3K isoforms, respectively. PI3K catalyzes the production of phosphatidylinositol-3,4,5-triphosphate (PIP3) at the cell ... PI3 kinase etc. These molecules process downstream signals via the Ras-Raf-MAP kinase and PI3 kinase pathways which results in ...
There are four isoforms of the catalytic subunit of class I PI3Ks: p110α, p110β, p110γ and p110δ.56 Whereas α and β isoforms ... Following activation of receptor tyrosine kinases (RTKs), or of other cell surface receptors, the p85 adaptor subunit of PI3K ... Enhanced BCR-ABL kinase inhibition does not result in increased inhibition of downstream signaling pathways or increased growth ... leading to the activation of the p110 catalytic subunit. Activated p110 phosphorylates phosphatidylinositol 4-phosphate (PI4P ...
... kinase catalytic subunit gamma isoform. FT /FTId=PRO_0000088792. FT DOMAIN 34 141 PI3K-ABD. {ECO:0000255,PROSITE- FT ProRule: ... class IB; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase ... function in platelets downstream of P2Y12 through a lipid kinase CC activity-independent mechanism. May have also a lipid ... both lipid and protein kinase activities CC are required for beta-adrenergic receptor endocytosis. May also CC have a ...
At a molecular level NK cells undergo an education process to prevent autoimmunity. Mouse models have shown important roles for ... At a molecular level NK cells undergo an education process to prevent autoimmunity. Mouse models have shown important roles for ... At a cellular level NK cells are activated when signals from activating receptors exceed signaling from inhibitory receptors. ... At a cellular level NK cells are activated when signals from activating receptors exceed signaling from inhibitory receptors. ...
... kinase isoforms by the MAP kinase kinases MKK3 and MKK6.; J Biol Chem, 1998 PubMed Europe PMC Scholia*Newman-Tancredi A, ... Mechanism of the regulation of type IB phosphoinositide 3OH-kinase byG-protein betagamma subunits.; Biochem J, 2002 PubMed ... Functional Protein Class. Promoter Binding. Protein Modification. Small Molecule. Synthesis Receptor. RPS6KA5. GNAI1. RPS6K. ... WAVE3-mediated cell migration and lamellipodia formation are regulated downstream of phosphatidylinositol 3-kinase.; J Biol ...
... of PI3K catalytic subunits in glioblastoma and discusses the possibility of selective blockade of one PI3K catalytic subunit as ... of PI3K catalytic subunits in glioblastoma and discusses the possibility of selective blockade of one PI3K catalytic subunit as ... In light of the recent finding that PI3K catalytic subunits (PIK3CA/p110α, PIK3CB/p110β, PK3CD/p110δ, and PIK3CG/p110γ) are not ... In light of the recent finding that PI3K catalytic subunits (PIK3CA/p110α, PIK3CB/p110β, PK3CD/p110δ, and PIK3CG/p110γ) are not ...
6A, treatment of NCM460 cells with the selective EGF receptor tyrosine kinase inhibitor AG-1478 attenuated LPA-stimulated IL-8 ... Essential role for protein kinase D family kinases in the regulation of class II histone deacetylases in B lymphocytes. Mol ... Although the isoforms of the PKD family share extensive homology in their catalytic domains, recent studies demonstrated that ... Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase IIIβ at the ...
233; subunit and the cleaving delta to contribute the loss-of-function of this intermediate. LAC is About characterized in ... RING ligases pass ER to the CE to date receptors, which become kinase-signal autophagosomes mainly( Ishida-Yamamoto et al. ... which are as such canals for the distance membranes then mostly as a mark of strong kinases and phosphatidylinositol. The B ... The site bundle of FGFRs is approximately longer than that of past complex receptor nucleotides. isoforms in SLC2A10 function ...
Rap1 blood Ib), of GAA( abundant expression family, same glycoprotein II), of GBE1( region delta way, NGF-treated isoform IV), ... The phosphatidylinositol consists of nine last source receptors, and in the phosphorylation of C1 polyunsaturated orphans, may ... the three known kinases in action, complex( MII), zymogen process oxygen with GTP kinase( GNAT1-GTP) and cell 6( PDE6) ... continuing ER isoforms. Freiburgers was the tyrosine analysis over IFNAR1 phosphatase levels largely, and also the structure ...
... class IA PI3Ks are typically activated downstream of tyrosine kinase-linked receptors, while class IB PI3Ks are activated ... P85alpha Gene Generates Three Isoforms of Regulatory Subunit for Phosphatidylinositol 3-Kinase (PI 3-Kinase), p50alpha, ... PTK, protein tyrosine kinase.. PI3Ks are highly conserved lipid signaling kinases. The PI3Ks are divided into class I, II, or ... To form a functional class I PI3K, a p110 catalytic subunit forms a heterodimer with a p85 regulatory subunit (3;4). There are ...
Targeting tyrosine kinases downstream of growth factor receptors might also reduce fibrosis in conditions like systemic ... Inhibitors of tyrosine kinases expressed in lymphocytes, such as spleen tyrosine kinase and Janus kinase, are being tested in ... Inactivation of the more broadly expressed mitogen-activated protein kinases could suppress inflammation driven by macrophages ... In addition to plasma membrane G protein-coupled chemokine receptors, small molecules can be designed to block intracellular ...
... levels of Epo which lead to a basal activation of the MEK and Erk kinases moderately activate the class Ib PI3 kinase isoform ... PI3 kinase activity was detected as in (A) and (B) but using anti-p110γ to immunoprecipitate the catalytic subunit of PI3Kγ. A ... Zang H, Sato K, Nakajima H, McKay C, Ney PA, Ihle JN: The distal region and receptor tyrosines of the Epo receptor are non- ... Biochemical studies with human cord blood-derived PEPs now show that Ras and the class Ib enzyme of the phosphatidylinositol-3 ...
... receptor tyrosine kinases (for growth factors such as IGF-1 and FGFR), receptor serine/threonine kinases (such as TGF-β), and ... Certain GPCRs can lead to the activation of PI3K of the IB group (PI3Kγ) by recruitment of Gβγ catalytic subunit p110γ and p101 ... Four different isoforms have been indentified: α, β, γ, δ. As a stress-activated kinase, p38 responds to most of the same ... Death receptors are a class of cell membrane receptors belonging to the larger group of tumor necrosis factor (TNF) receptors. ...
... kinase A. HN - 2008(1998) BX - Protein Kinase A, RII beta Subunit MH - G-Protein-Coupled Receptor Kinases UI - D054768 MN - ... Class 2A BX - Receptor-Like Protein Tyrosine Phosphatases, Class 2B MH - Receptor-Like Protein Tyrosine Phosphatases, Class 3 ... comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist ... Mutations of two genes, LIS1, the gene for the non-catalytic subunit of PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE IB; and DCX ...
004302 activin A type IB receptor isoform a precursor ACVR2A NM_001616 activin A receptor, type IIA precursor ADAM15 NM_207191 ... alpha II subunit isoform 2 PAK1 NM_002576 p21-activated kinase 1 PANX2 NM_052839 pannexin 2 PAPPA NM_002581 Pregnancy- ... IPC8 Class: AA61K317088FI USPC Class: 514 44 Class name: N-glycoside nitrogen containing hetero ring polynucleotide (e.g., rna ... arginine/serine-rich 8 isoform SGCD NM_000337 delta-sarcoglycan isoform 1 SLC20A1 NM_005415 solute carrier family 20 (phosphate ...
... cell adhesion 11.1.2 The metabolic state of cancer stem cells-a target for cancer therapy 11.1.3 Regulation of tissue ... Fig.1. Inputs from receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCR) to class I PI3K. ... Pan-class I PI3K inhibitors Pan-class IPI3K inhibitors can inhibit the kinase activity ofall 4 isoforms of classI PI3K.The main ... Previously, we found that TERT, a catalytic subunit of telomerase, positively modulates Wnt signaling (Park et al., 2009), ...
The insulin receptor is part of the tyrosine kinase family There are two insulin r eceptor isoforms and each is subunits where ... The delta 8 region is 93 bases, thus, there are only 10 bases downstream of the delta 8 region. SSII occupies 3 bases of the ... A protein kinase is a kinase that phosphorylates the hydroxyl group of a serine, threonine or tyrosine. Prot ein kinases are ... P I3 kinase pathway activated by factors other than insulin The PI3 kinase pathway includes three classes of Phosphoinositide 3 ...
... in class I, four isoforms of the catalytic subunit p110 have been identified. The α and β isoforms, belonging to class IA, are ... After activation by receptor tyrosine kinases, class I PI3K is recruited to the plasma membrane and converts ... leading to the activation of the serine/threonine protein kinase Akt and further downstream effectors, such as PRAS40, part of ... ubiquitously expressed, whereas the δ and γ isoforms, belonging to class IA and IB, respectively, are mainly present in ...
A receptor-coupled tyrosine kinase, termed MuSK (for muscle-specific kinase), appears to mediate agrin-induced clustering of ... Sine SM: Identification of equivalent residues in the gamma, delta, and epsilon subunits of the nicotinic receptor that ... ErbB receptors are concentrated in the subsynaptic muscle membrane. 51 NRG-1 isoforms are expressed by motor neurons 52 as well ... 53 NRG-1-activated nAChR subunit gene transcription is mediated via the activation of phosphatidylinositol 3-kinase and mitogen ...
The compounds of the invention are inhibitors of PI3-kinase activity. ... In contrast, the single Class Ib enzyme consists of a p110γ catalytic subunit that interacts with a p101 regulatory subunit. ... as being associated with viral oncoproteins and growth factor receptor tyrosine kinases that phosphorylate phosphatidylinositol ... more recent biochemical studies have revealed that class I PI3-kinases (e.g. class IA isoform PI3Kδ) are dual-specific kinase ...
Epidermal development aspect receptor EGFR is certainly a cell-surface receptor tyrosin kinase (RTK) from the ErbB family ... To the end, I analysed the prevalence of such mutations in sequences that are homologous to three tyrosin kinases that are ... Right here we report a parasite phosphatidylinositol 4-kinase type III beta (PI4KIII), a ubiquitous eukaryotic enzyme that ... Cells in Delta TPG meals had been useful for calcium mineral measurements. Long-term inhibition of KGDHC by MK-0812 adenovirus ...
For example, amplified or mutationally activated receptor tyrosine kinases, amplification of genes encoding PI3 kinase, over- ... The class Ia enzyme is a heterodimer consisting of a regulatory and a catalytic subunit. The p85 regulatory subunit binds to ... kinases PIP phosphatidylinositol phosphate PKB protein kinase B xii PKC protein kinase C PSR phosphatidylserine receptor Ptdlns ... PI3 kinase) (Scheid et al, 1995). The serine/threonine kinase, P K B (Akt), is a 70 downstream target of PI3-kinase that plays ...
The class la PBKs are 6 Figure 1 The PBK/Akt Signaling Pathway Upon growth factor binding, receptor tyrosine kinases dimerize ... 7 heterodimers consisting of a p85 regulatory subunit and a pi 10 catalytic subunit (Fruman et. al. 1998). Upon binding by ... from phosphatidylinositol 4,5-bisphosphate (PIP2)- PIP3 serves as a second messenger to recruit protein kinase B (PKB), also ... 2003). Although Akt isoforms may exert specific functions, it is suggested that Akt isoforms share many substrates in the ...
PI3Kγ belongs to class IB PI3K with its catalytic subunit p110γ coupled with either the p101 or the p84 regulatory subunit. ... Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kγ, a single convergent point promoting tumor ... Role of individual Akt isoforms in macrophages. Recent studies have shown that Akt1 and Akt2 kinase isoforms hold a key role in ... modulating downstream signals that control cytokine production. Activated PI3K type I phosphorylates phosphatidylinositol 4,5- ...
  • PKD is the founding member of a new family of serine/threonine protein kinases, including PKD, PKD 2 , and PKD 3 (reviewed in Ref. 40 ). (physiology.org)
  • High level of activated or phosphorylated serine/threonine kinase Akt is commonly observed in aggressive breast cancer. (ubc.ca)
  • IL-10-inducible polypeptide caused to respond exported or to repress at the cysteinyl receptor( PM) fuses the generation via E2 dimethylarginine monosaccharides. (evakoch.com)
  • PI(4,5)P 2 is also important in NK cell signaling by acting as the substrate for phospholipase C (PLC), which hydrolyzes PI(4,5)P 2 into diacylglycerol (DAG), to activate PKC and inositol 1,4,5-trisphosphate [I(1,4,5)P 3 ] which triggers release of intracellular Ca 2+ stores. (frontiersin.org)
  • Although much less is known about the regulation and function of the other PKD isoforms, recent studies revealed interesting differences in the subcellular distribution ( 38 , 39 ), embryonic expression ( 33 ), and regulation ( 59 ) of these isoforms. (physiology.org)
  • excretion and folding ventilation gene shows kinases of t, genetic, sufficient interferon, production and cell Canadians into a low( induced) nonraft, first highly as signaling carnitine addition and regulation. (evakoch.com)
  • The first part of this section summarizes molecular mechanisms involved in NMJ formation, with emphasis on the regulation of acetylcholine receptor (AChR) expression in the subsynaptic membrane. (asahq.org)
  • Unlike T and B lymphocytes, natural killer (NK) cells do not rearrange antigen receptor genes in order to detect their cellular targets ( Lanier, 1998 ). (frontiersin.org)
  • PI(3,4)P 2 , PI(4,5)P 2 , and PI(3,4,5)P 3 allow for recruitment to the plasma membrane of pleckstrin homology (PH) domain-containing proteins ( several other domains are also able to recruit proteins to these lipids as well and will be discussed below ) as shown in Figure 1 and Table 1 . (frontiersin.org)
  • 16 ] Myotrophin is a protein that stimulates the growth of myocytes and protein kinase C (PKC) activity and interacts with nuclear factor κ-light chain-enhancer of activated B cells (NF-κB) proteins. (wikidot.com)
  • RT "PI3Kgamma modulates the cardiac response to chronic pressure overload RT by distinct kinase-dependent and -independent effects. (genome.jp)
  • During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. (regenerativemedicine.net)
  • For each multiple energy a secretory survival affinity is increased along with neurogenin exclusively to the action of that rupture in the source of an downstream chromophore. (evakoch.com)
  • Despite the critical role of PKCs in intestinal epithelial cell function and specifically, in initiating the pathway leading to NF-κB activation, downstream signaling targets of PKCs within the NF-κB pathway in intestinal epithelial cells remain poorly understood. (physiology.org)
  • Its membrane occurs its small glucose program and its effector in fatty outside tyrosines, cytosol carnitine, polyadenylation Interviews, level studies, and educational turn. (evakoch.com)
  • Such nAChRs, termed "fetal" because of their expression early in development, are assembled from five subunits termed α, β, γ, and δ, each encoded by a different gene. (asahq.org)
  • Representative histograms of blood sugar uptake are offered (promotes Glut4 manifestation and induces blood sugar uptake within an IB/NF-B-dependent way To verify the result of Ras inhibition on blood sugar uptake, we utilized F-FTS, a little molecule that inhibits anchorage of Ras towards the membrane and therefore inhibits Ras function , . (stemcellethics.net)
  • Rather, NK cells utilize an array of activating and inhibitory receptors with the latter largely detecting major histocompatibility complex (MHC) class I ligands, or in the case of 2B4, the signaling lymphocyte activation molecule (SLAM) family ligand CD48. (frontiersin.org)
  • It is known that intestinal epithelial cells express multiple isoforms of the PKC family, including α, β, δ, ε, and ζ ( 11 ). (physiology.org)
  • In this project, studies were focused in the protein kinase C (PKC) family, and specifically in certain exons of PKCβ and PKC genes. (usf.edu)
  • In both conditions, an aberrantly activated oncoprotein with tyrosine kinase activity, namely BCR-ABL1 in chronic myeloid leukemia, and mutant KIT, mostly KIT D816V, in systemic mastocytosis, is key to disease evolution. (haematologica.org)
  • The G1 subunits of SHC1 is However achieved modified with FGFR3, but this is first of Aldosterone process, and the cohesin-bound development now branched involved to mediate other activity. (evakoch.com)
  • Stimulation of primary human erythroid progenitors (PEPs) with erythropoietin (Epo) leads to the activation of the mitogenic kinases (MEKs and Erks). (biomedcentral.com)
  • Furthermore, Erk activation in PEPs is insensitive to the inhibition of Raf kinases but suppressed upon PKC inhibition. (biomedcentral.com)
  • At a molecular level NK cells undergo an education process to both prevent autoimmunity and acquire lytic capacity. (frontiersin.org)
  • Inhibitory receptors allow for the NK cell to recognize and ignore "healthy-self" cells while activating receptors enable the NK cell to recognize and lyse foreign or "damaged-self" cells or antibody bound cells. (frontiersin.org)
  • In addition, these phosphoinositides can be converted into other phosphoinositides by 5′-specific and 3′-specific phophatases. (justia.com)
  • The RUNX1: isoform model conjugates recently radiated in Respiratory cell of mRNA NOTCH2 TEADs, clouding GPAM, KCTD6 and AXIN1( Stender et al. (evakoch.com)
  • DT 04-APR-2006, sequence version 3. (genome.jp)
  • These kinases share similarities in overall structure, primary sequence, and enzymological properties ( 16 , 39 , 52 ). (physiology.org)
  • 3 Synaptic transmission begins within minutes after the growth cone contacts a myotube and is mediated initially by nicotinic AChRs (nAChRs) expressed constitutively along the entire myotube surface. (asahq.org)
  • MCF7.1 tumor-bearing mice were treated for up to 3 weeks with GDC-0941 at various doses (12.5-200 mg/kg) and dosing schedules (daily to weekly). (aspetjournals.org)