Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
A 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.
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.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED 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)
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A mitogen-activated protein kinase kinase with specificity for a subset of P38 MITOGEN-ACTIVATED PROTEIN KINASES that includes MITOGEN-ACTIVATED PROTEIN KINASE 12; MITOGEN-ACTIVATED PROTEIN KINASE 13; and MITOGEN-ACTIVATED PROTEIN KINASE 14.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to CYTOKINES.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
A 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 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.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
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.
A 180-kDa MAP kinase kinase kinase with specificity for MAP KINASE KINASE 4 and MAP KINASE KINASE 6.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
Agents that inhibit PROTEIN KINASES.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
A 70-kDa MAP kinase kinase kinase with specificity for MAP KINASE KINASE 5. It is activated during the cellular response to GROWTH FACTORS, oxidative stress, and hyperosmotic conditions.
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.
A group of phenyl benzopyrans named for having structures like FLAVONES.
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.
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.
A 150-kDa MAP kinase kinase kinase that may play a role in the induction of APOPTOSIS. It has specificity for MAP KINASE KINASE 3; MAP KINASE KINASE 4; and MAP KINASE KINASE 6.
A ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
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.
Four carbon unsaturated hydrocarbons containing two double bonds.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
A regulatory calcium-calmodulin-dependent protein kinase that specifically phosphorylates CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 1; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 2; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 4; and PROTEIN KINASE B. It is a monomeric enzyme that is encoded by at least two different genes.
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.
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.
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.
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.
A 70-kDa MAPK kinase kinase with specificity for MAP KINASE KINASE 5.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
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.
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.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
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.
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.
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.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
Proteins prepared by recombinant DNA technology.
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.
A mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 7.
The rate dynamics in chemical or physical systems.
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.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
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.
Cellular proteins encoded by the c-mos genes (GENES, MOS). They function in the cell cycle to maintain MATURATION PROMOTING FACTOR in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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.
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.
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.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
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.
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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
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.
The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.
Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.
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.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
A 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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
A 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)
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.
Transforming proteins coded by mos oncogenes. The v-mos proteins were originally isolated from the Moloney murine sarcoma virus (Mo-MSV).
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.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
A 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.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
An 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.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A cell line derived from cultured tumor cells.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
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.
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.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
Elements of limited time intervals, contributing to particular results or situations.
The pressure required to prevent the passage of solvent through a semipermeable membrane that separates a pure solvent from a solution of the solvent and solute or that separates different concentrations of a solution. It is proportional to the osmolality of the solution.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
A 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.
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.
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.
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)
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A 110-kDa extracellular signal-regulated MAP kinase that is activated in response to cellular stress and by GROWTH FACTOR RECEPTORS-mediated pathways.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A 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.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
A family of closely-related serine-threonine kinases that were originally identified as the cellular homologs of the retrovirus-derived V-RAF KINASES. They are MAP kinase kinase kinases that play important roles in SIGNAL TRANSDUCTION.
A dual specificity phosphatase subtype that plays a role in intracellular signal transduction by inactivating MITOGEN-ACTIVATED PROTEIN KINASES. It has specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES and JNK MITOGEN-ACTIVATED PROTEIN 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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
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.
Cell surface receptors that bind CORTICOTROPIN; (ACTH, adrenocorticotropic hormone) with high affinity and trigger intracellular changes. Pharmacology suggests there may be multiple ACTH receptors. An ACTH receptor has been cloned and belongs to a subfamily of G-protein-coupled receptors. In addition to the adrenal cortex, ACTH receptors are found in the brain and immune systems.
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.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
A 38-kDa mitogen-activated protein kinase that is abundantly expressed in a broad variety of cell types. It is involved in the regulation of cellular stress responses as well as the control of proliferation and survival of many cell types. The kinase activity of the enzyme is inhibited by the pyridinyl-imidazole compound SB 203580.
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.
Compounds with three fused rings that appear like a naphthalene fused to piperidone or like a benz(de)isoquinoline-1,3-dione (not to be confused with BENZYLISOQUINOLINES which have a methyl separating the naphthyl from the benzyl rings). Members are CYTOTOXINS.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
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.
Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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).
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.
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.
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.
Cell surface proteins that bind cyclic AMP with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized cyclic AMP receptors are those of the slime mold Dictyostelium discoideum. The transcription regulator CYCLIC AMP RECEPTOR PROTEIN of prokaryotes is not included nor are the eukaryotic cytoplasmic cyclic AMP receptor proteins which are the regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASES.
Proteins found in any species of fungus.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 48 and 54 KD exist due to multiple ALTERNATIVE SPLICING.
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.
Proteins obtained from the species Schizosaccharomyces pombe. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
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.
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.
An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.
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).
An enzyme that catalyzes the phosphorylation of the guanidine nitrogen of arginine in the presence of ATP and a divalent cation with formation of phosphorylarginine and ADP. EC 2.7.3.3.
A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
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).)
Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).
An enzyme that catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside monophosphate, e.g., UMP, to form ADP and UDP. Many nucleoside monophosphates can act as acceptor while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.4.
The phosphoric acid ester of serine.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A family of ribosomal protein S6 kinases that are considered the major physiological kinases for RIBOSOMAL PROTEIN S6. Unlike RIBOSOMAL PROTEIN S6 KINASES, 90KDa the proteins in this family are sensitive to the inhibitory effects of RAPAMYCIN and contain a single kinase domain. They are referred to as 70kDa proteins, however ALTERNATIVE SPLICING of mRNAs for proteins in this class also results in 85kDa variants being formed.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.
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.
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.
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.
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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.
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.
The nonstriated involuntary muscle tissue of blood vessels.
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.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.
An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 2.7.1.20.
An antibiotic isolated from various Streptomyces species. It interferes with protein and DNA synthesis by inhibiting peptidyl transferase or the 80S ribosome system.
Serine protein kinases involved in the regulation of ACTIN polymerization and MICROTUBULE disassembly. Their activity is regulated by phosphorylation of a threonine residue within the activation loop by intracellular signaling kinases such as P21-ACTIVATED KINASES and by RHO KINASE.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
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.

All-trans-retinoic acid inhibits Jun N-terminal kinase by increasing dual-specificity phosphatase activity. (1/1457)

Jun N-terminal kinases (JNKs) are serine-threonine kinases that play a critical role in the regulation of cell growth and differentiation. We previously observed that JNK activity is suppressed by all-trans-retinoic acid (t-RA), a ligand for retinoic acid nuclear receptors (RARs), in normal human bronchial epithelial cells, which are growth inhibited by t-RA. In this study, we investigated the mechanism by which t-RA inhibits JNK and the possibility that this signaling event is blocked in non-small cell lung cancer (NSCLC) cells. Virtually all NSCLC cell lines are resistant to the growth-inhibitory effects of t-RA, and a subset of them have a transcriptional defect specific to retinoid nuclear receptors. We found that in NSCLC cells expressing functional retinoid receptors, serum-induced JNK phosphorylation and activity were inhibited by t-RA in a bimodal pattern, transiently within 30 min and in a sustained fashion beginning at 12 h. Retinoid receptor transcriptional activation was required for the late, but not the early, suppression of JNK activity. t-RA inhibited serum-induced JNK activity by blocking mitogen-activated protein (MAP) kinase kinase 4-induced signaling events. This effect of t-RA was phosphatase dependent and involved an increase in the expression of the dual-specificity MAP kinase phosphatase 1 (MKP-1). t-RA did not activate MKP-1 expression or inhibit JNK activity in a NSCLC cell line with retinoid receptors that are refractory to ligand-induced transcriptional activation. These findings provide the first evidence that t-RA suppresses JNK activity by inhibiting JNK phosphorylation. Retinoid receptor transcriptional activation was necessary for the sustained inhibition of JNK activity by t-RA, and this signaling event was disrupted in NSCLC cells with retinoid receptors that are refractory to ligand-induced transcriptional activation.  (+info)

Vitamin E succinate (VES) induces Fas sensitivity in human breast cancer cells: role for Mr 43,000 Fas in VES-triggered apoptosis. (2/1457)

Fas (CD95/APO-1) is an important mediator of apoptosis. We show that Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 human breast cancer cells become responsive to anti-Fas (CD95) agonistic antibody-triggered apoptosis after pretreatment or cotreatment with vitamin E succinate (VES; RRR-alpha-tocopheryl succinate). In contrast, no enhancement of anti-Fas agonistic antibody-triggered apoptosis was observed following VES pretreatment or cotreatment with Fas-sensitive primary cultures of human mammary epithelial cells, immortalized MCF-10A cells, or T47D human breast cancer cells. Although VES is itself a potent apoptotic triggering agent, the 6-h pretreatment procedure for Fas sensitization did not initiate VES-mediated apoptosis. The combination of VES plus anti-Fas in pretreatment protocols was synergistic, inducing 2.8-, 3.0-, and 6.3-fold enhanced apoptosis in Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 cells, respectively. Likewise, cotreatment of Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 cells with VES plus anti-Fas enhanced apoptosis 1.9-, 2.0-, and 2.6-fold, respectively. Functional knockout of Fas-mediated signaling with either Fas-neutralizing antibody (MCF-7-, MDA-MB-231-, and MDA-MB-435-treated cells) or Fas antisense oligomers (MDA-MB-435-treated cells only), reduced VES-triggered apoptosis by approximately 50%. Analyses of whole cell extracts from Fas-sensitive cells revealed high constitutive expression of Mr 43,000 Fas, whereas Fas-resistant cells expressed low levels that were confined to the cytosolic fraction. VES treatment of the Fas-resistant cells caused a depletion of cytosolic Mr 43,000 Fas with a concomitant increase in Mr 43,000 membrane Fas. These data show that VES can convert Fas-resistant human breast cancer cells to a Fas-sensitive phenotype, perhaps by translocation of cytosolic Mr 43,000 Fas to the membrane and show that VES-mediated apoptosis involves Mr 43,000 Fas signaling.  (+info)

Activation of c-fos promoter by Gbetagamma-mediated signaling: involvement of Rho and c-Jun N-terminal kinase. (3/1457)

Several extracellular stimuli mediated by G protein-coupled receptors activate c-fos promoter. Recently, we and other groups have demonstrated that signals from G protein-coupled receptors stimulate mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. The activation of these three MAPKs is mediated in part by the G protein betagamma subunit (Gbetagamma). In this study, we characterized the signals from Gbetagamma to c-fos promoter using transient transfection of c-fos luciferase into human embryonal kidney 293 cells. Activation of m2 muscarinic acetylcholine receptor and overexpression of Gbetagamma, but not constitutively active Galphai2, stimulated c-fos promoter activity. The c-fos promoter activation by m2 receptor and Gbetagamma was inhibited by beta-adrenergic receptor kinase C-terminal peptide (betaARKct), which functions as a Gbetagamma antagonist. MEK1 inhibitor PD98059 and kinase-deficient mutant of JNK kinase, but not p38 MAPK inhibitor SB203580, attenuated the m2 receptor- and Gbetagamma-induced c-fos promoter activation. Activated mutants of Ras and Rho stimulated the c-fos promoter activity, and the dominant negative mutants of Ras and Rho inhibited the c-fos promoter activation by m2 receptor and Gbetagamma. Moreover, c-fos promoter activation by m2 receptor, Gbetagamma, and active Rho, but not active Ras, was inhibited by botulinum C3 toxin. These data indicated that both Ras- and Rho-dependent signaling pathways are essential for c-fos promoter activation mediated by Gbetagamma.  (+info)

Regulation of JNK signaling by GSTp. (4/1457)

Studies of low basal Jun N-terminal kinase (JNK) activity in non-stressed cells led us to identify a JNK inhibitor that was purified and identified as glutathione S-transferase Pi (GSTp) and was characterized as a JNK-associated protein. UV irradiation or H2O2 treatment caused GSTp oligomerization and dissociation of the GSTp-JNK complex, indicating that it is the monomeric form of GSTp that elicits JNK inhibition. Addition of purified GSTp to the Jun-JNK complex caused a dose-dependent inhibition of JNK activity. Conversely, immunodepleting GSTp from protein extracts attenuated JNK inhibition. Furthermore, JNK activity was increased in the presence of specific GSTp inhibitors and a GSTp-derived peptide. Forced expression of GSTp decreased MKK4 and JNK phosphorylation which coincided with decreased JNK activity, increased c-Jun ubiquitination and decreased c-Jun-mediated transcription. Co-transfection of MEKK1 and GSTp restored MKK4 phosphorylation but did not affect GSTp inhibition of JNK activity, suggesting that the effect of GSTp on JNK is independent of the MEKK1-MKK4 module. Mouse embryo fibroblasts from GSTp-null mice exhibited a high basal level of JNK activity that could be reduced by forced expression of GSTp cDNA. In demonstrating the relationships between GSTp expression and its association with JNK, our findings provide new insight into the regulation of stress kinases.  (+info)

TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway. (5/1457)

Transforming growth factor-beta (TGF-beta) exerts its effects on cell proliferation, differentiation and migration in part through its modulation of extracellular matrix components, such as fibronectin and plasminogen activator inhibitor-1 (PAI-1). Although the SMAD family of proteins recently has been shown to be a key participant in TGF-beta signaling, other signaling pathways have also been shown to be activated by TGF-beta. We report here that c-Jun N-terminal kinase (JNK), a member of the MAP kinase family, is activated in response to TGF-beta in the human fibrosarcoma HT1080-derived cell line BAHgpt. Stable expression of dominant-negative forms of JNK1 and MKK4, an upstream activator of JNK, results in loss of TGF-beta-stimulated fibronectin mRNA and protein induction, while having little effect on TGF-beta-induced levels of PAI-1. The human fibronectin promoter contains three CRE elements, one of which has been shown to bind a c-Jun-ATF-2 heterodimer. Utilizing a GAL4 fusion trans-reporting system, we demonstrate a decrease in transactivating potential of GAL4-c-Jun and GAL4-ATF-2 in dominant-negative JNK1- and MKK4-expressing cells. Finally, we show that TGF-beta-induced fibronectin synthesis is independent of Smad4. These results demonstrate that TGF-beta-mediated fibronectin induction requires activation of JNK which in turn modulates the activity of c-Jun and ATF-2 in a Smad4independent manner.  (+info)

Requirement for nuclear factor-kappaB activation by a distinct subset of CD40-mediated effector functions in B lymphocytes. (6/1457)

CD40 stimulation, which is crucial for generating an effective T-dependent humoral response, leads to the activation of transcription factors NF-AT (nuclear factor of activated T cells), AP-1 (activator protein-1), and NF-kappaB (nuclear factor-kappaB). However, which CD40-mediated B cell functions actually require activation of specific transcription factors is unknown. We examined the causal relationship between NF-kappaB activation and CD40 effector functions by evaluating CD40 functions in the presence of an inducible mutant inhibitory kappaBalpha (IkappaBalpha) superrepressor. IkappaBalphaAA inhibited nuclear translocation of multiple NF-kappaB dimers without the complicating effect of depriving cells of NF-kappaB during development. This approach complements studies that use mice genetically deficient in single or multiple NF-kappaB subunits. Interestingly, only a subset of CD40 effector functions was found to require NF-kappaB activation. Both CD40-induced Ab secretion and B7-1 up-regulation were completely abrogated by expression of IkappaBalphaAA. Surprisingly, up-regulation of Fas, CD23, and ICAM-1 was partially independent, and up-regulation of LFA-1 was completely independent, of CD40-induced NF-kappaB activation. For the first time, it is clear that distinct transcription factors are required for the dynamic regulation of CD40 functions.  (+info)

Signal transduction and biological function of placenta growth factor in primary human trophoblast. (7/1457)

Placenta growth factor (PlGF), a member of the vascular endothelial growth factor family of angiogenic factors, is prominently expressed by trophoblast. In addition to its role as a paracrine angiogenic factor within the placenta and endometrium, presence of its receptor, Flt-1, on trophoblast suggests that PlGF also may have an autocrine role(s) in regulating trophoblast function. To elucidate its role in trophoblast, we examined the signal transduction and functional responses of primary human trophoblast to PlGF. Exogenous PlGF induced specific activation of the stress-activated protein kinase (SAPK) pathways, c-Jun-N terminal kinase (JNK) and p38 kinase, in primary term trophoblast with little to no induction of the extracellular signal regulated kinase (ERK-1 and -2) pathways. In contrast, PlGF induced significant ERK-1 and -2 activity in human umbilical vein endothelial cells but did not induce JNK or p38 activity. PlGF-induced activation of the SAPK signaling pathways protected trophoblast from growth factor withdrawal-induced apoptosis, but it did not protect trophoblast from apoptosis induced by the pro-inflammatory cytokines, interferon gamma and tumor necrosis factor alpha. These results provide the first direct evidence of a biochemical and functional role for PlGF/Flt-1 in normal trophoblast and suggest that aberrant PlGF expression during pregnancy may impact upon trophoblast function as well as vascularity within the placental bed.  (+info)

MEKK-1, a component of the stress (stress-activated protein kinase/c-Jun N-terminal kinase) pathway, can selectively activate Smad2-mediated transcriptional activation in endothelial cells. (8/1457)

Smad proteins are essential components of the intracellular signaling pathways utilized by members of the transforming growth factor-beta (TGF-beta) superfamily of growth factors. Certain Smad proteins (e.g. Smad1, -2, and -3) can act as regulated transcriptional activators, a process that involves phosphorylation of these proteins by activated TGF-beta superfamily receptors. We demonstrate that the intracellular kinase mitogen-activated protein kinase kinase kinase-1 (MEKK-1), an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase pathway, can participate in Smad2-dependent transcriptional events in cultured endothelial cells. A constitutively active form of MEKK-1 but not mitogen-activated protein kinase kinase-1 (MEK-1) or TGF-beta-activated kinase-1, two distinct intracellular kinases, can specifically activate a Gal4-Smad2 fusion protein, and this effect correlates with an increase in the phosphorylation state of the Smad2 protein. These effects do not require the presence of the C-terminal SSXS motif of Smad2 that is the site of TGF-beta type 1 receptor-mediated phosphorylation. Activation of Smad2 by active MEKK-1 results in enhanced Smad2-Smad4 interactions, nuclear localization of Smad2 and Smad4, and the stimulation of Smad protein-transcriptional coactivator interactions in endothelial cells. Overexpression of Smad7 can inhibit the MEKK-1-mediated stimulation of Smad2 transcriptional activity. A physiological level of fluid shear stress, a known activator of endogenous MEKK-1 activity in endothelial cells, can stimulate Smad2-mediated transcriptional activity. These data demonstrate a novel mechanism for activation of Smad protein-mediated signaling in endothelial cells and suggest that Smad2 may act as an integrator of diverse stimuli in these cells.  (+info)

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Pontus Jäntti Sulkapallokoulu, Ristihaantie 2, Espoo (2020) - Pontus Jäntti Sulkapallokoulu järjestää valmennusta sekä lapsille et
Certest tarjoaa laajan valikoiman kvalitatiivisia immunokromatografisia testejä mahasuolikanavan sairauksien sekä hengitystieinfektioiden diagnoosin…
MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines. Requirement of the JIP1 scaffold protein for stress-induced JNK activation
Following dissemination from a primary tumor, viable cancer cells that lodge at secondary sites (2 sites) can persist for extended periods of time before going on to form clinically detectable disease. It is puzzling why tumor cells that have lost checkpoint control of the cell cycle and evaded death at the 1 tumor site should fail to grow at remote sites in both experimental models and patients. No one knows how such cells ultimately initiate growth and complete the process of metastatic colonization which can ultimately lead to death. Previously we identified a novel function for MKK4/JNKK1, as a metastasis-suppressor gene for prostate cancer. MKK4/JNKK1 is a dual-specificity kinase that activates the JNK and p38 MAP kinases in response to extracellular stimuli. We have recently shown that ectopic expression of MKK4/JNKK1 results in the context-dependent suppression of metastatic colonization, and that MKK4/JNKK1 protein is down-regulated in clinical disease. Our laboratory is now ...
Flower Delivery to Písek FloraQueen is the Best Choice to Send Flowers to Písek , Same-day delivery and top local florists for international flower orders
Bid procedure, 2021-07-06BondsKOMMUNINVEST I SVERIGE: 2505. SE0011414010. 2025-05-12KOMMUNINVEST I SVERIGE: 2611, SE0012569572, 2026-11-12KOMMUNINVEST I SVERIGE: 2805, SE0015660139, 2028-05-12 BidsBids on interest and volume are entered via Bloomberg Bond Auction SystemBid date2021-07-06Bid times10.00-11.00 (CET/CEST) on the Bid dateRequested volume (corresponding nominal amount)2505: 500 mln SEK +/-250 mln SEK2611: 750 mln SEK +/-400 mln SEK2805: 750 mln SEK +/-400 mln SEK Highest permitted bid
A szérumok, kezelések és a boosterek igazi turbóerőt jelentenek a bőrápolásban, olyan pluszt adnak a bőrápolásodhoz, amivel elképesztő látványos változásokat érhetsz el. Legyen szó ráncokról, pigmentfoltokról vagy vízhiányról, itt a megoldás! A delux és mini kiszerelések ideálisak utazáshoz, vagy akár egy tartósabb teszthez is, a termékek ugyanis cirka 3-4 hétig elegendőek ...
A január 1-jétől alkalmazandó új vagy módosítandó vámfelfüggesztések és vámkontingensek, illetve vámfelfüggesztések meghosszabbítása iránti kérelmek 1. Új kérelmek KN kód TAXUD hivatkozási /Q
MAPK8 [ENSP00000378974]. Stress-activated protein kinase JNK1; Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including ...
MK08_HUMAN] Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In ...
Cerebral ischemia is associated with the activation of glial cells, infiltration of leukocytes and an increase in inflammatory mediators in the ischemic brain and systemic circulation. How this inflammatory response influences lesion size and neurological outcome remains unclear. D-JNKI1, an inhibitor of the c-Jun N-terminal kinase pathway, is strongly neuroprotective in animal models of stroke. Intriguingly, the protection mediated by D-JNKI1 is high even with intravenous administration at very low doses with undetectable drug levels in the brain, pointing to a systemic mode of action, perhaps on inflammation. We evaluated whether D-JNKI1, administered intravenously 3 h after the onset of middle cerebral artery occlusion (MCAO), modulates secretion of the inflammatory mediators interleukin-6 and keratinocyte-derived chemokine in the plasma and from the spleen and brain at several time points after MCAO. We found an early release of both mediators in the systemic circulation followed by an increase in
The c-Jun NH2-terminal kinases (JNK) are evolutionarily conserved serine/threonine protein kinases that are activated by proinflammatory cytokines, environmental stress, and genotoxic agents. These kinases play key regulatory roles within a cell by coordinating signals from the cell surface to nuclear transcription factors. JNK phosphorylates the amino terminal domain of all three Jun transcription factors (JunB, c-Jun and JunD) all members of the AP-1 family. The activated transcription factors modulate gene expression to generate appropriate biological responses, including cell migration, proliferation, differentiation and cell death. The role of the JNK signaling pathway in cell death/apoptosis is controversial, both pro-apoptotic and pro-survival roles have been attributed to JNK. The mechanism that enables the JNK signaling pathway to mediate both apoptosis and survival is unclear. The aim of this study is to examine the role of TNF-stimulated JNK activation on cell survival. The proinflammatory
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Tampereen teknillinen yliopisto on teknologisen kehityksen tiennäyttäjä sekä tutkimusmaailman ja elinkeinoelämän yhteistyökumppani. Yliopistosta valmistuu haluttuja osaajia yhteiskunnan eri aloille.. ...
Fingerprint Dive into the research topics of Saw palmetto extract suppresses insulin-like growth factor-I signaling and induces stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation in human prostate epithelial cells. Together they form a unique fingerprint. ...
Ursolic acid (UA), a pentacyclic triterpenoid, is known to have anti-tumor activity in various cancers including human non small cell lung cancer (NSCLC). However, the molecular mechanisms underlying the action of UA remain largely unknown. Cell viability was measured by MTT assays. Apoptosis was analyzed with Annexin V-FITC/PI Apoptosis Detection Kit by Flow cytometry. Western blot analysis was performed to measure the phosphorylation and protein expression of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), DNMT1 [DNA (cytosine-5)-methyltransferase 1], enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and SP1. Exogenous expression of SP1 and DNMT1 was carried out by transient transfection assays. We showed that UA inhibited the growth and induced apoptosis of NSCLC cells in the dose- and time-dependent fashion. Furthermore, we found that UA induced phosphorylation of SAPK/JNK and suppressed the protein expression of DNMT1 and EZH2. The inhibitor of SAPK/JNK (SP600125)
3VUM: Seven cysteine-deficient mutants depict the interplay between thermal and chemical stabilities of individual cysteine residues in mitogen-activated protein kinase c-Jun N-terminal kinase 1
3VUM: Seven cysteine-deficient mutants depict the interplay between thermal and chemical stabilities of individual cysteine residues in mitogen-activated protein kinase c-Jun N-terminal kinase 1
Cytokines and stress-inducing stimuli signal through c-Jun N-terminal kinase (JNK) using a diverse and only partially defined set of downstream effectors. In ...
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Objective: To explore the effect of minimally invasive hematoma aspiration (MIHA) on the c-Jun NH2-terminal kinase (JNK) signal transduction pathway after intracerebral hemorrhage (ICH). Methods: In this experiment, 300 adult male Wistar rats were randomly and averagely divided into sham-operated group, ICH group and MIHA group. In each group, 60 rats were used in the detection of indexes in this experiment, while the other 40 rats were used to replace rats which reached the exclusion criteria (accidental death or operation failure). In ICH group and MIHA group, ICH was induced by injection of 70 µL of autologous arterial blood into rat brain, while only the rats in MIHA group were treated by MIHA 6 h after ICH. Rats in sham-operated group were injected nothing into brains, and they were not treated either, like rats in ICH group. In each group, six rats were randomly selected to observe their Bedersons scales persistently (6, 24, 48, 72, 96, 120 h after ICH). According to the time they were
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Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK
As well as providing a structural framework, the actin cytoskeleton plays integral roles in cell death, survival, and proliferation. The disruption of the actin cytoskeleton results in the activation of the c-Jun N-terminal kinase (JNK) stress-activated protein kinase (SAPK) pathway; however, the
Background/Aims: aberrant c-Jun N-terminal kinase (JNK) activation has been linked to hepatocellular carcinoma (HCC) in mouse models. It remains unclear whether JNK activation plays an important role in human HCC and, if so, how JNK signaling contributes to the initiation or progression of HCC. Methods: the JNK activation, global gene expression, and the status of histone H3 methylations were mea
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The JNK signaling pathway is activated when cells such as neurons are exposed to environmental stress. The JIP proteins are likely to act in this pathway because they bind to JNK, as well as to upstream activators of JNK. A report from Whitmarsh et al. now strengthens the argument that JIPs are scaffolding proteins that coordinate the formation of a JNK-activating module. JIP1 localized to the cell body and to the growth-cone tips of extended neurites in unstimulated murine hippocampal neurons, but upon exposure to various stress stimuli, JIP1 relocalized to the perinuclear region where activated JNK was also found. Neurons from a JIP1-null mouse did not demonstrate stress-induced JNK activation or apoptosis, demonstrating that JIP is required for JNK activation in vivo. Because JIP1 was isolated in a complex with kinesin from mouse brain tissue, the authors speculate that JIP translocation may involve cellular motor proteins. Such a transport mechanism may facilitate signal transduction from ...
In the present study, we examined the role of Parathyroid hormone (PTH) on the c-Jun N-terminal kinase (JNK) 1/2 and p38 mitogen- activated protein kinase (MAPK) members of the MAPK family as it relates to ageing by measuring ...
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Background: Alzheimers Disease (AD) is a neuron related brain disorder leading to reasoning and memory loss. There is no specific cure identified for AD. JNK3 (c-Jun N-terminal kinase /stress-activated protein kinase) are highly revealed within the central nervous system, particularly neurons, playing vital role in functioning of brain. JNK3 hyper phosphorylation is a very common conclusion in neurodegenerative diseases. JNK3 in turn hyper phosphorylates Amyloid Precursor Protein (APP) which leads to the formation of Amyloid β peptides (an inductive agent of Alzheimers disease). Methods: Protein JNK-3 (PDB ID: 3KVX) was retrieved from protein data bank and later we docked a library of compounds against it. These were further validated by ADMET studies. Results: Thus, docking inhibitors of JNK3 may provide a promising sanitive approach. Based on best docking score and glide score a potential lead is identified against JNK3. Conclusion: Inhibiting JNK-3 may lead to less production of amyloidβ ...
Several studies have described abnormalities in the expression, distribution, and regulation of ventricular connexins in CHF. Absolute Cx43 expression is generally reduced in CHF ventricles,9,20,23-25 likely related to the activation of the mitogen-activated protein kinase c-Jun N-terminal kinase.26 Recent work suggests an important role for defects in Cx43 phosphorylation in CHF-induced ventricular cardiomyocyte uncoupling,9,10,20 thought to be attributable to increased dephosphorylating activity of protein phosphatase-2A colocalized with Cx43.20 Connexin dephosphorylation plays significant roles in targeting connexins to intercalated disks and in regulating connexin conductance.8,10 One study showed ventricular Cx40 upregulation in CHF,23 possibly as a compensation for Cx43 downregulation; however, the functional importance of this alteration is uncertain in view of low level ventricular Cx40 expression.. Clinical and experimental studies of gap junctional remodeling in the atria have produced ...
We have identified a novel serine/threonine kinase, NIK, that interacts with the SH3 domains of Nck. Overexpression of NIK constitutively activated the JNK/SAPK pathway. NIK interacts with MEKK1 in cells and likely signals through MEKK1 to activate JNK, suggesting that NIK directly regulates MEKK1 activity. We found that NIK contains a regulatory domain in its C‐terminus that is conserved in two other members of this kinase family. This domain mediates the association of NIK with MEKK1 and is critical for NIK activation of the SAPK pathway, suggesting that the C‐terminal domain of these proteins encodes a new protein domain family that couples these kinases to the SAPK pathway, possibly by interacting with MEKK1. Our finding that NIK also interacts with Nck suggests that SH2/SH3 adaptor proteins couple NIK and related kinases to activation of the SAPK/JNK pathway by different receptors.. Studies in Saccharomyces cerevisiae have shown that a serine/threonine kinase, Ste20, acts upstream of ...
TY - JOUR. T1 - Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-kB activation through TBK1. AU - Abe, Takayuki. AU - Barber, Glen N.. PY - 2014. Y1 - 2014. N2 - STING (stimulator of interferon genes) is known to control the induction of innate immune genes in response to the recognition of cytosolic DNA species, including the genomes of viruses such as herpes simplex virus 1 (HSV-1). However, while STING is essential for protection of the host against numerous DNA pathogens, sustained STING activity can lead to lethal inflammatory disease. It is known that STING utilizes interferon regulatory factor 3 (IRF3) and nuclear factor kB (NF-kB) pathways to exert its effects, although the signal transduction mechanisms remain to be clarified fully. Here we demonstrate that in addition to the activation of these pathways, potent induction of the Jun N-terminal protein kinase/stress-activated protein kinase (JNK/SAPK) pathway was similarly observed in ...
The structure-based design and synthesis of a novel series of c-Jun N-terminal kinase (JNK) inhibitors with selectivity against p38 is reported. The unique structure of 3,5-disubstituted quinolines (2) was developed from the previously reported 4-(2,7-phenanthrolin-9-yl)phenol (1). The X-ray crystal structure of 16a in JNK3 reveals an unexpected binding mode for this new scaffold with protein ...
387518839 - EP 1027429 A4 2002-11-20 - JNK3 MODULATORS AND METHODS OF USE - [origin: WO9918193A1] The c-Jun NH2-terminal kinase (JNK) group of MAP kinases are activated by exposure of cells to environmental stress. The role of JNK in the brain was examined by targeted disruption of the gene that encodes the neuronal isoform JNK3. It was found that JNK3 is required for the normal response to seizure activity. Methods of screening for molecules and compounds that decrease JNK3 expression or activity are described. Such molecules or compounds are useful for treating disorders involving excitotoxicity such as seizure disorders, Alzheimer s disease, Huntington disease, Parkinson s disease, and ischaemia.[origin: WO9918193A1] The c-Jun NH2-terminal kinase (JNK) group of MAP kinases are activated by exposure of cells to environmental stress. The role of JNK in the brain was examined by targeted disruption of the gene that encodes the neuronal isoform JNK3. It was found that JNK3 is required for the normal
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Venue: Edificio Povo 2, via Sommarive nr. 9, Povo (Tn) - Room B102 Time: 12.15 p.m. Speaker: Serras Rigalt Florencio - University of Barcelona Oxidative stress initiated by dying or damaged cells propagates to neighboring undamaged cells, activating the MAP kinases JNK and p38 for cytokine-dependent regenerative growth. However, the stress sensing mechanism by which
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MAP kinase-activating death domain protein is an enzyme that in humans is encoded by the MADD gene. Tumor necrosis factor alpha ... "Entrez Gene: MADD MAP-kinase activating death domain". Chow VT, Lee SS (1997). "DENN, a novel human gene differentially ... variant of a death domain protein that is regulated by a mitogen-activated kinase is a substrate for c-Jun N-terminal kinase in ... 4 (2): 141-50. doi:10.1093/dnares/4.2.141. PMID 9205841. Zhang Y, Zhou L, Miller CA (1998). "A splicing ...
September 2003). "cAMP analog mapping of Epac1 and cAMP kinase. Discriminating analogs demonstrate that Epac and cAMP kinase ... While protein kinase A (PKA) or cAMP-dependent protein kinase and cyclic nucleotide regulated ion channel (CNG and HCN) were ... opposing effects of exchange protein directly activated by cyclic AMP and cAMP-dependent protein kinase on protein kinase B ... "The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways". Nature. 437 (7058): 574-8. doi ...
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal- ... binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase ... The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 ( ...
December 2000). "Arabidopsis map kinase 4 negatively regulates systemic acquired resistance". Cell. 103 (7): 1111-20. doi: ... Gonzalez FA, Raden DL, Rigby MR, Davis RJ (June 1992). "Heterogeneous expression of four MAP kinase isoforms in human tissues ... Davis RJ (December 1995). "Transcriptional regulation by MAP kinases". Molecular Reproduction and Development. 42 (4): 459-67. ... MAP Kinase Resource Biology portal v t e. ... Mitogen-activated protein kinase 4 is an enzyme that in humans ...
MAP/microtubule affinity-regulating kinase 4 is an enzyme that in humans is encoded by the MARK4 gene. MARK4 belongs to the ... "Entrez Gene: MARK4 MAP/microtubule affinity-regulating kinase 4". Drewes G, Ebneth A, Preuss U, Mandelkow EM, Mandelkow E ( ... MARK4 kinase has been shown to be involved in microtubule organization in neuronal cells. Levels of MARK4 are elevated in ... Al-Hakim AK, Zagorska A, Chapman L, Deak M, Peggie M, Alessi DR (April 2008). "Control of AMPK-related kinases by USP9X and ...
Glantschnig H, Rodan GA, Reszka AA (2002). "Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylation ... kinase, which acts upstream of the stress-induced mitogen-activated protein kinase (MAPK) cascade. The encoded protein can ... Serine/threonine-protein kinase 4 is an enzyme that in humans is encoded by the STK4 gene. The protein encoded by this gene is ... Creasy CL, Chernoff J (1995). "Cloning and characterization of a human protein kinase with homology to Ste20". J. Biol. Chem. ...
"Chromosomal mapping of three human LAMMER protein-kinase-encoding genes". Hum Genet. 103 (4): 523-4. doi:10.1007/s004390050861 ... Dual specificity protein kinase CLK3 is an enzyme that in humans is encoded by the CLK3 gene. The CLK3 gene encodes a serine/ ... Clk dual-specificity kinases at the US National Library of Medicine Medical Subject Headings (MeSH) Human CLK3 genome location ... "Entrez Gene: CLK3 CDC-like kinase 3". Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure ...
... and decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. This protein also functions ... 1999). "Genomic organization, fine-mapping, and expression of the human islet-brain 1 (IB1)/c-Jun -amino-terminal kinase ... 1998). "A mammalian scaffold complex that selectively mediates MAP kinase activation". Science. 281 (5383): 1671-4. doi:10.1126 ... "A mammalian scaffold complex that selectively mediates MAP kinase activation". Science. 281 (5383): 1671-4. doi:10.1126/science ...
"Chromosomal mapping of three human LAMMER protein-kinase-encoding genes". Hum Genet. 103 (4): 523-4. doi:10.1007/s004390050861 ... Dual specificity protein kinase CLK1 is an enzyme that in humans is encoded by the CLK1 gene. This gene encodes a member of the ... "Entrez Gene: CLK1 CDC-like kinase 1". Colwill K, Feng LL, Yeakley JM, Gish GD, Cáceres JF, Pawson T, Fu XD (Oct 1996). "SRPK1 ... Colwill K, Feng LL, Yeakley JM, Gish GD, Cáceres JF, Pawson T, Fu XD (1996). "SRPK1 and Clk/Sty protein kinases show distinct ...
YopJ acetylates MAPK kinases at serines and threonines that are normally phosphorylated during activation of the MAP kinase ... YopO is a protein kinase also known as Yersinia protein kinase A (YpkA). YopO is a potent inducer of human macrophage apoptosis ... "Structural Requirements for Yersinia YopJ Inhibition of MAP Kinase Pathways". PLOS ONE. 3 (#1): e1375. Bibcode:2008PLoSO... ... Mittal, R.; Peak-Chew, S.-Y.; McMahon, H. T. (2006). "Acetylation of MEK2 and I B kinase (IKK) activation loop residues by YopJ ...
"Chromosomal mapping of three human LAMMER protein-kinase-encoding genes". Human Genetics. 103 (4): 523-4. doi:10.1007/ ... Dual specificity protein kinase CLK2 is an enzyme that in humans is encoded by the CLK2 gene. This gene encodes a member of the ... This protein kinase is involved in the regulation of several cellular processes and may serve as a link between cell cycle ... "Entrez Gene: CLK2 CDC-like kinase 2". Human CLK2 genome location and CLK2 gene details page in the UCSC Genome Browser. ...
Slattery ML, Lundgreen A, Wolff RK (2012). "MAP kinase genes and colon and rectal cancer". Carcinogenesis. 33 (12): 2398-408. ... Mitogen-activated protein kinase kinase kinase 3 is an enzyme that in humans is encoded by the MAP3K3 gene, which is located on ... "Entrez Gene: MAP3K3 mitogen-activated protein kinase kinase kinase 3". Gilmore PM, McCabe N, Quinn JE, Kennedy RD, Gorski JJ, ... pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative". The Journal of Biological ...
... "cAMP analog mapping of Epac1 and cAMP kinase. Discriminating analogs demonstrate that Epac and cAMP kinase act synergistically ... 38 (4): 578-88. doi:10.1016/j.mcn.2008.05.006. PMID 18583150. S2CID 871060. Gelinas JN, Banko JL, Peters MM, Klann E, Weeber EJ ... 64 (4): 1262-72. doi:10.2337/db14-0576. PMID 25315008. McPhee I, Gibson LC, Kewney J, Darroch C, Stevens PA, Spinks D, Cooreman ... 85 (4): 1303-42. doi:10.1152/physrev.00001.2005. PMID 16183914. S2CID 14539206. Schmidt M, Dekker FJ, Maarsingh H (Apr 2013). " ...
1990). "The human tyrosine kinase gene (FER) maps to chromosome 5 and is deleted in myeloid leukemias with a del(5q)". ... 1990). "Identification and chromosomal mapping of new human tyrosine kinase genes". Oncogene. 5 (3): 277-82. PMID 2156206. ... Ca2+-antagonized phosphorylation of calmodulin by casein kinase-2 and a spleen tyrosine protein kinase". FEBS Lett. 215 (2): ... Proto-oncogene tyrosine-protein kinase FER is an enzyme that in humans is encoded by the FER gene. Fer protein is a member of ...
"The mammalian formin FHOD1 interacts with the ERK MAP kinase pathway". Biochemical and Biophysical Research Communications. 335 ... is a cyclic GMP-dependent protein kinase I-binding protein and substrate in vascular smooth muscle cells". The Journal of ... 13 (4): 615-20. doi:10.3892/ijmm.13.4.615. PMID 15010865. Wang Y, El-Zaru MR, Surks HK, Mendelsohn ME (June 2004). "Formin ... doi:10.1016/S0378-1119(99)00127-4. PMID 10352228. Boehm MB, Milius TJ, Zhou Y, Westendorf JJ, Koka S (October 2005). " ...
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple ... and stimulate the phosphorylation of this kinase by MAP kinase kinase 4 (MKK4). Cyclin-dependent kinase 5 can phosphorylate, ... Mohit AA, Martin JH, Miller CA (1995). "p493F12 kinase: a novel MAP kinase expressed in a subset of neurons in the human ... MAP Kinase Resource . Overview of all the structural information available in the PDB for UniProt: P53779 (Mitogen-activated ...
Demetrick DJ, Zhang H, Beach DH (1994). "Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes". Cytogenet ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ...
The Arc transcript is dependent upon activation of the mitogen-activated protein kinase or MAP kinase (MAPK) cascade, a pathway ... Impey S, Obrietan K, Storm DR (1999). "Making new connections: role of ERK/MAP kinase signaling in neuronal plasticity". Neuron ... Treisman R (1996). "Regulation of transcription by MAP kinase cascades". Current Opinion in Cell Biology. 8 (2): 205-15. doi: ... mRNA induction by Ca2+ and cAMP requires protein kinase A and mitogen-activated protein kinase/extracellular regulated kinase ...
Camps M, Nichols A, Arkinstall S (January 2000). "Dual specificity phosphatases: a gene family for control of MAP kinase ... Protein kinases (PKs) are the effectors of phosphorylation and catalyse the transfer of a γ-phosphate from ATP to specific ... The addition of a phosphate group may activate or de-activate an enzyme (e.g., kinase signalling pathways) or enable a protein- ... Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (December 2002). "The protein kinase complement of the human genome". ...
Gell D, Jackson SP (September 1999). "Mapping of protein-protein interactions within the DNA-dependent protein kinase complex ... "Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit". J. Biol. Chem. 272 ( ... "Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit". J. Biol. Chem. 272 ( ... Tyrosine kinase 2, and Werner syndrome ATP-dependent helicase. GRCh38: Ensembl release 89: ENSG00000079246 - Ensembl, May 2017 ...
"Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation". Cell. 93 (4): 605-615. doi: ... leading to the activation of protein kinase C (PKC). PKC phosphorylates the mitogen-activated protein kinase (MAPK) ERK which ... The tyrosine kinase activity of VEGFR1 is less efficient than that of VEGFR2 and its activation alone is insufficient to bring ... Kobayashi M, Nishita M, Mishima T, Ohashi K, Mizuno K (February 2006). "MAPKAPK-2-mediated LIM-kinase activation is critical ...
The protein encoded by this gene is a member of the MAP kinase and JNK family. MAP kinases act as an integration point for ... binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 ( ... MAP Kinase Resource . This article incorporates text from the United States National Library of Medicine, which is in the ...
2008) Arabidopsis MAP kinase 4 regulates gene expression through transcription factor release in the nucleus. EMBO J. 27(16). ... 2002) MAP kinase signalling cascade in Arabidopsis innate immunity. Nature. 415(6875). 977-983 Deslandes, Olivier, Peeters, ... 2005) Tobacco Transcription Factor WRKY1 Is Phosphorylated by the MAP Kinase SIPK and Mediates HR-Like Cell Death in Tobacco. ... While kinases phosphorylating WRKY transcription factors are known, phosphatases removing phosphate groups have yet to be ...
December 2008). "MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts". Nature. ... 179 (4): EJE-18-0305. doi:10.1530/EJE-18-0305. PMID 30006373. Roy S, Khanna S, Hussain SR, Biswas S, Azad A, Rink C, et al. ( ... 456 (7224): 980-4. doi:10.1038/nature07511. PMID 19043405. S2CID 4333547. Sayed D, Rane S, Lypowy J, He M, Chen IY, Vashistha H ...
Miyata Y, Akashi M, Nishida E (May 1999). "Molecular cloning and characterization of a novel member of the MAP kinase ... MAPK/MAK/MRK overlapping kinase is an enzyme that in humans is encoded by the RAGE gene. GRCh38: Ensembl release 89: ... a member of the mitogen-activated protein kinase superfamily, in the intestinal epithelial cells". FEBS Letters. 573 (1-3): 147 ... 11 (4): 292-301. doi:10.1034/j.1600-0625.2002.110402.x. PMID 12190937. Götte K, Usener D, Riedel F, Hörmann K, Schadendorf D, ...
Pratt RL, Kinch MS (October 2002). "Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade". ... Liang Q, Mohan RR, Chen L, Wilson SE (July 1998). "Signaling by HGF and KGF in corneal epithelial cells: Ras/MAP kinase and Jak ... "The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of ... Janus kinase 1, Janus kinase 2, KHDRBS1, Linker of activated T cells, Lymphocyte cytosolic protein 2, MAP2, MAP3K1 MAP4K1, ...
Groom LA, Sneddon AA, Alessi DR, Dowd S, Keyse SM (July 1996). "Differential regulation of the MAP, SAP and RK/p38 kinases by ... They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are ... Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases ... a dual specificity MAP kinase phosphatase, in pancreatic cancer". Cytogenetics and Cell Genetics. 82 (3-4): 156-9. doi:10.1159/ ...
Schoeberl, B; Eichler-Jonsson, C; Gilles, ED; Müller, G (Apr 2002). "Computational modeling of the dynamics of the MAP kinase ... Phosphorylation of src tyrosine kinase (pronounced "sarc") by C-terminal Src kinase (Csk) induces a conformational change in ... Cole PA, Shen K, Qiao Y, Wang D (October 2003). "Protein tyrosine kinases Src and Csk: a tail's tale". Curr Opin Chem Biol. 7 ( ... Further information: Kinase. Within a protein, phosphorylation can occur on several amino acids. Phosphorylation on serine is ...
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple ... MAP kinase kinases 3, and 6 can phosphorylate and activate this kinase. Transcription factor ATF2, and microtubule dynamics ... This kinase is closely related to p38 MAP kinase, both of which can be activated by proinflammatory cytokines and cellular ... 2010). "Human p38 delta MAP kinase mediates UV irradiation induced up-regulation of the gene expression of chemokine BRAK/ ...
"Activation of RAW 264.7 cells by Astraeus hygrometricus-derived heteroglucan through MAP kinase pathway". Cell Biology ... The activation of macrophages by AE2 might be mediated by a mitogen-activated protein kinase pathway of signal transduction. ... 343 (4): 817-24. doi:10.1016/j.carres.2007.12.003. PMID 18206864. Maiti S, Bhutia SK, Mallick SK, Kumar A, Khadgi N, Maiti TK ( ... 23 (4): 499-503. doi:10.1111/j.1756-1051.2003.tb00423.x. Phosri C, Martín MP, Sihanonth P, Whalley AJ, Watling R (2007). " ...
Serine/threonine-protein kinase (By similarity). Phosphorylates the microtubule-associated protein MAPT/TAU (By similarity). ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR008271, Ser/Thr_kinase_AS. ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR008271, Ser/Thr_kinase_AS. ... PS00107, PROTEIN_KINASE_ATP, 1 hit. PS50011, PROTEIN_KINASE_DOM, 1 hit. PS00108, PROTEIN_KINASE_ST, 1 hit. PS50030, UBA ...
Furthermore, genes that encode two novel Drosophila MAP kinase kinases, D-MKK3 and D-MKK4, were identified [1]. ... A conserved p38 mitogen-activated protein kinase pathway regulates Drosophila immunity gene expression. Han, Z.S., Enslen, H., ...
MAP Kinase Kinase Kinases [D08.811.913.696.620.682.700.559]. *MAP Kinase Kinase Kinase 4 [D08.811.913.696.620.682.700.559.400] ... A 180-kDa MAP kinase kinase kinase with specificity for MAP KINASE KINASE 4 and MAP KINASE KINASE 6. ... "MAP Kinase Kinase Kinase 4" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... This graph shows the total number of publications written about "MAP Kinase Kinase Kinase 4" by people in this website by year ...
Keywords: p38α MAP kinase inhibitors, 1, 2, 4, 5-tetrasubstituted imidazoles, 1, 2, 4, 5-tetrasubstituted pyrimidines, 2, 4, 5- ... Keywords:p38α MAP kinase inhibitors, 1, 2, 4, 5-tetrasubstituted imidazoles, 1, 2, 4, 5-tetrasubstituted pyrimidines, 2, 4, 5- ... T. Scior, D. M. Domeyer, K. Cuanalo-Contreras and S. A. Laufer, " Pharmacophore Design of p38α MAP Kinase Inhibitors with ... Title: Pharmacophore Design of p38α MAP Kinase Inhibitors with Either 2,4,5-Trisubstituted or 1,2,4,5-Tetrasubstituted ...
... jnk activating kinase 1 jnkk jnkk1 map kinase kinase 4 map2k4 mapk erk kinase 4 mapkk 4 m ... c jun n terminal kinase kinase 1 mitogen activated protein kinase kinase 4 ... Dual specificity mitogen-activated protein kinase kinase 1,ERK activator kinase 1,MAP kinase kinase 1,MAP2K1,MAPK_ERK kinase 1, ... Dual specificity mitogen-activated protein kinase kinase 1,ERK activator kinase 1,MAP kinase kinase 1,Map2k1,MAPK_ERK kinase 1, ...
Effect of CSE Targeting siRNA on the Phosphorylation of MAP Kinase. Activated macrophages are induced by three families of MAP ... M. H. Cobb, "MAP kinase pathways," Progress in Biophysics and Molecular Biology, vol. 71, no. 3-4, pp. 479-500, 1999. View at ... Using this time point (30 min), we examined the effect of CSE targeting siRNA on the phosphorylation of ERK MAP kinase. Our ... P. P. Roux and J. Blenis, "ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological ...
A Golgi-associated bi-lobed framework was previously found to be essential for Golgi replication and cell department in is a parasitic virus leading to sleeping sickness Read More. ...
... phosphorylation-dependent MAP kinases, MAPK/ERK, SAPK/JNK and p38, and specific transcription factor substrates are ... Expression of stress-activated kinases c-Jun N-terminal kinase (SAPK/JNK-P) and p38 kinase (p38-P), and tau ... Active, phosphorylation-dependent MAP kinases, MAPK/ERK, SAPK/JNK and p38, and specific transcription factor substrates are ... "Active, Phosphorylation-dependent MAP Kinases, MAPK/ERK, SAPK/JNK and P38, and Specific Transcription Factor Substrates Are ...
MAP kinase MAP kinase kinase MAP kinase kinase kinase kinase List of unusual biological names Morrison, Deborah K. (2012-11-01 ... is a serine/threonine-specific protein kinase which acts upon MAP kinase kinase. Subsequently, MAP kinase kinase activates MAP ... These MAP kinases include the extracellular regulated kinases (ERKs), the c-Jun N-terminal Kinases (JNKs), and the p38 MAP ... MAP+Kinase+Kinase+Kinases at the US National Library of Medicine Medical Subject Headings (MeSH) EC 2.7.11.25 Biology portal. ...
Buxade, M; Parra-Palau, JL; Proud, CG The Mnks: MAPK kinase-interacting kinases (MAP kinase signal-integrating kinases). Front ... Schematic presentation of the different mammalian MAP kinase pathways. The conventional MAP kinase pathways, represented by the ... Luig, C; Köther, K; Eva Dudek, S; Gaestel, M; Hiscott, J; Wixler, V; Ludwig, S MAP kinase-activated protein kinases 2 and 3 are ... Mitogen-activated protein kinase-activated protein kinase-5 (MK5). MK5 is a 54 kD ser/thr kinase that can be activated in vitro ...
Kinase classification and number of kinases per classification are noted.A375 expressing the CCSB/Broad Institute Kinase ORF ... 600 kinase and kinase-related open reading frames (ORFs) in parallel to interrogate resistance to a selective RAF kinase ... COT drives resistance to RAF inhibition through MAP kinase pathway reactivation.. Johannessen CM1, Boehm JS, Kim SY, Thomas SR ... COT/MAP3K8 drives resistance to RAF inhibition through MAP kinase pathway reactivation ...
Here, the in vivo enzyme-substrate interaction of the Arabidopsis thaliana MAP kinase, MPK6, with an ethylene response factor ( ... Flg22 regulates the release of an ethylene response factor substrate from MAP kinase 6 in Arabidopsis thaliana via ethylene ... Flg22 regulates the release of an ethylene response factor substrate from MAP kinase 6 in Arabidopsis thaliana via ethylene ... Flg22 regulates the release of an ethylene response factor substrate from MAP kinase 6 in Arabidopsis thaliana via ethylene ...
1994 MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. Curr. Opin. Genet. Dev. 4: 82-89. ... 1992 Activation of mitogen-activated protein (MAP) kinase by a MAP kinase-kinase. J. Biol. Chem. 267: 13135-13137. ... 1993 A protein kinase similar to MAP kinase activator acts downstream of Raf kinase in Drosophila eye development. Cell 72: 407 ... Activation of the vulval pathway with MEK and MAP kinase is sufficient to cause vulval differentiation: Because MAP kinase is ...
Human P38 MAP kinase in complex with RL45. *DOI: 10.2210/pdb3GCQ/pdb ... Development of a fluorescent-tagged kinase assay system for the detection and characterization of allosteric kinase inhibitors. ... Mitogen-activated protein kinase 14. A. 360. Homo sapiens. Mutation(s): 4 Gene Names: MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2, ... Kinase disregulation disrupts the intricate network of intracellular signaling pathways and contributes to the onset of ...
Human p38 MAP Kinase in Complex with RL99. *DOI: 10.2210/pdb3LFC/pdb ... Mitogen-activated protein kinase 14. A. 360. Homo sapiens. Mutation(s): 4 Gene Names: MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2, ... 4-{5-[({4-[2-(benzyloxy)ethyl]-1,3-thiazol-2-yl}carbamoyl)amino]-3-tert-butyl-1H-pyrazol-1-yl}phenyl)acetic acid. C28 H31 N5 O4 ...
MAP kinase signaling specificity". Science. 296 (5577): 2345-7. doi:10.1126/science.1073344. PMID 12089430. Roskoski R (August ... Chadee DN, Yuasa T, Kyriakis JM (2002). "Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the ... Activation of RAF kinases requires interaction with RAS-GTPases. The three RAF kinase family members are: A-RAF B-RAF c-Raf ... RAF kinases are a family of three serine/threonine-specific protein kinases that are related to retroviral oncogenes. The mouse ...
Morrison, D. K. MAP kinase pathways. Cold Spring Harb. Perspect. Biol. 4, 4:a011254 (2012). ... Complexes of Ras.GTP with Raf-1 and mitogen-activated protein kinase kinase. Science 5, 1658-1661 (1993). ... SIN3A and KDM1A were found in proximity to an RRE in the FGFR4, HRAS and MAP2K2 promoters mapped in MCF-7 cells (SIN3A) or K562 ... In murine erythroleukemia cells, Sin3a binding has been mapped to the Fgfr4, Hras and Map2k2 promoters (Fig. 6f). We performed ...
MAP kinase and Elk-1 reporter assays. PC12 cells infected with retroviruses were serum-starved overnight and then treated with ... Recruitment of Dok-R to the EGF receptor through its PTB domain is required for attenuation of Erk MAP kinase activation. Curr ... Previous investigations have shown that p62dok and dok-2 associate with rasGAP, and inhibit the MAP kinase pathway (Jones and ... Dok-2 can also attenuate EGF receptor (EGFR)-induced MAP kinase activation, independent of its association with rasGAP (Jones ...
Koga, M., Zwaal, R., Guan, K.L., Avery, L., and Ohshima, Y. (2000). A Caenorhabditis elegans MAP kinase kinase, MEK-1, is ... Resistance to P. aeruginosa has been shown to involve a third pathway, a MAP kinase pathway, involving the MAP3K NSY-1 and the ... Nicholas, H.R., and Hodgkin, J. (2004). The ERK MAP kinase cascade mediates tail swelling and a protective response to rectal ... RNAi against this gene, which encodes one of the worms three p38-family MAP kinases, also results in an increased ...
Activates the PBS2 MAP kinase kinase by phosphorylation. ... Kinase involved in a signal transduction pathway that is ... MAP kinase kinase kinase activity Source: SGDInferred from direct assayi*. "Activation of the yeast SSK2 MAP kinase kinase ... Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.Curated ... MAP kinase kinase kinase SSK2Add BLAST. 1579. Amino acid modifications. Feature key. Position(s). DescriptionActions. Graphical ...
Phosphatases which activate map kinase pathways. US6943238. Oct 4, 2002. Sep 13, 2005. Amgen, Inc.. Antibodies to cyclin E2 ... Phosphatases which activate map kinase pathways. US20050153330 *. Nov 24, 2004. Jul 14, 2005. Amgen Inc.. Novel DKR ... Phosphatases which activate map kinase pathways. US7320796. Jul 17, 2003. Jan 22, 2008. Amgen Inc.. Isolation, identification ... A. Platelet Factor 4 (PF4) Promoter Cloning. An ˜1.1 kb fragment of the 5 region of the platelet factor 4 ("PF4") gene from a ...
We tested the ability of MAP kinase or PI 3-kinase inhibitors to block the effect of NT. Unfortunately, both inhibitors were ... Because NT stimulated both ERK1/2 and PI 3-kinase pathways, we tested the effect of the specific MAP kinase inhibitor PD98059 ... 1999) Phosphatidylinositol 3-kinase contributes to Erk1/Erk2 MAP kinase activation associated with hepatocyte growth factor- ... PI 3-kinase) and mitogen-activated protein (MAP) kinase pathways. The effect of neurotensin on cell migration was blocked by ...
Receptor Tyrosine Kinase-like Orphan Receptors * Ror2 protein, mouse * MAP Kinase Kinase 4 ... Wnt5a activates noncanonical Wnt signaling through receptor tyrosine kinase-like orphan receptor (Ror) proteins. We showed that ...
MAP Kinase Kinase 4 * Mitogen-Activated Protein Kinase Kinases / genetics * Mitogen-Activated Protein Kinase Kinases / ... 4) JNK1 wild-type expression vector increased HIF-1alpha protein expression probably in a phosphorylated state and, thus, ...
BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.
We examined the role of MKP-2 in the regulation of MAP kinase phosphorylation, cell proliferation, and survival responses in ... We examined the role of MKP-2 in the regulation of MAP kinase phosphorylation, cell proliferation, and survival responses in ... We examined the role of MKP-2 in the regulation of MAP kinase phosphorylation, cell proliferation, and survival responses in ... We examined the role of MKP-2 in the regulation of MAP kinase phosphorylation, cell proliferation, and survival responses in ...
Associated with p38 inhibition, Dex induced MAP kinase phosphatase-1 (MKP-1) in control, but not MGRKO, macrophages. Consistent ... To explore the role of glucocorticoids in regulation of kinase pathways during innate immune responses, we generated mice with ... conditional deletion of glucocorticoid receptor (GR) in macrophages (MGRKO). Activation of toll-like receptor 4 (TLR4) by ... MAP kinase phosphatase 1 controls innate immune responses and suppresses endotoxic shock. Qun Li Zhao, Xianxi Wang, +9 authors ...
keywords = "adenovirus, 2-furoyl(2f)-LIGKV-OH, human umbilical vein, endothelial cells, inhibitory kappa, B kinase, nuclear ... Cytokine upregulation of proteinase-activated-receptors 2 and 4 expression mediated by p38 MAP kinase and inhibitory kappa B ... kinase ß in human endothelial cells. E. Ritchie, M. Saka, C. MacKenzie, R.M. Drummond, C. Wheeler-Jones, T. Kanke, R.J. Plevin ... Cytokine upregulation of proteinase-activated-receptors 2 and 4 expression mediated by p38 MAP kinase and inhibitory kappa B ...
In this review we devoted our attention to ERK1 and ERK2, which are the effector kinases of the pathway. Whether ERK1 and ERK2 ... In this review we devoted our attention to ERK1 and ERK2, which are the effector kinases of the pathway. Whether ERK1 and ERK2 ... The MAP kinase signalling cascade Ras/Raf/MEK/ERK has been involved in a large variety of cellular and physiological processes ... The MAP kinase signalling cascade Ras/Raf/MEK/ERK has been involved in a large variety of cellular and physiological processes ...
Among these is activation of the MAP kinase pathway (21, 36). Indeed, treatment of ASCs with SDF1 at day 7 of culture led to ... In general, the importance of MAP kinase signaling in PC biology is suggested by the recurrent mutations of NRAS, KRAS, and ... TGF-β modulates SDF1 signaling to the ERK MAP kinase pathway. Among the genes differentially expressed in response to TGF-β3 at ... 5C). Receptor density has been identified as a means by which the MAP kinase pathway output from growth factor receptors can be ...
  • Phosphorylation and activation of extra cellular signal-regulated kinase 1/2 (ERK1/2) increased in LPS-induced macrophages. (hindawi.com)
  • Expression of active, phosphorylation-dependent mitogen-activated extracellular signal-regulated kinases (MAPK/ERKs), stress-activated c-Jun N-terminal kinases (SAPK/JNKs) and p38 kinases, as well as their putative active, phosphorylation-dependent specific transcriptional factor substrates CREB, Elk-1, ATF-2, c-Myc and c-Jun, has been examined following systemic administration of kainic acid (KA) at convulsant doses to rats. (unboundmedicine.com)
  • Activates the PBS2 MAP kinase kinase by phosphorylation. (uniprot.org)
  • We demonstrate, by using RT-PCR, photoaffinity labeling, and Western blot analysis, that the type I neurotensin receptor-3 was the only known neurotensin receptor expressed in these microglial cells and that its activation led to the phosphorylation of both extracellular signal-regulating kinases 1/2 and Akt. (jneurosci.org)
  • We examined the role of MKP-2 in the regulation of MAP kinase phosphorylation, cell proliferation, and survival responses in mouse embryonic fibroblasts (MEFs) derived from a novel MKP-2 (DUSP-4) deletion mouse. (strath.ac.uk)
  • Protein kinases are a large family of enzymes catalyzing protein phosphorylation. (mdpi.com)
  • There are several ways for kinases to become involved in cancers: mis-regulated expression and/or amplification, aberrant phosphorylation, mutation, chromosomal translocation, and epigenetic regulation. (mdpi.com)
  • Mitogen-activated protein kinases (MAP kinases) are Serine/Threonine phosphorylating enzymes which function in a cascade typically involving at least 3 enzymes which get activated in a series by sequential phosphorylation events. (biovision.com)
  • We demonstrate that in ex vivo murine peritoneal macrophages that are deficient in PTEN expression, FcγR-induced Akt and extracellular signal-regulated kinase phosphorylation are enhanced. (jimmunol.org)
  • Onset of apoptosis was preceded by an intense phosphorylation of the MAPKs, including extracellular signal-regulated kinase 1/2, c-Jun NH 2 -terminal kinase, and p38 in both SK-MEL-28 and MALME-3M cells. (aacrjournals.org)
  • Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4 (PubMed:9808624). (genecards.org)
  • Signal transduction is based on protein phosphorylation that is employed in mitogen-activated protein kinase (MAPK) cascades to integrate signals from receptors to cellular responses. (springer.com)
  • MAPK activity is determined by phosphorylation of amino acid residues within the kinase activation loop and their dephosphorylation by phosphatases is essential to control signal duration and intensity. (springer.com)
  • Constitutive receptor tyrosine kinase phosphorylation requires regulation of kinase and phosphatase activity to prevent aberrant signal transduction. (rupress.org)
  • Phosphorylation of Grb2 by FGFR2 abrogated its binding to the receptor, resulting in up-regulation of both FGFR2's kinase and Shp2's phosphatase activity. (rupress.org)
  • Growth factor binding perturbs this background cycling, promoting increased FGFR2 phosphorylation and kinase activity, Grb2 dissociation, and downstream signaling. (rupress.org)
  • This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product ( Rb ). (wikipedia.org)
  • Once thought of as global attenuators of phosphorylation ( 2 ), PPases are now known to recognize specific subsets of phosphoprotein targets ( 4 ⇓ ⇓ - 7 ). (mcponline.org)
  • hence, phosphorylation dynamics of kinases hold a wealth of information about phosphorylation networks. (mcponline.org)
  • Here, we investigated the site-specific phosphorylation dynamics of human kinases during mitosis using synchronization of HeLa suspension cells, kinase enrichment, and high resolution mass spectrometry. (mcponline.org)
  • In biological triplicate analyses, we identified 206 protein kinases and more than 900 protein kinase phosphorylation sites, including 61 phosphorylation sites on activation segments, and quantified their relative abundances across three specific mitotic stages. (mcponline.org)
  • Around 25% of the kinase phosphorylation site ratios were found to be changed by at least 50% during mitotic progression. (mcponline.org)
  • Importantly, our data cover most of the already known mitotic kinases and, moreover, identify attractive candidates for future studies of phosphorylation-based mitotic signaling. (mcponline.org)
  • hence, kinases require tight regulation to avoid unspecific phosphorylation, which can be deleterious to cells ( 5 ⇓ - 7 ). (mcponline.org)
  • Importantly, most kinases are also in turn regulated through autophosphorylation and phosphorylation by other kinases, thus generating complex phosphorylation networks. (mcponline.org)
  • In particular, phosphorylation on activation segments is a common mechanism to modulate kinase activities ( 9 ⇓ - 11 ), but additional phosphorylation sites are also frequently required for fine tuning of kinase localizations and functions ( 12 ). (mcponline.org)
  • Some kinases contain phosphopeptide binding domains that recognize prephosphorylated sites on other kinases, resulting in processive phosphorylation and/or targeting of kinases to distinct cellular locations ( 13 ⇓ ⇓ - 16 ). (mcponline.org)
  • Because such priming phosphorylation events depend on the activities of the priming kinases, these motifs act as conditional docking sites and restrict the interaction with docking kinases to a particular point in time and physiological state. (mcponline.org)
  • In addition, phosphorylation sites may act through combinatorial mechanisms or through cross-talk with other posttranslational modifications (PTMs) 1 ( 17 , 18 ), thus further increasing the complexity of kinase regulatory networks. (mcponline.org)
  • Regulation of kinases is of particular interest in mitosis as most of the mitotic events are regulated by reversible protein phosphorylation ( 19 ). (mcponline.org)
  • This kinase is regulated through direct phosphorylation by p38 MAP kinase. (genecards.org)
  • Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. (genecards.org)
  • Synthetic non-phosphopeptide derived from human MARK1/2/3/4 around the phosphorylation site of threonine 215 (L-D-T P -F-C). (abcam.com)
  • Western blot analysis was used to assess the phosphorylation of MAP kinases. (pubmedcentralcanada.ca)
  • Activation loop phosphorylation of the atypical MAP kinases ERK3 and ERK4 is required for binding, activation and cytoplasmic relocalization of MK5. (nih.gov)
  • In general, MAP kinases are activated by phosphorylation on tyrosine and threonine residues and inactivated by dephosphorylation. (ahajournals.org)
  • A common feature for activation of all MAP kinase isoforms is the requirement for phosphorylation of both a threonine and a neighboring tyrosine regulatory site by a specific upstream protein kinase for activation. (ahajournals.org)
  • 1 2 Binding of extracellular stimuli to their cell membrane receptors induces a sequence of protein kinase reaction, leading to phosphorylation and activation of MEK (MAP kinase/ERK kinase). (ahajournals.org)
  • Thus, highly specific protein kinase cascades lead to dual phosphorylation of tyrosine and threonine residues on these MAP kinases, inducing their full activation. (ahajournals.org)
  • In general, the extent of protein phosphorylation is balanced by an antagonism of kinases and phosphatases. (ahajournals.org)
  • A profile of phosphorylation of selected tyrosine kinases and MAP kinases from progressing hemangioma was performed and with consideration of the result, it led to change of treatment strategy with encouraging clinical response lasting for six months. (prolekare.cz)
  • Serine/threonine-protein kinase (By similarity). (uniprot.org)
  • Mitogen Activated Protein (MAP) kinase kinase kinase, MAPKKK (or MAP3K) is a serine/threonine-specific protein kinase which acts upon MAP kinase kinase. (wikipedia.org)
  • Oncogenic mutations in the serine/threonine kinase B-RAF (also known as BRAF) are found in 50-70% of malignant melanomas. (nih.gov)
  • Here, we present a description of the development and validation of this assay using the serine/threonine kinase p38alpha. (rcsb.org)
  • RAF kinases are a family of three serine/threonine-specific protein kinases that are related to retroviral oncogenes. (wikipedia.org)
  • RAF protein-serine/threonine kinases: structure and regulation" (PDF). (wikipedia.org)
  • PtdIn3,4,5P 3 , the lipid product of PtdIns3-kinase, is an important second messenger that is necessary for the activation of pleckstrin homology domain-containing enzymes such as the serine/threonine kinase Akt, the guanine nucleotide exchange factor Vav, and the Tec family tyrosine kinase Btk, involved in intracellular calcium mobilization ( 12 ). (jimmunol.org)
  • The deduced CTR1 protein sequence is most similar to the Raf family of serine/threonine protein kinases (41% amino acid identity in the kinase domain), suggesting that CTR1 may act in a mitogen-activated protein (MAP) kinase cascade ( 4 ). (pnas.org)
  • The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. (genecards.org)
  • The only known substrates of Mek1/2 are the serine-threonine kinases Erk1 and Erk2, also known as p44 MAPK and p42 MAPK, respectively ( Kohno and Pouysségur, 2006 ). (pubmedcentralcanada.ca)
  • Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. (genecards.org)
  • Perturbed action of signal transduction pathways, including the mitogen-activated protein (MAP) kinase pathways, is one of the hallmarks of many cancers. (jmolecularsignaling.com)
  • While the implication of the typical MAP kinase pathways ERK1/2-MEK1/2, p38 MAPK and JNK is well established, recent findings illustrate that the atypical MAP kinase ERK3/4-MK5 may also be involved in tumorigenic processes. (jmolecularsignaling.com)
  • Schematic presentation of the different mammalian MAP kinase pathways. (jmolecularsignaling.com)
  • The conventional MAP kinase pathways, represented by the MEK/ERK, JNK, p38 MAPK , and MEK5/ERK5 pathways, consist of a module of three kinases that subsequently phosphorylate and active each other. (jmolecularsignaling.com)
  • MAP kinases are key mediators of cellular differentiation and proliferation in all animals, and they function in receptor tyrosine kinase/Ras signaling pathways (reviewed in M arshall 1994 ). (genetics.org)
  • Kinase disregulation disrupts the intricate network of intracellular signaling pathways and contributes to the onset of diseases such as cancer. (rcsb.org)
  • At least 4 pathways have been shown to be involved in innate immunity in C. elegans and an overlap has been found between the genes involved in pathogen defense and longevity. (wormbook.org)
  • We used two in vitro assays, a wound-healing model and a chemotaxis assay, to show that the neuropeptide neurotensin elicited the migration of the human microglial cell line C13NJ by a mechanism dependent on both phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein (MAP) kinase pathways. (jneurosci.org)
  • Both the motility and the filopodia appearance induced by neurotensin were totally blocked by selective inhibitors of MAP kinases or PI 3-kinase pathways. (jneurosci.org)
  • To explore the role of glucocorticoids in regulation of kinase pathways during innate immune responses, we generated mice with conditional deletion of glucocorticoid receptor (GR) in macrophages (MGRKO). (semanticscholar.org)
  • In PC neoplasia, abnormalities in the niche play a key role in sustaining the neoplastic clone ( 4 ), whereas targets of recurrent mutation in PC neoplasia identify pathways of potential functional importance to the biology of ASCs. (jimmunol.org)
  • One of the most frequently deregulated pathways is that of RAS/RAF/MAP kinase signaling ( 5 ). (jimmunol.org)
  • As of February 2018, neXtProt has integrated the GO biological processes annotations captured in the framework of this project, representing both the signaling pathways in which each kinase is implicated, as well as the role of those pathways in higher level processes, such as apoptosis, cellular proliferation, and development. (mdpi.com)
  • Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. (genome.jp)
  • ESTs analysis has been proven to be an efficient and valuable tool in obtaining coding gene information, understanding the pathways involved in a given physiological or environmental stimulus [ 3 , 4 ]. (hindawi.com)
  • This study reveals that DENSPM potently activates the mitogen-activated protein kinase (MAPK) pathways in melanoma cells and investigates the role of this response in determining cellular outcomes. (aacrjournals.org)
  • Expression of activated MAP kinase in Xenopus laevis embryos: evaluating the roles of FGF and other signaling pathways in early induction and patterning. (xenbase.org)
  • These results point toward the involvement of other receptor tyrosine kinase signaling pathways in posterior neural patterning. (xenbase.org)
  • Overall, the findings of the present study indicated that apigenin attenuated the growth of A375SM melanoma cells by inducing apoptosis via regulating the Akt and mitogen‑activated protein kinase signaling pathways. (spandidos-publications.com)
  • Therefore, recently cloned dual-specificity protein tyrosine phosphatases (PTPases), which exhibit dual-catalytic activity toward phosphotyrosine and phosphothreonine in substrate proteins, may play a pivotal role in the regulation of MAP kinase-signaling pathways. (ahajournals.org)
  • 15 16 Furthermore, the kinetics of gene expression and the cellular localization are consistent with a role for MKP-1 in the compensatory inactivation of stimulated MAP kinase-signaling pathways. (ahajournals.org)
  • 9. Dorion S, Landry J. Activation of the mitogen‑activated protein kinase pathways by heat shock. (prolekare.cz)
  • Synthetic compounds with a tri- and tetra-substituted imidazole scaffold are known as selective inhibitors of the p38 mitogenactivated protein (MAP) kinase responsible for proinflammatory cytokine release. (eurekaselect.com)
  • Pre-clinical studies have demonstrated that the B-RAF(V600E) mutation predicts a dependency on the mitogen-activated protein kinase (MAPK) signalling cascade in melanoma-an observation that has been validated by the success of RAF and MEK inhibitors in clinical trials. (nih.gov)
  • Although several kinase inhibitors are on the market, inhibitor selectivity and drug resistance mutations persist as fundamental challenges in the development of effective long-term treatments. (rcsb.org)
  • Combined kinase inhibitors of MEK1/2 and either PI3K or PDGFR are efficacious in intracranial triple-negative breast cancer. (harvard.edu)
  • Remarkably, the chemical chaperone 4-phenylbutyric acid and small-molecule inhibitors of MAPK and 2-oxoglutarate-dependent collagen IV-modifying enzymes rescued ER retention of collagen IV and EC apoptosis and resulted in normal developmental angiogenesis. (jci.org)
  • CCNL2 increased the transactivation ability of p53, which was attenuated by protein kinase C (PKC) inhibitors or a dominant negative PKCa. (omicsonline.org)
  • We focus on a set of binding data obtained from 113 different protein kinases and 20 inhibitors. (altmetric.com)
  • To investigate the molecular mechanism underlying IL-1β-induced miR-146a expression, the effects of inhibitors of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase/extracellular signal-regulated kinases (MEK)-1/2, c-Jun N-terminal kinases (JNK)-1/2, p38 MAP kinase, and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) were analyzed. (arvojournals.org)
  • ERK1 and ERK2 Map Kinases: Specific Roles or Functional Redundancy? (frontiersin.org)
  • In this review we devoted our attention to ERK1 and ERK2, which are the effector kinases of the pathway. (frontiersin.org)
  • Accordingly, recent advances in this area demonstrated that phagocytosis is a highly regulated process involving negative regulation by protein tyrosine phosphatases as well as inositol phosphatases ( 2 , 3 , 4 , 5 , 6 ). (jimmunol.org)
  • the negative regulatory phosphatases that control MAP kinase signaling in neurons remain relatively poorly understood. (genetics.org)
  • The developmental outcome of ERK signalling relies, at least in part, on the competing actions of upstream activators and inhibitory MAP kinase phosphatases (MKPs). (biologists.org)
  • Protein phosphatases undo the post-translational modifications of kinase-signaling networks, but phosphatase activation in cells is difficult to measure and interpret. (mcponline.org)
  • Phosphatases (PPases) 1 reset post-translational modifications by kinases and thus help to sculpt the phosphoproteome ( 1 ⇓ - 3 ). (mcponline.org)
  • RAF kinases participate in the RAS-RAF-MEK-ERK signal transduction cascade, also referred to as the mitogen-activated protein kinase (MAPK) cascade. (wikipedia.org)
  • Docking proteins are substrates of tyrosine kinases and function in the recruitment and assembly of specific signal transduction molecules. (rupress.org)
  • Kinase involved in a signal transduction pathway that is activated by changes in the osmolarity of the extracellular environment. (uniprot.org)
  • In Arabidopsis thaliana , signal transduction of the hormone ethylene involves at least two receptors, ETR1 and ERS, both of which are members of the two-component histidine protein kinase family that is prevalent in prokaryotes. (pnas.org)
  • Thus, in the emerging view of ethylene signal transduction in Arabidopsis , ETR1 and ERS are predicted to be histidine autokinases whereas CTR1 is thought to function as a MAP kinase (MAPK) kinase kinase. (pnas.org)
  • Component of a protein kinase signal transduction cascade (PubMed:9808624). (genecards.org)
  • Uncontrolled kinase and/or phosphatase activity leads to aberrant signal transduction, thus regulation of the opposing catalytic functions is required to ensure that downstream response only occurs when an appropriate extracellular-stimulating ligand binds. (rupress.org)
  • Release of the interaction with Grb2 permits the FGFR2 kinase domain to access additional tyrosine residues on the receptor, and to recruit downstream effector proteins required for signal transduction. (rupress.org)
  • Specifically, we determined the effect of HNE on the activities of mitogen-activated protein (MAP) kinases involved in early signal transduction. (aspetjournals.org)
  • Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway. (nih.gov)
  • This depends on inducible gene expression mediated by the activation of mitogen-activated protein kinase (MAPK) and the transcription factor nuclear factor- κ B (NF- κ B) [ 16 - 18 ]. (hindawi.com)
  • The Caenorhabditis elegans mpk-1 gene encodes a MAP kinase protein that plays an important role in Ras-mediated induction of vulval cell fates. (genetics.org)
  • DBL-1 binds the heterodimeric DAF-4 / SMA-6 receptor and acts via the SMA-2 / SMA-3 / SMA-4 SMAD complex to control gene expression ( Figure 1 ). (wormbook.org)
  • Applying time course expression data and parsimonious gene correlation network analysis (PGCNA), a new approach established by our group, we map expression changes that occur during the maturation of proliferating plasmablast to quiescent plasma cell under survival conditions including the potential niche signal TGF-β3. (jimmunol.org)
  • The ETR1 and ERS gene products are predicted to function as histidine protein kinases based on their sequence similarities with the two-component regulator family. (pnas.org)
  • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) is a Protein Coding gene. (genecards.org)
  • Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity . (genecards.org)
  • Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene . (wikipedia.org)
  • The protein encoded by this gene is a member of the Ser/Thr protein kinase family . (wikipedia.org)
  • This gene encodes a member of the Ser/Thr protein kinase family. (genecards.org)
  • In conjunction with p38 MAP kinase, this kinase is known to be involved in many cellular processes including stress and inflammatory responses, nuclear export, gene expression regulation and cell proliferation. (genecards.org)
  • Deletions of exons 2-3 should result in loss of function of the Mark4 gene by deleting the catalytic domain and generating a frameshift (premature stop codon in exon 4). (taconic.com)
  • One of these, claudin-4, is a member of the claudin gene family that has been identified in several independent gene expression profiles to be up-regulated in a variety of tumors ( 8 - 13 ) and, importantly, in premalignant lesions of the pancreas ( 14 ) and esophagus ( 15 ). (aacrjournals.org)
  • PBS 2 , a yeast gene encoding a putative protein kinase, interacts with the RAS2 pathway and affects osmotic sensitivity of Saccharomyces cerevisiae . (springer.com)
  • Subsequently, MAP kinase kinase activates MAP kinase. (wikipedia.org)
  • Genetic studies have shown that the anchor cell signal activates a receptor tyrosine kinase/Ras pathway (reviewed in K ornfeld 1997 ). (genetics.org)
  • Wnt5a activates noncanonical Wnt signaling through receptor tyrosine kinase-like orphan receptor (Ror) proteins. (nih.gov)
  • Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway (PubMed:9808624). (genecards.org)
  • This led us to examine whether MAPK4 activates the key metabolic, prosurvival, and proliferative kinase AKT and mTORC1 signaling, independent of the canonical PI3K pathway. (jci.org)
  • 1 - 4 Binding of autoantibodies to TSH receptors, expressed on orbital fibroblasts, activates the T cell-dependent inflammatory process. (arvojournals.org)
  • Thus, HIPK2 phosphorylates the antiapoptotic transcriptional corepressor, CtBP, targeting it for proteasomal degradation ( 8 , 9 ), activates the c- Jun NH 2 -terminal kinase signaling pathway participating in transforming growth factor-β-induced c- Jun NH 2 -terminal kinase activation and apoptosis ( 10 ), and induces caspase-dependent apoptosis in sympathetic neurons ( 11 ). (aacrjournals.org)
  • Here we expressed ∼600 kinase and kinase-related open reading frames (ORFs) in parallel to interrogate resistance to a selective RAF kinase inhibitor. (nih.gov)
  • Last, we identified the b-Raf inhibitor sorafenib as a potent low nanomolar inhibitor of p38alpha and used protein X-ray crystallography to confirm a unique binding mode to the inactive kinase conformation. (rcsb.org)
  • The p38 MAP Kinase Inhibitor X, BIRB 796, also referenced under CAS 285983-48-4, controls the biological activity of p38 MAP Kinase. (fishersci.com)
  • The MAP/extracellular signal-regulated kinase-1 inhibitor PD 98059 reduced activation of all three kinases but failed to alter apoptosis in DENSPM-treated SK-MEL-28 cells. (aacrjournals.org)
  • The addition of nerve growth factor stimulated both outgrowth and kinase activity, whereas treating the cultures with the kinase inhibitor PD98059 had an opposite effect. (lu.se)
  • The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16 INK4a . (wikipedia.org)
  • Pretreatment of PC12 cells with SB203580, a specific inhibitor of p38 MAP kinase, had no effect on HNE-induced apoptosis. (aspetjournals.org)
  • 15 Ipilimumab , a cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor inhibitor that enhances T-cell activity, 16 was the first immunotherapy to be approved by the US Food and Drug Administration for metastatic melanoma. (gponline.com)
  • The MAP kinase signaling cascade Ras/Raf/MEK/ERK has been involved in a large variety of cellular and physiological processes that are crucial for life. (frontiersin.org)
  • The core of this pathway consists in activation of the cascade of three kinases Raf, MEK, and ERK. (frontiersin.org)
  • RT "MAP kinase signalling cascade in Arabidopsis innate immunity. (univ-lyon1.fr)
  • In addition, PD 098059, an antagonist of MEK (MAP kinase/ERK kinase), the upstream kinase of ERK, significantly reduced the PDGF-induced activation of ERK and potently inhibited the expression of MKP-1 after stimulation with PDGF, thereby demonstrating the induction of MKP-1 in response to activation of the ERK signaling cascade. (ahajournals.org)
  • Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors. (ebi.ac.uk)
  • A 180-kDa MAP kinase kinase kinase with specificity for MAP KINASE KINASE 4 and MAP KINASE KINASE 6. (umassmed.edu)
  • The specificity of receptor tyrosine kinase signaling has been investigated in great detail. (rupress.org)
  • MKP3 is a dual specificity phosphatase and a specific antagonist of ERK MAP kinases and we demonstrate that in somites Mkp3 transcription depends on the presence of active ERK. (biologists.org)
  • Therefore, MAP kinase phosphatase-1 (MKP-1), a dual-specificity protein tyrosine phosphatase that exhibits catalytic activity toward both regulatory sites on MAP kinases, is suggested to be responsible for the downregulation of extracellular signal-regulated kinase (ERK), stress-activated protein kinase (SAPK), and p38 MAP kinase. (ahajournals.org)
  • 3 MEK, the specific activator of ERK, is a dual-specificity protein kinase that phosphorylates both threonine and tyrosine regulatory sites in ERK. (ahajournals.org)
  • 10 Recently, MAP kinase phosphatase-1 (MKP-1), a mammalian VH-1-like dual-specificity PTPase, has been isolated. (ahajournals.org)
  • The human genome contains 518 protein kinase genes, 478 of which belong to the classical protein kinase family and 40 are atypical protein kinases. (mdpi.com)
  • In this review, we focus on the major advances that have been made in identifying both the virulence/avirulence factors of SMV and mapping of SMV resistant genes in soybean. (frontiersin.org)
  • RT "Mitogen-activated protein kinase cascades in plants: a new nomenclature. (univ-lyon1.fr)
  • Mitogen-activated protein kinase (MAP kinase) cascades are effectors for many growth factor signals implicated in developmental processes, including appendage outgrowth and organogenesis. (biologists.org)
  • Abstract -Mitogen-activated protein (MAP) kinase cascades are major signaling systems by which cells transduce extracellular cues into intracellular responses. (ahajournals.org)
  • These data suggest the induction of MKP-1, not only after stimulation of the cell growth-promoting ERK pathway but also in response to activation of stress-responsive MAP kinase signaling cascades. (ahajournals.org)
  • As a result, cells use a variety of mechanisms to ensure proper regulation of kinase activities ( 8 ). (mcponline.org)
  • For instance, the MAPKKK ASK-1 is activated by a receptor-tyrosine kinase specific for a tumor necrosis factor. (wikipedia.org)
  • Here we found that p62dok family members act as substrates for the c-Ret receptor tyrosine kinase. (rupress.org)
  • The phosphorylated ITAMs serve as docking sites for Src homology 2 domain-containing cytosolic proteins, including the tyrosine kinase Syk, the Ras adapter Shc, and the p85 subunit of phosphatidylinositol (PtdIns) 3-kinase. (jimmunol.org)
  • SPPs inhibit the NF-κB pathway without altering MAP kinase activation. (chemweb.com)
  • Protein substrates of interest are purified recombinantly, phosphorylated in vitro using the upstream kinase, and adsorbed to 96-well plates. (mcponline.org)
  • Stress-activated protein kinase kinase (SEK1), an upstream kinase of JNK, was also activated within 5 min after HNE treatment and remained activated for up to 60 min. (aspetjournals.org)
  • Marked activation of the JNK pathway through SEK1 and apoptosis signal-regulating kinase 1 (ASK1), an upstream kinase of SEK1, was demonstrated by the transient transfection of cDNA for wild-type SEK1 or ASK1 together with JNK into COS-7 cells. (aspetjournals.org)
  • Frye CA, Tang D and Innes RW (2001) Negative regulation of defense responses in plants by a conserved MAPKK kinase. (els.net)
  • 82 MAP/microtubule Affinity-Regulating Kinase 2 (MARK2) Antikörper von 14 Herstellern verfügbar auf www.antikoerper-online.de. (antikoerper-online.de)
  • Downstream of MAPK are substrates including other protein kinases referred to as MAPK-activated protein kinases (MAPKAPK). (jmolecularsignaling.com)
  • Substrates of MAPKs include protein kinases designated as MAPK-activated protein kinases (MAPKAPK). (jmolecularsignaling.com)
  • Mitogen-activated protein kinase (MAPK)-mediated responses are in part regulated by the repertoire of MAPK substrates, which is still poorly elucidated in plants. (nih.gov)
  • 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)
  • Once activated, a significant fraction of MAP kinase molecules translocate to the nucleus, and many important MAP kinase substrates are localized in the nucleus ( e.g. , the mammalian transcription factors Elk-1 and Ets-1 (reviewed in T reisman 1996 ). (genetics.org)
  • In addition to nuclear targets, some MAP kinase substrates are located in the cytoplasm, e.g. , the guanine nucleotide exchange factor SOS and the protein kinase pp90Rsk (reviewed in F errell 1996 ). (genetics.org)
  • Improved selectivity can be achieved with fluorescently labeled peptide substrates ( 32 , 33 ), but these peptides still lack the structural requirements important for specific recognition by PPases ( 4 ⇓ ⇓ - 7 ). (mcponline.org)
  • Heat shock protein HSP27 was shown to be one of the substrates of this kinase in vivo. (genecards.org)
  • The human ERK3 (~100 kD) and ERK4 (~70 kD) proteins have a similar structural organization and are 73% identical in their kinase domain. (jmolecularsignaling.com)
  • c-Ret/dok fusion proteins, in which Y1062 of c-Ret is deleted and replaced by the sequences of dok-4 or dok-5, induce ligand-dependent axonal outgrowth of PC12 cells, whereas a c-Ret fusion containing dok-2 sequences does not elicit this response. (rupress.org)
  • In addition, specific docking proteins of receptor tyrosine kinases have been discovered which mediate particular biological responses. (rupress.org)
  • The exotoxins comprise 3 proteins, pro- of anthrax [3, 4]. (cdc.gov)
  • In human, 518 protein kinases have been identified in the genome that phosphorylate the majority of cellular proteins and increase the diversity of the proteome by severalfold ( 4 ). (mcponline.org)
  • In recent years, human and animal studies have elucidated that many effects of hyperglycemia are mediated by glycated proteins ( 4 ). (diabetesjournals.org)
  • Mitogen-activated protein (MAP) kinases are important mediators involved in the intracellular network of interacting proteins that transduce extracellular cues to intracellular responses. (ahajournals.org)
  • The p38 MAPK is regulated by MEKK 1-4 and TAO 1/2 families of MAPKKKs and is responsible for inflammation, apoptosis, cell differentiation, and cell cycle regulation. (wikipedia.org)
  • The by-product of lipid peroxidation, 4-hydroxynonenal (HNE), was shown to cause apoptosis in PC12 cells. (aspetjournals.org)
  • Pretreatment of PC12 cells with a survival-promoting agent, 8-(4-chlorophenylthio)-cAMP, prevented both the HNE-induced JNK activation and apoptosis. (aspetjournals.org)
  • All these data suggest that the selective JNK activation by HNE is critical for the apoptosis of PC12 cells and that the HNE-mediated apoptosis is likely to be mediated through the activation of the ASK1-SEK1-JNK pathway without activation of extracellular signal-regulated kinase or p38 MAP kinase. (aspetjournals.org)
  • Mutations in BRAF lead to activation of the mitogen-activated protein kinase (MAPK) signalling pathway ( figure 1 ), which promotes cell growth, proliferation, differentiation and migration, and regulates apoptosis. (gponline.com)
  • In contrast to ERK, more recently described MAP kinases such as stress-activated protein kinase (SAPK), also referred to as c-Jun N-terminal kinase (JNK), and p38 MAP kinase are suggested to inhibit cellular proliferation and to induce apoptosis. (ahajournals.org)
  • PDF] Macrophage glucocorticoid receptors regulate Toll-like receptor 4-mediated inflammatory responses by selective inhibition of p38 MAP kinase. (semanticscholar.org)
  • β 1 integrin was required for FAK independent activation of all three MAP kinases, whereas cross-talk between β 1 integrin and Ang II receptors mediated FAK dependent regulation of ERK1/2. (pubmedcentralcanada.ca)
  • RT "Comprehensive analysis of protein-protein interactions between Arabidopsis RT MAPKs and MAPK kinases helps define potential MAPK signalling modules. (univ-lyon1.fr)
  • Erk1/2 mitogen-activated protein kinases (MAPKs) are often hyperactivated in human cancers, where they affect multiple processes, including proliferation. (pubmedcentralcanada.ca)
  • Map kinase kinase 4 (MKK4) suppresses metastasis in a preclinical prostate cancer model. (wiley.com)
  • In primary cancers, 123 of 125 (98.4%) were positive for claudin-4, 116 of 126 (94%) for MKK4, and 111 of 120 (92%) for stratifin. (aacrjournals.org)
  • In conclusion, claudin-4, MKK4, and stratifin immunolabeling detects precursor lesions of gastric adenocarcinoma that are otherwise clinically, radiographically, and endoscopically inapparent. (aacrjournals.org)
  • We identified three targets, claudin-4, mitogen-activated protein kinase kinase 4 (MKK4), and 14-3-3σ (stratifin), that were selectively expressed in intestinal metaplasia and gastric epithelial dysplasia but not in normal stomach. (aacrjournals.org)
  • Kinase classification and number of kinases per classification are noted.A375 expressing the CCSB/Broad Institute Kinase ORF collection were assayed for relative viability in 1 µM PLX4720 and normalized to constitutively active MEK1 (MEK1 DD ). (nih.gov)
  • 8. Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. (prolekare.cz)
  • Previous reports indicated that LPS-induced mitogen-activated protein kinase activation is down-regulated by phosphatidylinositol 3-kinase through the activation of Akt. (jimmunol.org)
  • The MAPK kinase kinase (MAP3K) phosphorylates MAPK kinase (MAP2K), which in turn phosphorylates MAPK. (jmolecularsignaling.com)
  • 4 Phosphorylated and activated ERK migrates to the nucleus, where it phosphorylates several transcription factors. (ahajournals.org)
  • Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5. (nih.gov)
  • Regulation of MAPK-activated protein kinase 5 activity and subcellular localization by the atypical MAPK ERK4/MAPK4. (nih.gov)
  • Does MK5 reconcile classical and atypical MAP kinases? (nih.gov)
  • We show that increased or decreased levels of phosphorylated ERK result in the loss of scleraxis transcripts and the loss of distal rib development, highlighting the importance of the MKP3-ERK-MAP kinase mediated feedback loop for cell specification and differentiation. (biologists.org)
  • Collectively, these data demonstrate that ERRα is required for normal skeletal myocyte differentiation via modulation of MAP kinase signaling. (physiology.org)
  • These MAP kinases include the extracellular regulated kinases (ERKs), the c-Jun N-terminal Kinases (JNKs), and the p38 MAP kinase. (wikipedia.org)
  • This is why they are also called Extracellular signal-regulated kinases (ERKs). (biovision.com)
  • The transient induction of MAP kinase phosphatase-1 (MKP-1), which mediates ERK dephosphorylation at the onset of myogenesis, was lost in ERRα−/− myocytes and in XCT790-treated C2C12. (physiology.org)
  • In addition, in apigenin‑treated A375P cells, phosphorylated (p)‑p38 was upregulated and p‑extracellular signal‑regulated kinase (ERK), p‑c‑Jun N‑terminal kinase (JNK) and p‑protein kinase B (Akt) were downregulated. (spandidos-publications.com)
  • The results showed that formation of reactive oxygen species and subsequent activation of ERK and P38, but not Jun NH2-terminal kinase, are molecular events underpinning retinal microglial TNF-α release during AGA treatment. (diabetesjournals.org)
  • Flg22 regulates the release of an ethylene response factor substrate from MAP kinase 6 in Arabidopsis thaliana via ethylene signaling. (nih.gov)
  • Here, the in vivo enzyme-substrate interaction of the Arabidopsis thaliana MAP kinase, MPK6, with an ethylene response factor (ERF104) is shown by fluorescence resonance energy transfer. (nih.gov)
  • We previously demonstrated a role for the myristoylated alanine-rich C kinase substrate (MARCKS) to serve as an adaptor protein in the anionic phospholipid phosphate-dependent regulation of the epithelial sodium channel (ENaC). (bireme.br)
  • Inducible Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome. (harvard.edu)
  • Mitogen-activated protein kinase phosphatase-2 (MKP-2) is a type 1 nuclear dual specific phosphatase (DUSP) implicated in a number of cancers. (strath.ac.uk)
  • We show that ppm-1 functions through its phosphatase activity in a parallel genetic pathway with glo-4 and fsn-1 to regulate both synapse formation in the GABAergic motorneurons and axon termination in the mechanosensory neurons . (genetics.org)
  • A dynamic mechanism is described here in which the adaptor protein, growth factor receptor-bound protein 2 (Grb2), controls fibroblast growth factor receptor 2 (FGFR2) signaling by regulating receptor kinase and SH2 domain-containing protein tyrosine phosphatase 2 (Shp2) phosphatase activity in the absence of extracellular stimulation. (rupress.org)
  • We illustrate the generality of the method by developing specific phosphatase-activity assays for the three canonical mitogen-activated protein phospho-kinases: ERK, JNK, and p38. (mcponline.org)
  • Several types of MAPKKK can exist but are mainly characterized by the MAP kinases they activate. (wikipedia.org)
  • This enzyme is a dual-specific protein kinase and requires mitogen-activated protein kinase kinase kinase (MAPKKK) for activation. (genome.jp)
  • Extracellular stimuli such as platelet-derived growth factor (PDGF), 12-O-tetradecanoylphorbol 13-acetate (TPA), and angiotensin II, which activated ERK but not SAPK/p38 MAP kinase, induced a transient induction of MKP-1 mRNA and its intracellular protein. (ahajournals.org)
  • Furthermore, anisomycin, a potent stimulus of SAPK and p38 MAP kinase, also induced MKP-1 mRNA expression. (ahajournals.org)
  • 8 9 Interestingly, the mechanism involved in the activation of SAPK and p38 MAP kinase is similar to that involved in the activation of ERK. (ahajournals.org)
  • MKP-1 (the human homologue is called CL100 [97% identity]) was demonstrated to dephosphorylate and inactivate not only ERK 11 12 13 14 but also SAPK and p38 MAP kinase. (ahajournals.org)
  • Extracellular signal-regulated kinase (ERK) remains the best characterized mammalian MAP kinase. (ahajournals.org)
  • 4 Banting and Best Department of Medical Research, Department of Molecular Genetics, and the Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario, Canada M5S 3E1. (sciencemag.org)
  • COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. (nih.gov)
  • We further identify combinatorial MAPK pathway inhibition or targeting of COT kinase activity as possible therapeutic strategies for reducing MAPK pathway activation in this setting. (nih.gov)
  • The prototype approach of this therapeutic modality relies on the inhibition of negative signals delivered by CTLA-4 expressed on T lymphocytes. (clinicaltrials.gov)
  • Sometimes new results raise new questions: the question marks between mitogen-activated protein kinase and ethylene signaling. (nih.gov)
  • Moreover, dok-4 and dok-5 enhance c-Ret-dependent activation of mitogen-activated protein kinase. (rupress.org)
  • We show that the scaffold protein Ste5, which organizes the yeast mating mitogen-activated protein (MAP) kinase pathway, does not use sequestration to prevent misactivation of the mating response. (sciencemag.org)
  • Analyzing the molecular events leading to PTEN influence on LPS/Toll-like receptor 4 (TLR4) signaling, we found that LPS-induced activation of mitogen-activated protein kinases is suppressed in PTEN −/− cells. (jimmunol.org)
  • The pathogenicity of Bacillus anthracis is primarily due mitogen-activated protein kinase kinase family, to effect to the action of its 3 main virulence factors, the g- an imbalance in the production or release of a range linked poly-D-glutamic acid capsule and the 2 protein of cytokines that may contribute to the pathogenesis exotoxins [1]. (cdc.gov)
  • RT "Molecular cloning and characterization of three cDNAs encoding putative RT mitogen-activated protein kinase kinases (MAPKKs) in Arabidopsis RT thaliana. (univ-lyon1.fr)
  • RT "Stomatal development and patterning are regulated by environmentally RT responsive mitogen-activated protein kinases in Arabidopsis. (univ-lyon1.fr)
  • RT "Surviving the passage: Non-canonical stromal targeting of an Arabidopsis RT mitogen-activated protein kinase kinase. (univ-lyon1.fr)
  • RT "A Pseudomonas syringae ADP-ribosyltransferase inhibits Arabidopsis RT mitogen-activated protein kinase kinases. (univ-lyon1.fr)
  • It is required for activation of EC 2.7.11.24 , mitogen-activated protein kinase. (genome.jp)
  • Constitutive mitogen-activated protein kinase (MAPK) activation is frequent in human cancer and is often the result of activating mutations in RAS ( 1 , 2 ). (aacrjournals.org)
  • We have used adult mouse superior cervical ganglia (SCG) to study the role of mitogen activated protein (MAP) kinase activity during axonal outgrowth in vitro. (lu.se)
  • Further network analysis of jointly regulated kinase groups suggested that Cyclin-dependent kinase- and mitogen-activated kinase-centered interaction networks are coordinately down- and up-regulated in late mitosis, respectively. (mcponline.org)
  • Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2, or MK2) is a kinase belonging to the MAPKAPK family, a group of kinases activated by MAPK signaling. (genecards.org)
  • Molecular genetic analysis indicated that the bud1 phenotype is a result of increased expression of Arabidopsis MAP KINASE KINASE7 ( MKK7 ), a member of plant mitogen-activated protein kinase kinase group D. We showed that BUD1/MKK7 is a functional kinase and that the kinase activity is essential for its biological functions. (plantcell.org)
  • An antibody specific for the activated form of mitogen-activated protein kinase ( MAPK ) was used to monitor FGF signaling in vivo during early Xenopus development. (xenbase.org)
  • Mitogen-activated protein (MAP) kinases have been implicated in hemodynamic load induced heart failure. (pubmedcentralcanada.ca)
  • The extracellular signal-regulated kinase 3 (mitogen-activated protein kinase 6 [MAPK6])-MAPK-activated protein kinase 5 signaling complex regulates septin function and dendrite morphology. (nih.gov)
  • RESULTS In 8-week diabetic retina, phospho-extracellular signal-related kinase (ERK) and P38 mitogen-activated protein kinases were localized in microglia, but not in Mueller cells or astrocytes. (diabetesjournals.org)
  • Krementsov DN , Noubade R, Dragon JA, Otsu K, Rincon M, Teuscher C. Sex-specific control of central nervous system autoimmunity by p38 mitogen-activated protein kinase signaling in myeloid cells. (uvm.edu)
  • The Hog1 mitogen-activated protein kinase is essential in the oxidative stress response and chlamydospore formation in Candida albicans . (springer.com)
  • Experimental and computed work is reviewed which evidence that the 2 position of the pyrimidine ring is amenable to the introduction of a side chain and the replacement of pyridine in SB203580 by a pyrimidine ring improves both inhibitory activity and selectivity for p38 over other kinases. (eurekaselect.com)
  • Deregulation of kinase activity can result in dramatic changes in these processes. (mdpi.com)
  • The secretome of endothelial progenitor cells promotes brain endothelial cell activity through PI3-kinase and MAP-kinase. (sigmaaldrich.com)
  • Preclinical evidence generated with SGI-110 in vivo demonstrated that besides having a direct activity on tumor growth as a single agent, SGI-110 was able to 'sensitize' neoplastic cells to the anti-tumor activity of CTLA-4 blockade, providing a sound scientific rationale to develop new immunotherapeutic approaches combining SGI-110 with therapeutic mAb to immune check-points. (clinicaltrials.gov)
  • Along this line, based on the preclinical evidence the investigators gained on the broad immunomodulatory activity of SGI-110, the exploratory phase 1 combination study NIBIT-M4 has been designed to provide proof-of-concept evidence to the immunologic and clinical efficacy of CTLA-4 blockade combined with DNA-HypomethylatingAgent (DHA). (clinicaltrials.gov)
  • This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. (genecards.org)
  • These results suggest that calpain-2 proteolysis of MARCKS promotes its interaction with lipids and ENaC at the plasma membrane to allow for the phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent regulation of ENaC activity in the kidney. (bireme.br)
  • The researchers further report that NF-κB can be activated in neurons by Ca2+, and that this requires the activity of the calcium-dependent kinase CaMKII. (alzforum.org)
  • Elimination of protein kinase MK5/PRAK activity by targeted homologous recombination. (nih.gov)
  • We suggest that this pattern of MKP-1 induction may be a negative feedback mechanism in the control of MAP kinase activity in VSMCs. (ahajournals.org)
  • Homeodomain-interacting protein kinase-2 (HIPK2) belongs to a family of corepressors for homeodomain transcription factors but, unlike other transcriptional corepressors, it has protein kinase activity ( 1 ). (aacrjournals.org)
  • Recurrent mutational activation of the MAP kinase pathway in plasma cell myeloma implicates growth factor-like signaling responses in the biology of Ab-secreting cells (ASCs). (jimmunol.org)
  • The pathway also contains a negative regulator of ethylene responses, CTR1, which closely resembles members of the Raf protein kinase family. (pnas.org)
  • CTR1 is a negative regulator of the ethylene-response pathway because ctr1 null mutants exhibit constitutive ethylene responses even in the absence of ethylene ( 4 ). (pnas.org)
  • however, objective clinical responses are limited, and only a minority of patients achieves long-term disease control.1 Therefore, several combination approaches are being explored to improve the efficacy of CTLA-4 blockade. (clinicaltrials.gov)
  • This hypothesis is supported by in vitro studies, in which cardiac myocytes cultured on collagen or laminin-coated deformable membranes, display hypertrophic responses when exposed to mechanical stretch [ 4 ]. (pubmedcentralcanada.ca)
  • Activation of toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) caused greater mortality and cytokine production in MGRKO mice than in controls. (semanticscholar.org)