Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation.Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin.Oncogene Proteins v-sis: Transforming proteins coded by sis oncogenes. Transformation of cells by v-sis is related to its interaction with the PDGF receptor and also its ability to alter other transcription factors.Oncogene Protein tpr-met: The GENETIC TRANSLATION product from a GENE FUSION between a sequence from the tpr protein gene on the human CHROMOSOME 1 and the gene for PROTO-ONCOGENE PROTEINS C-MET.Oncogene Protein v-maf: An oncogene protein that was originally isolated from a spontaneous musculo-aponeurotic FIBROSARCOMA in CHICKEN and shown to be the transforming gene of the avian retrovirus AS42. It is a basic leucine zipper TRANSCRIPTION FACTOR and the founding member of the MAF TRANSCRIPTION FACTORS.Protein C Deficiency: An absence or deficiency in PROTEIN C which leads to impaired regulation of blood coagulation. It is associated with an increased risk of severe or premature thrombosis. (Stedman's Med. Dict., 26th ed.)Oncogene Protein gp140(v-fms): Transforming glycoprotein coded by the fms oncogene from the Susan McDonough strain of feline sarcoma virus (SM-FeSV). The oncogene protein v-fms lacks sequences, which, in the highly homologous proto-oncogene protein c-fms (CSF-1 receptor), normally serve to regulate its tyrosine kinase activity. The missing sequences in v-fms mimic the effect of ligand and lead to constitutive cell growth. The protein gp120(v-fms) is post-translationally modified to generate gp140(v-fms).Oncogene Proteins v-mos: Transforming proteins coded by mos oncogenes. The v-mos proteins were originally isolated from the Moloney murine sarcoma virus (Mo-MSV).Protein C Inhibitor: A member of the serpin family of proteins that is found in plasma and urine. It is dependent on heparin and is able to inhibit activated PROTEIN C; THROMBIN; KALLIKREIN; and other SERINE ENDOPEPTIDASES.Oncogene Protein p55(v-myc): Transforming protein coded by myc oncogenes. The v-myc protein has been found in several replication-defective avian retrovirus isolates which induce a broad spectrum of malignancies.Oncogene Protein p65(gag-jun): Transforming protein coded by jun oncogenes (GENES, JUN). This is a gag-onc fusion protein of about 65 kDa derived from avian sarcoma virus. v-jun lacks a negative regulatory domain that regulates transcription in c-jun.Oncogene Proteins v-raf: A family of transforming proteins isolated from retroviruses such as MOUSE SARCOMA VIRUSES. They are viral-derived members of the raf-kinase family of serine-theonine kinases.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.Oncogene Proteins v-fos: Transforming proteins coded by fos oncogenes. These proteins have been found in the Finkel-Biskis-Jinkins (FBJ-MSV) and Finkel-Biskis-Reilly (FBR-MSV) murine sarcoma viruses which induce osteogenic sarcomas in mice. The FBJ-MSV v-fos gene encodes a p55-kDa protein and the FBR-MSV v-fos gene encodes a p75-kDa fusion protein.Activated Protein C Resistance: A hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). The activated form of Factor V (Factor Va) is more slowly degraded by activated protein C. Factor V Leiden mutation (R506Q) is the most common cause of APC resistance.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.Oncogene Protein v-crk: A signal transducing adaptor protein that is encoded by the crk ONCOGENE from TYPE C AVIAN RETROVIRUSES. It contains SRC HOMOLOGY DOMAINS and is closely related to its cellular homolog, PROTO-ONCOGENE PROTEIN C-CRK.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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Oncogene Protein v-cbl: An oncoprotein from the Cas NS-1 murine retrovirus that induces pre- B-CELL LYMPHOMA and MYELOID LEUKEMIAS. v-cbl protein is a tyrosine-phosphorylated, truncated form of its cellular homologue, PROTO-ONCOGENE PROTEIN C-CBL.Oncogene Proteins v-myb: Transforming proteins coded by myb oncogenes. Transformation of cells by v-myb in conjunction with v-ets is seen in the avian E26 leukemia virus.Oncogene Proteins v-erbB: Transforming proteins encoded by erbB oncogenes from the avian erythroblastosis virus. The protein is a truncated form of the EGF receptor (RECEPTOR, EPIDERMAL GROWTH FACTOR) whose kinase domain is constitutively activated by deletion of the ligand-binding domain.Oncogene Proteins v-abl: Transforming proteins encoded by the abl oncogenes. Oncogenic transformation of c-abl to v-abl occurs by insertional activation that results in deletions of specific N-terminal amino acids.Oncogenes: Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.Oncogene Proteins v-rel: Transforming proteins coded by rel oncogenes. The v-rel protein competes with rel-related proteins and probably transforms cells by acting as a dominant negative version of c-rel. This results in the induction of a broad range of leukemias and lymphomas.Protein S: The vitamin K-dependent cofactor of activated PROTEIN C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S; (PROTEIN S DEFICIENCY); can lead to recurrent venous and arterial thrombosis.Oncogene Proteins v-erbA: Transforming proteins encoded by erbA oncogenes from the avian erythroblastosis virus. They are truncated versions of c-erbA, the thyroid hormone receptor (RECEPTORS, THYROID HORMONE) that have retained both the DNA-binding and hormone-binding domains. Mutations in the hormone-binding domains abolish the transcriptional activation function. v-erbA acts as a dominant repressor of c-erbA, inducing transformation by disinhibiting proliferation.Oncogene Proteins: Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.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)Oncogene Protein p21(ras): Transforming protein encoded by ras oncogenes. Point mutations in the cellular ras gene (c-ras) can also result in a mutant p21 protein that can transform mammalian cells. Oncogene protein p21(ras) has been directly implicated in human neoplasms, perhaps accounting for as much as 15-20% of all human tumors. This enzyme was formerly listed as EC 3.6.1.47.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.Proto-Oncogene Proteins c-ets: A family of transcription factors that share a unique DNA-binding domain. The name derives from viral oncogene-derived protein oncogene protein v-ets of the AVIAN ERYTHROBLASTOSIS VIRUS.Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process.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.Pulmonary Surfactant-Associated Protein C: A pulmonary surfactant associated protein that plays a role in alveolar stability by lowering the surface tension at the air-liquid interface. It is a membrane-bound protein that constitutes 1-2% of the pulmonary surfactant mass. Pulmonary surfactant-associated protein C is one of the most hydrophobic peptides yet isolated and contains an alpha-helical domain with a central poly-valine segment that binds to phospholipid bilayers.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.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.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.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.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.Proto-Oncogene Protein c-ets-1: An ets proto-oncogene expressed primarily in adult LYMPHOID TISSUE; BRAIN; and VASCULAR ENDOTHELIAL CELLS.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Factor V: Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease.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.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.Mitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.Proto-Oncogene Protein c-ets-2: A ubiquitously expressed ets proto-oncogene protein that may play a role in regulation of CELL PROLIFERATION and CELL DIFFERENTIATION.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.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.Oncogene Protein pp60(v-src): A tyrosine-specific protein kinase encoded by the v-src oncogene of ROUS SARCOMA VIRUS. The transforming activity of pp60(v-src) depends on both the lack of a critical carboxy-terminal tyrosine phosphorylation site at position 527, and the attachment of pp60(v-src) to the plasma membrane which is accomplished by myristylation of its N-terminal glycine.Thrombin: An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.Factor Va: Activated form of factor V. It is an essential cofactor for the activation of prothrombin catalyzed by factor Xa.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.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 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.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.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.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.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.Oncogene Proteins, Fusion: The GENETIC TRANSLATION products of the fusion between an ONCOGENE and another gene. The latter may be of viral or cellular origin.MAP Kinase Kinase Kinases: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).Genes, ras: Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.Oncogene Proteins, Viral: Products of viral oncogenes, most commonly retroviral oncogenes. They usually have transforming and often protein kinase activities.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Oncogene Protein v-akt: A viral oncoprotein originally isolated from a murine T CELL LYMPHOMA infected with the acutely transforming retrovirus AKT8. v-akt protein is the viral homologue of PROTO-ONCOGENE PROTEINS C-AKT.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Kinetics: The rate dynamics in chemical or physical systems.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.Blood Coagulation: The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.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.Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.Casein Kinases: A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.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.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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.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.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.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.Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia.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.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.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.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).Cell Line, Tumor: A cell line derived from cultured tumor cells.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.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.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.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.Protein S Deficiency: An autosomal dominant disorder showing decreased levels of plasma protein S antigen or activity, associated with venous thrombosis and pulmonary embolism. PROTEIN S is a vitamin K-dependent plasma protein that inhibits blood clotting by serving as a cofactor for activated PROTEIN C (also a vitamin K-dependent protein), and the clinical manifestations of its deficiency are virtually identical to those of protein C deficiency. Treatment with heparin for acute thrombotic processes is usually followed by maintenance administration of coumarin drugs for the prevention of recurrent thrombosis. (From Harrison's Principles of Internal Medicine, 12th ed, p1511; Wintrobe's Clinical Hematology, 9th ed, p1523)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.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.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.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.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.Aurora Kinases: A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.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.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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.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.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.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.Receptors, Thrombin: A family of proteinase-activated receptors that are specific for THROMBIN. They are found primarily on PLATELETS and on ENDOTHELIAL CELLS. Activation of thrombin receptors occurs through the proteolytic action of THROMBIN, which cleaves the N-terminal peptide from the receptor to reveal a new N-terminal peptide that is a cryptic ligand for the receptor. The receptors signal through HETEROTRIMERIC GTP-BINDING PROTEINS. Small synthetic peptides that contain the unmasked N-terminal peptide sequence can also activate the receptor in the absence of proteolytic activity.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.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.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.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.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.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.PhosphoproteinsDiacylglycerol Kinase: An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.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.AMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.Thrombophilia: A disorder of HEMOSTASIS in which there is a tendency for the occurrence of THROMBOSIS.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.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.Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.Blood Coagulation Disorders: Hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors such as COAGULATION PROTEIN DISORDERS; BLOOD PLATELET DISORDERS; BLOOD PROTEIN DISORDERS or nutritional conditions.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.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.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.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.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Receptor, PAR-1: A thrombin receptor subtype that couples to HETEROTRIMERIC GTP-BINDING PROTEINS resulting in the activation of a variety of signaling mechanisms including decreased intracellular CYCLIC AMP, increased TYPE C PHOSPHOLIPASES and increased PHOSPHOLIPASE A2.Proto-Oncogene Proteins p21(ras): Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC 3.6.1.47.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 Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Myosin-Light-Chain Kinase: An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.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.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).Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.Partial Thromboplastin Time: The time required for the appearance of FIBRIN strands following the mixing of PLASMA with phospholipid platelet substitute (e.g., crude cephalins, soybean phosphatides). It is a test of the intrinsic pathway (factors VIII, IX, XI, and XII) and the common pathway (fibrinogen, prothrombin, factors V and X) of BLOOD COAGULATION. It is used as a screening test and to monitor HEPARIN therapy.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.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.Retroviridae Proteins, Oncogenic: Retroviral proteins that have the ability to transform cells. They can induce sarcomas, leukemias, lymphomas, and mammary carcinomas. Not all retroviral proteins are oncogenic.Protein Kinase C-epsilon: A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.MAP Kinase Kinase Kinase 1: A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Ribosomal Protein S6 Kinases, 90-kDa: A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.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.Anticoagulants: Agents that prevent clotting.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.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.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.MAP Kinase Kinase 2: A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Cyclin-Dependent Kinase 2: A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.Calcium-Calmodulin-Dependent Protein Kinase Type 2: A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Factor Xa: Activated form of factor X that participates in both the intrinsic and extrinsic pathways of blood coagulation. It catalyzes the conversion of prothrombin to thrombin in conjunction with other cofactors.Protein Kinase C beta: PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.1-Carboxyglutamic Acid: Found in various tissues, particularly in four blood-clotting proteins including prothrombin, in kidney protein, in bone protein, and in the protein present in various ectopic calcifications.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.ChromonesPrecipitin 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.Genes, myc: Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8.Proto-Oncogene Proteins c-myc: Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.Blood Coagulation Tests: Laboratory tests for evaluating the individual's clotting mechanism.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.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.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.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.Cyclin-Dependent Kinase 5: A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.Phosphoglycerate Kinase: An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Disseminated Intravascular Coagulation: A disorder characterized by procoagulant substances entering the general circulation causing a systemic thrombotic process. The activation of the clotting mechanism may arise from any of a number of disorders. A majority of the patients manifest skin lesions, sometimes leading to PURPURA FULMINANS.Aurora Kinase A: An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION.MorpholinesReceptor, 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.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Mice, Inbred C57BLEpidermal 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.Phosphorylase Kinase: An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.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.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Thrombosis: Formation and development of a thrombus or blood clot in the blood vessel.
... "p300/cAMP-responsive element-binding protein interactions with ets-1 and ets-2 in the transcriptional activation of the human ... Protein kinase B)/jun N-terminal kinase signaling pathway in macrophages of motheaten-viable mutant mice". Molecular and ... "Characterization and localization of the products of the human homologs of the v-ets oncogene". Oncogene. 2 (2): 99-103. PMID ... "Regulation of transcription of the human presenilin-1 gene by ets transcription factors and the p53 protooncogene". The Journal ...
The downstream target of Elk1 is the serum response element (SRE) of the c-fos proto-oncogene. To produce c-fos, a protein ... Elk1 can, thus, independently interact with an ETS binding site, as in the case of the lck proto-oncogene in Figure 2. Moreover ... Protein kinase C, which is activated by phorbol esters, can fulfill the same function as Ras. MEK kinase (MEKK) can also ... Zinck R, Hipskind RA, Pingoud V, Nordheim A (June 1993). "c-fos transcriptional activation and repression correlate temporally ...
"Cyclin D1 suppresses retinoblastoma protein-mediated inhibition of TAFII250 kinase activity". Oncogene. 19 (50): 5703-11. doi: ... Mulcahy LS, Smith MR, Stacey DW (1985). "Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 ... "Transforming p21ras mutants and c-Ets-2 activate the cyclin D1 promoter through distinguishable regions". J Biol Chem. 270: ... Cyclin D1-CDK4 also associates with several transcription factors and transcriptional co-regulators. Independent of CDK, cyclin ...
"The ETV6-NTRK3 gene fusion encodes a chimeric protein tyrosine kinase that transforms NIH3T3 cells". Oncogene. 19 (7): 906-15. ... "The ets family member Tel binds to the Fli-1 oncoprotein and inhibits its transcriptional activity". The Journal of Biological ... ETV6 is a clinically significant proto-oncogene in that it can fuse with other genes to drive the development and/or ... ETV6 and proteins with tyrosine kinase activity generally are converted from a protein with tightly regulated tyrosine kinase ...
"The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the ... Oncogene. 10 (3): 477-86. PMID 7845672. "Entrez Gene: BLK B lymphoid tyrosine kinase". Oda H, Kumar S, Howley PM (August 1999 ... 2002). "Physical and transcriptional map of the critical region for keratolytic winter erythema (KWE) on chromosome 8p22-p23 ... 2004). "Isoforms of the Ets transcription factor NERF/ELF-2 physically interact with AML1 and mediate opposing effects on AML1- ...
Proto-Oncogene Proteins c-met at the US National Library of Medicine Medical Subject Headings (MeSH) UniProtKB/Swiss-Prot entry ... The protein possesses tyrosine kinase activity. The primary single chain precursor protein is post-translationally cleaved to ... "Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene". Cancer Cell. 3 (4): 347-61. doi: ... MET promoter has four putative binding sites for Ets, a family of transcription factors that control several invasive growth ...
... is a proto-oncogene (its protein is Jun) and is the cellular homolog of the viral oncoprotein v-jun. Jun is the first ... C-jun regulates the transcriptional level of cyclin D1, which is a major Rb kinase. Rb is a growth suppressor, and it is ... "The Ets transcription factors interact with each other and with the c-Fos/c-Jun complex via distinct protein domains in a DNA- ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proceedings of the National ...
The protein kinases that are known to target this transcriptional activation domain of p53 can be roughly divided into two ... Finlay, C. A.; Hinds, P. W.; Levine, A. J. (1989-06-30). "The p53 proto-oncogene can act as a suppressor of transformation". ... "Regulation of transcription of the human presenilin-1 gene by ets transcription factors and the p53 protooncogene". The Journal ... "Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex". The ...
Navas TA, Baldwin DT, Stewart TA (November 1999). "RIP2 is a Raf1-activated mitogen-activated protein kinase kinase". J. Biol. ... Dimerization happens between the products of the c-jun and c-fos protooncogenes, and is required for DNA-binding. Jun proteins ... doi:10.1016/S0955-0674(97)80068-3. Yamashita, Junro; McCauley, Laurie K. (2006). "The Activating Protein-1 Transcriptional ... Wai PY, Mi Z, Gao C, Guo H, Marroquin C, Kuo PC (July 2006). "Ets-1 and runx2 regulate transcription of a metastatic gene, ...
Li R, Pei H, Watson DK (2000). "Regulation of Ets function by protein - protein interactions". Oncogene. 19 (55): 6514-23. doi: ... Reddy ES, Rao VN (1988). "Structure, expression and alternative splicing of the human c-ets-1 proto-oncogene". Oncogene ... In particular, ETS1 protein interacts with several DNA repair proteins. ETS1 binds with DNA-dependent protein kinase (DNA-PK) [ ... "Modulation of ETS-1 transcriptional activity by huUBC9, a ubiquitin-conjugating enzyme". Oncogene. 15 (12): 1489-95. doi: ...
STE20-related kinase adaptor protein α, RhoI, Klotho, N-acetylglucosaminyl transferase V, B-Raf proto-oncogene, casein kinase 2 ... regulation of stability and transforming potential of ETS transcriptional factor ESE-1 by p21-activated kinase 1". The Journal ... PAK proteins, a family of serine/threonine p21-activated kinases, include PAK1, PAK2, PAK3 and PAK4. These proteins serve as ... Shin YJ, Kim YB, Kim JH (September 2013). "Protein kinase CK2 phosphorylates and activates p21-activated kinase 1". Molecular ...
... hypermethylation of the genes coding for Death-Associated Protein Kinase (DAPK), p16, and Epithelial Membrane Protein 3 (EMP3) ... June 2006). "Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in ... In mammals, microRNAs (miRNAs) regulate about 60% of the transcriptional activity of protein-encoding genes. Some miRNAs also ... Oncogene. 22 (46): 7243-6. doi:10.1038/sj.onc.1206977. PMID 14562054. Bi FF, Li D, Yang Q (2013). "Hypomethylation of ETS ...
... "cAMP-response-element-binding-protein-binding protein (CBP) and p300 are transcriptional co-activators of early growth response ... "Regulation of transcription of the human presenilin-1 gene by ets transcription factors and the p53 protooncogene". J. Biol. ... Li QJ, Yang SH, Maeda Y, Sladek FM, Sharrocks AD, Martins-Green M (January 2003). "MAP kinase phosphorylation-dependent ... Oncogene. 22 (1): 151-6. doi:10.1038/sj.onc.1206067. PMID 12527917. Yamamoto N, Yamamoto S, Inagaki F, Kawaichi M, Fukamizu A, ...
Many transcription factors, especially some that are proto-oncogenes or tumor suppressors, help regulate the cell cycle and as ... Other proteins such as coactivators, chromatin remodelers, histone acetyltransferases, histone deacetylases, kinases, and ... Ets-type 3.5.3 Family: Interferon regulatory factors 3.6 Class: TEA ( transcriptional enhancer factor) domain 3.6.1 Family: TEA ... Cdx protein family DNA-binding protein Inhibitor of DNA-binding protein Nuclear receptor, a class of ligand activated ...
Myb proto-oncogene protein also known as transcriptional activator Myb is a protein that in humans is encoded by the MYB gene.[ ... Leverson JD, Koskinen PJ, Orrico FC, Rainio EM, Jalkanen KJ, Dash AB, Eisenman RN, Ness SA (1998). "Pim-1 kinase and p100 ... Myb proto-oncogene protein is a member of the MYB (myeloblastosis) family of transcription factors. The protein contains three ... Jacobs SM, Gorse KM, Westin EH (1994). "Identification of a second promoter in the human c-myb proto-oncogene". Oncogene. 9 (1 ...
... Proto-Oncogene Proteins at the US National Library of Medicine Medical Subject Headings (MeSH) ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proceedings of the National ... protein complex binding. • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence- ... MYC, MRTL, MYCC, bHLHe39, c-Myc, v-myc avian myelocytomatosis viral oncogene homolog, MYC proto-oncogene, bHLH transcription ...
Many transcription factors, especially some that are proto-oncogenes or tumor suppressors, help regulate the cell cycle and as ... Mitchell PJ, Tjian R (July 1989). "Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins". ... Other proteins such as coactivators, chromatin remodelers, histone acetyltransferases, histone deacetylases, kinases, and ... 3.5.2 Family: Ets-type. *3.5.3 Family: Interferon regulatory factors. *3.6 Class: TEA ( transcriptional enhancer factor) domain ...
The virus encodes a 135 kDa fusion protein which contains amino acid sequences derived from the viral Gag protein and the two ... cellular transcription factors c-Myb and c-Ets-1p68. Previously … ... Protein Biosynthesis * Protein-Tyrosine Kinases / metabolism * Proto-Oncogene Proteins / genetics* * Proto-Oncogene Proteins / ... Transcriptional Activation * Transfection Substances * DNA-Binding Proteins * Oligodeoxyribonucleotides * Proto-Oncogene ...
TNF alpha induced protein 3 (TNFAIP3), insulin receptor substrate 1 (IRS1), ETS proto-oncogene 1 (ETS1), insulin like growth ... cyclin dependent kinase 6;IGF1R: insulin like growth factor 1 receptor;SNAI2: snail family transcriptional repressor 2;IRS1: ... ETS proto-oncogene 1;TNFAIP3: TNF alpha induced protein 3;CCND1: cyclin D1 ... A. Western blotting for COL1A2 protein expression in CRC cell lines. B. Western blotting for COL1A2 protein expression in ...
... makingras the most widely mutated human proto-oncogene. Both mitogen-activated protein (MAP) kinase-dependent and MAP kinase- ... The Ets, c-Myc, and c-Jun proteins are Ras-responsive transcription factors required for cellular transformation in vitro (4) ... and this regulation occurs largely through the stimulation of the transcriptional function of the NF-κB RelA/p65 subunit (7). ... The ras proto-oncogene is frequently mutated in human tumors and functions to chronically stimulate signal transduction ...
ETS Proto-oncogene 1 Transcriptionally Up-regulates the Cholangiocyte Senescence-associated Protein Cyclin-dependent Kinase ... 2017) New Orthogonal Transcriptional Switches Derived from Tet Repressor Homologues for Saccharomyces cerevisiae Regulated by 2 ... 2017) Abl kinase regulation by BRAF/ERK and cooperation with Akt in melanoma. Oncogene. 2017 Apr 3;. PM ID: 28368422 ... Move your genome engineering projects forward with confidence with products for verifying Cas9 mRNA and protein expression. ...
ETS Proto-oncogene 1 Transcriptionally Up-regulates the Cholangiocyte Senescence-associated Protein Cyclin-dependent Kinase ... 2017) New Orthogonal Transcriptional Switches Derived from Tet Repressor Homologues for Saccharomyces cerevisiae Regulated by 2 ... 2017) Abl kinase regulation by BRAF/ERK and cooperation with Akt in melanoma. Oncogene. 2017 Apr 3;. PM ID: 28368422 ... 2017) The Highly Dynamic Nature of ERdj5 Is Key to Efficient Elimination of Aberrant Protein Oligomers through ER-Associated ...
... including c-Jun-Nterminal Kinase (JNK), p38/MAPK and ERK (Extracellular-signal Regulated Kinases). This phosphorylation event ... Elk-1 is present in its resting state in the cytoplasm, where it colocalizes with mitochondrial proteins or microtubules. In ... including c-Jun-Nterminal Kinase (JNK), p38/MAPK and ERK (Extracellular-signal Regulated Kinases). This phosphorylation event ... Elk-1 is present in its resting state in the cytoplasm, where it colocalizes with mitochondrial proteins or microtubules. In ...
Tyrosine protein kinases and their substrates: an overview. Adv Cyclic Nucleotide Protein Phosphorylation Res.. 1984;17:443-455 ... fos proto-oncogene.2 3 4 5 6 7 8 In the cytoplasm of ECs, MAPKs, including JNK and ERK, are activated by shear stress.9 10 11 ... Marais R, Wynne J, Treisman R. The SRF accessory protein Elk-1 contains a growth factor- regulated transcriptional activation ... an inhibitor of tyrosine kinases, inhibits shear stress activation of ERK and JNK.12 Transcription factors that contain the ETS ...
... complex by binding to the the serum response factor and the serum reponse element in the promoter of the c-fos proto-oncogene. ... The protein encoded by this gene is phosphorylated by the kinases, MAPK1 and MAPK8. Several transcript variants have been ... Involved in both transcriptional activation and repression. Interaction with SIRT7 leads to recruitment and stabilization of ... This gene is a member of the Ets family of transcription factors and of the ternary complex factor (TCF) subfamily. Proteins of ...
1991) Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF. Nature 350:158- ... 1993) The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain. Cell 73:381-393. ... a family of Ets domain-containing transcription factors (53, 62, 68). Upon exposure of PC12 cells to NGF, the TCF component of ... p38 MAPK is known to activate the Ser/Thr protein kinase MAPKAP kinase 2 (60) and a closely related kinase, MAPKAP kinase 3 (48 ...
RECEPTOR TYROSINE KINASE , TRANSCRIPTIONAL RESPONSE , Proto-Oncogene Proteins c-ets - genetics , ErbB Receptors - genetics , ... Protein Structure, Tertiary , Proto-Oncogene Proteins - metabolism , ras Proteins - genetics , Proto-Oncogene Proteins p21(ras) ... Stem Cells - cytology , HMGB Proteins - biosynthesis , Proto-Oncogene Proteins - biosynthesis , Drosophila Proteins - ... ras Proteins - metabolism , Pancreatic Neoplasms - genetics , Pinocytosis , Proto-Oncogene Proteins - genetics , Carcinoma, ...
Protein Coding), ELK1, ETS Transcription Factor, including: function, proteins, disorders, pathways, orthologs, and expression ... ets related protooncogene 1,activated by several mitogen-activated protein kinases (MAPKs),associating with a ternary complex ... transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding. IDA. 12750007. ... complex by binding to the the serum response factor and the serum response element in the promoter of the c-fos proto-oncogene ...
1998) A role for CREB binding protein and p300 transcriptional coactivators in ets-1 transactivation functions. Mol. Cell. Biol ... For example, the T-cell factor NFAT-1 and the T-cell proto-oncogene RBTN-2 contain two independent transactivator domains (36, ... Molecular cloning and expression of calcium/calmodulin-dependent protein kinase kinase. J. Biol. Chem. 270:19320-19324. ... upstream of pETS; pETS-ZEB-MYBcontains four myb binding sites upstream of pETS-ZEB. pETSmut-ZEB-MYB is as pETS-ZEB-MYB but with ...
The downstream target of Elk1 is the serum response element (SRE) of the c-fos proto-oncogene. To produce c-fos, a protein ... Elk1 can, thus, independently interact with an ETS binding site, as in the case of the lck proto-oncogene in Figure 2. Moreover ... Protein kinase C, which is activated by phorbol esters, can fulfill the same function as Ras. MEK kinase (MEKK) can also ... Zinck R, Hipskind RA, Pingoud V, Nordheim A (June 1993). "c-fos transcriptional activation and repression correlate temporally ...
For example, "AP-1" can refer to either "jun proto-oncogene" (Entrez Gene: 3725) or "FBJ murine osteosarcoma viral oncogene ... As shown in Figure 2, the TEL1 and TEL2 proteins are both ETS-family transcription factors with the ETS finger domain and GGAA ... is tagged as protein family because of its long form "transcriptional intermediary factor 1 family"). (4) If a mention occurs ... When searching for the gene identifier in Entrez Gene, TEL1 can map to two different concepts: ATM serine/threonine kinase ( ...
... "p300/cAMP-responsive element-binding protein interactions with ets-1 and ets-2 in the transcriptional activation of the human ... Protein kinase B)/jun N-terminal kinase signaling pathway in macrophages of motheaten-viable mutant mice". Molecular and ... "Characterization and localization of the products of the human homologs of the v-ets oncogene". Oncogene. 2 (2): 99-103. PMID ... "Regulation of transcription of the human presenilin-1 gene by ets transcription factors and the p53 protooncogene". The Journal ...
Pim kinases primarily deal with three broad categories of functions such as tumorigenesis, protecting cells from... ... Pim kinases are being implicated in oncogenic process in various human cancers. ... PIM3 proto-oncogene kinase is a common transcriptional target of divergent EWS/ETS oncoproteins. Mol Cell Biol 23:3897-3908 ... Saris CJ, Domen J, Berns A (1991) The pim-1 oncogene encodes two related protein-serine/threonine kinases by alternative ...
PIM1 is a proto-oncogene that encodes a serine/threonine kinase and is known to be frequently targeted by somatic hypermutation ... The ETV6 tumor suppressor gene encodes an Ets family transcriptional repressor factor required for hematopoeisis [30] and ... A variety of inhibitors are currently under development for PIM family proteins [42](Tab2), rendering these proteins attractive ... IRF2BP2 encodes a zinc finger protein that interacts with partners such as TP53 and the oncogene IRF2. IRF2BP2 acts as a ...
Mitogen-Activated Protein Kinases/metabolism , Proto-Oncogene Proteins c-pim-1/metabolism , Transcriptional Activation , ets- ... ets-Domain Protein Elk-1/genetics , ets-Domain Protein Elk-1/metabolism ... Animals , Humans , Early Growth Response Protein 1/genetics , Epithelial Cells/drug effects , Mitogen-Activated Protein Kinase ... Transcriptional Activation , Transfection , ets-Domain Protein Elk-1/genetics ...
Mitogen-Activated Protein Kinases/metabolism , Proto-Oncogene Proteins c-pim-1/metabolism , Transcriptional Activation , ets- ... Animals , Mice , Bone Morphogenetic Proteins/analysis , Hedgehog Proteins/analysis , Odontogenesis/physiology , Wnt Proteins/ ... Transcriptional Activation , Transfection , ets-Domain Protein Elk-1/genetics ... an oncogene encoding a serine-threonine kinase. This is a true oncogene which prolongs survival and inhibits apoptosis of ...
Proto-Oncogene Protein c-ets-1. *Transcriptional Regulator ERG. *Signal Transduction. *Leukaemia ... The p16 tumor suppressor gene encodes a specific inhibitor of cyclin-dependent kinase (CDK) 4 and 6 and is found altered in a ... ETS-1, ETS-2 and ETS variant gene‑4 (ETV‑4), in PCa as a proof of principle. Using western blot analysis, we show that ERG, ETS ... and ETS-1/ETS-2 and C/EBPα could interact with corresponding binding sites. In addition, overexpression of ETS-1/2 or C/EBPα ...
... melanoma subtype is characterized by aberrant and constitutive activation of the proto-oncogene receptor tyrosine kinase C-KIT ... Here, we show that Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ) in macrophages plays a major role in the development of ... Depletion of MNK1/2 in melanoma cells with oncogenic C-KIT inhibited cell migration and mRNA translation of the transcriptional ... and Ets1/2 physically interacted with and recruited Hdac3 to the evolutionarily conserved E-box-GATA-ETS composite element of a ...
... worse is the zinc finger transcription factor pax bsap recruits ets proto oncogene during mouse nephrogenesis in vitroa protein ... research paper on hurricanes The tools that calculate kt/v and creatinine kinase an electrocardiogram and chest pain a any ... ducts moore orgebin crist nistal and paniagua the molecular mechanisms regulating condensation gp encodes a transcriptional ... a f gilmore jcornish k g and kondo m cdna cloning and functional catheter placement and organization of the protein wt oncogene ...
... the beryllium-induced transcriptional activation of c-fos and c-jun is dependent on pathways of protein kinase C and MAP kinase ... c-myc and R-ras proto-oncogenes; stress response genes (5): HSP84, HSP86, heme oxygenase 2 gene, etoposide-induced p53- ... ets-related transcription factor gene activated by ras, colony-stimulating factor gene, A-myb, sky, cot, c-fos, c-jun, ...
The tcl-3 proto-oncogene altered by chromosomal translocation in T-cell leukemia codes for a homeobox protein. EMBO J. 1991;10( ... ETV6 encodes an ETS family transcriptional repressor strictly required for the development of hematopoietic stem cells (94, 95 ... A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science. 1997;278(5341):1309-1312.. View this ... Proto-oncogenes. The MYC oncogene is activated in 1% of T-ALLs as result of the t(8;14)(q24;q11) translocation (25). However, ...
... as well as peptides and antibodies corresponding to the GC6 protein can be used to identify senescent cells, distinguish ... Isolated, purified, and recombinant nucleic acids and proteins corresponding to the human GC6 gene and its mRNA and protein ... sulfatase H24504 159795 plasma retinol-binding protein H24956 160664 proto-oncogene tyrosine-protein kinase receptor RET H25136 ... W78163 346900 proto-oncogene ets-2 W92764 357031 hyaluronate-binding protein TSG-6 (TNF-inducible) W96211 358596 ornithine ...
  • In order to address molecular mechanism of this differentiation, we have investigated the role of mitogen-activated protein (MAP) kinase pathway and gene expressions of p21(waf1/cip1)and nuclear oncogenes (c-fos and c-myc) during AR42J cell differentiation. (bvsalud.org)
  • Inhibition of MAP kinase pathway by PD98059 resulted in further elevation of the dexamethasone-induced amylase mRNA and p21(waf1/cip1)gene expression. (bvsalud.org)
  • These results suggest that p21(waf1/cip1)and nuclear oncogenes are involved in dexamethasone-induced differentiation and inhibition of MAP kinase pathway accelerates the conversion of undifferentiated AR42J cells into amylase-secreting exocrine cells. (bvsalud.org)
  • The prototypical kinase cascade transducing Ras signals is the Raf-1/MEK/ Erk pathway, and there is a precedent for Elk-1 activation via this mechanism in the fibroblast (31). (nih.gov)
  • and tests of cell autonomy and epistasis frequently position the requirement for the protein in the pathway, even before its biochemical activity is known. (springer.com)
  • Duffy JB, Perrimon N. The torso pathway in Drosophila -Lessons on receptor tyrosine kinase signaling and pattern formation. (springer.com)
  • Significantly, the JNK (show MAPK8 ELISA Kits ) pathway is responsible for the majority of the phenotypes and transcriptional changes downstream of Notch (show NOTCH1 ELISA Kits )- Src (show SRC ELISA Kits ) synergy. (antibodies-online.com)
  • GnRH stimulates Mitogen-activated protein kinases ( JNK(MAPK8-10) ) activity by a pathway that includes sequential activation of PKC-epsilon / c-Src / Cell division cycle 42 ( CDC42 )/ Mitogen-activated protein kinase kinase kinase 1 ( MEKK1 ) [ 18 ]. (bio-rad.com)
  • MAP kinase plays an important role in the Ras signaling pathway because it can activate downstream substrates that directly mediate the cellular response to growth factors, suggesting that MAP kinase acts near or at the end of this signaling pathway (reviewed in T reisman 1996 ). (genetics.org)
  • Genetic studies have shown that the anchor cell signal activates a receptor tyrosine kinase/Ras pathway (reviewed in K ornfeld 1997 ). (genetics.org)
  • Tang R, Kacinski BM, Validire P, Beuvon F, Sastre X, Benoit P, de la Rochefordiere A, Mosseri V, Pouillart P, Scholl S. Oncogene amplification correlates with dense lymphocyte infiltration in human breast cancers: a role for hematopoieitic growth factor release by tumor cells? (springer.com)
  • Insulin-like growth factor-binding protein 7 (IGFBP7), a novel biomarker for tumor fibroblasts in epithelial cancer, has also been detected in CAFs through genetic screenings and immunohistochemical studies. (spandidos-publications.com)
  • Importantly, WT1 protein expression was demonstrated in tumor tissues and was absent in normal and benign tissues. (pubmedcentralcanada.ca)
  • The same complex also interacts with proteins of the Rb tumor suppressor family and the E2F transcription factor family. (stanford.edu)
  • This suggested that blocking MNK1/2 activity may inhibit tumor progression, at least in part, by blocking translation initiation of mRNAs encoding cell migration proteins. (jci.org)
  • We demonstrate that Elk-1, a protein closely related to p62TCF in function, is a nuclear target of two members of the MAP kinase family, ERK1 and ERK2. (nih.gov)
  • MEK inhibitors reduce activity of ERK1 and ERK2 and then relieve the feedback inhibition of RAF, resulting in enhancement of RAF kinase activity. (springeropen.com)
  • Active Motif also offers our FACE™ In-cell Western Phospho ELISAs for quantifying and comparing the phosphorylated and total amounts of ERK1/2 , JNK and p38 proteins. (activemotif.com)
  • Isolated, purified, and recombinant nucleic acids and proteins corresponding to the human GC6 gene and its mRNA and protein products, as well as peptides and antibodies corresponding to the GC6 protein can be used to identify. (google.es)
  • Investigators report the effects of lapatinib and neratinib on the mRNA and protein levels of the ErbB2 receptor. (mammarycellnews.com)
  • Myocardial levels of HGF mRNA and protein are increased for several days after myocardial infarction (MI), however, indicating a possible additional protective effect of HGF toward the progression of MI to heart failure. (aspetjournals.org)
  • Shear stress induction of the hemagglutinin (HA) epitope-tagged HA-JNK1 and the Myc epitope-tagged Myc-ERK2 was significantly attenuated by v-src(K295R) and c-src(K295R), the kinase-defective mutants of v-src and c-src, respectively. (ahajournals.org)
  • Phosphorylated by multiple kinases including MAPK1/ERK2 at THR-526. (genecards.org)
  • Histone deacetylases (HDACs) are critical regulators of gene expression that promote formation of heterochromatin by deacetylating histone and non-histone proteins. (jpatholtm.org)
  • To create a universal system for the control of gene expression, we have studied methods for the construction of novel polydactyl zinc finger proteins that recognize extended DNA sequences. (pnas.org)
  • Since Jacob and Monod questioned the chemical nature of the repressor and proposed a scheme by which the synthesis of individual proteins within a cell might be "provoked" or "repressed," specific experimental control of gene expression has been a tantalizing prospect ( 1 ). (pnas.org)
  • Often these protein factors act in a complex combinatorial manner allowing temporal, spatial, and environmentally responsive control of gene expression ( 2 ). (pnas.org)
  • L1s are the only known autonomously active human retrotransposons, as only they encode proteins (open reading frame 1 (ORF1) and ORF2) with which they can be mobilized. (beds.ac.uk)
  • TNFR-associated death domain protein (TRADD) interacts with tyrosines 384 and 385 in the CTAR2 domain, thereby recruiting TRAF2 to the complex ( 25 ). (asm.org)
  • Interestingly, fragments of c-Ets-1p68 with strong DNA binding activity could be produced by limited proteolysis, indicating that the DNA binding domain is repressed within the full-length molecule. (nih.gov)
  • Telerman A, Amson R, Zakut-Houri R, Givol D (1988) Identification of the human pim-1 gene product as a 33-kilodalton cytoplasmic protein with tyrosine kinase activity. (springer.com)
  • Located adjacent to the B domain, the R domain is involved in suppressing Elk1 transcriptional activity. (wikipedia.org)
  • Subsequent experiments showed that CD40 engagement also increased both Pim-1 protein levels and Pim-1 kinase activity in B cells. (jimmunol.org)
  • The dimeric combinations and transcriptional activity observed in vivo are largely influenced by the tissue-specific expression patterns of the individual proteins, and importantly by their specific activating mechanisms and post-translational modifications that facilitate their individual ability to dimerize with other basic leucine zipper (bZIP) domain proteins. (pubmedcentralcanada.ca)
  • As we usher in the era of genome-scale studies, it is clear that these elements have the potential to cause intra-individual and inter-individual variation and probably common disease through structural variation, deregulated transcriptional activity or epigenetic effects. (beds.ac.uk)
  • We anticipate that gene-specific transcriptional regulators of the type described here will find diverse applications in gene therapy, functional genomics, and the generation of transgenic organisms. (pnas.org)
  • ZEB is a zinc finger-homeodomain protein that represses transcription by binding to a subset of E-box sequences. (asm.org)
  • A rapid PCR assembly method was developed that, together with this predefined set of zinc finger domains, provides ready access to 17 million novel proteins that bind the 5′-(GNN) 6 -3′ family of 18-bp DNA sites. (pnas.org)
  • Our approach to this challenge is based on the recognition of the structural features unique to the Cys 2 -His 2 class of nucleic acid-binding, zinc finger proteins. (pnas.org)
  • Studies of natural zinc finger proteins have shown that three zinc finger domains can bind 9 bp of contiguous DNA sequence ( 7 , 9 ). (pnas.org)
  • Whereas recognition of 9 bp of sequence is insufficient to specify a unique site within even the small genome of Escherichia coli , we have demonstrated that polydactyl proteins containing six zinc finger domains can specify 18-bp recognition ( 10 ). (pnas.org)