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 family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A 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 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 group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
Agents that inhibit PROTEIN KINASES.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
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 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 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.
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 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
A 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.
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.
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 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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A 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.
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.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Substances that stimulate mitosis and lymphocyte transformation. They include not only substances associated with LECTINS, but also substances from streptococci (associated with streptolysin S) and from strains of alpha-toxin-producing staphylococci. (Stedman, 25th ed)
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
Established cell cultures that have the potential to propagate indefinitely.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Mitogen-activated protein kinase 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).
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.
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.
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.
The rate dynamics in chemical or physical systems.
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 ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
A 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 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.
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 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.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A 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.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A 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.
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.
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.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A 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 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.
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 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.
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.
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.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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 sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Proteins prepared by recombinant DNA technology.
Proteins isolated from the roots of the pokeweed, Phytolacca americana, that agglutinate some erythrocytes, stimulate mitosis and antibody synthesis in lymphocytes, and induce activation of plasma cells.
A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
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)
A group of phenyl benzopyrans named for having structures like FLAVONES.
Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
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.
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.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
A cell line derived from cultured tumor cells.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
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.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.
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).
Elements of limited time intervals, contributing to particular results or situations.
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.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
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 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.
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.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
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)
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.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
A 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.
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.
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.
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.
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 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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
Transport proteins that carry specific substances in the blood or across cell membranes.
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 c-jun amino-terminal kinase that is found predominantly within NEURONS of the BRAIN, suggesting a role in stress-induced neuronal APOPTOSIS. Several isoforms of the protein with molecular sizes of 47 kDa and 52 kDa exist due to multiple ALTERNATIVE SPLICING.
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
The phosphoric acid ester of serine.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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 compounds with three aromatic rings joined in linear arrangement.
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 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.
Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
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 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.
Four carbon unsaturated hydrocarbons containing two double bonds.
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.
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.
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.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
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.
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.
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.
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.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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)
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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 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.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
A 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.
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.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
A family of calcium/calmodulin-dependent PROETIN-SERINE-THREONINE KINASES. They are ubiquitously expressed in adult and embryonic mammalian tissues, and their functions are tightly related to the early stages of eukaryotic programmed cell death.
Compounds of four rings containing a nitrogen. They are biosynthesized from reticuline via rearrangement of scoulerine. They are similar to BENZYLISOQUINOLINES. Members include chelerythrine and sanguinarine.
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.
A cyclic GMP-dependent protein kinase subtype that is expressed in SMOOTH MUSCLE tissues and plays a role in regulation of smooth muscle contraction. Two isoforms, PKGIalpha and PKGIbeta, of the type I protein kinase exist due to alternative splicing of its mRNA.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.
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.
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.
Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A structurally-diverse family of intracellular-signaling adaptor proteins that selectively tether specific protein kinase A subtypes to distinct subcellular sites. They play a role in focusing the PROTEIN KINASE A activity toward relevant substrates. Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA.
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.
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.
A MANNOSE/GLUCOSE binding lectin isolated from the jack bean (Canavalia ensiformis). It is a potent mitogen used to stimulate cell proliferation in lymphocytes, primarily T-lymphocyte, cultures.
The sum of the weight of all the atoms in a molecule.
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).
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 110-kDa extracellular signal-regulated MAP kinase that is activated in response to cellular stress and by GROWTH FACTOR RECEPTORS-mediated pathways.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
Cellular DNA-binding proteins encoded by the c-jun genes (GENES, JUN). They are involved in growth-related transcriptional control. There appear to be three distinct functions: dimerization (with c-fos), DNA-binding, and transcriptional activation. Oncogenic transformation can take place by constitutive expression of c-jun.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
Compounds or factors that act on a specific enzyme to increase its activity.
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 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.
Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.
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 long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
A monomeric calcium-calmodulin-dependent protein kinase subtype that is primarily expressed in neuronal tissues; T-LYMPHOCYTES and TESTIS. The activity of this enzyme is regulated by its phosphorylation by CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
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.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
A 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.
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.
The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.
A type I cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIBETA SUBUNIT.
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.
Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
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.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.

A Drosophila TNF-receptor-associated factor (TRAF) binds the ste20 kinase Misshapen and activates Jun kinase. (1/5224)

Two families of protein kinases that are closely related to Ste20 in their kinase domain have been identified - the p21-activated protein kinase (Pak) and SPS1 families [1-3]. In contrast to Pak family members, SPS1 family members do not bind and are not activated by GTP-bound p21Rac and Cdc42. We recently placed a member of the SPS1 family, called Misshapen (Msn), genetically upstream of the c-Jun amino-terminal (JNK) mitogen-activated protein (MAP) kinase module in Drosophila [4]. The failure to activate JNK in Drosophila leads to embryonic lethality due to the failure of these embryos to stimulate dorsal closure [5-8]. Msn probably functions as a MAP kinase kinase kinase kinase in Drosophila, activating the JNK pathway via an, as yet, undefined MAP kinase kinase kinase. We have identified a Drosophila TNF-receptor-associated factor, DTRAF1, by screening for Msn-interacting proteins using the yeast two-hybrid system. In contrast to the mammalian TRAFs that have been shown to activate JNK, DTRAF1 lacks an amino-terminal 'Ring-finger' domain, and overexpression of a truncated DTRAF1, consisting of only its TRAF domain, activates JNK. We also identified another DTRAF, DTRAF2, that contains an amino-terminal Ring-finger domain. Msn specifically binds the TRAF domain of DTRAF1 but not that of DTRAF2. In Drosophila, DTRAF1 is thus a good candidate for an upstream molecule that regulates the JNK pathway by interacting with, and activating, Msn. Consistent with this idea, expression of a dominant-negative Msn mutant protein blocks the activation of JNK by DTRAF1. Furthermore, coexpression of Msn with DTRAF1 leads to the synergistic activation of JNK. We have extended some of these observations to the mammalian homolog of Msn, Nck-interacting kinase (NIK), suggesting that TRAFs also play a critical role in regulating Ste20 kinases in mammals.  (+info)

Activation of c-Abl tyrosine kinase requires caspase activation and is not involved in JNK/SAPK activation during apoptosis of human monocytic leukemia U937 cells. (2/5224)

Genotoxic stress triggers the activation of several sensor molecules, such as p53, JNK1/SAPK and c-Abl, and occasionally promotes the cells to apoptosis. We previously reported that JNK1/SAPK regulates genotoxic stress-induced apoptosis in p53-negative U937 cells by activating caspases. c-Abl is expected to act upstream of JNK1/SAPK activation upon treatment with genotoxic stressors, but its involvement in apoptosis development is still unclear. We herein investigated the kinase activities of c-Abl and JNK1/SAPK during apoptosis elicited by genotoxic anticancer drugs and tumor necrosis factor (TNF) in U937 cells and their apoptosis-resistant variant UK711 cells. We found that the activation of JNK1/SAPK and c-Abl correlated well with apoptosis development in these cell lines. Unexpectedly, however, the JNK1/SAPK activation preceded the c-Abl activation. Moreover, the caspase inhibitor Z-Asp suppressed c-Abl activation and the onset of apoptosis but not the JNK1/SAPK activation. Interestingly, c-Abl tyrosine kinase inhibition by CGP 57148 reduced apoptosis without interfering with JNK1/SAPK activation. These results indicate that c-Abl acts not upstream of JNK1/ SAPK but downstream of caspases during the development of p53-independent apoptosis and is possibly involved in accelerating execution of the cell death pathway.  (+info)

Activation of c-Jun N-terminal kinase 1 by UV irradiation is inhibited by wortmannin without affecting c-iun expression. (3/5224)

Activation of c-Jun N-terminal kinases (JNKs)/stress-activated protein kinases is an early response of cells upon exposure to DNA-damaging agents. JNK-mediated phosphorylation of c-Jun is currently understood to stimulate the transactivating potency of AP-1 (e.g., c-Jun/c-Fos; c-Jun/ATF-2), thereby increasing the expression of AP-1 target genes. Here we show that stimulation of JNK1 activity is not a general early response of cells exposed to genotoxic agents. Treatment of NIH 3T3 cells with UV light (UV-C) as well as with methyl methanesulfonate (MMS) caused activation of JNK1 and an increase in c-Jun protein and AP-1 binding activity, whereas antineoplastic drugs such as mafosfamide, mitomycin C, N-hydroxyethyl-N-chloroethylnitrosourea, and treosulfan did not elicit this response. The phosphatidylinositol 3-kinase inhibitor wortmannin specifically blocked the UV-stimulated activation of JNK1 but did not affect UV-driven activation of extracellular regulated kinase 2 (ERK2). To investigate the significance of JNK1 for transactivation of c-jun, we analyzed the effect of UV irradiation on c-jun expression under conditions of wortmannin-mediated inhibition of UV-induced stimulation of JNK1. Neither the UV-induced increase in c-jun mRNA, c-Jun protein, and AP-1 binding nor the activation of the collagenase and c-jun promoters was affected by wortmannin. In contrast, the mitogen-activated protein kinase/ERK kinase inhibitor PD98056, which blocked ERK2 but not JNK1 activation by UV irradiation, impaired UV-driven c-Jun protein induction and AP-1 binding. Based on the data, we suggest that JNK1 stimulation is not essential for transactivation of c-jun after UV exposure, whereas activation of ERK2 is required for UV-induced signaling leading to elevated c-jun expression.  (+info)

The Jun kinase 2 isoform is preferentially required for epidermal growth factor-induced transformation of human A549 lung carcinoma cells. (4/5224)

We have previously found that epidermal growth factor (EGF) mediates growth through the Jun N-terminal kinase/stress-activated kinase (JNK/SAPK) pathway in A549 human lung carcinoma cells. As observed here, EGF treatment also greatly enhances the tumorigenicity of A549 cells, suggesting an important role for JNK in cancer cell growth (F. Bost, R. McKay, N. Dean, and D. Mercola, J. Biol. Chem. 272:33422-33429, 1997). Several isoforms families of JNK, JNK1, JNK2, and JNK3, have been isolated; they arise from alternative splicing of three different genes and have distinct substrate binding properties. Here we have used specific phosphorothioate oligonucleotides targeted against the two major isoforms, JNK1 and JNK2, to discriminate their roles in EGF-induced transformation. Multiple antisense sequences have been screened, and two high-affinity and specific candidates have been identified. Antisense JNK1 eliminated steady-state mRNA and JNK1 protein expression with a 50% effective concentration (EC50) of <0.1 microM but did not alter JNK2 mRNA or protein levels. Conversely, antisense JNK2 specifically eliminated JNK2 steady-state mRNA and protein expression with an EC50 of 0.1 microM. Antisense JNK1 and antisense JNK2 inhibited by 40 and 70%, respectively, EGF-induced total JNK activity, whereas sense and scrambled-sequence control oligonucleotides had no effect. The elimination of mRNA, protein, and JNK activities lasted 48 and 72 h following a single Lipofectin treatment with antisense JNK1 and JNK2, respectively, indicating sufficient duration for examining the impact of specific elimination on the phenotype. Direct proliferation assays demonstrated that antisense JNK2 inhibited EGF-induced doubling of growth as well as the combination of active antisense oligonucleotides did. EGF treatment also induced colony formation in soft agar. This effect was completely inhibited by antisense JNK2 and combined-antisense treatment but not altered by antisense JNK1 alone. These results show that EGF doubles the proliferation (growth in soft agar as well as tumorigenicity in athymic mice) of A549 lung carcinoma cells and that the JNK2 isoform but not JNK1 is utilized for mediating the effects of EGF. This study represents the first demonstration of a cellular phenotype regulated by a JNK isoform family, JNK2.  (+info)

All-trans-retinoic acid inhibits Jun N-terminal kinase by increasing dual-specificity phosphatase activity. (5/5224)

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)

Jun kinase phosphorylates and regulates the DNA binding activity of an octamer binding protein, T-cell factor beta1. (6/5224)

POU domain proteins have been implicated as key regulators during development and lymphocyte activation. The POU domain protein T-cell factor beta1 (TCFbeta1), which binds octamer and octamer-related sequences, is a potent transactivator. In this study, we showed that TCFbeta1 is phosphorylated following activation via the T-cell receptor or by stress-induced signals. Phosphorylation of TCFbeta1 occurred predominantly at serine and threonine residues. Signals which upregulate Jun kinase (JNK)/stress-activated protein kinase activity also lead to association of JNK with TCFbeta1. JNK associates with the activation domain of TCFbeta1 and phosphorylates its DNA binding domain. The phosphorylation of recombinant TCFbeta1 by recombinant JNK enhances the ability of TCFbeta1 to bind to a consensus octamer motif. Consistent with this conclusion, TCFbeta1 upregulates reporter gene transcription in an activation- and JNK-dependent manner. In addition, inhibition of JNK activity by catalytically inactive MEKK (in which methionine was substituted for the lysine at position 432) also inhibits the ability of TCFbeta1 to drive inducible transcription from the interleukin-2 promoter. These results suggest that stress-induced signals and T-cell activation induce JNK, which then acts on multiple cis sequences by modulating distinct transactivators like c-Jun and TCFbeta1. This demonstrates a coupling between the JNK activation pathway and POU domain proteins and implicates TCFbeta1 as a physiological target in the JNK signal transduction pathway leading to coordinated biological responses.  (+info)

BLNK required for coupling Syk to PLC gamma 2 and Rac1-JNK in B cells. (7/5224)

Signaling through the B cell receptor (BCR) is essential for B cell function and development. Despite the key role of Syk in BCR signaling, little is known about the mechanism by which Syk transmits downstream effectors. BLNK (B cell LiNKer protein), a substrate for Syk, is now shown to be essential in activating phospholipase C (PLC)gamma 2 and JNK. The BCR-induced PLC gamma 2 activation, but not the JNK activation, was restored by introduction of PLC gamma 2 membrane-associated form into BLNK-deficient B cells. As JNK activation requires both Rac1 and PLC gamma 2, our results suggest that BLNK regulates the Rac1-JNK pathway, in addition to modulating PLC gamma 2 localization.  (+info)

Synergistic activation of JNK/SAPK by interleukin-1 and platelet-derived growth factor is independent of Rac and Cdc42. (8/5224)

The c-Jun N-terminal kinases (JNKs) are activated strongly by inflammatory cytokines and environmental stresses, but only weakly by growth factors. Here we show that platelet-derived growth factor (PDGF) strongly potentiates activation of JNK by interleukin 1 (IL-1) in human fibroblasts and a pig aortic endothelial (PAE) cell line. This synergistic activation of JNK by IL-1 and PDGF was unaffected by bacterial toxins that inactivate Rho proteins and Ras. Since Rho proteins have been implicated in JNK activation, their possible involvement was investigated further using stably expressed, inducible N17 or V12 mutants in PAE cell lines. N17 Rac non-selectively reduced JNK activity by 30% in resting or stimulated cells (IL-1 alone, or with PDGF). N17 Cdc42 had no effect. V12 Rac weakly activated JNK and synergized with IL-1, but not with PDGF. V12 Cdc42 weakly activated JNK, but synergized with PDGF and not IL-1. Our results imply that Rho GTPases are not directly involved in mediating IL-1-induced JNK activation, or in the potentiation of this activation by PDGF.  (+info)

Oxidative stress is an underlying component of acute and chronic kidney disease. Apoptosis signal-regulating kinase 1 (ASK1) is a widely expressed redox-sensitive serine threonine kinase that activates p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase kinases, and induces apoptotic, inflammatory, and fibrotic signaling in settings of oxidative stress. We describe the discovery and characterization of a potent and selective small-molecule inhibitor of ASK1, GS-444217, and demonstrate the therapeutic potential of ASK1 inhibition to reduce kidney injury and fibrosis. Activation of the ASK1 pathway in glomerular and tubular compartments was confirmed in renal biopsies from patients with diabetic kidney disease (DKD) and was decreased by GS-444217 in several rodent models of kidney injury and fibrosis that collectively represented the hallmarks of DKD pathology. Treatment with GS-444217 reduced progressive inflammation and fibrosis in the kidney and halted glomerular filtration ...
Oxidative stress is an underlying component of acute and chronic kidney disease. Apoptosis signal-regulating kinase 1 (ASK1) is a widely expressed redox-sensitive serine threonine kinase that activates p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase kinases, and induces apoptotic, inflammatory, and fibrotic signaling in settings of oxidative stress. We describe the discovery and characterization of a potent and selective small-molecule inhibitor of ASK1, GS-444217, and demonstrate the therapeutic potential of ASK1 inhibition to reduce kidney injury and fibrosis. Activation of the ASK1 pathway in glomerular and tubular compartments was confirmed in renal biopsies from patients with diabetic kidney disease (DKD) and was decreased by GS-444217 in several rodent models of kidney injury and fibrosis that collectively represented the hallmarks of DKD pathology. Treatment with GS-444217 reduced progressive inflammation and fibrosis in the kidney and halted glomerular filtration ...
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. ...
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
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 ...
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 ...
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 ...
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
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)
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
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 ...
Although accumulating evidence supports that JNK activation is involved in cancer development and progression [37, 38], the biological significance of JNK in gastric cancer remains unclear. The present study showed that constitutive activation of JNK was associated with specific clinicopathological factors, including pTNM stages, lymphatic invasion, and a better prognosis. We believe that this is the first report regarding the clinical implications of JNK in human gastric cancer. Furthermore, we found that JNK negatively regulates FOXO1 activation in gastric cancer cells. This finding contrasts with the results of the previous studies [22, 27-31], which showed JNK-induced activation of FOXO proteins in human cancer cells.. In the present study, JNK activation (evaluated by pJNK staining) was mainly observed in the proliferative zone of the gastric gland and in the areas showing intestinal metaplasia, which is known to be a predictor of gastric neoplasia [39], in the non-neoplastic gastric ...
Interleukin 6 (IL-6) is an independent predictor of type 2 diabetes and cardiovascular disease and is correlated with insulin resistance. Insulin stimulates nitric oxide (NO) production through the IRS-1/PI3-kinase/Akt/eNOS pathway (where IRS-1 is insulin receptor substrate 1, PI3-kinase is phosphatidylinositol 3-kinase, and eNOS is endothelial NO synthase). We asked if IL-6 affects insulin vasodilator action both in human umbilical vein endothelial cells (HUVEC) and in the aortas of C57BL/6J mice and whether this inhibitory effect was caused by increased Ser phosphorylation of IRS-1. We observed that IL-6 increased IRS-1 phosphorylation at Ser312 and Ser616; these effects were paralleled by increased Jun N-terminal protein kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and reversed by JNK and ERK1/2 inhibition. In addition, IL-6 treatment resulted in impaired IRS-1 phosphorylation at Tyr612, a site essential for engaging PI3-kinase. Furthermore, IL-6 ...
The stress-induced kinase, c-Jun-N-terminal kinase 1 (JNK1) has previously been implicated in the pathogenesis of lung fibrosis. However, the exact cell type(s) wherein JNK1 exerts its pro-fibrotic role(s) remained enigmatic. Herein we demonstrate prominent activation of JNK in bronchial epithelia using the mouse models of bleomycin- or AdTGFbeta1-induced fibrosis. Furthermore, in lung tissues of patients with idiopathic pulmonary fibrosis (IPF), active JNK was observed in various regions including type I and type II pneumocytes and fibroblasts. No JNK activity was observed in adjacent normal tissue or in normal control tissue. To address the role of epithelial JNK1, we ablated Jnk1 form bronchiolar and alveolar type II epithelial cells using CCSP-directed Cre recombinase-mediated ablation of LoxP-flanked Jnk1 alleles. Our results demonstrate that ablation of Jnk1 from airway epithelia resulted in a strong protection from bleomycin- or adenovirus expressing active transforming growth factor beta-1
The data reported herein show the capacity of NSC 651016 to act as an inhibitor of CXCL12-mediated angiogenesis in a variety of in vitro and in vivo angiogenesis assays. Furthermore, these data suggest the potential application of NSC 651016 as an antiangiogenic therapy because it blocked endothelial cell migration, capillary-like tube formation, and angiogenesis. Furthermore, NSC 651016 may have wider applications in cancer therapy. CXCL12 has been implicated in the proliferation of astrocytes (14) by activating extracellular signal-regulated kinase 1/2 but not p38 or stress-activated protein kinase/c-Jun NH2-terminal kinase pathways (14) , therefore, CXCL12 may have a direct role in pathological glial cell proliferation such as reactive gliosis and brain tumor formation. Thus, blockade of CXCL12 function by NSC 651016 may have direct therapeutic benefits for certain brain cancers, one of the most refractory tumor types known. Additionally, CXCL12 participates in cancer cell metastasis by ...
Changes in cell shape affect many critical cellular and bodily processes, like wound healing and developmental events, and when gone awry, metastatic processes in cancer. Evolutionarily conserved signaling pathways govern regulation of these cellular changes. The Jun-N-terminal kinase pathway regulates cell stretching during wound healing and normal development. An extensively studied developmental process is embryonic dorsal closure in fruit flies, a well-established model for the regulation and manner of this cell shape changes.. Here researchers from the National Autonomous University of Mexico describe and characterize a processed, long non-coding RNA locus, acal, that adds a new layer of complexity to the Jun-N-terminal kinase signaling, acting as a negative regulator of the pathway. acal modulates the expression of two key genes in the pathway: the scaffold protein Cka, and the transcription factor Aop. Together, they enable the proper level of Jun-N-terminal kinase pathway activation to ...
Distinct and evolutionarily conserved signal-transduction cascades mediate the survival or death of cells during development. The c-Jun amino-terminal kinases (JNKs) of the mitogen-activated protein kinase superfamily are involved in apoptotic signalling in various cultured cells. However, the role …
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 ...
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
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
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 this study, we demonstrated a protective function of ERK in apoptotic events trigged by the physiological stress factor methylglyoxal. Activation of the ERK pathway after PMA treatment resulted in the inhibition of mitochondrial death machinery induced by exposure to MG. Because MG caused JNK activation and activated JNK was sufficient for inducing cytochrome c release from mitochondria, we speculated that ERK is involved in the regulation of JNK-mediated mitochondrial dysfunction. In support of this hypothesis, the ERK and the JNK signals, which are triggered by PMA and MG, respectively, were integrated on mitochondria. We further demonstrated that active ERK represses JNK-induced leakage of cytochrome c in vitro. Because the protective effect of ERK on JNK-induced mitochondrial death machinery has not been demonstrated directly in previous studies, our study is the first in which direct evidence of their opposing effects on mitochondrial injury was obtained using a cell-free system.. Our ...
BLASTX 2.0a10MP-WashU [15-May-1997] [Build 16:56:44 May 19 1997] Reference: Gish, Warren (1994-1997). unpublished. Gish, Warren and David J. States (1993). Identification of protein coding regions by database similarity search. Nat. Genet. 3:266-72. Notice: statistical significance is estimated under the assumption that the equivalent of one entire reading frame in the query sequence codes for protein and that significant alignments will involve only coding reading frames. Query= 914074 (611 letters) Translating both strands of query sequence in all 6 reading frames Database: ../../_tempdbs/nrdb 267,798 sequences; 79,948,537 total letters. Searching....10....20....30....40....50....60....70....80....90....100% done Smallest Sum Reading High Probability Sequences producing High-scoring Segment Pairs: Frame Score P(N) N A gi,1916549 (U50966) DJNK [Drosophila melanog... +2 184 2.0e-13 1 A gi,1656058 (U73196) Jun-N-terminal kinase [D... +2 184 3.2e-13 1 A gi,1857041 (U49180) JNK protein kinase ...
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
The c-Jun N-terminal protein kinase signaling pathway mediates Bax activation and subsequent neuronal apoptosis in the course interaction with Bim after transitory centred cerebral ischemia. High internal tension of the bladder has a occasion likelihood to d‚nouement develop in bladderВ-ureter reflux and harm the kidney in a retrograde frame, which is the dean origin of cessation for the benefit of the new produce of SCI [9, 10]. Unfortunately, Pneumovax 23 does not protect against nonbacteremic disease (ie, pneumonia without bloodstream infection) (French et al 2000; Whitney et al 2003) buy 5 mg zyrtec with visa allergy medicine 4h2. When a neonate who has previously been diagnosed with an innate mistaken of metabolism is hospitalized, the sister must decide the prescribed fast and medications so these may be continued while in the sickbay setting. On place against, another over inaugurate a significant reduction in the troop of rapid ripples recorded with pier clinical electrodes ...
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 ...
The involvement of JNK and NRF2 pathway in apoptosis induced by AATBC knockdownA. 36 hours after transfection, levels of JNK, p-JNK, p-p38, p-ERK1/2 and NRF2 we
Pendedahan sel Jurkat kepada ekstrak biji anggur - GSE mengakibatkan peningkatan dose- dan masa yang bergantung kepada di apoptosis dan pengaktifan caspase,
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
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 ...
TY - JOUR. T1 - Stimulation of Jun N-terminal kinase (JNK) by gonadotropin-releasing hormone in pituitary αt3-1 cell line is mediated by protein kinase C, c-Src, and CDC42. AU - Levi, N. L.. AU - Hanoch, T.. AU - Benard, Outhiriaradjou. AU - Rozenblat, M.. AU - Harris, D.. AU - Reiss, N.. AU - Naor, Z.. AU - Seger, R.. PY - 1998. Y1 - 1998. N2 - The signaling of ligands operating via heterotrimeric G proteins is mediated by a complex network that involves sequential phosphorylation events. Signaling by the G protein-coupled receptor GnRH was shown to include elevation of Ca2+ and activation of phospholipases, protein kinase C (PKC) and extracellular signal-regulated kinase (ERK). In this study, GnRH was shown to activate Jun N-Terminal Kinase (JNK)/SAPK in αT3-1 cells in a PKC- and tyrosine kinase-dependent manner. GnRH as well as tumor-promoting agent (TPA) also increased c-Src activity, which peaked at 2 min after GnRH stimulation and was sensitive both to PKC and to tyrosine kinase ...
TT-232 is a somatostatin analogue containing a five-residue ring structure. The present report describes TT-232-induced signalling events in A431 cells, where a 4-h preincubation with the peptide irreversibly induced a cell death program, which involves DNA-laddering and the appearance of shrunken nuclei, but is unrelated to somatostatin signalling. Early intracellular signals of TT-232 include a transient two-fold activation of the extracellular signal-regulated kinase (ERK2) and a strong and sustained activation of the stress-activated protein kinases c-Jun NH(2)-terminal kinase (JNK)/SAPK and p38MAPK. Blocking the signalling to ERK or p38MAPK activation had no effect on the TT-232-induced cell killing. At the commitment time for inducing cell death, TT-232 decreased EGFR-tyrosine phosphorylation and prevented epidermial growth factor (EGF)-induced events like cRaf-1 and ERK2 activation. Signalling to ERK activation by FCS, phorbol 12-myristate 13-acetate (PMA) and platelet-derived growth ...
Stress-activated protein kinases (SAPKs) are stimulated by cell damaging agents as well as by physiological receptor agonists. In this study we show that human platelets contain the isoforms SAPK2a, SAPK2b, SAPK3 and SAPK4 as determined by immunoblotting with specific antibodies. All four kinases were activated in thrombin-stimulated platelets whereas only SAPK2a and SAPK2b were significantly stimulated by collagen. All four isoforms were able to phosphorylate wild-type human cPLA2in vitro, although to different extents, but not cPLA2 mutants that had Ser505 replaced by alanine. Phosphorylation at Ser505 was confirmed by phosphopeptide mapping using microbore HPLC. SAPK2a and 42-kDa mitogen-activated protein kinase incorporated similar levels of phosphate into cPLA2 relative to the ability of each kinase to stimulate phosphorylation of myelin basic protein. SAPK2b and SAPK4 incorporated less phosphate, and cPLA2 was a poor substrate for SAPK3. The inhibitor of SAPK2a and SAPK2b, SB 202190, ...
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The regulation of innate immune responses to pathogens occurs through the interaction of Toll-like receptors (TLRs) with pathogen-associated molecular patterns and the activation of several signaling pathways whose contribution to the overall innate immune response to pathogens is poorly understood. We demonstrate a mechanism of control of murine macrophage responses mediated by TLR1/2 heterodimers through c-Jun N-terminal kinase 1 (JNK1) activity. JNK controls tumor necrosis factor alpha production and TLR-mediated macrophage responses to Borrelia burgdorferi, the causative agent of Lyme disease, and the TLR1/TLR2-specific agonist PAM(3)CSK(4). JNK1, but not JNK2, activity regulates the expression of the tlr1 gene in the macrophage cell line RAW264.7, as well as in primary CD11b(+) cells. We also show that the proximal promoter region of the human tlr1 gene contains an AP-1 binding site that is subjected to regulation by the kinase and binds two complexes that involve the JNK substrates c-Jun, ...
c-Jun is induced in lots of neuronal death paradigms. additional JNK substrates may be critical for neuronal death. As potential mediators, we identified additional nuclear MLK/JNK substrates, including Nup214 subunit of the nuclear pore complex. Introduction One of the hallmarks of neuronal cell death is the activation of JunCNH2-terminal kinase (JNK) pathway and the rapid induction of its downstream target AP-1 transcription factor c-Jun (for review see Ham et al., 2000; Herdegen et al., 1997). c-Jun induction plays a major role in the transcription of several proapoptotic genes, most notably the BH3-only Bcl-2 family member Bim (Harris and Johnson, 2001; Whitfield et al., 2001). Inhibition of AP-1 activity by dominant-negative c-Jun overexpression, neutralizing antibody injection, or genetic deletion retards sympathetic neuronal apoptosis after NGF deprivation (Estus et al., 1994; Ham et al., 1995; Palmada et al., 2002). Moreover, hippocampal neurons carrying a mutant c-Jun gene (allele (gene ...
The nuclear factor (NF)-κB pathway is involved in arterial inflammation. Although the signaling pathways that regulate transcriptional activation of NF-κB are defined, the mechanisms that regulate the expression levels of NF-κB transcription factors are uncertain.We studied the signaling mechanisms that regulate RelA NF-κB subunit expression in endothelial cells (ECs) and their role in arterial inflammation.Gene silencing and chromatin immunoprecipitation revealed that RelA expression was positively regulated by c-Jun N-terminal kinase (JNK) and the downstream transcription factor ATF2 in ECs. We concluded that this pathway promotes focal arterial inflammation as genetic deletion of JNK1 reduced NF-κB expression and macrophage accumulation at an atherosusceptible site. We hypothesized that JNK signaling to NF-κB may be controlled by mechanical forces because atherosusceptibility is associated with exposure to disturbed blood flow. This was assessed by positron emission tomography imaging of
Background Roux‐en‐Y gastric bypass (RYGB) reduces obesity‐associated comorbidities and cardiovascular mortality. RYGB improves endothelial dysfunction, reducing c‐Jun N‐terminal kinase (JNK) vascular phosphorylation. JNK activation links obesity with insulin resistance and endothelial dysfunction. Herein, we examined whether JNK1 or JNK2 mediates obesity‐induced endothelial dysfunction and if pharmacological JNK inhibition can mimic RYGB vascular benefits. Methods and Results After 7 weeks of a high‐fat high‐cholesterol diet, obese rats underwent RYGB or sham surgery; sham-operated ad libitum-fed rats received, for 8 days, either the control peptide D‐TAT or the JNK peptide inhibitor D‐JNKi‐1 (20 mg/kg per day subcutaneous). JNK peptide inhibitor D‐JNKi‐1 treatment improved endothelial vasorelaxation in response to insulin and glucagon‐like peptide‐1, as observed after RYGB. Obesity increased aortic phosphorylation of JNK2, but not of JNK1. RYGB and JNK peptide ...
The JUN amino terminal kinases (JNK) are activated by cellular stress and play a part in apoptosis. Genetic susceptibility to psychiatric disorders in humans is associated with disruption of JNK pathway signalling, and this stress kinase appears to regulate anxiety and depression-like behaviours in mice. JNK1 plays an active role in the developing brain. It is also expressed in adulthood, but we know less about its role. Even so, might JNK inhibitors have therapeutic potential?. This is the question being asked by Eleanor Coffey, University of Turku, Finland.. JNK1 knockout animals display less anxiety than wild type animals. Dr Coffey and colleagues were not able to show that acute inhibition of JNK1 altered anxiety behaviour. But chronic treatment with an inhibitor decreased anxious behaviour in adult mice and increased neurogenesis in the hippocampus. In patients, hippocampal neurogenesis is required for the action of antidepressants; so this phenomenon may be relevant to treatment. In Dr ...
Gasdermin D Protects Mouse Podocytes Against High-Glucose-Induced Inflammation and Apoptosis via the C-Jun N-Terminal Kinase (JNK) Pathway - Order reprints #928411
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Aim of the project is to test whether JNK1 and JNK2 (c-Jun N-termina kinases) have essential functions in the liver. Mice and liver cells lacking JNK1, JNK2 or any JNK activity will be subjected to defined stimuli of hepatocyte proliferatoon, apoptosis and call injury. Specific in vitro and in vivo experiments may identify JNKs as crucial components of signal transduction cascades which ...
The stress-activated protein kinase (SAPK) p38 can induce apoptosis, and its inhibition facilitates mammary tumorigenesis. g38 signaling forms regular mammary acinar morphogenesis and inhibits HER2/neu-driven tumorigenesis. Our data also define at what stage of mammary gland advancement g38 might action to suppress tumorigenesis and how its inhibition could speed up disease development. Outcomes Reduction of ECM connection activates MKK6-g38 signaling and anoikis in MCF-10A cells Integrin and development aspect signaling become uncoupled in MCF-10A cells harvested in suspension system, starting a tension indication that outcomes in cell loss of life (19). Consistent with prior research (7), immunoblot (IB) evaluation indicated that g38 phosphorylation was MK-2866 elevated in separate MCF-10A cells essential contraindications to that in attached cells (Fig. 1A). We also noticed account activation of g38 in principal mouse MECs (mMECs) and immortalized mouse embryonic fibroblasts (MEFs) harvested ...
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
Homodimer. Forms higher oligomers under stress conditions. Interacts with BCL2L11. Interaction with BCL2L11 promotes BAX oligomerization and association with mitochondrial membranes, with subsequent release of cytochrome c. Forms heterodimers with BCL2, BCL2L1 isoform Bcl-X(L), BCL2L2, MCL1 and A1. Interacts with SH3GLB1 and HN. Interacts with SFN and YWHAZ; the interaction occurs in the cytoplasm. Under stress conditions, JNK-mediated phosphorylation of SFN and YWHAZ, releases BAX to mitochondria. Isoform Sigma interacts with BCL2A1 and BCL2L1 isoform Bcl-X(L). Interacts with RNF144B, which regulates the ubiquitin-dependent stability of BAX. Interacts with CLU under stress conditions that cause a conformation change leading to BAX oligomerization and association with mitochondria. Does not interact with CLU in unstressed cells. Interacts with FAIM2/LFG2. Interacts with RTL10/BOP. Interacts (via a C-terminal 33 residues) with NOL3 (via CARD domain); inhibits BAX activation and translocation and ...
Because silymarin exhibits anticarcinogenic, anti-inflammatory, and cytoprotective effects, we hypothesized that these effects of silymarin are mediated through suppression of NF-κB activation, an early mediator of the pleiotropic effects of TNF. Our results clearly demonstrate that silymarin is a potent inhibitor of NF-κB activation induced by a wide variety of inflammatory agents. The inhibition of NF-κB activation by silymarin correlated with suppression of IκBα phosphorylation and degradation, p65 nuclear translocation, and NF-κB-dependent reporter gene transcription. Silymarin also inhibited the activation of MEK and JNK and the apoptosis induced by TNF.. There are several possibilities for how silymarin might inhibit TNF-induced NF-κB activation. We showed that silymarin does not interfere with the binding of NF-κB to the consensus DNA binding site. NF-κB activation requires sequential phosphorylation, ubiquitination, and degradation of IκBα. Because silymarin blocks IκBα ...
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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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TRAF6 is a signal transducer that activates IkappaB kinase (IKK) and Jun amino-terminal kinase (JNK) in response to pro-inflammatory mediators such as interleukin-1 (IL-1) and lipopolysaccharides (LPS). IKK activation by TRAF6 requires two intermediary factors, TRAF6-regulated IKK activator 1 (TRIKA …
You are viewing an interactive 3D depiction of the molecule anthra[2,1,9-def:6,5,10-def]diisoquinoline-1,3,8,10(2h,9h)-tetrone, 2,9-dimethyl- (C26H34N2O4) from the PQR.
Kubasiak, L.A., Frazier, D., Dougherty, C. J., Li, H., Bishopric, N.H., and Webster, K.A. (2004) Mitochondrial Signals Initiate the Activation of c-Jun N-terminal Kinase (JNK) by Hypoxia-Reoxygenation. FASEB Journal. 18(10), 1060-1070. ...
Click on a genes description to view its network relationships with genes known to be involved in positive regulation of jnk cascade ...
December 1994). "Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK". Science. 266 ( ... a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-1 and MEK ... Mitogen-activated protein kinase kinases (MAP2Ks) are substrates for direct phosphorylation by the MAP3K1 protein kinase. The ... Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is an enzyme that in humans is encoded by the MAP3K1 gene. MAP3K1 (or ...
"Independent regulation of JNK/p38 mitogen-activated protein kinases by metabolic oxidative stress in the liver". Proc. Natl. ... "Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions". Mol. Cell. Biol. 17 (6): 3094-102 ... JUNB+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ... Fuchs SY, Xie B, Adler V, Fried VA, Davis RJ, Ronai Z (1998). "c-Jun NH2-terminal kinases target the ubiquitination of their ...
JNK mitogen-activated protein kinase, and actin filament assembly by the exchange factor FGD1". J. Biol. Chem. 273 (25): 15453- ... FGD1 also activates the c-Jun N-terminal kinase (JNK) signaling cascade, important in cell differentiation and apoptosis. It ... The mature human protein contains several characteristic motifs and domains that are involved in the protein's function. The ... FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) also known as faciogenital dysplasia 1 protein (FGDY), zinc finger FYVE ...
"Scaffold role of a mitogen-activated protein kinase phosphatase, SKRP1, for the JNK signaling pathway". The Journal of ... "Scaffold role of a mitogen-activated protein kinase phosphatase, SKRP1, for the JNK signaling pathway". The Journal of ... "A novel dual specificity phosphatase SKRP1 interacts with the MAPK kinase MKK7 and inactivates the JNK MAPK pathway. ... "A novel dual specificity phosphatase SKRP1 interacts with the MAPK kinase MKK7 and inactivates the JNK MAPK pathway. ...
JNK) mitogen-activated protein kinase". J. Biol. Chem. 272 (7): 4219-24. doi:10.1074/jbc.272.7.4219. PMID 9020136. Janknecht R ... a novel mitogen-activated protein kinase with distinct properties". J. Biol. Chem. 272 (31): 19509-17. doi:10.1074/jbc.272.31. ... Kamakura S, Moriguchi T, Nishida E (1999). "Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. ... The protein encoded by this gene is phosphorylated by the kinases, MAPK1 and MAPK8. Several transcript variants have been ...
... the mesenteric lymph node triggers the amelioration of the JNK-mitogen-activated protein kinases (MAPKs) and p38 mitogen- ... activated protein kinases (p38MAPKs) signaling cascades. The same pathway was observed in peripheral blood lymphocytes. ... These pharmacology benefits arise through the modulating action of geniposide on several proteins and genes that are associated ... When this receptor is activated neurotrophic effects were induced in cells, such as neurite outgrowth, reducing amyloid plaques ...
... stress-activated protein kinase (SAPK)/JNK, and p38 mitogen-activated protein kinase (p38 MAPK). Activation of the IRAK/MAPK ... The exact mechanism by which various concentrations of ethanol either activates or inhibits TLR4/IL-1RI signaling is not ... Ethanol interacts with the TLR4 and IL-1RI receptors on these cells to activate intracellular signal transduction pathways. ... This acetylation is an activating mark for pronociceptin. The nociceptin/nociceptin opioid receptor system is involved in the ...
... c-Jun N-terminal kinase (JNK), mitogen-activated protein kinases (MAPKs), and protein kinase B (PKB). While IL-10R2 is ... In addition, IL-26 activates extracellular signal-regulated kinases (ERK)-1/2, ... Interleukin-26 (IL-26) is a protein that in humans is encoded by the IL26 gene. IL-26 is the most recently identified member of ... IL-26 is a 171-amino acid protein that exhibits six alpha helices connected by loops and four conserved cysteine residues. ...
It activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases in a Raf-independent fashion in response ... characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase ... "Entrez Gene: MAP3K5 mitogen-activated protein kinase kinase kinase 5". Yoon KW, Cho JH, Lee JK, Kang YH, Chae JS, Kim YM, et al ... Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase 5 (MAP3K5) is a member of MAP kinase ...
Mitogen-activated protein kinase for JNK signaling pathway description GRCh38: Ensembl release 89: ENSG00000127863 - Ensembl, ... and to activate c-Jun N-terminal kinases (JNK) signaling pathway when overexpressed in cells. This receptor is capable of ... 2000). "TAJ, a novel member of the tumor necrosis factor receptor family, activates the c-Jun N-terminal kinase pathway and ... The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is highly expressed during ...
Cyt A is thought to induce apoptosis by activating c-Jun N-terminal Kinase (JNK), p38 mitogen-activated protein kinase (MAPK), ... Cyt A also activates c-Jun N-terminal kinase, and its apoptotic effects are inhibited by dominant negative c-Jun. While the ... Kakeya, H.; Onose, R.; Osada, H. "Caspase-mediated activation of a 36-kDa myelin basic protein kinase during anticancer drug- ... and p36 myelin basic protein (MBP) kinase. Cytotrienin A is an ansamycin with a macrocyclic, twenty-one carbon, lactam, ...
In collaboration with another mitogen-activated protein kinase kinase MKK4, MKK7 work as crucial transducers upstream of JNK ... MKK7 JNK-activated kinase 2 MAPK/ERK kinase 7 (MEK7) Stress-activated protein kinase kinase 4 (SAPK kinase 4, SAPKK4) c-Jun N- ... "Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly conserved c-Jun N-terminal kinase/stress-activated protein ... terminal kinase kinase 2 (JNK kinase 2, JNKK2) Stress-activated / extracellular signal-regulated protein kinase kinase 2 (SEK2 ...
... virus type 1 and its coat protein gp120 induce apoptosis and activate JNK and ERK mitogen-activated protein kinases in human ... JNK)-binding protein that enhances the activation of JNK by MEK kinase 1 and TGF-beta-activated kinase 1". FEBS Lett. 457 (3): ... Mitogen-activated protein kinase 10 also known as c-Jun N-terminal kinase 3 (JNK3) is an enzyme that in humans is encoded by ... "Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3". Mol. Cell. Biol. 20 (3): ...
The p38 mitogen activated protein kinase (MAPK) pathway is similar to the JNK pathway but differs from the ERK pathway. The p38 ... MAP kinase, JNK MAP kinase, and ERK MAP kinase are all types of mammalian MAP kinases. The p38 MAP kinase is activated by two ... MAPK Phosphatase 1 negatively regulates the activity of mitogen activate protein kinase (MAPK) activity. A deficiency of this ... MKK4 is also known to activate the JNK MAP kinase, however, MKK3 is unique to the p38 MAP kinase. The p38 MAPK pathway is ...
Johnson GL, Lapadat R (Dec 2002). "Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases". ... "Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase ... "Mitogen-activated protein kinase 14". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). "Entrez Gene: MAPK14 mitogen- ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proceedings of the National ...
... mitogen-activated protein) kinases such as JNK, ERK and p38. In particular, JNK can be found in both cell death and survival ... to activate JNK (c-Jun N-terminal Kinases), it may be related to epidermal growth factor receptor signalling and it is largely ... to bind to the IkB kinase or IKK complex. To activate IKK, TAB2 and TAB3 adaptor proteins recruit TAK1 or MEKK3, which ... including RIPK1 and another enzyme from the Receptor Interacting Protein kinases family, RIPK3, as well as other proteins such ...
... a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway". ... Mitogen-activated protein kinase 9 is an enzyme that in humans is encoded by the MAPK9 gene. The protein encoded by this gene ... "The JIP group of mitogen-activated protein kinase scaffold proteins". Molecular and Cellular Biology. 19 (10): 7245-54. doi: ... "Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3". Molecular and Cellular ...
... mitogen-activated protein kinase) proteins ERK, JNK, and p38 with specificity distinct from that of individual MKP proteins. ... a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase". J ... 2004). "Identification of protein tyrosine phosphatases with specificity for the ligand-activated growth hormone receptor". Mol ... Dual specificity protein phosphatase 7 is an enzyme that in humans is encoded by the DUSP7 gene. Dual-specificity phosphatases ...
... which then activates the downstream kinases, Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), ... Those processes are mainly regulated by three factors: protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating ... proteins in the ER activates the integrated stress response through protein kinase RNA-like endoplasmic reticulum kinase (PERK ... double-stranded RNA-activated protein kinase (PKR) iron deficiency through heme-regulated inhibitor kinase (HRI) stress from ...
They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are ... a dual specificity MAP kinase protein phosphatase". Proteins. 66 (1): 253-8. doi:10.1002/prot.21224. PMID 17078075. S2CID ... Dual specificity protein phosphatase 5 is an enzyme that in humans is encoded by the DUSP5 gene. The protein encoded by this ... Martell KJ, Kwak S, Hakes DJ, Dixon JE, Trent JM (Jul 1994). "Chromosomal localization of four human VH1-like protein-tyrosine ...
They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are ... affinity of mitogen-activated protein kinase subfamily members for MAP kinase phosphatase-2 and their ability to activate the ... Chu Y, Solski PA, Khosravi-Far R, Der CJ, Kelly K (Mar 1996). "The mitogen-activated protein kinase phosphatases PAC1, MKP-1, ... which selectively dephosphorylates the mitogen-activated protein kinase". The Journal of Biological Chemistry. 270 (13): 7197- ...
They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which is ... Dual specificity protein phosphatase 12 is an enzyme that in humans is encoded by the DUSP12 gene. The protein encoded by this ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. Bibcode: ... gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by ...
They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are ... 1995). "Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual ... Dual specificity protein phosphatase 2 is an enzyme that in humans is encoded by the DUSP2 gene. The protein encoded by this ... 1994). "Control of MAP kinase activation by the mitogen-induced threonine/tyrosine phosphatase PAC1". Nature. 367 (6464): 651-4 ...
They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are ... a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase". ... "Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and ... "Mitogen-activated protein kinase phosphatase-3 (MKP-3) in the surgical wound is necessary for the resolution of postoperative ...
They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which is ... Dual specificity phosphatase 8 is a protein that in humans is encoded by the DUSP8 gene. The protein encoded by this gene is a ... This gene product inactivates SAPK/JNK and p38, is expressed predominantly in the adult brain, heart, and skeletal muscle, is ... Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases ...
They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are ... Hao L, ElShamy WM (2007). "BRCA1-IRIS activates cyclin D1 expression in breast cancer cells by downregulating the JNK ... Dual specificity protein phosphatase 3 is an enzyme that in humans is encoded by the DUSP3 gene. The protein encoded by this ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. Bibcode: ...
... mitogen-activated protein kinases) such as ERK and JNK, bring about an increase in the synthesis of inflammatory factors that ... astrocytes were generated by exposing human glial precursor cells to bone morphogenetic protein (bone morphogenetic protein is ... ERK also further activates AMPARs and NMDARs in neurons. Nociception is further sensitized by the association of ATP and ... In this chronic signaling pathway, p38 is activated as a result of IL-1β signaling, and there is a presence of chemokines that ...
JNK (MKK4 and MKK7), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways. The acronym MEK ... Signal transduction MAP kinase MAP kinase kinase kinase MAP kinase kinase kinase kinase Dérijard B, et al. (1995). "Independent ... Mitogen-activated protein kinase kinase (also known as MAP2K, MEK, MAPKK) is a kinase enzyme which phosphorylates mitogen- ... Mitogen-Activated+Protein+Kinase+Kinases at the US National Library of Medicine Medical Subject Headings (MeSH) Biology portal ...
... interferes with the mitogen-activated protein (MAP) kinase activities of c-Jun N-terminal kinase (JNK), p38, and extracellular ... enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2 ... Yersinia pseudotuberculosis-derived mitogens (YpM) are superantigens, which are able to excessively activate T cells by binding ... Galyov EE, Håkansson S, Forsberg A, Wolf-Watz H (1993). "A secreted protein kinase of Yersinia pseudotuberculosis is an ...
... vitro experiments indicate that PaSCs influence the activation and proliferation process for mitogen activated protein kinase ( ... p38 kinase and JNK. The inhibition of the majority of MAPK pathways leads to a reduction in the activation and proliferation of ... Protein kinases such as MAPKs are primary mediators of activating signals initiated by the growth factors, angiotensin II and ... PaSCs express the intermediate filament proteins desmin and glial fibrillary acidic protein. The expression of a diverse range ...
"Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway". ... Deacon K, Blank JL (1997). "Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. ...
JUN kinase binding. • mitogen-activated protein kinase kinase binding. • mitogen-activated protein kinase kinase kinase binding ... 2001). "c-Jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer's amyloid precursor protein with ... "Entrez Gene: MAPK8IP1 mitogen-activated protein kinase 8 interacting protein 1".. *^ a b c d e f Yasuda, J; Whitmarsh A J; ... MAP-kinase scaffold activity. • protein kinase inhibitor activity. • protein binding. • kinesin binding. • protein kinase ...
... enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2 ... YopJ, que comparte un operón con YpkA, "...interfire coas actividades de quinase MAP (proteína activada por mitóxeno) da JNK (c ... Galyov EE, Håkansson S, Forsberg A, Wolf-Watz H (1993). "A secreted protein kinase of Yersinia pseudotuberculosis is an ... "En Ladant, Daniel; Alouf, Joseph E.; Popoff, Michel R. The Comprehensive Sourcebook of Bacterial Protein Toxins. Academic Press ...
Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase, in Proc. Natl. Acad. Sci. U.S.A., ... A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors, in Proc. Natl. Acad. Sci. U.S.A., ... Iijima S, Teraoka H, Date T, Tsukada K, DNA-activated protein kinase in Raji Burkitt's lymphoma cells. Phosphorylation of c-Myc ... Rob M Ewing, Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, et al., Large-scale mapping of human protein-protein interactions ...
"Role of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinase kinase in adenosine A2B receptor ... signalni put G-protein spregnutog receptora. • aktivnost adenilat ciklaze. • JNK kaskada. • izlučivanje. ... Adenozinski A2B receptor (ADORA2B) je G-protein spregnuti adenozinski receptor. Ovaj protein je kodiran humanim ADORA2B genom.[ ... aktivnost A2B adenouinskog receptora, G-protein spregnutog. • receptorska aktivnost. Celularna komponenta. • integralno sa ...
mitogen-activated protein kinase kinase kinase binding. • protein binding. • thioesterase binding. • protein kinase binding. • ... "The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily ... Activated Cdc42 activates by conformational changes[4] p21-activated kinases PAK1 and PAK2, which in turn initiate actin ... Joberty G, Petersen C, Gao L, Macara IG (August 2000). "The cell-polarity protein Par6 links Par3 and atypical protein kinase C ...
The activators of p38 (MKK3 and MKK6), JNK (MKK4 and MKK7), and ERK (MEK1 and MEK2) define independent MAP kinase signal ... Mitogen-activated protein kinase kinase (also known as MAP2K, MEK, MAPKK) is a kinase enzyme which phosphorylates mitogen- ... Mitogen-Activated+Protein+Kinase+Kinases at the US National Library of Medicine Medical Subject Headings (MeSH) ... Retrieved from "https://en.wikipedia.org/w/index.php?title=Mitogen-activated_protein_kinase_kinase&oldid=921615706" ...
1997). „Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S ... 1995). „Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun ... 1997). „Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. ENGLAND. 16 (8): 1909- ... 2003). „The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 ...
Mitogen-activated protein kinase (MAPK) signaling pathways includes three pathways: the classical MAPK/ERK pathway, p38 MAPK ... Bark H, Choi CH (May 2010). "PSC833, cyclosporine analogue, downregulates MDR1 expression by activating JNK/c-Jun/AP-1 and ... For example, miR-27a up-regulates P-gp expression by suppressing Raf kinase inhibitor protein (RKIP);[27] alternatively, miR- ... The protein belongs to the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules ...
... and increases mitogen-activated protein kinase (MAP kinase) concentration. Alternatively, in some rare cases CB1 receptor ... protein kinase C (PKC), Raf-1, ERK, JNK, p38, c-fos, c-jun, and others.[15] ... which are activated by cAMP-dependent interaction with such molecules as protein kinase A (PKA), ... Cannabinoid receptor type 1 (CB1), also known as cannabinoid receptor 1, is a G protein-coupled cannabinoid receptor that in ...
de 1997). «Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase». Proc. Natl. Acad. Sci. ... de 2001). «Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate ... Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase ... de 2000). «Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase». J ...
... mitogen-activated protein kinases) such as ERK and JNK, bring about an increase in the synthesis of inflammatory factors that ... astrocytes were generated by exposing human glial precursor cells to bone morphogenetic protein (Bone morphogenetic protein is ... A 2012 study[54] of the effects of marijuana on short term memories found that THC activates CB1 receptors of astrocytes which ... Astrocytes in vitro become activated by low glucose and are in vivo this activation increases gastric emptying to increase ...
Oncogenes often produce mitogens, or are involved in transcription of DNA in protein synthesis, which creates the proteins and ... The p53 protein, one of the most important studied tumor suppressor genes, is a transcription factor activated by many cellular ... abl fusion protein, an oncogenic tyrosine kinase. Small-scale mutations include point mutations, deletions, and insertions, ... "JNK is a novel regulator of intercellular adhesion". Tissue Barriers. 1 (5): e26845. doi:10.4161/tisb.26845. PMC 3942331. PMID ...
"Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated ... "Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 (MAPKK 6) or MAPK/ERK kinase 6 is ... protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • protein ...
... is also known as MEK1 (see Mitogen-activated protein kinase kinase). MEK1 is a meiotic chromosome-axis-associated kinase ... a Novel Jun N-Terminal Protein Kinase (JNK)-Binding Protein That Functions as a Scaffold Factor in the JNK Signaling Pathway". ... protein tyrosine kinase activity. • nucleotide binding. • MAP kinase kinase activity. • protein kinase activity. • protein ... "Entrez Gene: MAP2K1 mitogen-activated protein kinase kinase 1".. *^ a b Goldfarb T, Lichten M (2010). "Frequent and efficient ...
A second pathway contributing to cell survival occurs through activation of the mitogen-activated protein kinase (MAPK) kinase ... are both recruited to activate c-Jun N-terminal kinase (JNK); which phosphorylates c-Jun. The activated transcription factor c- ... The active Ras protein phosphorylates several proteins, along with the serine/threonine kinase, Raf.[7] Raf in turn activates ... positive regulation of Ras protein signal transduction. • transmembrane receptor protein tyrosine kinase signaling pathway. • ...
... an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase". The Journal of Biological ... phospholipase C-activating G-protein coupled receptor signaling pathway. • JNK cascade. • positive regulation of cell ... protein kinase binding. • ion channel binding. • signaling receptor activity. Cellular component. • integral component of ... G-protein coupled receptor activity. • amino acid binding. • protein homodimerization activity. • metal ion binding. • ...
"Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proceedings of the National ... A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors". Proceedings of the National ... Iijima S, Teraoka H, Date T, Tsukada K (June 1992). "DNA-activated protein kinase in Raji Burkitt's lymphoma cells. ... activating transcription factor binding. Cellular component. • cytosol. • nucleoplasm. • protein complex. • nucleolus. • ...
Nihalani D, Wong HN, Holzman LB (Aug 2003). "Recruitment of JNK to JIP1 and JNK-dependent JIP1 phosphorylation regulates JNK ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ... MAP kinase kinase kinase (MAP3K or MKKK). *MAP kinase kinase kinases *MAP3K1 ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ...
Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH (2001). "Mitogen-activated protein (MAP) kinase ... Aktivatori p38 (MKK3 i MKK6), JNK (MKK4 i MKK7), i ERK (MEK1 i MEK2) kinaza definišu nezavisne MAP kinazne puteve prenosa ... Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 izd.). Wiley- ... Nicholas C. Price, Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins ( ...
... mitogen-activated protein kinases) such as ERK and JNK, bring about an increase in the synthesis of inflammatory factors that ... astrocytes were generated by exposing human glial precursor cells to bone morphogenetic protein (Bone morphogenetic protein is ... A 2012 study[62] of the effects of marijuana on short term memories found that THC activates CB1 receptors of astrocytes which ... ERK also further activates AMPARs and NMDARs in neurons. Nociception is further sensitized by the association of ATP and ...
"Entrez Gene: MAPK8IP3 mitogen-activated protein kinase 8 interacting protein 3". CS1 maint: discouraged parameter (link) ... a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway". ... "Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3". Mol Cell Biol. 20 (3): 1030 ... MAPK8IP3 has been shown to interact with ASK1, C-Raf, PTK2, MAPK10, Mitogen-activated protein kinase 9, MAPK8, MAP2K1, KLC2, ...
"Adaptor proteins Grb2 and Crk couple Pyk2 with activation of specific mitogen-activated protein kinase cascades". J. Biol. Chem ... Girardin SE, Yaniv M (2001). "A direct interaction between JNK1 and CrkII is critical for Rac1-induced JNK activation". EMBO J ... involves the Src homology 2 domain of v-Crk and sustained activation of the Ras/mitogen-activated protein kinase pathway". J. ... The name Crk is from "CT10 Regulator of Kinase" where CT10 is the avian virus from which was isolated a protein, lacking kinase ...
Navas TA, Baldwin DT, Stewart TA (November 1999). "RIP2 is a Raf1-activated mitogen-activated protein kinase kinase". The ... Increases in the levels of Jun and Fos proteins and JNK activity have been reported in scenarios in which cells undergo ... of mitogen-activated protein kinase and NF-kappaB pathways by a Kaposi's sarcoma-associated herpesvirus K15 membrane protein". ... "Human cytomegalovirus IE1 protein activates AP-1 through a cellular protein kinase(s)". The Journal of General Virology. 80 ( ...
Mitogen-activated protein kinase kinase kinase 7-interacting protein 2 is an enzyme that in humans is encoded by the MAP3K7IP2 ... which is required for the IL-1 induced activation of nuclear factor kappaB and MAPK8/JNK. This protein forms a kinase complex ... "Entrez Gene: MAP3K7IP2 mitogen-activated protein kinase kinase kinase 7 interacting protein 2". Thienpont B, Zhang L, Postma AV ... activates TAK1 mitogen-activated protein kinase kinase kinase through a signaling complex containing RANK, TAB2, and TRAF6". ...
"Catalytic activation of mitogen-activated protein (MAP) kinase phosphatase-1 by binding to p38 MAP kinase: critical role of the ... Slack DN, Seternes OM, Gabrielsen M, Keyse SM (May 2001). "Distinct binding determinants for ERK2/p38alpha and JNK map kinases ... and specifically inactivates mitogen-activated protein (MAP) kinase in vitro by the concomitant dephosphorylation of both its ... "Expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) in primary human ovarian carcinoma". International Journal ...
"Entrez Gene: MAPKAP1 mitogen-activated protein kinase associated protein 1". Colicelli J, Nicolette C, Birchmeier C, et al. ( ... "The human stress-activated protein kinase-interacting 1 gene encodes JNK-binding proteins". Cell. Signal. 17 (6): 761-7. doi: ... This gene encodes a protein that is highly similar to the yeast SIN1 protein, a stress-activated protein kinase. Alternatively ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ...
... Zama T., Aoki R., ... Stress-activated protein kinase (SAPK) pathway-regulating phosphatase 1 (SKRP1) has been identified as a member of the mitogen- ... activated protein kinase (MAPK) phosphatase (MKP) family that interacts physically with the MAPK kinase (MAPKK) MKK7, a c-Jun N ... apoptosis signal-regulating kinase 1 (ASK1), but not with MAP kinase kinase kinase 1 (MEKK1). Consistent with these findings, ...
Growth factors activate mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs) and ... Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK ... Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK ... Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK ...
Selective involvement of ERK and JNK mitogen-activated protein kinases in early rheumatoid arthritis (1987 ACR criteria ... Selective involvement of ERK and JNK mitogen-activated protein kinases in early rheumatoid arthritis (1987 ACR criteria ...
mitogen-activated protein kinase 9 - JNK subfamily. Detailed annotation on the structure, function, physiology, pharmacology ... stress activated protein kinase alpha II , Stress-activated protein kinase 1a , stress-activated protein kinase JNK2 ... JNK subfamily: mitogen-activated protein kinase 9. Last modified on 30/10/2019. Accessed on 26/05/2020. IUPHAR/BPS Guide to ... JNK-55 , c-Jun N-terminal kinase 2 , JNK/SAPK alpha , Jun kinase , MAP kinase 9 , PRKM9 , SAPK1A , SAPK-alpha , ...
JNK) mitogen-activated protein kinase (MAPK) pathways, as further confirmed by OCP crystal-induced p38 and JNK MAPK ... our data suggest that the transcriptional inducible NOS response to OCP crystals involved both the p38 and the JNK MAPK ... and involved p38 and c-Jun amino-terminal kinase ( ... pathways, probably under the control of activator protein-1. NO ... JNK) mitogen-activated protein kinase (MAPK) pathways, as further confirmed by OCP crystal-induced p38 and JNK MAPK ...
... mitogen activated protein kinase kinase 4 jnk activating kinase 1 jnkk jnkk1 map kinase kinase 4 map2k4 mapk erk kinase 4 mapkk ... C-JUN N-terminal kinase kinase 1,Dual specificity mitogen-activated protein kinase kinase 4,JNK kinase 1,JNK-activating kinase ... c-Jun N-terminal kinase kinase 2,Dual specificity mitogen-activated protein kinase kinase 7,JNK kinase 2,JNK-activating kinase ... c-Jun N-terminal kinase kinase 2,Dual specificity mitogen-activated protein kinase kinase 7,JNK kinase 2,JNK-activating kinase ...
JNK Mitogen-Activated Protein Kinases/metabolism. *JNK Mitogen-Activated Protein Kinases/physiology ... In IRE1-deficient cells or cells treated with c-Jun N-terminal kinase (JNK) inhibitor, the autophagy induced by ER stress was ... Autophagy after ER stress is activated by the IRE1-JNK pathway. (A) Schematic structures of full-length IRE1α (IRE1α full) as ... Eukaryotic cells deal with accumulation of unfolded proteins in the endoplasmic reticulum (ER) by the unfolded protein response ...
JNK Mitogen-Activated Protein Kinases. Grant support. *R01 GM085081/GM/NIGMS NIH HHS/United States ... We discovered that caspase activity and jun N-terminal kinase (JNK) signaling both play a role in OSN death, and inhibition of ... The levels of the kinase itself - both the 46kD (JNK1) and 54kD (JNK2/3) JNK family members - remain unchanged. (c) Caspase-3 ... a) Survival of OSNs is extended when treated with pan-caspase inhibitors Boc-D-FMK (boc, 45 µM) and QVD-OPH (qvd, 3 µM) or JNK ...
JNK Mitogen-Activated Protein Kinases * Mitogen-Activated Protein Kinases * p38 Mitogen-Activated Protein Kinases ... In contrast, Dex and RA failed to inhibit the activation of the p38 mitogen-activated protein kinase cascade. As a number of ... JNK Mitogen-Activated Protein Kinases * Lymphokines / metabolism * Mitogen-Activated Protein Kinases / antagonists & inhibitors ... inhibit the activation of c-Jun N-terminal kinase (JNK) and extracellular-regulated kinase (ERK) signalling pathways by the pro ...
Jnk) and RhoGTPase family members; these signals dynamically direct Actin remodeling proteins (ARPs) to catalyze the ... src-Family Kinases * JNK Mitogen-Activated Protein Kinases * rho GTP-Binding Proteins ... Surprisingly, they were also regulators of Jnk pathway activity: both Src and the small GTPase Rho1 activated Jnk in a manner ... Jnk) and RhoGTPase family members; these signals dynamically direct Actin remodeling proteins (ARPs) to catalyze the ...
Hepatocyte I kappaB kinase beta (IKK beta) inhibits hepatocarcinogenesis by suppressing accumulation of reactive oxygen species ... I-kappa B Kinase * JNK Mitogen-Activated Protein Kinases * p38 Mitogen-Activated Protein Kinases ... Hepatocyte I kappaB kinase beta (IKK beta) inhibits hepatocarcinogenesis by suppressing accumulation of reactive oxygen species ...
... the mechanisms by which Gadd45 proteins inhibit cell cycle con ... The Gadd45 family of proteins, which includes alpha, beta, and ... 0/Nuclear Proteins; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases ... JNK Mitogen-Activated Protein Kinases / metabolism*. Liver Neoplasms / enzymology, metabolism*, pathology. MAP Kinase Signaling ... 0/Cell Cycle Proteins; 0/GADD45A protein, human; 0/GADD45G protein, human; 0/Intracellular Signaling Peptides and Proteins; ...
JNK Mitogen-Activated Protein Kinases / metabolism. Myocytes, Cardiac / metabolism*. Proto-Oncogene Proteins c-jun / metabolism ... 0/Proto-Oncogene Proteins c-jun; 0/Troponin T; 0/Tubulin; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases ... Expression of troponin T and beta-tubulin protein, c-jun protein, protein kinase Ca (PKCa), and c-jun N-terminal kinase (JNK) ... The c-jun protein, PKCa, and JNK were significantly expressed in the non-transfected group, and they reached a maximum at the ...
... mitogen-activated protein kinase/jun amino-terminal kinases (MAPK/JNK, 3 genes); nuclear factor-kappa beta (NFkB, 18 genes); ... and NFkB and MAP/JNK (7 genes). After controlling for self-reported and genomic estimates of race and ethnicity, polymorphisms ... the final SNPs were evaluated for their potential impact on protein function using two bioinformational tools. The following ... inflammatory pathways were represented: chemokines (3 genes); cytokines (12 genes); inflammasome (11 genes); Janus kinase/ ...
... kinase); EC 2.7.11.20 (Elongation Factor 2 Kinase); EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases); O41630Y8V3 ( ... EEF2K protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.13 (Protein Kinase C-delta); EC 2.7.11.2 ( ... An in vitro kinase assay revealed that the resultant c-Jun phosphorylation was primarily mediated via activated c-Jun N- ... terminal protein kinase (JNK). Moreover, flow cytometry indicated that ectopically overexpressed c-Jun in conjunction with ...
JNK Mitogen-Activated Protein Kinases); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases). ... Antiapoptotic gene and protein expression diminished and proapoptotic gene and protein expression increased noscapine-induced ... Prote nas Quinases JNK Ativadas por Mit geno/metabolismo. Lipossomos. Camundongos. Microt bulos/efeitos dos f rmacos. Microt ... Apoptosis related proteins (Cyt-c, Bax, Bcl-2 and Bcl-xL) levels were evaluated by western blot. RESULTS: Compared to the ...
... mitogen-activated protein kinase) in neurons. The results reveal new role of RG as a modulator of resolution of ... RG induced phosphorylation of p38 and JNK MAPK ( ... RG induced phosphorylation of p38 and JNK MAPK (mitogen- ... mitogen-activated kinase (MAPK); rosiglitazone (RG); thiazolidinedione (TZD) toll-like receptor (TLR); poly I:C (PIC); ... activated protein kinase) in neurons. The results reveal new role of RG as a modulator of resolution of neuroinflammation. View ...
We compared this genome, based on protein-coding gene orthology, with other publicly available coral genomes (Cnidaria, ... activation of NF-κB-inducing kinase, and positive regulation of JNK cascade (Table 3). The mitogen-activated protein kinase JNK ... with 40 proteins in A. digitifera. The P. damicornis genome contained 39 proteins with TNFR cysteine-rich domains, suggesting ... containing protein repertoire of nine anthozoan species reveals coral-specific expansions and uncharacterized proteins. Dev. ...
MAPK p-38, mitogen-activated protein kinases p-38; JNK, c-Jun N-terminal kinase; ERK, extracellular-signal-regulated kinase; -P ... mitogen-activated protein kinases p-38; JNK, c-Jun N-terminal kinase; ERK, extracellular-signal-regulated kinase; −P, ... Mitogen-activated protein kinases (MAPKs) p-38, JNK, and ERK. The levels were determined in lung tissue though an ELISA tests ... The p-38 mitogen-activated protein kinase is required for NF-kappaB-dependent gene expression: the role of TATA-binding protein ...
... p38 mitogen activated protein kinase (MAPK), SAPK/JNK and c-Jun; (5) phosphorylation of inhibitor of κB (IκB) kinase-αβ and I ... SAPK/JNK), c-Jun, and extracellular signal regulated kinase 1/2; and (3) expression of inducible nitric oxide synthase (iNOS) ... and cyclooxygenase (COX)-2 proteins in mouse skin. The treatment of RAW 264.7 cells with LicE (2.5-7.5 μmol/L) induced a ... transcriptional activity of activator protein (AP)-1. These results indicate that the LicE inhibition of NF-κB and AP-1 ...
Together, our data suggest that central ERK is involved in the analgesic and hyperalgesic effects of morphine while JNK, p38 ... However, i.t. injection of SB20358, a p38 inhibitor and SP660125, a JNK inhibitor, decreased the morphine-induced hyperalgesia ... Moreover, phospho-p38 and phospho-JNK levels are upregulated 96 h after morphine injection, time that coincides with the ... However, i.t. injection of SB20358, a p38 inhibitor and SP660125, a JNK inhibitor, decreased the morphine-induced hyperalgesia ...
... might contribute to PE and LPS-induced PE-like symptom by damaging trophoblast invasion and SA remodeling via activating ... phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and inflammatory cytokines IL-6 and MCP-1 were significantly ... might contribute to PE and LPS-induced PE-like symptom by damaging trophoblast invasion and SA remodeling via activating ... Johnson, G. L., and Lapadat, R. (2002). Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases ...
... mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP2) antibody (catalog #06-534), and MAPKAP2 peptide substrate ... because CEP-1347 did not inhibit p38-regulated mitogen-activated protein kinase-activated protein kinase-2 (MAPKAP2) activity ... 1994) Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science 266:1719-1724. ... Overexpression of mitogen-activated kinase kinase kinase 1 (MEKK1) and JNK1 in Cos7 cells. Cos7 cells were plated to 80% ...
Protein Isoforms (Isoforms)IBA 08/2012. 1. JNK Mitogen-Activated Protein KinasesIBA 08/2012. ... rho-Associated KinasesIBA 09/2015 - 09/2012. 2. Cyclic AMP-Dependent Protein Kinases (cAMP-Dependent Protein Kinase)IBA 05/2015 ... Role of cAMP-dependent protein kinase A activity in low-dose endothelial monocyte-activating polypeptide-II-induced opening of ... Role of ATP synthase alpha subunit in low-dose endothelial monocyte-activating polypeptide-II-induced opening of the blood- ...
Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298: 1911-1912. ... JNK, and AP-1 signaling, as well as Gi-protein(s), Jak, p38 MAPK/JNK, and NF-κB signaling. ... Anti-phospho-p38 MAPK Ab, or anti-phospho-JNK Ab were used to detect phosphorylated p38 MAPK or phosphorylated JNK levels by ... Because SPC also stimulated p38 MAPK and JNK activity in HUVECs, we investigated the roles of p38 MAPK and JNK in the ...
Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298: 1911-1912. ... The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation. Nature 438: 508-511. ... and downstream proteins (ERK1/2 and p38) observed to peak within 2-4 min. A wave of PTP activity is also activated by BCR ... and results in activation of protein kinase C and NF-κB. Syk interacts with PLCγ2 via adapters, whereas Btk can interact ...
1997) Role of p38 and JNK mitogen-activated protein kinases in the activation of ternary complex factors. Mol Cell Biol 17:2360 ... 1995) A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc Natl Acad Sci USA 92:7686-7689. ... MKK4 is a kinase upstream of JNK that phosphorylates and thus activates JNK (Natali et al., 1992; Sanchez et al., 1994). To ... 1996) Induction of acetylcholine receptor gene expression by ARIA requires activation of mitogen-activated protein kinase. J ...
In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits ... an important role for BCL-2 proteins at the endoplasmic reticulum is now well established. Signaling pathways emanating from ... with particular emphasis on the BCL-2 family proteins. ... both JNK and p38 mitogen-activated protein kinase are activated ... 2000). Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287: 664 ...
JNK. Introduction. The c-Jun NH2-terminal kinase (JNK) belongs to a family of mitogen-activated protein kinases, together with ... The JNK subgroup of mitogen-activated protein kinases is encoded by three loci: Jnk1 and Jnk2 are ubiquitously expressed, and ... which includes the activation of JNKs and p38 mitogen-activated protein kinase ( 17). ... Kinase activities were measured by immune complex kinase assays. C, analysis of JNK activation after treatment with MNU (100 μg ...
2012) Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement. Am J Physiol Lung ... a member of the mitogen-activated protein kinase kinase kinase family (Goldmann et al., 2013), is considered a key intermediate ... p38 mitogen-activated protein kinase, and NF-κB signaling in the obstructed kidney, and activation of JNK, p38, and the ... 2013) Calcineurin inhibitors recruit protein kinases JAK2 and JNK, TLR signaling and the UPR to activate NF-κB-mediated ...
  • and involved p38 and c-Jun amino-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, as further confirmed by OCP crystal-induced p38 and JNK MAPK phosphorylation. (inserm.fr)
  • Mitogen-activated protein kinase kinases (MAP2Ks) are substrates for direct phosphorylation by the MAP3K1 protein kinase. (wikipedia.org)
  • RG induced phosphorylation of p38 and JNK MAPK (mitogen-activated protein kinase) in neurons. (mdpi.com)
  • Specifically, activation of ras leads to phosphorylation and activation of extracellular receptor-activated kinase (ERK), which has been linked biologically to growth and differentiation processes, whereas stimulation of rac/cdc42 leads to an increase in the activity of JNK and p38, a response that is associated with stress and apoptosis. (jneurosci.org)
  • BCR cross-linking by Ag triggers phosphorylation of tyrosines within the ITAM motif domains of Igα and Igβ by Src family member tyrosine kinases (e.g. (jimmunol.org)
  • PLCγ2 and PI3K also initiate kinase cascades that result in phosphorylation of the MAPK family proteins ERK1/2 and p38. (jimmunol.org)
  • UVB (50-800 mJ/cm 2 ) dose-dependently induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun-NH 2 -kinase 1/2 (JNK1/2), and p38 kinase (p38K) as well as Akt, with an optimum response at 400 mJ/cm 2 UVB dose. (aacrjournals.org)
  • We show that the phosphorylation of the stress-activated protein kinases is not modulated by TORC2 nor is the heat-induced upregulation of heat-shock proteins. (biologists.org)
  • This kinase is activated by phosphorylation at threonine and tyrosine residues, catalyzed by the dual-specificity kinase MAPK kinase 6 (MKK6) ( 11 , 23 , 42 ). (asm.org)
  • Although protein phosphorylation via mitogen-activated protein kinases (MAPKs) has been suggested to be important in ABA signaling, the corresponding phosphatases are largely unknown. (plantphysiol.org)
  • The function of brown adipose tissue is to directly transfer energy from nutrients to heat by uncoupling protein (UCP) 1, which mediates uncoupling of oxidative phosphorylation from ATP synthesis (conferred thermogenesis) [ 8 - 10 ]. (hindawi.com)
  • Early, but not late, ERK1/2 phosphorylation in response to wounding, LPA, and ATP was EGFR independent, but sensitive to the inhibitors of calcium influx, protein kinase C and Src kinase. (arvojournals.org)
  • To test the potential for members of the mitogen-activated protein (MAP) kinase family to contribute to type 2 diabetes, we examined basal and insulin-stimulated Erk 1/2, JNK, and p38 phosphorylation in adipocytes isolated from healthy and type 2 diabetic individuals. (diabetesjournals.org)
  • Maximal insulin stimulation increased the phosphorylation of Erk 1/2 and JNK in healthy control subjects but not type 2 diabetic patients. (diabetesjournals.org)
  • In type 2 diabetic adipocytes, the basal phosphorylation status of these MAP kinases was significantly elevated and was associated with decreased IRS-1 and GLUT4 in these fat cells. (diabetesjournals.org)
  • Moreover, it repressed the LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation without affecting the activity of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. (aspetjournals.org)
  • MAPKKs typically have smaller regulatory domains and are activated by dual phosphorylation of serine and threonine residues within the activation loop of the catalytic domain. (biologists.org)
  • Ribonucleic acid interference and in vitro phosphorylation experiments showed that serine 376 is the target of the hematopoietic progenitor kinase 1 (HPK-1). (rupress.org)
  • These data reveal a novel negative feedback loop involving HPK-1-dependent serine phosphorylation of SLP-76 and 14-3-3 protein recruitment, which tunes T cell activation. (rupress.org)
  • Furthermore, DHA significantly increased phosphorylation of peroxisome proliferator-activated receptor-gamma (PPARγ), and combined with PPARγ stealth RNAi oligonucleotide, we confirmed that DHA inhibition of AGEs-induced microglia activation was partially through the PPARγ/NFκB pathway. (omega-research.com)
  • The AGEs-RAGE axis downstream signal transducers increased mitogen-activated protein kinase (p38 and JNK) phosphorylation. (omega-research.com)
  • During neutrophil activation two cytosolic proteins, p67 phox and p47 phox , the latter following phosphorylation, also associate to complete formation of the holoenzyme. (plantphysiol.org)
  • Depletion of LOX by RNAi enhanced phosphorylation of Smad2 by a focal adhesion kinase (FAK)-dependent mechanism. (biomedcentral.com)
  • The anti-inflammatory properties of E. japonica leaf extract resulted from inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions through downregulation of nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinases (MAPK) phosphorylation. (omicsonline.org)
  • Although p38 is topologically similar to the MAP kinase ERK2, the phosphorylation Lip (a regulatory loop near the active site) adopts a different fold in p38. (pnas.org)
  • While MAP kinases are selective in their interactions with activators and substrates, they share a common regulatory mechanism, being activated 100- to 1000-fold or more ( 21 - 23 ) by dual phosphorylation on a conserved threonine and a conserved tyrosine residue in the phosphorylation Lip (residues Leu-171-Val-183) near the active site ( 24 ). (pnas.org)
  • The structure is compared with that of ERK2, which we solved previously ( 27 ) to understand how the common mechanism of activation by dual phosphorylation and the common specificity for proline is integrated with the unique specificity of these kinases for their activating enzymes, substrates, and inhibitors. (pnas.org)
  • MAPKs are activated via phosphorylation on threonine and tyrosine and are inactivated by a unique family of dual specificity phosphatases, MAPK phosphatases, which are encoded by immediate early genes and induced in response to environmental stressors and growth factor stimulation. (aacrjournals.org)
  • MAPKs are activated upon dual phosphorylation by MAPK kinase, which in turn is activated by the Ras/Raf pathway ( 17 ). (aacrjournals.org)
  • We used a well-characterized monocrotaline (MCT)-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK) phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt) pathway and nuclear factor (NF)-?B activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. (jove.com)
  • The mitogen-activated protein kinases ERK1/2, SAPK/JNK and p38 were activated via phosphorylation following 1-h exposures. (cdc.gov)
  • Hexavalent chromium up-regulated p-38 phosphorylation 23-fold and SAPK/JNK phosphorylation 17-fold, with a comparatively modest 4-fold increase in ERK1/2 phosphorylation. (cdc.gov)
  • Manganese caused a two- to four-fold increase in SAPK/JNK and ERK 1/2 phosphorylation, with no observed effects on p38 kinase. (cdc.gov)
  • Western blotting revealed that barbigerone inhibited phosphorylation of AKT, FAK and MAPK family members, including ERK, JNK, and p38 MAPKs, in B16F10 cells mainly through the MEK3/6/p38 MAPK signaling pathway. (koreascience.or.kr)
  • Changes in phosphorylation and protein expression of p38, Erk1/2, JNK, c-Jun, and XIAP were detected by Western blot analysis. (biomedcentral.com)
  • Herein, we show that JSI-124 activates c-Jun N-terminal kinase (JNK) and increases both the expression and serine phosphorylation of c-Jun protein in the B leukemic cell lines BJAB, I-83 and NALM-6. (biomedcentral.com)
  • The expression of Runx2, OCN and OSX was up-regulated by the supplement of Cyto D. ALP activity, calcium deposition, and phosphorylation level of p38 protein were also improved. (eurekaselect.com)
  • Adenine inhibited the phosphorylation of signaling molecules important to FcɛRI-mediated allergic reactions such as Syk, PLCγ2, Gab2, Akt, and mitogen activated protein kinases ERK and JNK. (sigmaaldrich.com)
  • Growth factors activate mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs) and Jun kinases (JNKs). (sciencemag.org)
  • The aim of our investigation was to analyze the molecular mechanism that explain the anti-inflammatory effects of anesthetic pre-conditioning with sevoflurane focusing on its effects on MAPKs (mitogen-activated protein kinases), NF-κB (nuclear factor kappa beta) pathways, and apoptosis in an experimental lung autotransplant model. (scielo.br)
  • The mitogen activated protein kinases (MAPKs) family of proteins is intracellular signal-transduction pathways that have been shown to play an important role in the development of IR injury. (scielo.br)
  • SPC treatment caused the activation of NF-κB and AP-1, which are essential for SPC-induced CCL2 production, and induced the activation of three MAPKs, ERK, p38 MAPK, and JNK. (jimmunol.org)
  • Whereas Arabidopsis plants depleted of PP2C5 show an enhanced ABA-induced activation of MPK3 and MPK6, ectopic expression of PP2C5 in tobacco ( Nicotiana benthamiana ) resulted in the opposite effect, with the two MAPKs salicylic acid-induced protein kinase and wound-induced protein kinase not being activated any longer after ABA treatment. (plantphysiol.org)
  • Pathway specificity is regulated at several levels, including kinase-kinase and kinase-substrate interactions, colocalization of kinases by scaffold proteins, and inhibition of cross-talk/output by the MAPKs themselves. (biologists.org)
  • MAPKs bind stably to substrates, MAPKKs and scaffold proteins through multiple docking domains (e.g. (biologists.org)
  • Cell survival and cell death are tightly controlled by numerous signal enzymes and regulators such as mitogen-activated protein kinases (MAPKs) and heat shock proteins (HSPs). (aacrjournals.org)
  • After the final treatment, brain tissues were isolated for the immunohistochemical analysis of glial markers and choline acetyltransferase (ChAT), as well as for the western blot analysis of proinflammatory cytokines, toll-like receptor (TLR)-related pathway, receptor for advanced glycation end products (RAGE), angiotensin-II (Ang-II), and phosphorylated mitogen-activated protein kinases (MAPKs). (thefreelibrary.com)
  • GBE also attenuated the BCCAo-related increases in the hippocampal expression of proinflammatory cytokines (TNF-[alpha], IL-1[beta], and IL-6), TLR4, myeloid differentiation primary response gene 88, RAGE, Ang-II, and phosphorylated MAPKs (ERK, p38, and JNK). (thefreelibrary.com)
  • MAPKs (mitogen-activated protein kinases) regulate a variety of cellular processes in response to extracellular signals. (biochemj.org)
  • MAPKs are activated through a protein kinase cascade in which a MAP3K (MAPK kinase kinase) activates an MKK (MAPK kinase, also known as MAP2K) that, in turn, activates a MAPK [ 1 ]. (biochemj.org)
  • MAPKs can be grouped into three families: extracellular signal-regulated kinase (ERK), c-Jun-NH 2 kinase, and p38 ( 12 ). (aacrjournals.org)
  • In addition, the LPS- induced translocation of nuclear factor-κB (NF-κB), as well as activation of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol‑3 kinase (PI3K)/Akt pathways were inhibited by schisandrin A. Furthermore, schisandrin A significantly diminished the LPS-stimulated accumulation of intracellular reactive oxygen species, and effectively enhanced the expression of NF erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). (spandidos-publications.com)
  • Accumulating evidence suggests that LPS causes overproduction of pro-inflammatory mediators and cytokines through the activation of nuclear factor-κB (NF-κB) associated with the mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3 kinase (PI3K)/Akt pathways ( 12 - 14 ). (spandidos-publications.com)
  • Three mitogen-activated protein kinases, (MAPKs), ERK1/2, JNK and p38, contribute uniquely and combinatorially to the expression of each of these subunit genes. (scienceblogs.com)
  • Growth control and apoptosis in mammalian cells are highly regulated by receptor tyrosine kinase receptors (RTKs), which, upon ligand-dependent activation, launch the activation of a series of downstream signal transduction pathways, including MAPKs and the cell survival-promoting protein kinase B (Akt) ( 33 , 45 ). (physiology.org)
  • That osmotic stress activates MAPKs was first described in Saccharomyces cerevisiae ( 28 ) and later also in mammalian cells ( 67 ). (physiology.org)
  • Co-precipitation analysis between SKRP1 and MKK7-activating MAPKK kinases (MAPKKKs) revealed that SKRP1 also interacted with the MAPKKK, apoptosis signal-regulating kinase 1 (ASK1), but not with MAP kinase kinase kinase 1 (MEKK1). (uniprot.org)
  • Apoptosis related proteins (Cyt-c, Bax, Bcl-2 and Bcl-xL) levels were evaluated by western blot. (bireme.br)
  • Neurons undergoing apoptosis can be rescued by trophic factors that simultaneously increase the activity of extracellular signal-regulated kinase (ERK) and decrease c-Jun N-terminal kinase (JNK) and p38. (jneurosci.org)
  • Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the endoplasmic reticulum is now well established. (nature.com)
  • In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits metabolic stress, genomic instability and tumorigenesis. (nature.com)
  • JNK activation has been shown to induce apoptosis, cell proliferation, or transformation, depending on the cell type and stimuli ( 5 ). (aacrjournals.org)
  • In addition, DR6(-/)- T cells showed preference toward Th2 differentiation in vitro.Therefore, DR6, working through JNK, rather than apoptosis, functions to attenuate the Th2 response.This is the first demonstration of a role in the activation and differentiation of Th cells by DR6 in particular and DRs in general. (nih.gov)
  • Arsenite-induced apoptosis in cortical neurons is mediated by c-Jun N-terminal protein kinase 3 and p38 mitogen-activated protein kinase. (semanticscholar.org)
  • Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. (semanticscholar.org)
  • The phosphatidylinositol 3-kinase (PI3K)/Akt pathway acts as a critical regulator of apoptosis, cell cycle regulation, and tumor proliferation in MM ( 4 ). (aacrjournals.org)
  • Mitogen-activated protein kinase (MAPK) pathways regulate diverse processes ranging from proliferation and differentiation to apoptosis. (biologists.org)
  • In this study, we investigated the function of p38 mitogen-activated protein kinase (MAPK) and caspase-8 in DATS-induced apoptosis of human CNE2 cells using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], flow cytometry assay, and Western blotting. (scielo.br)
  • Caspase is an inactive enzyme zymogen under normal circumstances, but once activated it will trigger the caspase cascade, eventually leading to apoptosis. (scielo.br)
  • In the central control and effective stage of apoptosis, activated caspase-8 can lead directly to the appearance of apoptotic structural characteristics in cells, and play a key role in the process of apoptosis (6,7). (scielo.br)
  • In mouse embryo fibroblast cells, DUSP1 protein abundance is greatly increased after oxidative stress in a p53-dependent manner and also when apoptosis is triggered. (aacrjournals.org)
  • showed that hyperglycemia can enhance apoptosis of anulus fibrosis cells in a JNK pathway and p38 mitogen-activated protein kinase (MAPK) pathway dependent fashion. (portlandpress.com)
  • This imbalance between pro- and anti-inflammatory molecules seem to activate JNK pathway and p38 MAPK pathway to induce apoptosis of anulus fibrosis and nucleus pulposus cells. (portlandpress.com)
  • Apoptosis signal-regulating kinase 1 (ASK1) is a widely expressed redox-sensitive serine threonine kinase that activates p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase kinases, and induces apoptotic, inflammatory, and fibrotic signaling in settings of oxidative stress. (jci.org)
  • Inhibition of the JNK signaling pathway failed to effect cell cycle arrest or apoptosis induced by JSI-124 but repressed JSI-124 induced c-Jun expression in these leukemia cells. (biomedcentral.com)
  • Taken together, our data demonstrates that JSI-124 activates the JNK signaling pathway independent of apoptosis and cell cycle arrest, leading to increased VEGF expression. (biomedcentral.com)
  • The blockage of apoptosis in cells destined to die can activate alternative pathways leading to cell death, normally involving necrosis ( 2 ). (aacrjournals.org)
  • Apart from c-Jun, JNK has been reported to phosphorylate other transcription factors, such as activating transcription factor 2, E-26-like protein-1, p53, and c-Myc ( 4 ), as well as members of the B-cell leukemia/lymphoma 2 (Bcl-2) family of apoptosis regulators ( 5 ). (aacrjournals.org)
  • Scaffold role of a mitogen-activated protein kinase phosphatase, SKRP1, for the JNK signaling pathway. (uniprot.org)
  • Stress-activated protein kinase (SAPK) pathway-regulating phosphatase 1 (SKRP1) has been identified as a member of the mitogen-activated protein kinase (MAPK) phosphatase (MKP) family that interacts physically with the MAPK kinase (MAPKK) MKK7, a c-Jun N-terminal kinase (JNK) activator, and inactivates the MAPK JNK pathway. (uniprot.org)
  • Although these findings indicated that SKRP1 contributes to the precise regulation of JNK signaling, it remains to be elucidated how SKRP1 is integrated into this pathway. (uniprot.org)
  • Although the signaling cascade from growth factor receptors to ERKs is relatively well understood, the pathway leading to JNK activation is more obscure. (sciencemag.org)
  • Here, we found that the autophagy system is activated as a novel signaling pathway in response to ER stress. (nih.gov)
  • In IRE1-deficient cells or cells treated with c-Jun N-terminal kinase (JNK) inhibitor, the autophagy induced by ER stress was inhibited, indicating that the IRE1-JNK pathway is required for autophagy activation after ER stress. (nih.gov)
  • Surprisingly, they were also regulators of Jnk pathway activity: both Src and the small GTPase Rho1 activated Jnk in a manner dependent on ARPs during invasion. (nih.gov)
  • Low-dose endothelial monocyte-activating polypeptide-ii increases permeability of blood-tumor barrier by caveolae-mediated transcellular pathway. (curehunter.com)
  • Inhibition by CEP-1347 of the JNK1 signaling pathway appeared to be selective, because CEP-1347 did not inhibit p38-regulated mitogen-activated protein kinase-activated protein kinase-2 (MAPKAP2) activity in Cos7 cells subjected to osmotic shock. (jneurosci.org)
  • The Jak/STAT3 pathway was also activated upon SPC stimulation of HUVECs. (jimmunol.org)
  • The membrane-bound proteins decay-accelerating factor (DAF, CD55), protectin (CD59), and membrane cofactor protein (MCP, CD46) are expressed on many cell types and provide protection against the constant low-level activation of the alternative pathway. (bloodjournal.org)
  • Progressive degeneration of human mesencephalic neuron-derived cells triggered by dopamine-dependent oxidative stress is dependent on the mixed-lineage kinase pathway. (semanticscholar.org)
  • Inhibition of the c-Jun N-terminal kinase signaling pathway by the mixed lineage kinase inhibitor CEP-1347 (KT7515) preserves metabolism and growth of trophic factor-deprived neurons. (semanticscholar.org)
  • Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development. (springer.com)
  • However, inhibition of the p38 pathway prevented the insulin-stimulated decrease in GLUT4 protein levels. (diabetesjournals.org)
  • Major MM growth factors, such as interleukin-6 (IL-6) and insulin-like growth factor-I (IGF-I), also activate the PI3K pathway ( 9 , 10 ). (aacrjournals.org)
  • Each MAPK pathway contains a three-tiered kinase cascade comprising a MAP kinase kinase kinase (MAPKKK, MAP3K, MEKK or MKKK), a MAP kinase kinase (MAPKK, MAP2K, MEK or MKK) and the MAPK. (biologists.org)
  • In treated normal human fibroblasts, all four agents induced the adaptive cell survival response: heat shock, unfolded protein, autophagic and antioxidant responses and the c-jun N-terminal kinase pathway, at the transcriptional and translational levels. (elsevier.com)
  • Scaffold proteins simultaneously associate with various components of the MAPK signalling pathway and play a crucial role in signal transmission and MAPK regulation. (biochemj.org)
  • In addition, some of the scaffold proteins are able to allosterically activate the associated kinase or, alternatively, they may restrict the activation of the signalling pathway to a specific subcellular compartment [ 3 ]. (biochemj.org)
  • Knockdown of GOPC increases activation of the mitogen‑activated protein kinase‑extracellular signal‑regulated kinase 1/2 pathway and cancer cell progression in colorectal cancer. (spandidos-publications.com)
  • The present study focused on the Golgi-associated PDZ- and coiled-coil motif-containing (GOPC) since it has been reported that the knockdown of GOPC in cells increases activation of the mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (Erk) 1/2 pathway. (spandidos-publications.com)
  • The mitogen-activated protein kinase (MAPK) cascade is a predominant pathway for cell growth and proliferation. (aacrjournals.org)
  • The activation of production of PGE2 (due to activation of COX-2 pathway) seems to be dependent on p38/c-Fos and JNK/c-Jun activation in an AP-1-dependent manner. (portlandpress.com)
  • Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK)1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. (jove.com)
  • Interestingly, data strongly suggests that tolerance to ∆9-THC, but not the other two synthetic agonists, is partially mediated through a c-Jun N-terminal kinase (JNK) signaling pathway. (elsevier.com)
  • The MALT1 paracaspase plays an essential role in Activated B-cell like Diffuse Large B cell Lymphoma (ABC DLBCL) downstream of B cell and Toll-like receptor pathway genes mutated in these tumors. (jci.org)
  • The JNK pathway activation c-Jun leads to transcriptional activation of many genes. (biomedcentral.com)
  • The JNK pathway is activated by a variety of stimuli including UV radiation and DNA damaging agents. (biomedcentral.com)
  • Conclusion: Cyto D can promote the osteogenic differentiation of MC3T3 cells via the p38-MAPK signaling pathway, but not the ERK1/2 or JNK, and it is a potential agent to improve the osteogenesis of MC3T3 cells. (eurekaselect.com)
  • It is thus likely that cell swelling via activation of ERK1/2 and cell shrinkage via activation of the p38 and JNK pathway and inhibition of the PDGFR signaling pathway may act as key players in the regulation of tissue homeostasis. (physiology.org)
  • Taken together, our data suggest that the transcriptional inducible NOS response to OCP crystals involved both the p38 and the JNK MAPK pathways, probably under the control of activator protein-1. (inserm.fr)
  • Here we show that the synthetic glucocorticoid dexamethasone (Dex) and retinoic acid (RA) inhibit the activation of c-Jun N-terminal kinase (JNK) and extracellular-regulated kinase (ERK) signalling pathways by the pro-angiogenic agents tumor necrosis factor and vascular endothelial growth factor in endothelial cells. (nih.gov)
  • As a number of pro-angiogenic factors activate AP-1 transcription factor via the JNK and ERK pathways, our results suggest that the antagonism with AP-1 may underlie at least partially the anti-angiogenic effect of glucocorticoids and retinoids. (nih.gov)
  • Gadd45-alpha and Gadd45-gamma utilize p38 and JNK signaling pathways to induce cell cycle G2/M arrest in Hep-G2 hepatoma cells. (biomedsearch.com)
  • Importantly, we found that expression of either Gadd45alpha or Gadd45gamma activated the P38 and JNK kinase pathways to induce G2/M arrest. (biomedsearch.com)
  • The intracellular signaling systems (signal transduction pathways) can reversibly modify the activity of many inflammatory proteins. (scielo.br)
  • This review provides an overview of ER-associated apoptotic and autophagic signaling pathways, with particular emphasis on the BCL-2 family proteins. (nature.com)
  • This finding highlights both an additional connection between apoptotic and autophagic pathways and a novel role for BCL-2 family proteins at the ER. (nature.com)
  • Similar to V12Rac1, Tiam1 stimulates the activity of the c-Jun NH2-terminal kinase (JNK).This Rac-dependent stimulation of JNK also requires membrane association of Tiam1.We conclude that the regulated membrane localization of Tiam1 through its NH2-terminal PH domain determines the activation of distinct Rac-mediated signaling pathways. (nih.gov)
  • Here, we used tumor promoter-sensitive JB6 mouse epithelial cell model and studied the effect of silibinin on two different mitogens [UVB and epidermal growth factor (EGF)] that induce mitogenic and cell survival signaling pathways. (aacrjournals.org)
  • However, Syk(hi)/ZAP-70(-) T cells differ from control T cells with respect to the T cell antigen receptor (TCR)-mediated activation of the MAPK cascades: extracellular signal-regulated kinase activity and recruitment of the JNK and p38 stress-related MAPK pathways are diminished. (cnrs.fr)
  • The protein functions primarily as a transcription factor, targeting and activating multiple downstream genes that ultimately regulate these pathways. (aacrjournals.org)
  • Signal transduction pathways activated and required for mammary carcinogenesis in response to specific oncogenes. (koreascience.or.kr)
  • Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. (koreascience.or.kr)
  • Inhibition of MAPK Kinase signaling pathways suppressed renal cell carcinoma growth and angiogenesis in vivo. (koreascience.or.kr)
  • However, induction of these responses by β-CDODA-Me was PPARγ-independent and due to activation of phosphatidylinositol-3-kinase, mitogen-activated protein kinase, and jun N-terminal kinase pathways by this compound. (aspetjournals.org)
  • In contrast, β-CDODA-Me also decreased androgen receptor (AR) and prostate-specific antigen (PSA) mRNA and protein levels through kinase-independent pathways. (aspetjournals.org)
  • Thus, potent inhibition of LNCaP cell survival by β-CDODA-Me is due to PPARγ-independent activation of multiple pathways that selectively activate growth-inhibitory and proapoptotic responses. (aspetjournals.org)
  • In conclusion, combining diabetes and hypertension-potentiated retinal oxidative/inflammatory stress promoted imbalance between the JNK stress and survival Akt pathways resulting in accelerated retinal cell death and acellular capillary formation. (molvis.org)
  • Our results identify key molecular mechanisms involved such as imbalance between the stress Jun N-terminal kinase (JNK) and survival protein kinase B (PKB/Akt) pathways and increased systemic and retinal oxidative/inflammatory stress, resulting in increased retinal cell death and exacerbated acellular capillary formation. (molvis.org)
  • MAP3K1 (or MEKK1) is a serine/threonine kinase and ubiquitin ligase that performs a pivotal role in a network of enzymes integrating cellular receptor responses to a number of mitogenic and metabolic stimuli, including: TNF receptor superfamily (TNFRs), T-cell receptor (TCR), Epidermal growth factor receptor (EGFR), and TGF beta receptor (TGFβR). (wikipedia.org)
  • Roles of Serine/Threonine Phosphatases in Low-Dose Endothelial Monocyte-Activating Polypeptide-II-Induced Opening of Blood-Tumor Barrier. (curehunter.com)
  • Activation of the small GTP binding proteins leads to modulation of serine/threonine kinases in the mitogen-activated protein kinase (MAPK) family. (jneurosci.org)
  • Once activated, these serine/threonine kinases translocate to the nucleus and phosphorylate target transcription factors, including AP-1 ( 8 - 12 ). (aacrjournals.org)
  • Further, Akt, the downstream serine/threonine kinase of phosphatidylinositol-3-kinase family members, is also critical for UVB-induced tumor promotion ( 17 ). (aacrjournals.org)
  • Target of rapamycin (TOR) is a conserved serine/threonine kinase of the phosphoinositide 3-kinase (PI3K)-related kinase family, and functions in two distinct complexes, TOR complex 1 (TORC1) and TOR complex 2 (TORC2). (biologists.org)
  • PKC is a family of at least 12 serine/threonine protein kinase isoforms which are involved in diverse cellular responses ( 24 , 43 ). (asm.org)
  • Serine and threonine kinases may contribute to insulin resistance and the development of type 2 diabetes. (diabetesjournals.org)
  • Serine and threonine kinases are believed to play an important role in the onset of insulin resistance by regulating IRS-1 and GLUT4 protein levels through both pre- and posttranslational mechanisms ( 6 , 10 ). (diabetesjournals.org)
  • Not unexpectedly, insulin resistance in cells and animals is associated with increased serine kinase activity toward IRS-1 ( 12 ). (diabetesjournals.org)
  • Furthermore, serine/threonine kinases are often involved with the regulation of gene expression by serving as intermediates in signal transduction cascades that link extracellular and intracellular stimuli to the nucleus ( 13 ). (diabetesjournals.org)
  • Thus serine/threonine kinases have the potential to contribute to the diminished GLUT4 mRNA levels in insulin-resistant adipose tissue. (diabetesjournals.org)
  • Specifically, members of the mitogen-activated protein (MAP) kinase family of serine-threonine kinases may contribute to the development of insulin resistance. (diabetesjournals.org)
  • PI3K activates phosphatidylinositol-dependent kinase 1 ( 6 ), which in turns activates the serine-threonine kinase Akt, a mediator of MM proliferation ( 7 , 8 ). (aacrjournals.org)
  • We discovered that caspase activity and jun N-terminal kinase (JNK) signaling both play a role in OSN death, and inhibition of JNK activity suppresses effector caspase (caspase-3) activation. (nih.gov)
  • Furthermore, insulin promotes survival of fetal chick forebrain neurons concomitant with inhibition of p38 in the absence of an effect on ERK and JNK activity ( Heidenreich and Kummer, 1996 ). (jneurosci.org)
  • Inhibition of p38 MAPK or JNK by specific inhibitors caused a dramatic decrease in SPC-induced CCL2 production. (jimmunol.org)
  • These granules are formed in response to protein translation inhibition imposed by heat stress that appears to be less efficient in the absence of TORC2 function. (biologists.org)
  • Inhibition of extracellular signal-regulated kinase activation abrogates matrix-induced insulin secretion and effectively preserves the insulin content of adherent β-cells. (diabetesjournals.org)
  • Inhibition of Erk 1/2, JNK, or p38 had no effect on insulin-stimulated reduction of IRS-1 protein levels. (diabetesjournals.org)
  • This increase was associated with significant increases in phosphorylated-Jun N-terminal kinase (pJNK) activation, phosphorylated-Akt inhibition, plasma and retinal lipid peroxides, and soluble intracellular adhesion molecule-1 (sICAM-1) levels. (molvis.org)
  • Knockdown of c-Jun expression and inhibition of JNK activation significantly blocked JSI-124 induced VEGF expression. (biomedcentral.com)
  • Pharmacologic inhibition of JNK provoked a further increase of the Δ Ψ M , an increase in reactive oxygen species (ROS) production, and a sustained decrease in cell viability due to necrosis. (aacrjournals.org)
  • Accordingly, the reduction in neural tumor cell viability induced by JNK inhibition was largely attenuated in serum-deprived fibroblasts. (aacrjournals.org)
  • Silibinin also suppressed UVB-induced activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) activation, which are activated by ERK1/2 and Akt. (aacrjournals.org)
  • In the present study, the role of extracellular signal-regulated kinases 1/2 (ERK1/2) in regulating EGFR transactivation was investigated. (arvojournals.org)
  • In human U251 glioblastoma and A549 lung cancer cell lines, Erk1/2 and JNK/SAPK were found to mediate this effect of HO3089 since inhibitors of these kinases ameliorated it. (jove.com)
  • In murine 4T1 breast cancer cell line, p38 MAPK rather than Erk1/2 or JNK/SAPK was identified as the main mediator of HO3089's radiosensitizing effect. (jove.com)
  • JSI-124 also activated MAPK p38 and MAPK Erk1/2 albeit at lower levels than JNK activation. (biomedcentral.com)
  • JNK is a member of the mitogen activated protein kinase (MAPK) family that includes p38 and Erk1/2. (biomedcentral.com)
  • Based on these results, we conclude that ligand-dependent activation of PDGFR-β and its downstream effectors Akt, MEK1/2, and ERK1/2 is strongly modulated (inhibited) by hyperosmotic cell shrinkage, whereas cell swelling does not seem to affect the activation of the receptor but rather to activate ERK1/2 via a different mechanism. (physiology.org)
  • A screen of 72 inhibitors against 456 human kinases. (guidetopharmacology.org)
  • A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfiler TM service. (guidetopharmacology.org)
  • A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase Hotspot SM platform. (guidetopharmacology.org)
  • It is strongly induced by mitogenic and proinflammatory stimuli, superinduced by inhibitors of protein synthesis, and acutely regulated at both transcriptional and posttranscriptional levels ( 17 , 37-39 , 46 , 47 ). (asm.org)
  • Wounding-, LPA-, and ATP-induced HB-EGF shedding and EGFR activation were attenuated by the MAPK/ERK kinase (MEK) inhibitors PD98059 and U0126, as well as by ADAM10 and -17 inhibitors. (arvojournals.org)
  • To determine whether MAP kinases were involved in the downregulation of IRS-1 and GLUT4 protein levels, selective inhibitors were used to inhibit these MAP kinases in 3T3-L1 adipocytes treated chronically with insulin. (diabetesjournals.org)
  • The results indicated that DATS activates p38MAPK and caspase-8, but both inhibitors have an effect on P38MAPK and caspase-8 activity. (scielo.br)
  • The results explain why MAP kinases are specific for different activating enzymes, substrates, and inhibitors. (pnas.org)
  • A pyrimidine imidazole compound found to inhibit the synthesis of tumor necrosis factor has been shown to bind tightly to p38 ( 2 ), suggesting that pharmacological inhibitors can bind to individual members of this kinase family. (pnas.org)
  • Materials and methods: Clonogenic survival assays and Western blot examinations were performed following telecobalt irradiation of cancer cells in the presence or absence of various combinations of PARP- and selective mitogen-activated protein kinase (MAPK) inhibitors. (jove.com)
  • Cell migration was repressed by interfering with distinct signalling systems through inhibitors of PI3K, JNK, p38 mitogen-activated protein kinase and/or mTOR. (bmj.com)
  • The present studies demonstrated that treatment of U-937 and HL-60 myeloid leukemia cells with TPA, phorbol-12,13-dibutyrate, or bryostatin 1 was associated with the induction of stress-activated protein kinase (SAPK). (asm.org)
  • We showed that TPA induced the association of PKCβ with MEK kinase 1 (MEKK-1), an upstream effector of the SAPK/ERK kinase 1 (SEK1)→SAPK cascade. (asm.org)
  • The observed effects of welding fume metals on cellular signaling in lung epithelium demonstrate a potentially significant interplay between stress-response signaling (p38 and SAPK/JNK) and anti-apototic signaling (ERK 1/2) that is dependant on the specific metal or combination of metals involved. (cdc.gov)
  • These results demonstrate the existence of two distinct Ras-dependent MAPK cascades--one initiated by Raf-1 leading to ERK activation, and the other initiated by MEKK leading to JNK activation. (sciencemag.org)
  • Growth factors may mediate neuronal survival by regulating signaling cascades downstream of the small GTP binding proteins ras, rac, and cdc42 (for review, see Denhardt, 1996 ). (jneurosci.org)
  • Taken together, our results demonstrate important roles of c-JUN and JNK in neuregulin-mediated expression of the AChR ε-subunit gene and suggest that neuregulin activates multiple signaling cascades that converge to regulate AChR ε-subunit gene expression. (jneurosci.org)
  • By interacting with a range of cochaperones and client proteins, both constitutive and inducible HSPs regulate the functioning of other proteins and indeed whole signaling cascades. (asahq.org)
  • A model presented for substrate and activator interactions has implications for the evolution of protein kinase cascades. (pnas.org)
  • Oxidative stress and neurohumoral factors play important role in the development of hypertension-induced vascular remodeling, likely by disregulating kinase cascades and transcription factors. (jove.com)
  • HB-EGF is synthesized as a type-1 transmembrane protein that can be cleaved to release a soluble 14- to 20-kDa growth factor via ectodomain shedding, 7 8 9 which has emerged as an important posttranslational mechanism to regulate the functions of various membrane proteins. (arvojournals.org)
  • IRF family members regulate transcription through interactions with proteins that share similar DNA-binding motifs, such as IFN-stimulated response elements (ISRE), IFN consensus sequences (ICS), and IFN regulatory elements (IRF-E) (2). (cellsignal.com)
  • Additional SH2 domain binding motifs in the N-terminal region of SLP-76, encompassing phosphorylated Y113, Y128, and Y145, recruit the adaptor Nck, the guanine-nucleotide exchange factor Vav-1 and the inducible T cell kinase, which regulate actin cytoskeleton reorganization and PLC-γ1 activation ( 9 ). (rupress.org)
  • HEAT shock proteins (HSP), also called stress proteins , are induced by specific types of stress, including heat, and they are highly conserved from bacteria to humans. (asahq.org)
  • Mitogen-activated protein kinase activation and heat shock proteins expression were determined by immunoblot with specific antibodies. (aacrjournals.org)
  • and (6) transcriptional activity of activator protein (AP)-1. (mdpi.com)
  • Activated JNKs phosphorylate c-Jun, JunD, activating transcription factor, and other transcriptional factors, which are involved in the formation and activation of the activator-protein 1 (AP-1) complex ( 4 ). (aacrjournals.org)
  • The Tiam1 gene encodes an activator of Rac1, and similarly to constitutively activated (V12)Rac1, overexpression of Tiam1 in fibroblasts induces the formation of membrane ruffles. (nih.gov)
  • Transcription factors nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) are stoutly implicated in UVB-mediated cell transformation and tumor promotion ( 5 - 7 ). (aacrjournals.org)
  • The chimeric transcript was stabilized by a constitutively active form of MAPK kinase 6, an activator of p38. (asm.org)
  • Irisolidone significantly inhibited the DNA binding and transcriptional activity of nuclear factor (NF)-κB and activator protein-1. (aspetjournals.org)
  • For instance, LAT binds phospholipase C (PLC)-γ1 ( 5 ), which regulates Ca 2+ - and diacylglycerol-dependent events (e.g., activation of the NFAT transcription factor and protein kinase C [PKC]), and Grb2, which recruits the Ras-specific activator SOS or the E3-ubiquitin ligase Casitas B lineage lymphoma proto-oncogene ( 8 ). (rupress.org)
  • In turn, activated p38 phosphorylates numerous substrates which include kinases such as MAPK-activated protein kinase 2 (MAPKAPK-2) and -3 ( 18 , 34 , 49 ). (asm.org)
  • Substrates of MAPKAPK-2 and -3 include the small heat shock protein hsp27, an abundant cytoplasmic protein of uncertain function ( 15 , 18 , 53 ). (asm.org)
  • TCR engagement activates the protein tyrosine kinases Lck, Fyn, and ζ chain-associated protein of 70 kD that initiate the signaling cascade and contribute to the assembly of a "signalosome," a multiprotein complex including various enzymes, their substrates, and scaffold/adaptor proteins ( 4 ). (rupress.org)
  • Scaffold proteins act as multidomain-interacting surfaces that serve as a meeting platform for kinases and substrates to orchestrate specific transmission of signalling. (biochemj.org)
  • By the interaction with two or more components of the cascade, scaffold proteins increase the efficiency of signalling by concentrating proteins locally and positioning kinases in close proximity to their substrates. (biochemj.org)
  • Each MAP kinase is characterized by the substrates it phosphorylates and by the distinct MAP/ERK kinases (MEKs) by which it is preferentially activated. (pnas.org)
  • MAP kinases also share a common specificity for substrates containing proline in the P+1 position ( 25 , 26 ). (pnas.org)
  • Protein substrates of interest are purified recombinantly, phosphorylated in vitro using the upstream kinase, and adsorbed to 96-well plates. (mcponline.org)
  • Numerous different MAPKKKs exist, including Raf isoforms, Ste11 relatives MEKK1-MEKK4, mixed lineage kinases (MLKs), Tao proteins and Mos. (biologists.org)
  • WDR62 interacts with all JNK isoforms through a D domain motif located at the C-terminus. (biochemj.org)
  • Cytokine signaling through MAP3K1 utilises two-stage cell signaling to recruit the signal transduction mechanism to cytokine receptors and then release the activated signal transduction components, altered by post-translational modification, from the cellular membrane. (wikipedia.org)
  • 12 13 16-18 Thrombin exerts its effects via a family of G-protein-coupled protease-activated receptors (PAR). (bloodjournal.org)
  • Each complex comprises the kinase along with specific regulatory subunits that give the kinase its functional specificity and structural distinction. (biologists.org)
  • During the last decade, the importance of scaffold proteins for providing signal specificity and fidelity has become evident [ 2 ]. (biochemj.org)
  • We report here that p53 regulates DUSP1 , a dual-specific threonine and tyrosine phosphatase with stringent substrate specificity for mitogen-activated protein kinase (MAPK). (aacrjournals.org)
  • These sites are bound with specificity by the p53 protein, leading to the transcriptional control of these target genes ( 3 ). (aacrjournals.org)
  • Conditions that disrupt the luminal environment and these core ER functions, including oxidative stress, perturbation of Ca 2+ or energy stores and accumulation of unfolded/misfolded proteins result in an evolutionarily conserved adaptive response termed the UPR. (nature.com)
  • The main cellular antioxidant systems responsible for recycling REDOX sensitive proteins are the thioredoxin (Trx) and glutathione (GSH) systems that reduce active cysteine residues present in ROS scavenging proteins (reestablishing their antioxidant function) and other proteins, whose functions are regulated by the oxidative status of key reactive cysteine residues (e.g., protein tyrosine phosphatases (PTPs), transcription factors, and the phosphatase and tensin homolog, PTEN) (Figure 1 ). (hindawi.com)
  • Active JNK has been shown to promote ROS detoxification and to confer tolerance to oxidative stress ( 12 , 13 ). (aacrjournals.org)
  • Impaired c-Jun amino terminal kinase activity and T cell differentiation in death receptor 6-deficient mice. (nih.gov)
  • c-Jun amino terminal kinase (JNK) regulates Th cell differentiation by activating a transcriptional program required for cytokine production. (nih.gov)
  • When DR6(-/-) mice were challenged with protein antigen, their T cells hyperproliferate and display a profound polarization toward a Th2 response whereas Th1 differentiation is not equivalently affected. (nih.gov)
  • Human myeloid leukemia cells respond to 12- O -tetradecanoylphorbol-13-acetate (TPA) and other activators of protein kinase C (PKC) with induction of monocytic differentiation. (asm.org)
  • In this context, treatment of U-937 and HL-60 cells with agents that activate protein kinase C (PKC), including 12- O -tetradecanoylphorbol-13-acetate (TPA) and phorbol-12,13-dibutyrate (PDBu), induces differentiation along the monocytic lineage. (asm.org)
  • Bryostatin 1, a macrocyclic lactone, also activates PKC and induces monocytic differentiation of myeloid leukemia cells ( 51 ). (asm.org)
  • The activation of these protein kinases leads to diverse regulatory events, particularly proliferation and differentiation. (pnas.org)
  • Three main modules exist in mammals: the ERKs (extracellular-signal-regulated kinases), SAPKs [stress-activated protein kinases, also known as JNKs (c-Jun N-terminal kinases)] and p38. (biochemj.org)
  • The c-Jun NH 2 -terminal kinase (JNK) was initially described as a stress-activated kinase able to phosphorylate the NH 2 -terminal transactivation domain of the transcription factor c-Jun in response to UV light ( 3 ). (aacrjournals.org)
  • The core adaptor proteins of TORC1 are Raptor and LST8, whereas LST8, Rictor and Sin1 are the conserved components of TORC2. (biologists.org)
  • The c-jun antisense gene recombinant transfection alleviates injury to cardiomyocytes treated with burn serum and hypoxia, probably through low expression of PKCa and JNK. (biomedsearch.com)
  • Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is an enzyme that in humans is encoded by the MAP3K1 gene. (wikipedia.org)
  • We compared this genome, based on protein-coding gene orthology, with other publicly available coral genomes (Cnidaria, Anthozoa, Scleractinia), as well as genomes from other anthozoan groups (Actiniaria, Corallimorpharia), and two basal metazoan outgroup phlya (Porifera, Ctenophora). (nature.com)
  • Transcription factor jun-B is a protein that in humans is encoded by the JUNB gene. (wikipedia.org)
  • These mechanisms were studied in A549 lung epithelial cells to investigate the hypothesis that nontoxic Cr(VI) exposures selectively activate cell signaling that shifts the balance of gene transcription. (nih.gov)
  • Previous studies have demonstrated that the extracellular signal-regulated kinase (ERK) subgroup of MAP kinases is required for neuregulin-induced AChR gene expression. (jneurosci.org)
  • Treatment of muscle cells with cycloheximide to inhibit c-JUN synthesis at the protein level and suppression of c-JUN function by a dominant-negative mutant blocked neuregulin-induced expression of the ε-subunit gene, indicating an essential role of c-JUN in neuregulin signaling. (jneurosci.org)
  • Several proinflammatory treatments which induce Cox-2 gene expression also stimulate the mitogen-activated protein kinase (MAPK) p38. (asm.org)
  • We show that such losses can be attributed to protracted, extracellular signal-regulated kinase (ERK)-dependent insulin secretion and simultaneous suppression of insulin gene transcription. (diabetesjournals.org)
  • Overall, the repression of proinflammatory cytokines and iNOS gene expression in activated microglia by isoflavones such as irisolidone might have therapeutic potential for various neurodegenerative diseases including ischemic cerebral disease. (aspetjournals.org)
  • Mitogen-activated protein kinase (MAPK), an important intracellular signal transduction system, has a marked effect on the regulation of gene expression and cytoplasmic functional activities (1-3). (scielo.br)
  • β-CDODA-Me induced p21 and p27, down-regulated cyclin D1 protein expression, and induced two other proapoptotic proteins, namely nonsteroidal anti-inflammatory drug-activated gene-1 and activating transcription factor-3. (aspetjournals.org)
  • The latter is achieved through boosting the ultrasensitive behavior of FSHβ gene expression by increasing the number of MAPK dependencies, and through modulating the feedforward effects of JNK activation on the GnRH receptor (GnRH-R). Our findings contribute to understanding the role of changing GnRH pulse-frequency in controlling transcription of the pituitary gonadotropins, which comprises a crucial aspect in regulating reproduction. (scienceblogs.com)
  • Regulatory phosphatase activity in IgM B cells was BCR-mediated and initiated more slowly than kinase activity. (jimmunol.org)
  • The homogenate was then diluted (∼65 μg protein/mL) and assayed for phosphohistone phosphatase activity in the presence of the indicated amount of cantharidin as described in Materials and Methods. (aacrjournals.org)
  • Here, we show that a member of the Protein Phosphatase 2C (PP2C) family in Arabidopsis ( Arabidopsis thaliana ), PP2C5, is acting as a MAPK phosphatase. (plantphysiol.org)
  • Furthermore, MKK7β1 recruits a protein phosphatase that dephosphorylates WDR62. (biochemj.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)
  • 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)
  • Mitogen-activated protein kinases (MAPK) are a family of evolutionarily conserved molecules that transduce extracellular stimuli into intracellular responses, by changing transcription as well as inducing posttranslational modifications of target proteins. (frontiersin.org)
  • SPC signaling has been found to involve intracellular signaling components such as pertussis toxin (PTX)-sensitive G proteins, which act in processes such as chemotactic migration ( 12 ). (jimmunol.org)
  • However, JNK activation in response to Cr(VI) and exogenous H(2)O(2) (1 mM) shared requirements for intracellular thiol oxidation, activation of Src family kinases, and p130(cas) (Cas). (nih.gov)
  • The ER lumen represents both the major site of intracellular Ca 2+ storage and the site at which transmembrane and secreted proteins are folded and post-translationally modified. (nature.com)
  • 20-24 The binding of thrombin to PAR1 results in receptor cleavage and exposure of a tethered ligand that is capable of activating the receptor and inducing intracellular signaling. (bloodjournal.org)
  • The Golgi‑associated PDZ‑ and coiled‑coil motif‑containing (GOPC) protein controls the intracellular trafficking of numerous integral membrane proteins. (spandidos-publications.com)
  • JNKs are activated by stress signals and proinflammatory stimuli. (aacrjournals.org)
  • Mitogen-activated protein (MAP) kinases are ubiquitous signaling molecules responsive to hormones, cytokines, environmental stresses, and other extracellular stimuli. (pnas.org)
  • In particular, macrophages are activated when exposed to inflammatory stimuli such as LPS, resulting in excessive production of pro-inflammatory mediators and cytokines as well as reactive oxygen species (ROS) ( 3 - 5 ). (spandidos-publications.com)
  • Meanwhile, expanding on the role of JNKs as effectors of harmful stimuli, it has also been shown that JNK can favor cell viability. (aacrjournals.org)
  • Because ATM and ATR are the kinases responsible not only for DNA repair, but also for the regulation of the cell cycle ( 10 ), they are expected to respond to growth factors and oncogenes for the regulation of p53. (aacrjournals.org)
  • A tetracycline-regulated reporter system was used to investigate the regulation of cyclooxygenase 2 (Cox-2) mRNA stability by the mitogen-activated protein kinase (MAPK) p38 signaling cascade. (asm.org)
  • A short (123-nucleotide) fragment of the Cox-2 3′ UTR was necessary and sufficient for the regulation of mRNA stability by the p38 cascade and interacted with a HeLa protein immunologically related to AU-rich element/poly(U) binding factor 1. (asm.org)
  • It has been reported that these agents induce a specific cellular stress response program, which includes the activation of JNKs and p38 mitogen-activated protein kinase ( 17 ). (aacrjournals.org)
  • We hypothesized that targeting both Akt and heat shock protein (HSP) 90 would induce cytotoxic activity against multiple myeloma (MM) cells and target the bone marrow (BM) microenvironment to inhibit angiogenesis, osteoclast formation, as well as migration and adhesion of MM cells. (aacrjournals.org)
  • Activating mutations of beta-catenin and HGF/Met induce cancer stem cells in head and neck and mammary gland tumors. (mdc-berlin.de)
  • In the present study, schisandrin A significantly suppressed the lipopolysaccharide (LPS)-induced production of the key pro-inflammatory mediators nitric oxide (NO) and prostaglandin E2 by suppressing the expression of inducible NO synthase and cyclooxygenase-2 at the mRNA and protein levels in RAW 264.7 macrophages. (spandidos-publications.com)
  • this was accompanied by a simultaneous decrease in the respective mRNA and protein levels in the macrophages. (spandidos-publications.com)
  • VEGF expression was determined by mRNA and protein levels by RT-PCR and western blotting. (biomedcentral.com)
  • In contrast, Dex and RA failed to inhibit the activation of the p38 mitogen-activated protein kinase cascade. (nih.gov)
  • however, the mechanisms by which Gadd45 proteins inhibit cell cycle control are not fully understood. (biomedsearch.com)
  • In the present study, we first found that in human PE placentas levels of toll-like receptor 4 (TLR4), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and inflammatory cytokines IL-6 and MCP-1 were significantly upregulated. (frontiersin.org)
  • These findings elaborated potential mechanisms that aberrant TLR4/p38 signaling might contribute to PE and LPS-induced PE-like symptom by damaging trophoblast invasion and SA remodeling via activating inflammatory cytokines including IL-6 and MCP-1. (frontiersin.org)
  • MAP kinase p38 ( 1 - 4 ) is activated by proinflammatory cytokines and environmental stresses such as osmotic shock and UV light, and is essential for the lipopolysaccharide-induced translation of tumor necrosis factor in monocytes. (pnas.org)
  • Raf-1 contributes directly to ERK activation but not to JNK activation, whereas MEKK participated in JNK activation but caused ERK activation only after overexpression. (sciencemag.org)
  • This stabilization was blocked by SB203580, an inhibitor of p38, and by two different dominant negative forms of MAPK-activated protein kinase 2 (MAPKAPK-2), a kinase lying downstream of p38. (asm.org)
  • These genes crosstalk with different downstream signalling systems, and activate migration-promoting genes. (bmj.com)
  • All IRF proteins share homology in their amino-terminal DNA-binding domains. (cellsignal.com)
  • Selective activation of Src family kinases and JNK by low levels of chromium(VI). (nih.gov)
  • Hepatocyte I kappaB kinase beta (IKK beta) inhibits hepatocarcinogenesis by suppressing accumulation of reactive oxygen species (ROS) and liver damage, whereas JNK1 activation promotes ROS accumulation, liver damage, and carcinogenesis. (nih.gov)
  • These studies demonstrated that nontoxic doses of Cr(VI) (10 microM) increased reactive oxygen species and selectively activated c-Jun N-terminal kinase (JNK), relative to ERK or p38 MAP kinase. (nih.gov)
  • Although JNK activation normally occurs in the nucleus, it can also be activated in the mitochondria, usually in association with the increased production of reactive oxygen species (ROS). (aacrjournals.org)
  • In the present study we demonstrate the association of WDR62 with endogenous and overexpressed proteins of both JNK2 and the JNK2-activating kinase MKK7 (MAPK kinase 7). (biochemj.org)
  • Association of WDR62 with JNK2 and MKK7 occurs via direct protein-protein interactions. (biochemj.org)
  • WDR62 association with JNK2 requires both the JNK CD and ED domains, and the binding requisite is distinct from that of the previously described JNK2 association with JIP1 (JNK-interacting protein 1). (biochemj.org)
  • p38 is phosphorylated and activated specifically by MEK3 ( 15 , 16 ) and MEK6 ( 16 - 19 ), and together with c-Jun N-terminal kinases 1 and 2 (JNK1 and JNK2) by MEK4 ( 15 , 20 ). (pnas.org)
  • Ras activates two protein kinases, Raf-1 and MEK (MAPK, or ERK, kinase) kinase (MEKK). (sciencemag.org)
  • The results also demonstrated that PKCβ phosphorylated and activated MEKK-1 in vitro. (asm.org)
  • The response depended on activation of protease-activated receptor 1 (PAR1) and was inhibited by pharmacologic antagonists of protein kinase C (PKC), p38 and p42/44 mitogen-activated protein kinase, and nuclear factor-κB. (bloodjournal.org)
  • MAP kinase p38 phosphorylates and activates both nuclear transcription factors ATF2 ( 12 ) and GADD153 ( 13 ), and protein kinase targets such as MAPKAP kinases 2 and 3 ( 3 , 4 , 14 ). (pnas.org)
  • Autophagy is activated for cell survival after endoplasmic reticulum stress. (nih.gov)
  • Eukaryotic cells deal with accumulation of unfolded proteins in the endoplasmic reticulum (ER) by the unfolded protein response, involving the induction of molecular chaperones, translational attenuation, and ER-associated degradation, to prevent cell death. (nih.gov)
  • In immunohistochemical analyses or using expression of fluorescence-tagged proteins, treatment with sorafenib and vorinostat together (sorafenib + vorinostat) promoted colocalization of CD95 with caspase 8 and CD95 association with the endoplasmic reticulum markers calnexin, ATG5, and Grp78/BiP. (aspetjournals.org)
  • Cr(VI) did not mimic H(2)O(2)-mediated stimulation of JNK in fibroblasts containing only Src and did not activate Src or Yes in A549 cells. (nih.gov)
  • Immunoreactivity for active JNK was also observed in the mitochondria of neuroblastoma 1E-115 and neuroblastoma 2a neuroblastoma cell lines on serum withdrawal, whereas active JNK was barely detected in serum-deprived fibroblasts. (aacrjournals.org)
  • Fus3 is activated by the MAPKK Ste7 on the Ste5 scaffold through localizing interactions involving a heterotrimeric G protein and Cdc42 GTPase, which guide the MAPKKK Ste11 to the MAPKKKK Ste20. (biologists.org)
  • Role of cAMP-dependent protein kinase A activity in low-dose endothelial monocyte-activating polypeptide-II-induced opening of blood-tumor barrier. (curehunter.com)
  • Similar to V12Rac1, Tiam1 stimulates the activity of the c-Jun NH2-terminal kinase (JNK). (nih.gov)
  • The structure of mitogen-activated protein (MAP) kinase p38 has been solved at 2.1-Å to an R factor of 21.0%, making p38 the second low activity MAP kinase solved to date. (pnas.org)
  • In this context, JNK activity is related to tumor cell expansion ( 9 - 11 ), although it is presently unclear whether this is due to stimulation of tumor cell survival or to a direct effect on the cell cycle machinery. (aacrjournals.org)
  • Instead, Fyn and Lck were activated in A549 cells, indicating activation of specific Src family kinases in response to Cr(VI). (nih.gov)
  • The c-Jun NH 2 -terminal kinase (JNK) belongs to a family of mitogen-activated protein kinases, together with extracellular regulated kinases and p38. (aacrjournals.org)
  • 1-4 The HSP70 family facilitates the folding of newly synthesized polypeptides in an adenosine triphosphate (ATP)-dependent manner, plays an important role in maintaining the dynamic stability of protein folding and protein-protein interactions within the cell, and inhibits protein aggregation. (asahq.org)
  • In summary, type 2 diabetes is associated with an increased basal activation of the MAP kinase family. (diabetesjournals.org)
  • Heat shock protein (HSP) 90 is a member of a family of chaperone proteins involved in the chaperoning and refolding of proteins, which have been destabilized by stress ( 13 ). (aacrjournals.org)
  • c-Jun NH 2 -terminal kinase (JNK) links several cellular processes, including proliferation and survival, and is believed to be involved in carcinogenesis. (aacrjournals.org)
  • Both Syk and Btk can activate PI3K following BCR cross-linking ( 18 ). (jimmunol.org)
  • The impairment of insulin-mediated glucose uptake is correlated to the circulating FFA levels, and such resistance to insulin might be due to FFA-mediated inactivation of phosphoinositide 3-kinase (PI3K) [ 7 ]. (pubmedcentralcanada.ca)
  • SPC stimulation induced production of the CCL2 chemokine in a PTX-sensitive G-protein-dependent manner. (jimmunol.org)
  • This Rac-dependent stimulation of JNK also requires membrane association of Tiam1. (nih.gov)
  • For instance, SLP-76 detaches from plasma membrane-proximal protein complexes a few minutes after TCR stimulation and translocates to a perinuclear compartment ( 12 ). (rupress.org)
  • Octacalcium phosphate crystals directly stimulate expression of inducible nitric oxide synthase through p38 and JNK mitogen-activated protein kinases in articular chondrocytes. (inserm.fr)
  • and (3) expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins in mouse skin. (mdpi.com)
  • In a colon cancer cell line containing inducible ectopic p53 , DUSP1 protein level is significantly increased upon activation of p53, leading to cell death in response to nutritional stress. (aacrjournals.org)
  • Pretreatment with a Jak inhibitor blocked not only SPC-induced p38 MAPK and JNK activation, but also NF-κB and AP-1 activation. (jimmunol.org)
  • The complement system consists of a large group of plasma proteins that plays a central role in the defense against infections and in the modulation of inflammatory responses. (bloodjournal.org)
  • lipopolysaccharide induced CXC chemokine (LIX), monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)-1? (jove.com)
  • These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension. (jove.com)
  • interleukin-1β (IL-1β ), tumor necrosis factor alpha, and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid were higher in the VILI group compared with the control group. (elsevier.com)
  • The white blood cell count and the levels of H2O2, interleukin-1β (IL-1β ), tumor necrosis factor alpha, and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid were higher in the VILI group compared with the control group. (elsevier.com)
  • Research studies have shown that Stat3 is constitutively activated in a number of human tumors (3,4) and possesses oncogenic potential (5) and anti-apoptotic activities (3). (cellsignal.com)
  • Activation of JNK by epidermal growth factor (EGF) or nerve growth factor (NGF) was dependent on H-Ras activation, whereas JNK activation by tumor necrosis factor alpha (TNF-alpha) was Ras-independent. (sciencemag.org)
  • Previous studies have shown that wounding of human corneal epithelial cells (HCECs) results in the release of G-protein-coupled receptor ligands such as ATP and lysophosphatidic acid (LPA), which in turn transactivate epidermal growth factor (EGF) receptor (EGFR) through ectodomain shedding of heparin-binding EGF-like growth factor (HB-EGF). (arvojournals.org)
  • However, JNK also facilitates the survival and cell cycle progression of tumor cells by mechanisms that are poorly defined. (aacrjournals.org)
  • We report that SKRP1 also plays a scaffold role for the JNK signaling, judged by the following observations. (uniprot.org)
  • Thus, our findings are, to our knowledge, the first evidence to show that an MKP also functions as a scaffold protein for the particular MAPK signaling. (uniprot.org)
  • MAP3K1 contains a protein kinase domain, PHD finger (which has a RING finger domain-like structure), and scaffold protein regions that mediate protein-protein interactions. (wikipedia.org)
  • MAPK scaffold proteins may function similarly ( Elion, 2001 ). (biologists.org)
  • WDR62 (WD repeat domain 62) is a JNK scaffold protein. (biochemj.org)
  • The association of the signalling components with the scaffold protein allows signal channelling to a specific outcome. (biochemj.org)
  • Multiple scaffold proteins have now been described for the MAPK cascade and have been found to enhance signal transduction by promoting the assembly of multiprotein complexes [ 4 - 8 ]. (biochemj.org)