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 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 group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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).
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
Agents that inhibit PROTEIN KINASES.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
A 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.
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 serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A 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 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 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.
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 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.
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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
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 phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
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.
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.
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)
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
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.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
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 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.
The rate dynamics in chemical or physical systems.
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.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
A 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.
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.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
A mitogen-activated protein kinase 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 family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
A 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.
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 protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
The 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 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.
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 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.
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.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
A 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.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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)
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.
Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.
Proteins prepared by recombinant DNA technology.
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 specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
A group of phenyl benzopyrans named for having structures like FLAVONES.
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.
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.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
A 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.
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 group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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).
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
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.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
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.
Elements of limited time intervals, contributing to particular results or situations.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
A 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 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 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.
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 cell line derived from cultured tumor cells.
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.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A 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)
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
A 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.
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.
Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
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.
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).
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
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)
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.
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.
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.
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.
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
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.
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.
Four carbon unsaturated hydrocarbons containing two double bonds.
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.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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 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.
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)
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
A 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.
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 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.
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.
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 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.
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.
A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
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 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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A mitogen-activated protein kinase kinase with specificity for a subset of P38 MITOGEN-ACTIVATED PROTEIN KINASES that includes MITOGEN-ACTIVATED PROTEIN KINASE 12; MITOGEN-ACTIVATED PROTEIN KINASE 13; and MITOGEN-ACTIVATED PROTEIN KINASE 14.
A 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.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
The sum of the weight of all the atoms in a molecule.
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 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 broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
The 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.
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.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A 110-kDa extracellular signal-regulated MAP kinase that is activated in response to cellular stress and by GROWTH FACTOR RECEPTORS-mediated pathways.
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 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).
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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.
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.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
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 long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.
Compounds or factors that act on a specific enzyme to increase its activity.
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.
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 positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
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.
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.
The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.
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.
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)
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 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.
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.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
An imidazole derivative which is a metabolite of the antineoplastic agents BIC and DIC. By itself, or as the ribonucleotide, it is used as a condensation agent in the preparation of nucleosides and nucleotides. Compounded with orotic acid, it is used to treat liver diseases.
An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.
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.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
A specific inhibitor of phosphoserine/threonine protein phosphatase 1 and 2a. It is also a potent tumor promoter. (Thromb Res 1992;67(4):345-54 & Cancer Res 1993;53(2):239-41)
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.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3 by phosphorylating it at Ser579. (1/6166)

The extracellular receptor stimulated kinase ERK2 (p42(MAPK))-phosphorylated human cAMP-specific phosphodiesterase PDE4D3 at Ser579 and profoundly reduced ( approximately 75%) its activity. These effects could be reversed by the action of protein phosphatase PP1. The inhibitory state of PDE4D3, engendered by ERK2 phosphorylation, was mimicked by the Ser579-->Asp mutant form of PDE4D3. In COS1 cells transfected to express PDE4D3, challenge with epidermal growth factor (EGF) caused the phosphorylation and inhibition of PDE4D3. This effect was blocked by the MEK inhibitor PD98059 and was not apparent using the Ser579-->Ala mutant form of PDE4D3. Challenge of HEK293 and F442A cells with EGF led to the PD98059-ablatable inhibition of endogenous PDE4D3 and PDE4D5 activities. EGF challenge of COS1 cells transfected to express PDE4D3 increased cAMP levels through a process ablated by PD98059. The activity of the Ser579-->Asp mutant form of PDE4D3 was increased by PKA phosphorylation. The transient form of the EGF-induced inhibition of PDE4D3 is thus suggested to be due to feedback regulation by PKA causing the ablation of the ERK2-induced inhibition of PDE4D3. We identify a novel means of cross-talk between the cAMP and ERK signalling pathways whereby cell stimuli that lead to ERK2 activation may modulate cAMP signalling.  (+info)

Activation of c-Jun N-terminal kinase 1 by UV irradiation is inhibited by wortmannin without affecting c-iun expression. (2/6166)

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)

Role of the extracellular signal-regulated protein kinase cascade in human neutrophil killing of Staphylococcus aureus and Candida albicans and in migration. (3/6166)

Killing of Staphylococcus aureus and Candida albicans by neutrophils involves adherence of the microorganisms, phagocytosis, and a collaborative action of oxygen reactive species and components of the granules. While a number of intracellular signalling pathways have been proposed to regulate neutrophil responses, the extent to which each pathway contributes to the killing of S. aureus and C. albicans has not been clearly defined. We have therefore examined the effect of blocking one such pathway, the extracellular signal-regulated protein kinase (ERK) cascade, using the specific inhibitor of the mitogen-activated protein kinase/ERK kinase, PD98059, on the ability of human neutrophils to kill S. aureus and C. albicans. Our data demonstrate the presence of ERK2 and a 43-kDa form of ERK but not ERK1 in human neutrophils. Upon stimulation with formyl methionyl leucyl phenylalanine (fMLP), the activities of both ERK2 and the 43-kDa form were stimulated. Despite abrogating the activity of both ERK forms, PD98059 only slightly reduced the ability of neutrophils to kill S. aureus or C. albicans. This is consistent with our finding that PD98059 had no effect on neutrophil adherence or degranulation, although pretreatment of neutrophils with PD98059 inhibited fMLP-stimulated superoxide production by 50%, suggesting that a change in superoxide production per se is not strictly correlated with microbicidal activity. However, fMLP-stimulated chemokinesis was markedly inhibited, while random migration and fMLP-stimulated chemotaxis were partially inhibited, by PD98059. These data demonstrate, for the first time, that the ERK cascade plays only a minor role in the microbicidal activity of neutrophils and that the ERK cascade is involved primarily in regulating neutrophil migration in response to fMLP.  (+info)

CD40 signaling of monocyte inflammatory cytokine synthesis through an ERK1/2-dependent pathway. A target of interleukin (il)-4 and il-10 anti-inflammatory action. (4/6166)

Ligation of CD40 on monocytes through its interaction with CD40 ligand (CD154) present on activated T helper cells, results in activation of monocyte inflammatory cytokine synthesis and rescue of monocytes from apoptosis induced through serum deprivation. Both of these consequences of CD40 stimulation have been shown to be dependent on the induction of protein tyrosine kinase activity. CD40-mediated activation of protein tyrosine kinase activity and subsequent inflammatory cytokine production are abrogated by treatment of monocytes with the T helper type 2 cytokines interleukin 4 (IL-4) and interleukin 10 (IL-10). In the current study we demonstrate that stimulation of monocytes through CD40 resulted in the phosphorylation and activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) mitogen-activated protein kinases, whereas phosphorylation of mitogen-activated protein kinases family members p38 and c-Jun N-terminal kinase was not observed in response to this stimuli over the time course examined. PD98059, an inhibitor of the upstream activator of ERK1/2, the MAP/ERK kinase MEK1/2, suppressed IL-1beta and tumor necrosis factor-alpha production in a dose-dependent fashion. Pretreatment of monocytes with IL-4 and IL-10 inhibited CD40-mediated activation of ERK1/2 kinase activity when used individually, and are enhanced in effectiveness when used in combination. Together, the data demonstrate that CD40-mediated induction of IL-1beta and tumor necrosis factor-alpha synthesis is dependent on a MEK/ERK pathway which is obstructed by signals generated through the action of IL-4 and IL-10.  (+info)

Alternatively spliced EDA segment regulates fibronectin-dependent cell cycle progression and mitogenic signal transduction. (5/6166)

Fibronectin (FN) is comprised of multiple isoforms arising from alternative splicing of a single gene transcript. One of the alternatively spliced segments, EDA, is expressed prominently in embryonic development, malignant transformation, and wound healing. We showed previously that EDA+ FN was more potent than EDA- FN in promoting cell spreading and cell migration because of its enhanced binding affinity to integrin alpha5beta1 (Manabe, R., Oh-e, N., Maeda, T., Fukuda, T., and Sekiguchi, K. (1997) J. Cell Biol. 139, 295-307). In this study, we compared the cell cycle progression and its associated signal transduction events induced by FN isoforms with or without the EDA segment to examine whether the EDA segment modulates the cell proliferative potential of FN. We found that EDA+ FN was more potent than EDA- FN in inducing G1-S phase transition. Inclusion of the EDA segment potentiated the ability of FN to induce expression of cyclin D1, hyperphosphorylation of pRb, and activation of mitogen-activated protein kinase extracellular signal regulated kinase 2 (ERK2). EDA+ FN was also more potent than EDA- FN in promoting FN-mediated tyrosine phosphorylation of p130(Cas), but not focal adhesion kinase, which occurred in parallel with the activation of ERK2, suggesting that p130(Cas) may be involved in activation of ERK2. These results indicated that alternative splicing at the EDA region is a novel mechanism that promotes FN-induced cell cycle progression through up-regulation of integrin-mediated mitogenic signal transduction.  (+info)

Mesalamine blocks tumor necrosis factor growth inhibition and nuclear factor kappaB activation in mouse colonocytes. (6/6166)

BACKGROUND & AIMS: Derivatives of 5-aminosalicylic acid (mesalamine) represent a mainstay in inflammatory bowel disease therapy, yet the precise mechanism of their therapeutic action is unknown. Because tumor necrosis factor (TNF)-alpha is important in the pathogenesis of inflammatory bowel disease, we investigated the effect of mesalamine on TNF-alpha-regulated signal transduction and proliferation in intestinal epithelial cells. METHODS: Young adult mouse colon cells were studied with TNF-alpha, epidermal growth factor, or ceramide in the presence or absence of mesalamine. Proliferation was studied by hemocytometry. Mitogen-activated protein (MAP) kinase activation and IkappaBalpha expression were determined by Western blot analysis. Nuclear transcription factor kappaB (NF-kappaB) nuclear translocation was determined by confocal laser immunofluorescent microscopy. RESULTS: The antiproliferative effects of TNF-alpha were blocked by mesalamine. TNF-alpha and ceramide activation of MAP kinase were inhibited by mesalamine, whereas epidermal growth factor activation of MAP kinase was unaffected. TNF-alpha-stimulated NF-kappaB activation and nuclear translocation and the degradation of Ikappa-Balpha were blocked by mesalamine. CONCLUSIONS: Mesalamine inhibits TNF-alpha-mediated effects on intestinal epithelial cell proliferation and activation of MAP kinase and NF-kappaB. Therefore, it may function as a therapeutic agent based on its ability to disrupt critical signal transduction events in the intestinal cell necessary for perpetuation of the chronic inflammatory state.  (+info)

Expression of dominant negative Erk2 inhibits AP-1 transactivation and neoplastic transformation. (7/6166)

The mitogen activated protein (MAP) kinases or extracellular signal-regulated kinases (Erks) are activated in response to Ras expression or exposure to tumor promoters or to growth factors, and have been implicated in AP-1 transactivation in some models. We have shown that tumor promoter induced activation of the transcription factor AP-1 is required for induced neoplastic transformation in the Balb/C JB6 cell model. Jun and Fos family protein levels have been found not to be limiting for AP-1 response. The present study asks whether activation of Erks1 and 2 is required for AP-1 transactivation and transformation of JB6 cells and whether Erks might be targeted for cancer prevention. Expression of either of two different dominant negative kinase inactive Erk2 mutants in transformation sensitive (P+) JB6 cells substantially inhibited the tumor promoter induced activation of Erks1 and 2 and of AP-1 measured by a collagenase-luciferase reporter. Multiple mutant Erk2 expressing clonal lines were also rendered non-responsive to induced neoplastic transformation. These observations, together with our recent finding attributing AP-1 non-responsiveness to Erk deficiency in a clonal line of transformation resistant (P-) cells, argue for a requirement for Erks1 and/or 2 activation in AP-1 transactivation in the mouse JB6 neoplastic progression model, and suggest the utility of Erks as a prevention target.  (+info)

PDGF (alpha)-receptor is unresponsive to PDGF-AA in aortic smooth muscle cells from the NG2 knockout mouse. (8/6166)

A line of null mice has been produced which fails to express the transmembrane chondroitin sulfate proteoglycan NG2. Homozygous NG2 null mice do not exhibit gross phenotypic differences from wild-type mice, suggesting that detailed analyses are required to detect subtle alterations caused by the absence of NG2. Accordingly, dissociated cultures of aortic smooth muscle cells from null mice were compared to parallel cultures from wild-type mice for their ability to proliferate and migrate in response to specific growth factors. Both null and wild-type smooth muscle cells exhibited identical abilities to proliferate and migrate in response to PDGF-BB. In contrast, only the wild-type cells responded to PDGF-AA in both types of assays. NG2 null cells failed to proliferate or migrate in response to PDGF-AA, implying a defect in the signaling cascade normally initiated by activation of the PDGF (alpha)-receptor. In agreement with this idea, activation of the extracellular signal-regulated kinase (ERK) in response to PDGF-AA treatment occured only in wild-type cells. Failure to observe autophosphorylation of the PDGF (alpha)-receptor in PDGF-AA-treated null cells indicates that the absence of NG2 causes a defect in signal transduction at the level of (alpha)-receptor activation.  (+info)

We showed previously that p90 RSK was activated in cells expressing an activated mutant of MEK5, the activator of the MAP kinase ERK5. Based on the following evidence, we suggest that ERK5 can directly activate RSK in cells. ERK5 binds to RSK in vitro and co-immunoprecipitates from cell extracts; ac …
Mutational activation of Ras (H-Ras, K-Ras, and N-Ras) is associated with a diverse spectrum of human cancers (1). For example, 50% of colorectal carcinomas harbor mutated K-RAS, and 25% of melanomas contain mutated N-RAS alleles. Consequently, there is considerable interest and effort in the development of anti-Ras strategies for cancer treatment (2, 3). One approach involves the inhibition of Ras-mediated signal transduction. Of these efforts, inhibitors of signaling mediated by the Ras effectors, the Raf serine/threonine kinases (c-Raf-1, A-Raf, and B-Raf), have attracted the most interest. Ras promotes Raf activation, which in turn, activates the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) 1 and MEK2 dual-specificity protein kinases. MEK1/2 kinases then activate the ERK1 and ERK2 mitogen-activated protein kinases and inhibitors of this cascade have been developed and are currently under evaluation in clinical trials (4). These include kinase ...
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008 ...
The mammalian genome contains two mitogen-activated protein kinase (MAPK) kinase (MEK)-encoding genes, Mek1 and Mek2. MEKs phosphorylate and activate the two extracellular signal-regulated kinase (ERK) isoforms ERK1 and ERK2. Mek1−/− embryos die due to placental defects, whereas Mek2−/− mice survive with a normal life span and fertility, suggesting that MEK1 has functions not shared by MEK2. However, most Mek1+/−Mek2+/− embryos also die from placental defects, indicating that both Mek genes contribute to placental development. To assess the functional specificity of the Mek1 and Mek2 genes, we produced a Mek1 knock-in allele in which the Mek2 coding sequences were placed under the control of Mek1 regulatory sequences (Mek12 allele). Mek12/2 mice were viable with no apparent phenotype, indicating rescue by MEK2 and functional redundancy between the two MEK proteins. However, Mek12/− embryos with Mek2 in only one of the Mek1 alleles and the other Mek1 allele null died from abnormal ...
The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAP kinase) family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described.[3] ...
Platelet-derived growth factor (PDGF) is a family of signaling molecules that stimulates cell growth, survival and migration. PDGF is recognized by specific transmembrane proteins, the PDGF receptors, which relay the signals to the cell activating the Mitogen-activated protein (MAP) kinases and other signaling pathways. Aberrant activation of these pathways is frequently detected in cancer. Hence, the study of these processes is essential for identifying potential drug targets or diagnostic markers.. In paper I, we identified Receptor Subfamily 4 Group A Member 1 NR4A1 to be regulated by PDGF via MAP kinases, clarifying the role of Extracellular signal-regulated kinases (Erk) 1/2, Erk5 and Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in its regulation. NR4A1 was found to be important for the tumorigenic potential, measured as anchorage-independent growth, of glioblastoma cells.. Since the cellular responses elicited by PDGF result from the balance between phosphorylation ...
Extracellular signal-regulated protein kinase (ERK) is a mitogen-activated protein kinase (MAPK) that mediates intracellular signal transduction in response to a variety of stimuli. ERK is involved in cell proliferation and differentiation and in neuronal plasticity, including long-term potentiation …
S. Xie*, B. Schurink, F. Wolbers, R. Luttge*, and G. Hassink. Nanoscaffolds stiffness affects primary cortical cell network formation. J. Vac. Sci. Technol. B. 2014, 32(6), 06FD03.. S. Xie*, R. Luttge*. Imprint lithography provides topographical nanocues to guide cell growth in primary cortical cell culture. Microelectron. Eng. 2014, 124, 30-36.. Xie, S. J.; Lu, Y. X.; Zhang, S. C.; Wang, L.D.; Zhang X.R.*. Electro-optical gas sensor based on a planar light-emitting electrochemical cell microarray, Small. 2010, 6(17), 1897-1899.. Xiaoyan Wang, Kenichi Harimoto,Sijia Xie, Hao Cheng, Jing Liu, and Zhao Wang*. Matrix Protein Biglycan Induces Osteoblast Differentiation through Extracellular Signal-Regulated Kinase and Smad Pathways. Biol. Pharm. Bull. 2010, 33(11) 1891-1897. ...
Figure 4: Effects of 50 μM DHA, EPA, SA, and PA or 25 μM OA and LA on IL-2-induced extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Lymphocytes were incubated with 5 μg/mL ConA for 24 h. Afterwards, lymphocytes were washed with PBS and cultured with the different fatty acids in the presence or absence of IL-2 (30 ng/mL) for 1 h. Total proteins were extracted from lymphocytes for western-blotting analysis. Blots were analyzed by densitometry and the results normalized to their respective controls, which were set to a value of 100% for each experiment. The values are presented as the means ± SEM. ###p,0.001 for comparison with the control in the absence IL-2); *p,0.05, **p,0.01, and ***p,0.001 for comparison with the control treated with IL-2 ...
Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signal-regulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a ...
Compounds. Compound I [IUPAC name: N-(3-fluoro-4-((7-methoxy-4-quinolinyl)oxy)phenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide] was synthesized at Amgen, Inc. The MAPK/extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2) inhibitor U0126 was obtained from Calbiochem.. Cells. KATOIII (gastric), PC3 (prostate), HT-29 (colorectal), Colo205 (colorectal), BxPC3 (pancreatic), and U-87 MG (glioblastoma) cancer cell lines were obtained from the American Type Culture Collection. NIH3T3 TPR-Met or NIH3T3 RON cells were generated by stable transfection of TPR-Met, a constitutively active, ligand-independent form of c-Met ( 31) or wild-type RON in NIH3T3 cells. Cells were grown as monolayers using standard cell culture conditions.. Antibodies and reagents. Antibodies against c-Met (C-12), RON (C-20), and actin (1615-R) were acquired from Santa Cruz Biotechnology. Antibodies against phospho-c-Met (Y1234/1235), phospho-Gab1 (Y627), phospho-ERK1/2 ...
Platelet-derived growth factor (PDGF) is a family of signaling molecules that stimulates cell growth, survival and migration. PDGF is recognized by specific transmembrane proteins, the PDGF receptors, which relay the signals to the cell activating the Mitogen-activated protein (MAP) kinases and other signaling pathways. Aberrant activation of these pathways is frequently detected in cancer. Hence, the study of these processes is essential for identifying potential drug targets or diagnostic markers.. In paper I, we identified Receptor Subfamily 4 Group A Member 1 NR4A1 to be regulated by PDGF via MAP kinases, clarifying the role of Extracellular signal-regulated kinases (Erk) 1/2, Erk5 and Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in its regulation. NR4A1 was found to be important for the tumorigenic potential, measured as anchorage-independent growth, of glioblastoma cells.. Since the cellular responses elicited by PDGF result from the balance between phosphorylation ...
Fingerprint Dive into the research topics of Dopamine D2 receptor stimulation of mitogen-activated protein kinases mediated by cell type-dependent transactivation of receptor tyrosine kinases. Together they form a unique fingerprint. ...
Constitutive activation of the mitogen-activated protein kinase (MAPK) pathway is implicated in the development and progression of many human cancers, including
Fingerprint Dive into the research topics of Activin A stimulates mitogenesis in Swiss 3T3 fibroblasts without activation of mitogen-activated protein kinases. Together they form a unique fingerprint. ...
Recombinant Mitogen-Activated Protein Kinase 8 (MAPK8) Protéine. Origine: Humain. Source: Baculovirus infected Insect Cells. Commandez ABIN593493.
Low temperature is one of the most common environmental stresses affecting plant growth and agricultural production. The mitogen-activated protein kinase (MAPK) cascade plays a pivotal role in...
Recombinant Mitogen-Activated Protein Kinase 8 (MAPK8) Protein (GST tag). Spezies: Human. Quelle: Wheat germ. Jetzt Produkt ABIN1310303 bestellen.
Ovarian cancer is a complex disease with heterogeneity among the gene expression molecular subtypes (GEMS) between patients. Patients with tumors of a mesenchymal (Mes) subtype have a poorer prognosis than patients with tumors of an epithelial (Epi) subtype. We evaluated GEMS of ovarian cancer patients for molecular signaling profiles and assessed how the differences in these profiles could be leveraged to improve patient clinical outcome. Kinome enrichment analysis identified AXL as a particularly abundant kinase in Mes-subtype tumor tissue and cell lines. In Mes cells, upon activation by its ligand GAS6, AXL coclustered with and transactivated the receptor tyrosine kinases (RTKs) cMET, EGFR, and HER2, producing sustained extracellular signal-regulated kinase (ERK) activation. In Epi-A cells, AXL was less abundant and induced a transient activation of ERK without evidence of RTK transactivation. AXL-RTK crosstalk also stimulated sustained activation of the transcription factor FRA1, which ...
Although transforming growth factor β (TGF-β) is known to be a potent growth inhibitor of breast cancer cells (BCCs), the signaling mechanisms mediating TGF-β responses have not been defined. We have demonstrated previously that TGF-β can activate Ras and extracellular signal-regulated kinase (ERK) 1 in untransformed epithelial cells (K. M. Mulder and S. L. Morris, J. Biol. Chem., 267: 5029-5031, 1992; M. T. Hartsough and K. M. Mulder, J. Biol. Chem., 270: 7117-7124, 1995). We have also shown that TGF-β signaling is altered in epithelial cells when Ras activation is blocked (Hartsough et al., J. Biol. Chem., 271: 22368-22375). Here we demonstrate the ability of the TGF-β3 isoform to activate the signaling component ERK2 in TGF-β-sensitive BCCs but not in TGF-β-resistant cells. The ERK2 isoform was activated by 6-fold within 10 min of TGF-β3 addition to the TGF-β-sensitive BCC line Hs578T. Moreover, the IC50 for inhibition of DNA synthesis by TGF-β3 in this cell line correlated with ...
Gooney M, Shaw K, Kelly Á, OMara SM, Lynch MA. Gooney M, Shaw K, Kelly A, OMara SM, Lynch MA. Gooney M, Shaw K, Kelly A, OMara SM, Lynch MA., Long-term potentiation and spatial learning are associated with increased phosphorylation of TrkB and extracellular signal-regulated kinase (ERK) in the dentate gyrus: evidence for a role for brain-derived neurotrophic factor., Behavioural Neuroscience, 116, (3), 2002, p455 - 463 Journal Article, 2002 URL ...
Huntingtons disease (HD) is an inherited, progressive and ultimately fatal neurodegenerative disorder that is characterized by psychiatric, cognitive and motor symptoms. Among the pathways implicated in HD are those involving mitogen-activated protein kinase signaling and particularly the Ras-extracellular signal-regulated kinase (ERK) cascade. Studies in both cells and animal models suggest that ERK activation might provide a novel therapeutic target for the treatment of HD but compounds that specifically activate ERK are few. To test the hypothesis that pharmaceutical activation of ERK might be protective for HD, a polyphenol, fisetin, which was previously shown to activate the Ras-ERK cascade, was tested in three different models of HD: PC12 cells expressing mutant Httex1 under the control of an inducible promoter, Drosophila expressing mutant Httex1 and the R6/2 mouse model of HD. The results indicate that fisetin can reduce the impact of mutant huntingtin in each of these disease models. ...
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The Alpha SureFire® Ultra™ HV Multiplex p-ERK 1/2 + Total ERK assay kit is used to measure both the phosphorylation (Thr202/Tyr204) and total levels of endogenous
ERK1 / ERK2, 0.1 ml. Erk1 and Erk2 are closely related mitogen activated protein (MAP) kinases which are activated by many growth factors, mitogens and differentiation-promoting agents via a protein kinase cascade.
The extracellular-signal-regulated kinase (ERK) pathway is one of the major signaling cassettes of the mitogen activated protein kinase (MAPK) signaling ..
Fujishita Teruaki , Kajino-Sakamoto Rie , Kojima Yasushi , Taketo Makoto Mark , Aoki Masahiro Extracellular signal-regulated kinase is an MAPK that is most closely associated with cell proliferation, and the MEK/ERK signaling pathway is implicated in various human cancers. Although epidermal g … Cancer Science 106(6), 692-699, 2015-06 IR Ichushi Web ...
Mitogen-activated protein kinase (MAPK)-triggered protein kinase 2 (MAPKAPK2) mediates multiple p38 MAPK-dependent inflammatory responses. at Ser-58. Computational modeling and calculation of theoretical binding energies predicted that both phosphorylation at Ser-58 and mutation of Ser-58 to Asp (S58D) jeopardized the ability of 14-3-3 to dimerize. Experimentally, S58D mutation significantly impaired both 14-3-3 dimerization and binding to Raf-1. These data suggest that MAPKAPK2-mediated phosphorylation regulates 14-3-3 functions, and this MAPKAPK2 activity may symbolize a novel pathway mediating p38 MAPK-dependent swelling. A diverse group of cellular responses are elicited by activation of a highly conserved family of mitogen-activated protein kinase (MAPK) signaling pathways, which includes extracellular signal-regulated kinases (ERKs), c-jun N-terminal kinases (JNKs), ERK5, and p38 MAPKs. A large body of evidence shows that p38 MAPK activity is critical to immune and inflammatory responses. ...
TY - JOUR. T1 - Activation of mitogen-activated protein kinases by lysophosphatidylcholine- induced mitochondrial reactive oxygen species generation in endothelial cells. AU - Watanabe, Nobuo. AU - Zmijewski, Jaroslaw W.. AU - Takabe, Wakako. AU - Umezu-Goto, Makiko. AU - Le Goffe, Claire. AU - Sekine, Azusa. AU - Landar, Aimee. AU - Watanabe, Akira. AU - Aoki, Junken. AU - Arai, Hiroyuki. AU - Kodama, Tatsuhiko. AU - Murphy, Michael P.. AU - Kalyanaraman, Raman. AU - Darley-Usmar, Victor M.. AU - Noguchi, Noriko. PY - 2006/5. Y1 - 2006/5. N2 - Lysophosphatidylcholine (lysoPC) evokes diverse biological responses in vascular cells including Ca2+ mobilization, production of reactive oxygen species, and activation of the mitogen-activated protein kinases, but the mechanisms linking these events remain unclear. Here, we provide evidence that the response of mitochondria to the lysoPC-dependent increase in cytosolic Ca2+ leads to activation of the extracellular signal-regulated kinase (ERK) ...
Sun QY.,Wu GM.,Lai LX.,Bonk A.,Cabot R.,...&Schatten H.(2002).Regulation of mitogen-activated protein kinase phosphorylation, microtubule organization, chromatin behavior, and cell cycle progression by protein phosphatases during pig oocyte maturation and fertilization in vitro.Biology of Reproduction,66(3),580-588 ...
AIMS/HYPOTHESIS: The beta cell destruction and insulin deficiency that characterises type 1 diabetes mellitus is partially mediated by cytokines, such as IL-1beta, and by nitric oxide (NO)-dependent and -independent effector mechanisms. IL-1beta activates mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK), and the nuclear factor kappa B (NFkappaB) pathway. Both pathways are required for expression of the gene encoding inducible nitric oxide synthase (iNOS) and for IL-1beta-mediated beta cell death. The molecular mechanisms by which these two pathways regulate beta cell Nos2 expression are currently unknown. Therefore, the aim of this study was to clarify the putative crosstalk between MAPK and NFkappaB activation in beta cells. MATERIALS AND METHODS: The MAPKs ERK, p38 and JNK were inhibited by SB203580, PD98059 or Tat-JNK binding domain or by cells overexpressing the JNK binding domain. The effects
Looking for the definition of p38 mitogen-activated protein kinases? Find out what is the full meaning of p38 mitogen-activated protein kinases on Abbreviations.com! Protein Kinase C is one option -- get in to view more @ The Webs largest and most authoritative acronyms and abbreviations resource.
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as MAPK1, extracellular signal-regulated kinase 2, PRKM1, PRKM2, ERT1, p41-ERK1, p41-MAPK, p42-MAPK, MAP kinase 1, MAP kinase 2, MAPK1, MAPK2, p38, p40, and p41.. ...
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as MAPK1, extracellular signal-regulated kinase 2, PRKM1, PRKM2, ERT1, p41-ERK1, p41-MAPK, p42-MAPK, MAP kinase 1, MAP kinase 2, MAPK1, MAPK2, p38, p40, and p41.. ...
Mitogen-activated protein kinases (MAPKs) are proline-directed serine and threonine protein kinases that regulate numerous physiological cell responses including: embryogenesis, cell differentiation, proliferation, migration, apoptosis and death. Extracellular signal-regulated kinases (ERKs) 1 and 2 (ERK1/2), also known as p44 MAPK and p42 MAPK respectively, belong to one of the five major groups of MAPKs. Closely-related ERK1/2 isoforms are uniquely activated by several extracellular signals including growth factors, cytokines, hormones, and neuro-transmitters. Activation of ERK1/2 by the upstream kinases MEK1 and MEK2 occurs via dual phosphorylation on specific threonine (Thr202) and tyrosine (Tyr204) residues on the T*EY* motif. MEK1 and MEK2 are activated through receptors (tyrosine kinases or integrins) via pathways involving adaptor proteins, guanine nucleotide exchange factors, small GTP binding proteins, and MAPKKs. Activated ERK1/2 phosphorylates both, cytosolic (SOS, MNK1/2, RSKs) and ...
LOC100996792 (dual specificity mitogen-activated protein kinase kinase 3), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
MAPKK 6 is a member of the dual specificity protein kinase family, which functions as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. As an essential component of p38 MAP kinase mediated signal transduction pathway, this gene is involved in many cellular processes such as stress-induced cell cycle arrest, transcription activation and apoptosis.[6] ...
Mitogen-Activated Protein Kinases (MAPKs): Activation, Functions and Regulation opens with a summary of the present knowledge about MAPK, with special emphasis on p38 and c-Jun N-terminal kinase. The authors focus on how these signaling pathways are engaged during some infections with intracellular parasites.. The authors also describe selected regulatory aspects of circadian clocks in vertebrates, exploring an intriguing link to MAPK. Circadian clocks are time-tracking systems that provide organisms with a survival advantage.. Cadmium, one of the toxic metals, is an important occupational and environmental pollutant that damages various organs, especially the kidney. The concluding study proposes that the type of kidney cell and severity of cadmium-induced cellular stress appear to determine the effect of MAPK on cell fate ...
Mitogen-Activated Protein Kinases (MAPKs): ERKs, JNKs, and p38s - CHEMICAL BIOLOGY - reflects the multidimensional character of chemical biology, focusing in particular on the fundamental science of biological structures and systems, the use of chemical and biological techniques to elucidate
Fingerprint Dive into the research topics of Involvement of mitogen-activated protein kinase in hippocampal long-term potentiation. Together they form a unique fingerprint. ...
Ran-Binding Protein M (RanBPM) has been previously shown to inhibit c-Raf expression, however how this was achieved remains unclear. c-Raf is the central component of the extracellular signal-regulated kinase (ERK) pathway which has been linked to many cancer types. Furthermore, RanBPM was recently identified as part of the E3 ubiquitin ligase complex and the CTLH (C-terminal to LisH) complex (McTavish et al., 2019). Lastly, RanBPM has been linked to various signaling pathways related to numerous cellular processes which include - apoptosis, cell adhesion, migration, transcription, nuclear-cytoplasmic transport and also plays a significant role during development (Salemi et al., 2017). ...
Although several multiprotein complexes containing MAPKs (mitogen-activated protein kinases) have been identified using overexpression of kinases and scaffold proteins, the components of the complexes and their physical properties at endogenous expression levels have not been defined. We characterized a large protein complex containing a nerve-growth-factor-activated ERK (extracellular-signal-regulated kinase) and MEK (MAPK/ERK kinase) in rat pheochromocytoma (PC12) cells. This protein complex fractionated into a high-speed pellet and was resistant to non-ionic detergent treatments that solubilized membranes. Disruption of protein-protein interactions by treatment with high salt was required to facilitate immunoprecipitation of active ERK1 and co-precipitation of MEK1. Microtubule fragments were also present in the detergent-resistant high-speed pellet, and some kinases were bound to them, especially ERK1b (an alternatively spliced isoform of ERK1), which showed a strong preference for binding ...
This trial aims to evaluate the efficacy of fulvestrant +/- selumetinib [AZD6244] in patients with advanced stage breast cancer progressing after aromatase
Background Multi-drug proneness and level of resistance to metastasize are main clinical complications in cancers treatment. on cell migration and in cell protein-protein association Neurog1 had been researched by wound-healing and closeness ligation assays, respectively. Outcomes We present right here, that N11 treatment network 336113-53-2 marketing leads to i) significant caspase-mediated apoptotic cell loss of […]. Read More ». ...
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Yan Z, Ohuchida K, Fei S, Zheng B, Guan W, Feng H, Kibe S, Ando Y, Koikawa K, Abe T, Iwamoto C, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Hashizume M, Nakamura M. Inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis. J Exp Clin Cancer Res. 2019 May 27; 38(1):221 ...
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008 ...
ERK1 and ERK2 (also known as MAPK3 and MAPK1) are 44 and 42 kDa Ser/Thr kinases, respectively. They are part of the Ras-Raf-ERK signal transduction cascade often found downstream of growth factor receptor activation. ERK1 and ERK2 were initially isolated and cloned as kinases activated in response to insulin and NGF. They are expressed in most, if not all, mammalian tissues. Dual threonine and tyrosine phosphorylation activate both ERKs, at Thr202/Tyr204 for human ERK1 and Thr185/Tyr187 for human ERK2 ...
ERK1 / ERK2, 0.1 mg. The activation of signal transduction pathways by growth factors, hormones and neurotransmitters is mediated through two closely related MAP kinases, p44 and p42, designated extracellular-signal related kinase 1 (ERK 1) and ERK 2,
MAPK4 antibody [N1C1] (mitogen-activated protein kinase 4) for ICC/IF, IHC-P, WB. Anti-MAPK4 pAb (GTX104128) is tested in Human samples. 100% Ab-Assurance.
Extracellular-signal regulated kinases 1 and 2 (ERK1/2) are the prototypical intracellular mitogen activated protein kinases (MAPK). ERK1/2 are activated by mul...
CMPD-1 is a non-ATP-competitive, selective inhibitor of p38α-mediated MK2a (mitogen-activated protein kinase-2a) phosphorylation (apparent Ki = 330 nM).
VX 954 was selected in October 2000 as a drug development candidate from Vertex Pharmaceuticals p38 mitogen-activated protein (MAP) kinase research programme.
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Yang X, Gabuzda D (November 1998). "Mitogen-activated protein kinase phosphorylates and regulates the HIV-1 Vif protein". The ... Vif is a 23-kilodalton protein that is essential for viral replication. Vif inhibits the cellular protein, APOBEC3G, from ... Viral infectivity factor, or Vif, is an accessory protein found in HIV and other lentiviruses. Its role is to disrupt the ... vif+Protein at the US National Library of Medicine Medical Subject Headings (MeSH). ...
"MAP2K1 mitogen-activated protein kinase kinase 1 [Homo sapiens (human)] - Gene - NCBI". Lones MA, Raphael M, McCarthy K, ... encoding a guanylate kinase which interacts with BCL10 and activates NF-κB to regulate cell survival); 2) changes in the ... that is involved in activating T-cells), CDKN2A (encoding p16INK4a and p14arf tumor suppressor proteins) or CDKN2B (encoding ... Phosphoinositide 3-kinase inhibitors such as copanlisib, duvelisib, and idelalisib which block the phosphoinositide 3-kinase ...
... is also known as MEK1 (see Mitogen-activated protein kinase kinase). MEK1 is a meiotic chromosome-axis-associated kinase ... 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 ... Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the MAP2K1 gene.[5][6] ...
Hutter D, Chen P, Barnes J, Liu Y (Nov 2000). "Catalytic activation of mitogen-activated protein (MAP) kinase phosphatase-1 by ... 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 ... "Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual ...
"Histone deacetylase isoforms regulate innate immune responses by deacetylating mitogen-activated protein kinase phosphatase-1 ... Non-histone proteins such as transcription factors are also targets for acetylation with varying functional effects. ... through modulating the acetylation/deactylation of histones and/or non-histone proteins such as transcription factors. Histone ... 23 (1): 66-84. doi:10.1089/ars.2014.5863. PMC 4492771. PMID 24512308. Gryder BE, Rood MK, Johnson KA, Patil V, Raftery ED, Yao ...
"Docking sites on mitogen-activated protein kinase (MAPK) kinases, MAPK phosphatases and the Elk-1 transcription factor compete ... Wu, J. J.; Zhang, L.; Bennett, A. M. (16 May 2005). "The Noncatalytic Amino Terminus of Mitogen-Activated Protein Kinase ... Wu, J. J.; Zhang, L.; Bennett, A. M. (16 May 2005). "The Noncatalytic Amino Terminus of Mitogen-Activated Protein Kinase ... Camps, M. (22 May 1998). "Catalytic Activation of the Phosphatase MKP-3 by ERK2 Mitogen-Activated Protein Kinase". Science. 280 ...
Zheng Q, Yin G, Yan C, Cavet M, Berk BC (March 2004). "14-3-3beta binds to big mitogen-activated protein kinase 1 (BMK1/ERK5) ... 14-3-3 protein beta/alpha is a protein that in humans is encoded by the YWHAB gene. This gene encodes a protein belonging to ... Yuryev A, Wennogle LP (February 2003). "Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid ... "Binding of 14-3-3beta regulates the kinase activity and subcellular localization of testicular protein kinase 1". J. Biol. Chem ...
... mitogen-activated protein kinase pathway". The Journal of Biological Chemistry. 271 (19): 11272-9. doi:10.1074/jbc.271.19.11272 ... mitogen-activated protein kinase pathway". The Journal of Biological Chemistry. 271 (19): 11272-9. doi:10.1074/jbc.271.19.11272 ... "GTP-binding proteins in human platelet membranes serving as the specific substrate of islet-activating protein, pertussis toxin ... "Entrez Gene: GNAI1 Guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1". Schiaffino MV, ...
... and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase ... Mitogen-activated protein kinase kinase kinase 3 is an enzyme that in humans is encoded by the MAP3K3 gene, which is located on ... "Entrez Gene: MAP3K3 mitogen-activated protein kinase kinase kinase 3". Gilmore PM, McCabe N, Quinn JE, Kennedy RD, Gorski JJ, ... "BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". ...
... coupled receptor agonists requires both extracellular-signal-regulated kinase and p38 mitogen-activated protein kinase". ... Deak M, Clifton AD, Lucocq LM, Alessi DR (September 1998). "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly ... Markou T, Lazou A (2002). "Phosphorylation and activation of mitogen- and stress-activated protein kinase-1 in adult rat ... 1999). "Repression of Stat3 activity by activation of mitogen-activated protein kinase (MAPK)". Oncogene. 17 (24): 3157-67. doi ...
"Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase ... "Specificities of protein-protein and protein-DNA interaction of GABP alpha and two newly defined ets-related proteins". Genes ... and stress-activated protein kinase 1 (MSK1)". Oncogene. 22 (5): 746-55. doi:10.1038/sj.onc.1206185. PMID 12569367. S2CID ... ETV1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) v t e. ...
... 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 ... "MAP3K1 mitogen-activated protein kinase kinase kinase 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved ...
"Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1)". The EMBO ... including glycogen-synthase kinase-3β (GSK3β), AKT/phosphatidylinositol 3-kinase (PI3K) and NF-κB activating kinase (NAK, i.e. ... On the other hand, mitogen and stress-activated kinase 1 (MSK1) are also able to phosphorylate RELA at residue 276 under TNFα ... Phosphorylation of serine 311 by protein kinase C zeta type (PKCζ) serves the same purpose. Two residues in the TAD region are ...
"Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 ( ... "Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. 16 (8): 1909-20. doi:10.1093/ ... "The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine ... "A novel 14-kilodalton protein interacts with the mitogen-activated protein kinase scaffold mp1 on a late endosomal/lysosomal ...
JUN kinase binding. • mitogen-activated protein kinase kinase binding. • mitogen-activated protein kinase kinase kinase binding ... "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 ... MAPK8IP1 has been shown to interact with MAP3K10,[8] DUSP16,[9] Mitogen-activated protein kinase 9,[8][10] MAPK8,[10][11] LRP2, ...
... family of proteins that regulate growth factor-induced activation of the MAP kinase cascade. GRCh38: Ensembl release 89: ... Sprouty-related, EVH1 domain-containing protein 3 also known as Spread-3 is a protein that in humans is encoded by the SPRED3 ... kinase activation in hematopoietic cells". The Journal of Biological Chemistry. 279 (50): 52543-51. doi:10.1074/jbc.M405189200 ... "Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation". Biochemical and Biophysical ...
The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade. ... Sprouty-related, EVH1 domain-containing protein 1 (Spread-1) is a protein that in humans is encoded by the SPRED1 gene located ... This mutation may result in a truncated nonfunctional protein. Blast cells analysis displayed the same abnormality as germline ... "The Sprouty-related protein, Spred-1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with ...
Waskiewicz AJ, Flynn A, Proud CG, Cooper JA (1997). "Mitogen-activated protein kinases activate the serine/threonine kinases ... "Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. ENGLAND. 16 (8): 1909-20. doi: ... "The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high ... "Negative regulation of protein translation by mitogen-activated protein kinase-interacting kinases 1 and 2". Mol. Cell. Biol. ...
"Entrez Gene: MAPKAP1 mitogen-activated protein kinase associated protein 1". Colicelli J, Nicolette C, Birchmeier C, et al. ( ... This gene encodes a protein that is highly similar to the yeast SIN1 protein, a stress-activated protein kinase. Alternatively ... Schroder W, Bushell G, Sculley T (2005). "The human stress-activated protein kinase-interacting 1 gene encodes JNK-binding ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ...
"Tumorigenesis Suppressor Pdcd4 Down-Regulates Mitogen-Activated Protein Kinase Kinase Kinase Kinase 1 Expression to Suppress ... Programmed cell death protein 4 is a protein that in humans is encoded by the PDCD4 gene. It is one of the targets of an ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ... Göke R, Gregel C, Göke A, Arnold R, Schmidt H, Lankat-Buttgereit B (2004). "Programmed Cell Death Protein 4 (PDCD4) Acts As a ...
Mitogen-activated protein kinase kinase kinase kinase 1 is a protein kinase that in humans is encoded by the MAP4K1 gene. It is ... "SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1". J. Biol. Chem. 272 (44): 27804-11 ... "The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of ... a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade". Genes Dev. 10 (18): 2251-64. doi: ...
Deak M, Clifton AD, Lucocq LM, Alessi DR (1998). "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated ... a novel member of the small heat shock protein family, binds and activates the myotonic dystrophy protein kinase". J Cell Biol ... Heat shock protein beta-2 is a protein that in humans is encoded by the HSPB2 gene. HSPB2 has been shown to interact with: ... Park KJ, Gaynor RB, Kwak YT (2003). "Heat shock protein 27 association with the I kappa B kinase complex regulates tumor ...
Mitogen-activated protein kinase kinase kinase 7-interacting protein 1 is an enzyme that in humans is encoded by the TAB1 gene ... "Entrez Gene: MAP3K7IP1 mitogen-activated protein kinase kinase kinase 7 interacting protein 1". "TAB1 (human)". www.phosphosite ... Kishimoto K, Matsumoto K, Ninomiya-Tsuji J (2000). "TAK1 mitogen-activated protein kinase kinase kinase is activated by ... This protein can also interact with and activate the mitogen-activated protein kinase 14 (MAPK14/p38alpha), and thus represents ...
... it also stimulates cells to activate Extracellular signal-regulated kinases (ERKs), Protein kinase B (also known as Akt), c-Jun ... phosphoinositide 3-kinase, protein kinase C, proto-oncogene tyrosine-protein kinase Src, and (by inducing the proteolytic ... BLT2 receptors, similar to BLT1 receptors, are G protein coupled receptors that, when ligand-bound, activate G proteins that ... human prostate cancer cell line to activate several pro-growth and/or pro-survival signaling pathways including protein kinase ...
This gene encodes mitogen-activated protein kinase kinase kinase 14, NIK, which is a serine/threonine protein-kinase. This ... Mitogen-activated protein kinase kinase kinase 14 also known as NF-kappa-B-inducing kinase (NIK) is an enzyme that in humans is ... Nemoto S, DiDonato JA, Lin A (1998). "Coordinate Regulation of IκB Kinases by Mitogen-Activated Protein Kinase Kinase Kinase 1 ... "Entrez Gene: MAP3K14 mitogen-activated protein ki kinase kinase 14". Luftig MA, Cahir-McFarland E, Mosialos G, Kieff E (May ...
Redlitz A, Daum G, Sage EH (1999). "Angiostatin diminishes activation of the mitogen-activated protein kinases ERK-1 and ERK-2 ... Another proposed mechanism of action is that angiostatin binds to Angiomotin (AMOT) and activating focal adhesion kinase (FAK ... Angiostatin is a 38 kDa fragment of a larger protein, plasmin (itself a fragment of plasminogen) enclosing three to five ... Angiostatin is known to bind many proteins, especially to angiomotin and endothelial cell surface ATP synthase but also ...
Extracellular regulated kinase/mitogen activated protein kinase is up-regulated in pulmonary emphysema and mediates matrix ... Expression of syndecan-1 and expression of epidermal growth factor receptor are associated with survival in patients with ... The course of neurofibromatiosis Type 1 on immunosuppression after lung transplantation: Report of 2 cases. Merlo, C.A., Studer ... metalloproteinase-1 induction by cigarette smoke. Mercer, B.A., Kolesnikova N, Sonett, J.R., D'Armiento J. Journal of ...
... mitogen-activated protein kinase pathway". The Journal of Biological Chemistry. 271 (19): 11272-9. doi:10.1074/jbc.271.19.11272 ... mitogen-activated protein kinase pathway". The Journal of Biological Chemistry. 271 (19): 11272-9. doi:10.1074/jbc.271.19.11272 ... a protein that specifically interacts with the trimeric G protein G alpha i3, is a member of a protein family with a highly ... a protein that specifically interacts with the trimeric G protein G alpha i3, is a member of a protein family with a highly ...
2003). "The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta- ... This enzyme is a member of the Mitogen-activated protein kinase (MAPK) family, although not explicitly designated as such (it ... Coulombe P, Meloche S (August 2007). "Atypical mitogen-activated protein kinases: structure, regulation and functions". Biochim ... lacking most features so characteristic of most mitogen-activated protein kinases (e.g. it does not have the dual ...
"The neuropeptide substance P activates p38 mitogen-activated protein kinase resulting in IL-6 expression independently from NF- ... "Metalloproteinases and transforming growth factor-alpha mediate substance P-induced mitogen-activated protein kinase activation ... "Substance P induces rapid and transient membrane blebbing in U373MG cells in a p21-activated kinase-dependent manner". PLOS ONE ... The molecule, which is rapidly inactivated (or at times further activated by peptidases) is rapidly released - repetitively and ...
Mijelin protein nula • Osteonektin • Protein C • Protein S • Proteoglikan • Serum amiloid P komponenta • Sialoglikoprotein ( ... 1999). "Identification and characterization of a novel cytokine, THANK, a TNF homologue that activates apoptosis, nuclear ... factor-kappaB, and c-Jun NH2-terminal kinase.". J. Biol. Chem. 274 (23): 15978-81. PMID 10347144. doi:10.1074/jbc.274.23.15978. ... 1-50. CD1 (a-c, 1A, 1D, 1E) • CD2 • CD3 (γ, δ, ε) • CD4 • CD5 • CD6 • CD7 • CD8 (a) • CD9 • CD10 • CD11 (a, b, c) • CD13 • CD14 ...
... mitogen-activated protein kinase) cascade that is itself a kinase. RSK2 phosphorylates cellular proteins (including histone H3 ... RSK2 is normally activated by the ERK MAP kinase. Mutated RSK2 may be deficient for activation by ERK, or its kinase activity ... Mutations in the RPS6KA3 gene can result in expression of an RSK2 protein (ribosomal S6 kinase 2) with reduced or absent kinase ... The protein RSK2 which is encoded by the RPS6KA3 gene is a kinase which phosphorylates some substrates like CREB and histone H3 ...
"Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... 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. ... "Entrez Gene: MAP2K4 mitogen-activated protein kinase kinase 4". Marti, A; Luo Z; Cunningham C; Ohta Y; Hartwig J; Stossel T P; ...
Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... The ligands interact with the two tyrosine kinase receptor monomers, PDGFRα (PDGFRA) and -Rβ (PDGFRB).[6] The PDGF family also ... There are five different isoforms of PDGF that activate cellular response through two different receptors. Known ligands ... is a potent mitogen for cells of mesenchymal origin, including fibroblasts, smooth muscle cells and glial cells. In both mouse ...
Mitogen-activated protein kinase (EC 2.7.11.24). *Extracellular signal-regulated *MAPK1. *MAPK3 ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene ...
GHB inhibits mitogen activated protein (MAP) kinase action via the GABAB receptor mechanism. MAP kinase is imperative for ... Ren, X.; Mody, I. (2003). "Gamma-hydroxybutyrate reduces mitogen-activated protein kinase phosphorylation via GABAB receptor ... GABA acts via binding to its receptors which include the ligand gated ion channels, GABAA and GABAC and the G-protein couple ... Taurine is a non-protein sulfur amino acid that is found in high concentrations in human milk. It has been shown to have ...
... mitogen-activated protein kinase) kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) ... mitogen-activated protein kinase) kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) ... The β chain of IL-15R recruits and also activates protein tyrosine kinases of the Src family including Lck, Fyn and Lyn kinase ... kinases of the Src family including Lck and Fyn are activated, and subsequently activates PI3K and MAPK signaling pathway.[18] ...
kinase binding. • mitogen-activated protein kinase kinase binding. • guanylate kinase activity. • protein binding. • protein ... SAP97 is a mammalian MAGUK-family member protein that is similar to the Drosophila protein Dlg1 (the protein is alternatively ... brain-enriched guanylate kinase-associated protein), a novel neuronal PSD-95/SAP90-binding protein". The Journal of Biological ... protein kinase binding. • L27 domain binding. • ligand-gated ion channel activity. • potassium channel regulator activity. • ...
... factor depends on heparan sulfate proteoglycans and sustained phosphorylation of mitogen-activated protein kinases p42/44". The ... protein heterodimerization activity. • growth factor activity. • serine-type endopeptidase activity. • protein tyrosine kinase ... positive regulation of protein kinase B signaling. • positive regulation of protein phosphorylation. • cytokine-mediated ... regulation of tau-protein kinase activity. • proteolysis. • positive chemotaxis. • MAPK cascade. • peptidyl-tyrosine ...
... and/or 271 by Mitogen-activated protein kinases, S6 kinase, protein kinase A (PKA), protein kinase C, Cdc2, and/or a Ca2+/ ... This chemotactic factor stimulation concurrently causes the activation of mitogen-activated protein kinases (MAPK) which in ... ALOX5 binds with the F actin-binding protein, coactin-like protein. Based on in vitro studies, this protein binding serves to ... "5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes". J. ...
... cyclin-dependent kinases, and other cell cycle proteins. The phases follow one another in strict order and there are " ... the motor activates, using energy from ATP to "crawl" up the tube toward the originating centrosome. This motor activity, ... Mitogen. *Mitosis Promoting Factor. *Mitotic bookmarking. *Motor protein. References[edit]. *^ "Cell division and growth". ... Generation of pressure is dependent on formin-mediated F-actin nucleation[71] and Rho kinase (ROCK)-mediated myosin II ...
Hardie DG, Hawley SA (December 2001). "AMP-activated protein kinase: the energy charge hypothesis revisited". Bioessays 23 (12 ... Pri vseh adenozinskih receptorjih opazimo aktivacijo najmanj ene poddružine mitogen - aktiviranih proteinskih kinaz. Učinek ... 1. 2. N. A. D. H. +. c. y. t. c. o. x. +. A. D. P. +. P. i. ⟺. 1. 2. N. A. D. +. +. c. y. t. c. r. e. d. +. A. T. P. {\ ... Lin X, Ayrapetov M, Sun G (2005). "Characterization of the interactions between the active site of a protein tyrosine kinase ...
... and gp130-mediated stimulation of mitogen-activated protein kinase. Evidence for participation of multiple signaling pathways ... Mijelin protein nula • Osteonektin • Protein C • Protein S • Proteoglikan • Serum amiloid P komponenta • Sialoglikoprotein ( ... 2000). „Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines.". ... Glikoprotein 130 (takođe poznat kao gp130, IL6ST, IL6-beta ili CD130) je transmembranski protein. On je osnivački član klase ...
... synaptic NMDA excitation caused a decrease in the intracellular concentration of p38 mitogen-activated protein kinase (p38MAPK ... which contain residues that can be directly modified by a series of protein kinases and protein phosphatases, as well as ... The NMDA receptor is a glutamate and ion channel protein receptor that is activated when glycine and glutamate bind to it.[2] ... Yu XM, Askalan R, Keil GJ, Salter MW (January 1997). "NMDA channel regulation by channel-associated protein tyrosine kinase Src ...
... enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2 ... 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 ... "Impact of the Yersinia pseudotuberculosis-derived mitogen (YPM) on the murine immune system". Adv. Exp. Med. Biol. 529: 133-5. ...
Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase, 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 ... Gazin C, Rigolet M, Briand JP, et al., Immunochemical detection of proteins related to the human c-myc exon 1, in EMBO J., vol ...
... element-binding protein through a phosphatidylinositol 3-kinase-dependent stimulation of the mitogen-activated protein kinase ... and Mitogen-activated protein kinases (MAPK).[28] Messages are translated on the rough endoplasmic reticulum (rough ER) and ... CaMKII activates the Ras proteins, which go on to activate p42/44 MAPK, which drives AMPAR insertion directly into the ... which in turn activates protein phosphatases PP1 and calcineurin. However, AMPAR endocytosis has also been activated by voltage ...
... cell division is necessary for permanent neurotensin cell sensitization and leads to chronic mitogen-activated protein kinase ... 1999). "TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction.". J. Biol. Chem. ... aktivnost neurotenzinskog receptora, G-protein spregnutog. Celularna komponenta. • endoplazmatični retikulum. • Goldži aparat. ... 1998). "Correlative ultrastructural distribution of neurotensin receptor proteins and binding sites in the rat substantia nigra ...
"Role of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinase kinase in adenosine A2B receptor ... Adenozinski A2B receptor (ADORA2B) je G-protein spregnuti adenozinski receptor. Ovaj protein je kodiran humanim ADORA2B genom.[ ... signalni put G-protein spregnutog receptora. • aktivnost adenilat ciklaze. • JNK kaskada. • izlučivanje. ... aktivnost A2B adenouinskog receptora, G-protein spregnutog. • receptorska aktivnost. Celularna komponenta. • integralno sa ...
protein tyrosine kinase activity. • phosphatidylinositol-4,5-bisphosphate 3-kinase activity. • Ras guanyl-nucleotide exchange ... positive regulation of epidermal growth factor-activated receptor activity. • تمايز خلوي. • positive regulation of cytokine ... "Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin.". ... positive regulation of protein kinase activity. • ERBB2 signaling pathway. • regulation of cell motility. • epidermal growth ...
Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... phospholipase C-activating G-protein coupled receptor signaling pathway. • retina development in camera-type eye. • Ras protein ... protein complex binding. • signal transducer activity. • protein binding. • GTPase activity. • GTPase binding. • G-protein ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ...
... a hyaluronan-binding protein that regulates ras signaling, correlates with overexpression of mitogen-activated protein kinase ... It forms links with several protein kinases associated with cell locomotion, for example, extracellular signal-regulated ... MAP kinase (MAPK), pp60(c-src), and the downstream targets of Rho kinase (ROK).[22] RHAMM can also cooperate with CD44 to ... protein kinase (ERK), p125fak, and pp60c-src.[32][33][34] During fetal development, the migration path through which neural ...
... mitogen-activated-protein kinase-activating protein kinase) has a preference for Ser40, but also phosphorylates Ser19 about ... "Phosphorylation and activation of human tyrosine hydroxylase in vitro by mitogen-activated protein (MAP) kinase and MAP-kinase- ... that are phosphorylated by a variety of protein kinases.[12][25] Ser40 is phosphorylated by the cAMP-dependent protein kinase.[ ... Tyrosine hydroxylase is activated by phosphorylation dependent binding to 14-3-3 proteins.[34] Since the 14-3-3 proteins also ...
protein binding. • protein kinase binding. Cellular component. • membrane. • plasma membrane. • caveola. • cytosol. • cell ... The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade.[5] ... negative regulation of protein kinase activity. • negative regulation of angiogenesis. • regulation of MAPK cascade. • negative ... protein serine/threonine kinase inhibitor activity. • phosphatase binding. • stem cell factor receptor binding. • ...
"Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated protein kinase/heat shock protein 27 pathway ... 2003). "The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic ... aktivnost G-protein spregnutog receptora. { • lipidno vezivanje. Celularna komponenta. • ćelijska membrana. • integralno sa ... Receptor slobodnih masnih kiselina 2 (FFA2) je G protein spregnuti receptor kodiran FFAR2 genom.[1] ...
... mitogen-activated protein kinase, MAPK)訊息的梯瀑效應(cascade)的活化、粒線體活性氧(reactive oxygen species, ROS)的產生、C型磷脂酶(phospholipase C, PLC)及 ... Regulation of Na+-K+-ATPase by cAMP-dependent protein kinase anchored on membrane via its anchoring protein Kinji Kurihara, ... 3.6.5.1: 异三聚体G蛋白(英语:Heterotrimeric G protein). *Gαs ... 4.1/2/3/4/5/6 · 5.1/2/3/4/5/99 · 6.1-3(英语:Template:Ligases CO CS and CN)/4/
mitogen-activated protein kinase kinase kinase binding. • protein binding. • thioesterase binding. • protein kinase binding. • ... Activated Cdc42 activates by conformational changes[4] p21-activated kinases PAK1 and PAK2, which in turn initiate actin ... "The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily ... Joberty G, Petersen C, Gao L, Macara IG (August 2000). "The cell-polarity protein Par6 links Par3 and atypical protein kinase C ...
... (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" ... The activators of p38 (MKK3 and MKK6), JNK (MKK4 and MKK7), and ERK (MEK1 and MEK2) define independent MAP kinase signal ...
Norway rat protein-coding gene Mapk1. Represented by 134 ESTs from 65 cDNA libraries. Corresponds to reference sequence NM_ ... Protein sequence * * Protein/EST matches (ProtEST) * * Protein/protein matches (BLink) * mitogen-activated protein kinase 1. C ... Protein sequence * * Protein/EST matches (ProtEST) * * Protein/protein matches (BLink) * mitogen-activated protein kinase 1. X ... Protein sequence * * Protein/EST matches (ProtEST) * * Protein/protein matches (BLink) * mitogen-activated protein kinase 8. C ...
A mitogen-activated protein kinase 14 phosphorylated form that has been activated by Thr and Tyr phosphorylation within the TxY ... mitogen-activated protein kinase 14 phosphorylated 1. Go to external page http://purl.obolibrary.org/obo/PR_000003109 Copy ... mitogen-activated protein kinase 14 phosphorylated form. *has_part some O-phospho-L-threonine ...
mitogen-activated protein kinase kinase kinase binding IEA Inferred from Electronic Annotation. more info ... mitogen-activated protein kinase 8 interacting protein 1provided by HGNC. Primary source. HGNC:HGNC:6882 See related. Ensembl: ... MAPK8IP1 mitogen-activated protein kinase 8 interacting protein 1 [ Homo sapiens (human) ] Gene ID: 9479, updated on 7-Dec-2018 ... mitogen-activated protein kinase kinase binding IEA Inferred from Electronic Annotation. more info ...
Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 ... Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of ... ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein] UniProt ...
Probably by activating skn-1, involved in the up-regulation of gcs-1 and glutathione-S-transferase gst-4 expression upon ... May play a redundant role with other MAP kinases in susceptibility to anoxia, downstream of tir-1/nsy-1 (PubMed:21212236). ... Serine/threonine kinase which responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating ... Phosphorylates snk-1 which probably regulates skn-1 nuclear translocation in response to oxidative stress (PubMed:16166371). ...
... likely by activating gck-3 (PubMed:21160027). Plays a role in response to M.nematophilum-mediated bacterial infection by ... By up-regulating cep-1 and down-regulating gld-1 expression in the late pachytene stage, plays a role in germline apoptosis in ... By phosphorylating transcription factor skn-1 (isoform c) may play a role in increasing life span downstream of lin-45, let-60 ... acts downstream of lin-45 raf kinase, but before the lin-1 gene product in controlling vulval cell differentiation (PubMed: ...
Mitogen-activated protein (MAP) kinase is regulated by the MAP kinase phosphatase (MKP-1) in vascular smooth muscle cells. J ... Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase). EMBO J. 1991;10: ... PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J Biol ... Mitogen-activated protein (MAP) kinases are important mediators involved in the intracellular network of interacting proteins ...
... p38 mitogen-activated protein kinase, and peroxisome proliferator-activated receptor alpha. Diabetes 2006;55:2562-2570pmid: ... Activated AMP-activated protein kinase and increased peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) have ... p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling ... p38 is a member of the mitogen-activated protein kinase (MAPK) family and has been identified as a downstream molecule in the ...
wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary ... knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound ...
Enhanced activation of mitogen-activated protein kinase and myosin light chain kinase by the Pro33 polymorphism of integrin ... Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector. Orth, K., Palmer, L.E., Bao, Z.Q ... Cell-cycle-dependent activation of mitogen-activated protein kinase kinase (MEK-1/2) in myeloid leukemia cell lines and ... Identification of a C-terminal region that regulates mitogen-activated protein kinase kinase-1 cytoplasmic localization and ERK ...
The p38/reactivity kinase mitogen-activated protein kinase cascade mediates the activation of the transcription factor insulin ... The Role of p38 Mitogen-Activated Protein Kinase in IL-1β Transcription. Joseph J. Baldassare, Yanhua Bi and Clifford J. ... Pyridinyl imidazole inhibitors of p38 mitogen-activated protein kinase bind in the ATP site. J. Biol. Chem. 272: 12116. ... Phosphorylation at threonine-235 by a Ras-dependent mitogen-activated protein kinase C cascade is essential for transcription ...
TNFalpha increased the activity of the p38 substrate MAP kinase-activated-protein (MAPKAP) kinase 2 and the subsequent ph … ... kinase signalling cascade in human umbilical vein endothelial cells. ... alpha was found to stimulate the p38 mitogen activated protein (MAP) ... p38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level Biochem Biophys ...
1 Duroy A. Navarre , 2 and Isgouhi Kaloshian 1...© 2006 The American Phytopathological Society...The tomato Mi-1 gene confers ... Using virus-induced gene silencing, one or more mitogen-activated protein kinase (MAPK) cascades required for Mi-1-mediated ... Silencing plants for MAPK kinase (LeMKK2) and MAPKs (LeMPK2 and LeMPK1, or LeMPK3) resulted in attenuation of Mi-1-mediated ... Qi Li , 1 Qi-Guang Xie , 1 Jennifer Smith-Becker , 1 Duroy A. Navarre , 2 and Isgouhi Kaloshian 1 ...
Mitogen-Activated Protein Kinase Kinase 1 ELISA Kits * Mitogen-Activated Protein Kinase Kinase 1 Interacting Protein 1 ELISA ... Mitogen-Activated Protein Kinase Associated Protein 1 ELISA Kits * Mitogen-Activated Protein Kinase Binding Protein 1 ELISA ... Mitogen-Activated Protein Kinase Kinase 7 ELISA Kits * Mitogen-Activated Protein Kinase Kinase Kinase 1 ELISA Kits ... This gene encodes a member of the mitogen-activated protein (MAP) kinase family. MAP kinases act as an integration point for ...
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 ...
Uric Acid Stimulates Monocyte Chemoattractant Protein-1 Production in Vascular Smooth Muscle Cells Via Mitogen-Activated ... Protein Kinase and Cyclooxygenase-2. John Kanellis, Susumu Watanabe, Jin H. Li, Duk Hee Kang, Ping Li, Takahiko Nakagawa, Ann ... Uric Acid Stimulates Monocyte Chemoattractant Protein-1 Production in Vascular Smooth Muscle Cells Via Mitogen-Activated ... Protein Kinase and Cyclooxygenase-2. John Kanellis, Susumu Watanabe, Jin H. Li, Duk Hee Kang, Ping Li, Takahiko Nakagawa, Ann ...
To test the hypothesis that mitogen-activated protein kinase phosphatase (MKP)-1 is actively involved in atherogenesis. ... Multiple protein kinases have been implicated in cardiovascular disease; however, little is known about the role of their ... but not c-Jun N-terminal kinase and p38, pathway activation. In line with this, MKP-1-null atheroma exhibited less macrophage ... In addition, MKP-1-null mice had higher levels of plasma stromal cell-derived factor-1a, which negatively correlated with ...
Hyperexpression of mitogen-activated protein kinase in human breast cancer. J Clin Invest 1997; 99: 1478-83. ... Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer 2004; 4: ... Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors. Oncogene 1999; 18 ... Recent reports have described multifaceted interactions between the mitogen-activated protein kinase (MAPK) and AKT signaling ...
... such as G-protein α subunit, Ras, nitric oxide synthase, protein kinase C, and protein kinase A ( 2, 7, 10, 16- 25). However, ... In addition, signaling studies show p38 mitogen-activated protein kinase (MAPK) as the upstream regulator of Sp1-mediated ... activation of p38 mitogen-activated protein kinase (MAPK) → Sp1-mediated activation of GC-rich caveolin-1 promoter elements → ... Activation of Ras-MAP kinase and protein kinase a signaling cascades transcriptionally down-regulates caveolin-1 promoter ...
MAPKs are activated by intracellular tyrosine kinases and inactivated by mitogen-activated protein kinase phosphatases (MKPs), ... Mitogen-activated protein kinase phosphatase 1 (MKP-1) is a tyrosine phosphatase superfamily member that dephosphorylates and ... ABBREVIATIONS: MAPK, mitogen-activated protein kinase; MKP-1, mitogen-activated protein kinase phosphatase-1; DSP, dual ... Wu JJ and Bennett AM (2005) Essential role for mitogen-activated protein (MAP) kinase phosphatase-1 in stress-responsive MAP ...
G-protein-coupled receptor agonists are powerful stimulators of mitogen-activated protein kinase (MAPK) cascades in cardiac ... coupled receptor agonists requires both extracellular-signal-regulated kinase and p38 mitogen-activated protein kinase Thomais ... coupled receptor agonists requires both extracellular-signal-regulated kinase and p38 mitogen-activated protein kinase. Biochem ... We examined the activation of mitogen- and stress-activated protein kinase-1 (MSK1), a downstream target of MAPKs, in adult rat ...
E6201, a Novel Kinase Inhibitor of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase-1 and Mitogen- ... E6201, a Novel Kinase Inhibitor of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase-1 and Mitogen- ... E6201, a Novel Kinase Inhibitor of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase-1 and Mitogen- ... E6201, a Novel Kinase Inhibitor of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase-1 and Mitogen- ...
Protein kinase C epsilon is required for the induction of mitogen-activated protein kinase phosphatase-1 in lipopolysaccharide- ... Dephosphorylation and inactivation of the mitogen-activated protein kinase by a mitogen-induced Thr/Tyr protein phosphatase. J ... Protein phosphatases and the regulation of mitogen-activated protein kinase signalling. Curr. Opin. Cell Biol. 12:186-192. ... The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU- ...
... activates its substrate, MEK kinase. MEK activates mitogen-activated protein kinase (MAPK), which phosphorylates other kinases ... we show that GA does not affect the ability of protein kinase C alpha to be activated by phorbol esters, but it does block ... The serine/threonine kinase Raf-1 functions downstream of Rats in a signal transduction cascade which transmits mitogenic ... function as a signal transducer and that the effects observed cannot be attributed to a general impairment of protein kinase ...
... where it is then able to phosphorylate and activate mitogen-activated protein kinase kinases (MEK) 1 and 2, which are dual ... Purpose: The Ras-Raf-mitogen-activated protein kinase kinase (MEK) pathway is overactive in many human cancers and is thus a ... Interdependent domains controlling the enzymatic activity of mitogen-activated protein kinase kinase 1. Biochemistry 1996;35: ... Ballif BA, Blenis J. Molecular mechanisms mediating mammalian mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK cell ...
mitogen-activated protein kinase. MOR. μ-opioid receptor. MSK. mitogen- and stress-activated protein kinase. NaB. sodium ... involving mitogen-activated protein kinase (MAPK) activation and mitogen- and stress-activated protein kinase 1 (MSK1)-ranges ... Hwang CK, Wagley Y, Law P-Y, Wei L-N and Loh HH (2011) p38 mitogen-activated protein kinase and PI3-kinase are involved in up- ... can lead to the phosphorylation and activation of the downstream kinase, mitogen- and stress-activated protein kinase 1 (MSK1 ...
Regulation of the Mitogen Activated Protein Kinase Kinase (MEK)-1 by NAD-Dependent Deacetylases. ECU Author/Contributor (non- ... Here, we demonstrate that acetylation of the mitogen-activated protein kinase kinase-1 (MEK1) stimulates its kinase activity, ... Regulation of the Mitogen Activated Protein Kinase Kinase (MEK)-1 by NAD-Dependent Deacetylases. http://hdl.handle.net/10342/ ... Treatment of cells with sirtuin inhibitors, or siRNA knockdown of SIRT1 or SIRT2 proteins, increases MEK1 acetylation and ...
MAP kinase, mitogen-activated protein kinase; MEK, MAP kinase/Erk kinase; MEK-A, dominant-negative MEK; MEK-E, constitutively ... Dual role for mitogen-activated protein kinase (Erk) in insulin-dependent regulation of Fra-1 (fos-related antigen-1) ... Dual role for mitogen-activated protein kinase (Erk) in insulin-dependent regulation of Fra-1 (fos-related antigen-1) ... Dual role for mitogen-activated protein kinase (Erk) in insulin-dependent regulation of Fra-1 (fos-related antigen-1) ...
Mitogen-activated protein kinase kinase (MEK or MAPK/ERK kinase) is a critical enzyme in the RAS/RAF/MEK/ERK pathway that ... AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signalregulated kinase kinase 1/2 ... The mitogen-activated protein/extracellular signalregulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest ... Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral, Small-Molecule Mitogen-Activated Protein Kinase Kinase 1/2 ...
  • Both MAP2K1 /MEK1 and MAP2K2 /MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3 /ERK1 and MAPK1 /ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. (rcsb.org)
  • One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma ( PPARG ), a nuclear receptor that promotes differentiation and apoptosis. (rcsb.org)
  • Mitochondrial contents, expression, and activation status of p38 mitogen-activated protein kinase (MAPK) and PPARγ coactivator 1α (PGC-1α) were compared between skeletal muscle samples from adiponectin gene knockout, adiponectin-reconstituted, and control mice. (diabetesjournals.org)
  • Adenovirus-mediated adiponectin and MAPK phosphatase-1 (MKP1) overexpression were used to verify the relationship of MKP1 and PGC-1α in adiponectin-enhanced mitochondrial biogenesis using cultured C2C12 myotubes and PGC-1α knockout mice. (diabetesjournals.org)
  • Overexpression of MKP1 attenuated adiponectin-enhanced mitochondrial biogenesis, with significantly decreased PGC-1α expression and p38 MAPK phosphorylation. (diabetesjournals.org)
  • Therefore, our study indicates that adiponectin enhances p38 MAPK/PGC-1α signaling and mitochondrial biogenesis in skeletal muscle by suppressing MKP1 expression. (diabetesjournals.org)
  • p38 is a member of the mitogen-activated protein kinase (MAPK) family and has been identified as a downstream molecule in the adiponectin-signaling pathway ( 15 , 18 , 19 ). (diabetesjournals.org)
  • Activation of p38 MAPK increases not only PGC-1α gene expression but also PGC-1α activity ( 24 - 27 ). (diabetesjournals.org)
  • Inhibition of p38 MAPK completely blocks Ca 2+ -induced PGC-1α gene expression ( 28 ). (diabetesjournals.org)
  • Therefore, p38 MAPK may play a pivotal role in mediating adiponectin-stimulated PGC-1α gene expression, activation, and mitochondrial biogenesis in skeletal muscle. (diabetesjournals.org)
  • Several reports have shown that bicyclic imidazoles, specific inhibitors of the p38 mitogen-activated protein kinase (MAPK), block cytokine synthesis at the translational level. (jimmunol.org)
  • In this study, we examined the role of p38 MAPK in the regulation of the IL-1β cytokine gene in monocytic cell lines using the bicyclic imidazole SB203580. (jimmunol.org)
  • LPS-stimulated p38 MAPK activity in the RAW264.7 cells was blocked by SB203580, as measured by the inhibition of MAPKAP2 kinase activity, a downstream target of the p38 MAPK. (jimmunol.org)
  • CCAATT/enhancer binding protein (C/EBP)/NFIL-6-driven chloramphenicol acetyltransferase (CAT) reporter activity was sensitive to SB203580, indicating that C/EBP/NFIL-6 transcription factor(s) are also targets of p38 MAPK. (jimmunol.org)
  • Overall, the results demonstrate, for the first time, a role for p38 MAPK in IL-1β transcription by acting through C/EBP/NFIL-6 transcription factors. (jimmunol.org)
  • Because it is known that 1) these transcription factors are activated by phosphorylation ( 30 , 31 ), and 2) the activation of CHOP, a member of the C/EBP transcription factor family, is dependent upon phosphorylation at serine residues 78 and 81 by the p38 MAPK ( 32 ), we examined the possibility that the p38 MAPK, through C/EBPβ and -δ factors, might also be important for IL-1β transcription. (jimmunol.org)
  • Using virus-induced gene silencing, one or more mitogen-activated protein kinase (MAPK) cascades required for Mi-1- mediated aphid resistance were identified. (apsnet.org)
  • Silencing plants for MAPK kinase ( LeMKK2) and MAPKs ( LeMPK2 and LeMPK1 , or LeMPK3) resulted in attenuation of Mi-1 -mediated aphid resistance. (apsnet.org)
  • Ras activates two protein kinases, Raf-1 and MEK (MAPK, or ERK, kinase) kinase (MEKK). (sciencemag.org)
  • 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)
  • Recent reports have described multifaceted interactions between the mitogen-activated protein kinase (MAPK) and AKT signaling networks and the splice regulatory machinery. (aacrjournals.org)
  • Alterations in the splice pattern and resulting expression of MAPK kinase are implicated in mediating the antitumoral effects resulting from SRPK1 down-regulation. (aacrjournals.org)
  • In addition, signaling studies show p38 mitogen-activated protein kinase (MAPK) as the upstream regulator of Sp1-mediated activation of the caveolin-1 promoter following oxidative stress. (aacrjournals.org)
  • Inhibition of p38 MAPK prevents the oxidant-induced Sp1-mediated up-regulation of caveolin-1 protein expression and development of premature senescence. (aacrjournals.org)
  • Mitogen-activated protein kinase phosphatase 1 (MKP-1) is a tyrosine phosphatase superfamily member that dephosphorylates and inactivates cardinal mitogen-activated protein kinase (MAPK) substrates, such as p38, c-Jun NH 2 -terminal kinase, and extracellular signal-regulated kinase. (aspetjournals.org)
  • G-protein-coupled receptor agonists are powerful stimulators of mitogen-activated protein kinase (MAPK) cascades in cardiac myocytes. (portlandpress.com)
  • Maximal activation of MSK1 in adult cardiomyocytes temporally coincided with maximal p38 MAPK activation while activation of the extracellular-signal-regulated kinase (ERK) cascade was more rapid. (portlandpress.com)
  • These data demonstrate that MSK1 activation in adult rat cardiac myocytes by G-protein-coupled receptor agonists requires the simultaneous activation of both the ERK and p38 MAPK pathways. (portlandpress.com)
  • Members of the three mitogen-activated protein kinase (MAPK) families mediate transcriptional and posttranscriptional changes in gene expression in response to proinflammatory stimuli (reviewed in references 15 , 25 , and 33 ). (asm.org)
  • MEK activates mitogen-activated protein kinase (MAPK), which phosphorylates other kinases as well as transcription factors. (asm.org)
  • In this study, we examined whether Raf-1 destabilization is sufficient to block the Raf-1-MEK-MAPK signalling pathway and whether GA specifically inactivates the Raf-1 component of this pathway. (asm.org)
  • Using the model system of NIH 3T3 cells stimulated with phorbol 12-myristate 13-acetate (PMA), we show that GA does not affect the ability of protein kinase C alpha to be activated by phorbol esters, but it does block activation of MEK and MAPK. (asm.org)
  • Finally, disruption of the Raf-1-MEK-MAPK signalling pathway by GA prevents both the PMA-induced proliferative response and PMA-induced activation of a MAPK-sensitive nuclear transcription factor. (asm.org)
  • In this study, we demonstrate that MOR epigenetic regulation requires multiple coordinated signals converging at the MOR promoter, involving mitogen-activated protein kinase (MAPK) activation and mitogen- and stress-activated protein kinase 1 (MSK1)-ranges of intracellular signaling pathways similar to those activated by opioid agonists. (aspetjournals.org)
  • Mitogen-activated protein kinase kinase (MEK or MAPK/ERK kinase) is a critical enzyme in the RAS/RAF/MEK/ERK pathway that regulates key cellular activities including proliferation, survival, and cell cycle regulation. (pubmedcentralcanada.ca)
  • The report provides comprehensive information on the Mitogen Activated Protein Kinase 1 (MAP Kinase 1 or MAPK 1 or Extracellular Signal Regulated Kinase 2 or ERK-2 or Protein Tyrosine Kinase ERK2 or EC 2.7.11.24), targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (reportsnreports.com)
  • Additionally, the report provides an overview of key players involved in Mitogen Activated Protein Kinase 1 (MAP Kinase 1 or MAPK 1 or Extracellular Signal Regulated Kinase 2 or ERK-2 or Protein Tyrosine Kinase ERK2 or EC 2.7.11.24) targeted therapeutics development and features dormant and discontinued projects. (reportsnreports.com)
  • The mechanism of mitogen-activated protein kinase (MAPK, ERK) stimulation by the GnRH analog [D-Trp6]GnRH (GnRH-a) was investigated in the gonadotroph-derived alphaT3-1 cell line. (semanticscholar.org)
  • GnRH-a as well as the protein kinase C (PKC) activator 12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulated a sustained response of MAPK activity, whereas epidermal growth factor (EGF) stimulated a transient response. (semanticscholar.org)
  • MAPK kinase (MEK) is also activated by GnRH-a, but in a transient manner. (semanticscholar.org)
  • We have found that lethal toxin from Clostridium sordellii, which specifically inactivates the low molecular weight G proteins Ras, Rap, and Rac, inhibits the activation of p38 mitogen-activated protein kinase (MAPK) by interleukin-1 (IL-1) in EL4.NOB-1 cells and primary fibroblasts. (tcd.ie)
  • The target protein involved appeared to be Ras, because transient transfections with dominant negative RasN17 inhibited p38 MAPK activation by IL-1. (tcd.ie)
  • Furthermore, transfections of cells with constitutively active RasVHa-activated p38 MAPK. (tcd.ie)
  • Intriguingly, transfection of cells with dominant negative Rap1AN17 activated p38 MAPK. (tcd.ie)
  • Furthermore, constitutively active Rap1AV12 inhibited p38 MAPK activation by IL-1, consistent with Rap antagonizing Ras function. (tcd.ie)
  • Our studies therefore provide clear evidence using multiple approaches for Ras as a signaling component in the activation of p38 MAPK by IL-1, with Rap having an inhibitory effect. (tcd.ie)
  • MAP kinase-interacting kinases (MNK1 and MNK2) are often activated downstream of ERK and p38 MAPK in the MAP kinase family. (eurekaselect.com)
  • We find that ERK activity is essential for serum-induced osteoblast proliferation in vitro because inhibition of MAPK/ERK kinase activity by U0126 completely abolished both serum-induced activation of ERK and proliferation of mouse (MBA-15.4) and human (MG-63) osteoblast cell lines. (ox.ac.uk)
  • Coupled with the rapidity of Dex action, this indicates immediate-early gene phosphatase involvement, and we therefore used quantitative, real-time PCR to examine expression profiles of the dual-specificity MAPK phosphatases, MKP-1 and MKP-3. (ox.ac.uk)
  • In liver there was 30 - 40-fold activation of c-Jun N-terminal kinase (JNK) and 5-fold activation of both JNK kinases, mitogen-activated protein kinase (MAPK) kinase (MKK)4 and MKK7. (ox.ac.uk)
  • IL-1α also caused 2 - 3-fold activation of p38 MAPK and degradation of the inhibitor of nuclear factor KB ('IκB'), although no activation of extracellular signal-regulated protein kinase (ERK) (p42/44 MAPK) was observed. (ox.ac.uk)
  • To evaluate the roles of MAPKs and NF-κB in CD38 regulation, astrocytes were treated with MAPK inhibitors (SB203580, SP600125, U0126), NF-κB interfering peptide (SN50) or transfected with dominant negative IκBα mutant (IκBαM) prior to IL-1β activation. (biomedcentral.com)
  • In astrocytes, IL-1β-induced increases in CD38 levels were regulated through the MAPK signaling pathway and by the transcription factor NF-κB. (biomedcentral.com)
  • We provide causal evidence that this effect of GC is mediated by induction of the dual-specificity MAPK phosphatase, MKP-1/DUSP1. (ox.ac.uk)
  • Neither c-jun N-terminal kinase nor p38 MAPK is activated by the mitogenic cocktail in 20% fetal calf serum, but their activation by a DNA-damaging agent (UV irradiation) was inhibited by either GC treatment or overexpression of MKP-1, indicating regulation of all three MAPKs by MKP-1 in osteoblasts. (ox.ac.uk)
  • However, an inhibitor of the MAPK/ERK kinase-ERK pathway inhibited osteoblast proliferation whereas inhibitors of c-jun N-terminal kinase or p38 MAPK had no effect, suggesting that ERK is the MAPK that controls osteoblast proliferation. (ox.ac.uk)
  • Mitogen-activated protein kinase phosphatase 1 (MKP-1) is shown to negatively regulate MAPK signaling in various peripheral tissues as well as the central nervous system such as cortex, striatum and hippocampus. (fujita-hu.ac.jp)
  • In this study, we examined whether MKP-1 regulates MAPK signaling in the mouse hypothalamus. (fujita-hu.ac.jp)
  • TNFα treatment induced increases in MKP-1 expression at both mRNA and protein levels, accompanied by the inactivation of MAPK signaling in mouse hypothalamic explants. (fujita-hu.ac.jp)
  • Inhibition of MKP-1 by its inhibitor or siRNA increased MAPK activity in the explants. (fujita-hu.ac.jp)
  • Our data indicate that MKP-1 negatively regulates MAPK signaling in the mouse hypothalamus. (fujita-hu.ac.jp)
  • The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. (nih.gov)
  • Activation of RAS leads to activation of several effector pathways, the best characterized of which are the RAF/MEK/ERK pathway ["the classical mitogen-activated protein kinase (MAPK) pathway"], the PI3 kinase (PI3K) pathway, and the Ral-GEFs ( 1 - 6 ). (aacrjournals.org)
  • Constitutive MAPK pathway activation can result from activating mutations in RAS, BRAF, and MEK1, loss of the tumor suppressor NF1 ( 7 ), or upstream activation mediated by mutations, amplification, or ligand-mediated activation of cell surface receptors ( Fig. 1 ). (aacrjournals.org)
  • The classical MAPK pathway is activated in human tumors by several mechanisms including the binding of ligand to receptor tyrosine kinases (RTK), mutational activation of an RTK, by loss of the tumor suppressor NF1, or by mutations in RAS, BRAF, and MEK1. (aacrjournals.org)
  • Innate immunity in takes a conserved PMK-1 p38 mitogen-activated protein kinase (MAPK) pathway that regulates the basal and pathogen-induced expression of immune system effectors. (bcl-2-protein.com)
  • MAPK, are similar to the system of legislation mediated with the matching ancestral Sko1p and Hog1p protein in the fungus response to osmotic tension. (bcl-2-protein.com)
  • Previously, we have established that a conserved PMK-1 p38 mitogen-activated protein kinase (MAPK) pathway regulates immunity in innate immune response, we have characterized the transcription factor ATF-7, a conserved member of the basic-region leucine zipper (bZIP) transcription factor family orthologous to mammalian ATF2. (bcl-2-protein.com)
  • Notably, the increased loss of PMK-1 p38 MAPK activity in on nonpathogenic bacterias. (bcl-2-protein.com)
  • This protein is part of a signaling pathway called the RAS/MAPK pathway, which transmits chemical signals from outside the cell to the cell's nucleus. (medlineplus.gov)
  • The genetic changes abnormally activate the protein, which disrupts the tightly regulated RAS/MAPK signaling pathway in many types of cells. (medlineplus.gov)
  • The mutations lead to the production of a version of the protein that is overactive, which increases RAS/MAPK signaling in bone tissue. (medlineplus.gov)
  • The genetic changes lead to an overactive MEK1 protein kinase, which increases activation of the RAS/MAPK signaling pathway in particular tissues. (medlineplus.gov)
  • Six post-implantation lethal knockouts of genes for lipophilic MAPK pathway proteins are expressed in preimplantation mouse embryos and trophoblast stem cells. (qxmd.com)
  • This is consistent with data that showed that S1P activated both c-Src and p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) in a pertussis toxin (PTX)-sensitive manner in these cells. (strath.ac.uk)
  • We have also shown that phosphoinositide 3-kinase (PI-3K) inhibitors (wortmannin and LY294002) decreased p42/p44 MAPK activation. (strath.ac.uk)
  • These results demonstrate that S1P activates c-Src and Grb-2-PI-3K (intermediates in the p42/p44 MAPK cascade) via a PTX-sensitive mechanism. (strath.ac.uk)
  • When examined for its effect on other signaling pathways, flavopiridol inhibited TNF-induced activation of various mitogen-activated protein kinases, including c-Jun NH(2)-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and p44/p42 MAPK. (qxmd.com)
  • Genetic deletion of PKR abrogates TNF-induced activation of IkappaBalpha kinase, JNK, Akt and cell proliferation but potentiates p44/p42 MAPK and p38 MAPK activation. (qxmd.com)
  • Genetic deletion of glycogen synthase kinase-3beta abrogates activation of IkappaBalpha kinase, JNK, Akt, and p44/p42 MAPK but potentiates apoptosis induced by tumor necrosis factor. (qxmd.com)
  • Sphingosine-1-phosphate mediates ICAM-1-dependent monocyte adhesion through p38 MAPK and p42/p44 MAPK-dependent Akt activation. (qxmd.com)
  • Pretreatment with extracellular signal-regulated kinase (ERK) inhibitor (PD98059) blocked both PGD 2 -induced ERK mitogen-activated protein kinase (MAPK) activation and MUC5B expression. (elsevier.com)
  • In conclusion, activation of MAPK, nuclear factor-κB (NF-κB), and activator protein-1 (AP-1) may be the upstream signaling for cerulein-induced IL-8 expression in pancreatic acinar cells. (elsevier.com)
  • The RAS-mitogen-activated protein kinase (MAPK) pathway is an essential signaling mechanism that regulates cellular processes and culminates in the activation of specific gene expression programs. (umanitoba.ca)
  • Stimulation of the RAS-RAF-MEK-MAPK pathway leads to activation of mitogen- and stress-activated protein kinases 1 and 2 (MSK1/2) which are responsible for the phosphorylation of histone H3 on S10 and S28. (umanitoba.ca)
  • We postulate that deregulation of the RAS-MAPK pathway produced by constitutive activation and/ or over-expression of upstream components or mitogen stimulation consequently leads to enhanced MSK1 activity and elevated histone H3 phosphorylation levels. (umanitoba.ca)
  • We demonstrate that the RAS-MAPK pathway is induced and enhances the association of MSK1 and H3 phosphorylation on the IEG Trefoil Factor 1 resulting in transcriptional activation. (umanitoba.ca)
  • and p38] is the dual specificity phosphatase CL100, also called MAPK phosphatase-1 (MKP-1). (unav.edu)
  • Immunohistochemistry in NSCLC resection specimens showed high levels of CL100/MKP-1 and activation of the three MAPK compared with normal lung. (unav.edu)
  • Immunohistochemical analyses revealed that phosphorylated (p)-protooncogenic protein kinase 1, p-ribosomal protein S6 kinase, p-ERK1/2, and p-P38 MAPK proteins were present at low levels in a majority of endometrial cells but were most abundant in the nuclei of endometrial luminal epithelium and conceptus trophectoderm of pregnant ewes. (elsevier.com)
  • IGF-II also elicited a rapid increase in p-ERK1/2 and p-P38 MAPK proteins that was maximal at 15 or 30 min posttreatment. (elsevier.com)
  • Dipyridamole also inhibited LPS-stimulated p38 mitogen-activated protein kinase (p38 MAPK) and IκB kinase-beta (IKK-β) activities in RAW 264.7 cells. (elsevier.com)
  • A p38 MAPK inhibitor, SB 203580, inhibited LPS-stimulated COX-2 expression and IKK-β activation suggesting that LPS may activate the NF-κB signaling pathway via upstream p38 MAPK activation. (elsevier.com)
  • Furthermore, dipyridamole stimulated transient activation of MKP-1, a potent inhibitor of p38 MAPK function. (elsevier.com)
  • Taken together, these data suggest that dipyridamole exerts its anti-inflammatory effect via activation of MKP-1, which dephosphorylates and inactivates p38 MAPK. (elsevier.com)
  • Furthermore, we found that Siah1 prohibited cell proliferation and invasion in CRC partially through promoting AKT (the serine-threonine protein kinase) and YAP (yes associated protein) ubiquitylation and proteasome degradation to regulate the activity of MAPK(mitogen-activated protein kinase 1), PI3K-AKT (phosphatidylinositol 3-kinase-the serine-threonine protein kinase) and Hippo signaling pathways. (springer.com)
  • These results prompt the hypothesis that the neuroprotection afforded by A 2A R blockade might result from this particular ability of A 2A R to control IL-1β-induced exacerbation of excitotoxic neuronal damage, through the control of MAPK activation and late calcium deregulation. (biomedcentral.com)
  • FK stimulated the phosphorylation of extracellular signal-activated kinases (ERK) 1/2 in a subpopulation of dopaminergic neurons, suggesting that the mitogen-activated protein kinase (MAPK) pathway was involved in the effects of cAMP-elevating agents. (aspetjournals.org)
  • Accordingly, inhibition of the upstream kinases of ERK 1/2 by 2′-amino-3′-methoxyflavone (PD98059) not only suppressed MAPK activation caused by FK but also abolished the survival promoting activity that this compound exerts on TH + neurons. (aspetjournals.org)
  • Three major MAPK families have been identified: the extracellular signal-regulated kinases (ERKs), the c-Jun amino-terminal protein kinases (JNKs) and the p38 kinases. (springer.com)
  • A mitogen-activated protein kinase ( MAPK or MAP kinase ) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase ). (wikipedia.org)
  • MAPKs belong to the CMGC (CDK/MAPK/GSK3/CLK) kinase group. (wikipedia.org)
  • Because MAP2 kinases display very little activity on substrates other than their cognate MAPK, classical MAPK pathways form multi-tiered, but relatively linear pathways. (wikipedia.org)
  • In comparison to the three-tiered classical MAPK pathways, some atypical MAP kinases appear to have a more ancient, two-tiered system. (wikipedia.org)
  • A mitogen-activated protein kinase 14 phosphorylated form that has been activated by Thr and Tyr phosphorylation within the TxY motif. (ebi.ac.uk)
  • In general, MAP kinases are activated by phosphorylation on tyrosine and threonine residues and inactivated by dephosphorylation. (ahajournals.org)
  • A common feature for activation of all MAP kinase isoforms is the requirement for phosphorylation of both a threonine and a neighboring tyrosine regulatory site by a specific upstream protein kinase for activation. (ahajournals.org)
  • 1 2 Binding of extracellular stimuli to their cell membrane receptors induces a sequence of protein kinase reaction, leading to phosphorylation and activation of MEK (MAP kinase/ERK kinase). (ahajournals.org)
  • Thus, highly specific protein kinase cascades lead to dual phosphorylation of tyrosine and threonine residues on these MAP kinases, inducing their full activation. (ahajournals.org)
  • In general, the extent of protein phosphorylation is balanced by an antagonism of kinases and phosphatases. (ahajournals.org)
  • TNFalpha increased the activity of the p38 substrate MAP kinase-activated-protein (MAPKAP) kinase 2 and the subsequent phosphorylation of the small heat shock protein Hsp27 about two to three fold. (nih.gov)
  • Serine-arginine proteins comprise a family of splice factors that are activated after phosphorylation by SRPKs in the cytoplasm. (aacrjournals.org)
  • Activation of MAPKs requires phosphorylation of both threonine and tyrosine residues within a Thr-Xxx-Tyr activation motif, where the central residue is glutamic acid in the case of the extracellular-signal-regulated kinase (ERK) family, proline in the case of the JNK family, and glycine in the case of the p38 family ( 15 , 25 , 33 ). (asm.org)
  • Its effects on extracellular signal-regulated kinase (ERK) phosphorylation and proliferation in several cell lines were also determined. (aacrjournals.org)
  • Treatment of cells with sirtuin inhibitors, or siRNA knockdown of SIRT1 or SIRT2 proteins, increases MEK1 acetylation and subsequent phosphorylation of the extracellular signal-regulated kinase (ERK). (uncg.edu)
  • Furthermore, we found that insulin induces the serine phosphorylation of Fra-1 and reduces its mobility during SDS/PAGE as a result of phosphorylation. (biochemj.org)
  • The ability of insulin to induce the accumulation of Fra-1 mRNA, stimulate the fra-1 promoter and stimulate phosphorylation of Fra-1 all require the mitogen-activated protein (MAP) kinase cascade, which leads to the activation of extracellular-signal-regulated kinase (Erk) 1/2. (biochemj.org)
  • Consequently, our results demonstrate that the Erk cascade plays a dual role in the co-ordinated regulation of the transcription and the phosphorylation of Fra-1 by insulin. (biochemj.org)
  • Regulation of lymphoid enhancer factor 1/ T-cell factor by mitogen-activated protein kinase-related Nemo-like kinase-dependent phosphorylation in Wnt/ beta-catenin signaling. (ihop-net.org)
  • A gene on chromosome 14q31-q32.1 that encodes a p90 ribosomal S6 serine/threonine-protein kinase required for the mitogen or stress-induced phosphorylation of transcription factors CREB1 and ATF1, as well as for regulating transcription factors RELA, STAT3 and ETV1/ER81. (thefreedictionary.com)
  • The activation of this kinase requires its phosphorylation by upstream kinases. (nih.gov)
  • Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4. (nih.gov)
  • The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. (rcsb.org)
  • Inhibition of ERK phosphorylation decreased the induction of both MKP-1 and COX-2. (uconn.edu)
  • At 4 h post FSS inhibition of PKA decreased MKP-1 and increased the FSS induction of both ERK phosphorylation and COX-2 mRNA. (uconn.edu)
  • In POBs from MKP-1 knockout (KO) mice, the FSS induction of ERK phosphorylation and COX-2 mRNA was increased compared to POBs from wild type (WT) POBs. (uconn.edu)
  • These data suggest that FSS-stimulated MKP-1 expression decreases FSS-stimulated ERK phosphorylation and subsequent COX-2 expression. (uconn.edu)
  • Phosphorylation of mitogen activated protein (MAP) kinaseHog-1 MAP kinase has been identified as a homolog of human p38 MAP kinase in fungi. (idhinhibitor.com)
  • To determine whether aspirin activates Hog-1 kinase in G. lucidum, antibody against the phosphorylated form of human P38 was used to detect the phosphorylation of Hog-1. (idhinhibitor.com)
  • After incubation of fungal mycelium with 2 mM 25033180 aspirin, Hog-1 phosphorylation was observed after 2 min of aspirin treatment, and reached a maximum after 5 to 10 min incubation (Figure 8A). (idhinhibitor.com)
  • Phosphorylation of p38 MAP kinase has been shown to be significantly enhanced by aspirin in colorectal cancer cells. (idhinhibitor.com)
  • This study is the first to show aspirin induces Hog-1 phosphorylation, which indicates that Hog-1 may be involved in process of aspirin-induced fungal apoptosis. (idhinhibitor.com)
  • Our recent findings have also revealed that ROS and UV-B radiation are able to induce GA production and Hog-1 phosphorylation in G. lucidum [19]. (idhinhibitor.com)
  • Phosphorylation of Hog-1 MAP kinases of Ganoderma lucidum in response to aspirin. (idhinhibitor.com)
  • Furthermore, our results indicate that ROS production and Hog-1 phosphorylation areinduced by aspirin. (idhinhibitor.com)
  • This provides insights into the regulation of triterpenoid biosynthesis and t.Phosphorylation of mitogen activated protein (MAP) kinaseHog-1 MAP kinase has been identified as a homolog of human p38 MAP kinase in fungi. (idhinhibitor.com)
  • MKK1 contains a consensus phosphorylation site for p34cdc2, a serine/threonine protein kinase that regulates the cell division cycle, at Thr-286 and a related site at Thr-292. (cshl.edu)
  • Accordingly, these effects can be reversed by active antioxidant compounds to inhibit the expression of MMPs, including MMP-1, by suppressing mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 phosphorylation [ 8 , 9 ]. (mdpi.com)
  • This study shows that chemokine receptor engagement by both CCR5-dependent (R5) and CXCR4-dependent (X4) gp120 led to rapid phosphorylation of the focal adhesion-related tyrosine kinase Pyk2 in macrophages. (ashpublications.org)
  • Pyk2 phosphorylation was also induced by macrophage inflammatory protein-1β (MIP-1β) and stromal cell-derived factor-1α, chemokine ligands for CCR5 and CXCR4. (ashpublications.org)
  • In addition, we confirmed that phosphorylation of HSPB1 and MAP kinase-activated protein kinase 2 (MAPKAPK2) increased in TS cells during differentiation. (qxmd.com)
  • In vitro exposure of neutrophils to C5a led to reduced surface expression of C5aR and defective assembly of NADPH oxidase, as defined by failure in phosphorylation of p47 phox and its translocation to the cell membrane, together with failure in phosphorylation of p42/p44 mitogen-activated protein kinases. (jimmunol.org)
  • The effect of SCH58261 on the IL-1β-induced phosphorylation of the mitogen-activated protein kinases (MAPKs) c-Jun N-terminal kinase (JNK) and p38 was evaluated by western blotting and immunocytochemistry. (biomedcentral.com)
  • IL-1β (10 to 100 ng/ml) enhanced both JNK and p38 phosphorylation, and these effects were prevented by the IL-1 type 1 receptor antagonist IL-1Ra (5 μg/ml), in accordance with the neuronal localization of IL-1 type 1 receptors, including pre-synaptically and post-synaptically. (biomedcentral.com)
  • The selective A 2A R antagonist, SCH58261 (50 nmol/l), prevented both the IL-1β-induced phosphorylation of JNK and p38, as well as the IL-1β-induced deregulation of calcium and the consequent enhanced neurotoxicity, whereas it had no effect on glutamate actions. (biomedcentral.com)
  • This tandem activation loop phosphorylation (that was proposed to be either distributive or processive, dependent on cellular environment) is performed by members of the Ste7 protein kinase family, also known as MAP2 kinases . (wikipedia.org)
  • MAP2 kinases in turn, are also activated by phosphorylation, by a number of different upstream serine-threonine kinases ( MAP3 kinases ). (wikipedia.org)
  • However, the signaling pathway from adiponectin receptors to PGC-1α gene expression is still largely unknown. (diabetesjournals.org)
  • The NahG transgene that eliminates endogenous salicylic acid (SA) was used to test the role of the SA signaling pathway in the resistance mediated by Mi-1 to potato aphids. (apsnet.org)
  • Aphid resistance in Mi-1 NahG plants was completely abolished and the phenotype was successfully rescued by application of BTH (benzo(1,2,3)-thiaiazole-7-carbothioic acid S -methyl ester), indicating that the SA signaling pathway is an important component of Mi-1 -mediated aphid resistance. (apsnet.org)
  • Acts as a scaffold protein that coordinates with SH3RF1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. (nih.gov)
  • Growth factors activate mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs) and Jun kinases (JNKs). (sciencemag.org)
  • It is now widely recognized that mammalian cells use mitogen-activated protein kinases (MAPKs) as distal effectors for many extracellular growth factors, stress detectors, and drug sensors. (aspetjournals.org)
  • MAPKs are activated by intracellular tyrosine kinases and inactivated by mitogen-activated protein kinase phosphatases (MKPs), which are dual specificity phosphatases (DSPs) capable of dephosphorylating both phosphotyrosine and phosphothreonine on the same protein substrate. (aspetjournals.org)
  • We examined the activation of mitogen- and stress-activated protein kinase-1 (MSK1), a downstream target of MAPKs, in adult rat cardiac myocytes by phenylephrine and endothelin-1. (portlandpress.com)
  • We also investigated the role of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB in astrocyte CD38 regulation. (biomedcentral.com)
  • 1] Mitogen-activated protein kinases (PRKMs, or MAPKs) are serine-threonine protein kinases that are activated in response to a wide variety of extracellular stimuli. (humbio.ru)
  • In mammals, the initial encounter between cells of the immune system and pathogenic bacteria triggers the activation of the innate immune response Nitrarine 2HCl to contamination, which is under the control of the transcription factor Rabbit polyclonal to Ki67 NF-kB and stress-activated mitogen-activated protein kinases (MAPKs) p38 and JNK [3]. (bcl-2-protein.com)
  • OBJECTIVE: To investigate whether NADPH oxidase induces MCP-1 expression and the activation of mitogen-activated protein kinases (MAPKs) in H. pylori-infected gastric epithelial cells. (yonsei.ac.kr)
  • RESULTS: H. pylori induced increase in ROS, NADPH oxidase activity, MCP-1 expression, and the activation of MAPKs including extracellular signal-regulated kinases, p38, and jun N-terminal kinases in AGS cells, which was inhibited by DPI. (yonsei.ac.kr)
  • With the stimulation of many types of cell surface receptors, MAPKs are activated. (elsevier.com)
  • This study aims to investigate whether cerulein induces IL-8 expression in pancreatic acinar cells, and whether cerulein-induced IL-8 expression is inhibited in the cells transfected with mutant genes for c-jun (TAM-67), or IκBα (MAD-3) or treated inhibitors of mitogen-activated protein kinases (MAPKs). (elsevier.com)
  • An increase in the activity of the mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vitro and in vivo. (unav.edu)
  • This study was designed to examine the involvement of CL100/MKP-1 and stress-related MAPKs in lung cancer. (unav.edu)
  • EXPERIMENTAL DESIGN: We assessed the expression of CL100/MKP-1 and the activation of the MAPKs in a panel of 18 human cell lines [1 primary normal bronchial epithelium, 8 non-small cell lung cancer (NSCLC), 7 small cell lung cancer (SCLC), and 2 carcinoids] and in 108 NSCLC surgical specimens. (unav.edu)
  • CONCLUSIONS: Our data indicate the relevance of MAPKs and CL100/MKP-1 in lung cancer and point at CL100/MKP-1 as a potential positive prognostic factor in NSCLC. (unav.edu)
  • MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens , osmotic stress , heat shock and proinflammatory cytokines . (wikipedia.org)
  • The closest relatives of MAPKs are the cyclin-dependent kinases (CDKs). (wikipedia.org)
  • These pathways can effectively convey stimuli from the cell membrane (where many MAP3Ks are activated) to the nucleus (where only MAPKs may enter) or to many other subcellular targets. (wikipedia.org)
  • [4] In contrast to the classical MAP kinases, these atypical MAPKs require only a single residue in their activation loops to be phosphorylated. (wikipedia.org)
  • This stimulation was blocked almost completely by the specific p38 MAP kinase inhibitor SB203580. (nih.gov)
  • This inhibitor also suppressed the TNFalpha-induced surface expression of the endothelial adhesion molecule vascular cell adhesion molecule (VCAM)-1. (nih.gov)
  • The crystal or solution structure for MKP-1 is not available to guide any rational inhibitor design. (aspetjournals.org)
  • Furthermore, in HeLa cells dexamethasone induced the sustained expression of mitogen-activated protein kinase phosphatase 1 (MKP-1), a potent inhibitor of p38 function. (asm.org)
  • To assess the tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of the mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancer. (pubmedcentralcanada.ca)
  • This inhibition is reversed by cotreatment with the protein synthesis inhibitor, cycloheximide, and by the GC receptor antagonist, RU486, suggesting a classical transcriptional mechanism. (ox.ac.uk)
  • Phosphatase activity was up-regulated by Dex treatment, and inhibition of ERK activity by Dex was also reversed by the protein tyrosine phosphatase inhibitor, vanadate. (ox.ac.uk)
  • Carbachol-stimulated activation of Egr-1 was reduced 35% by genistein, a tyrosine kinase inhibitor, and 60% by PD098059, an inhibitor of mitogen-activated protein kinase kinases 1/2 (MEK1/2) that activates extracellular-regulated kinases 1/2 (ERK1/2). (elsevier.com)
  • Application of a specific inhibitor to antagonize p38 kinase activation blocked aspirin-induced apoptosis, indicating p38 kinase mediated aspirin-induced apoptosis [41]. (idhinhibitor.com)
  • Sorafenib (Nexavar) was the first RAF kinase inhibitor to enter human clinical testing. (aacrjournals.org)
  • Although this compound was initially developed as a selective inhibitor of RAF, later studies revealed other biologically relevant targets, including vascular endothelial growth factor receptor (VEGFR2/3), platelet-derived growth factor receptor (PDGFR), Flt-3, c-kit, and FGFR-1 ( 18 ). (aacrjournals.org)
  • Fulvestrant With or Without AZD6244, a Mitogen-Activated Protein Kinase Kinase (MEK) 1/2 Inhibitor, in Advanced Stage Breast Cancer Progressing After Aromatase Inhibitor: A Randomized Placebo-Controlled Double-Blind Phase II Trial. (springer.com)
  • MATERIAL: H. pylori in Korean isolates, human gastric epithelial AGS cells TREATMENT: AGS cells pretreated with or without an NADPH oxidase inhibitor diphenyleneiodonium (DPI) are cultured in the presence of H. pylori at a bacterium/cell ratio of 300:1. (yonsei.ac.kr)
  • Although flavopiridol, a semisynthetic flavone, was initially thought to be a specific inhibitor of cyclin-dependent kinases, it has now been shown that flavopiridol mediates antitumor responses through mechanism(s) yet to be defined. (qxmd.com)
  • The small-molecule Bcl-2 inhibitor HA14-1 interacts synergistically with flavopiridol to induce mitochondrial injury and apoptosis in human myeloma cells through a free radical-dependent and Jun NH2-terminal kinase-dependent mechanism. (qxmd.com)
  • A phase 1 dose-escalation study of checkpoint kinase 1 (CHK1) inhibitor prexasertib in combination with p38 mitogen-activated protein kinase (p38 M. (cdc.gov)
  • Purpose The primary objective was to determine the recommended Phase 2 dose (RP2D) of checkpoint kinase 1 inhibitor, prexasertib, in combination with the p38 mitogen-activated protein kinase inhibitor, ralimetinib, which may be safely administered to patients with advanced cancer. (cdc.gov)
  • The poster titled "eFT508, a Potent and Selective Mitogen-Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 Inhibitor, is Efficacious in Preclinical Models of Diffuse Large B-Cell Lymphoma (DLBCL)" was presented by Kevin R. Webster, Ph.D., on December 5, 2015 at the 57th Annual 2015 American Society of Hematology (ASH) meeting in Orlando, FL. (effector.com)
  • Knockdown of MKP-1 by transfecting MKP-1 siRNA or inhibition of MKP-1 by the specific inhibitor, triptolide, significantly reduced the inhibitory effects of dipyridamole on COX-2 expression induced by LPS. (elsevier.com)
  • The Kinase Selectivity Profiling Systems provide a convenient 8-tube strip format that is optimized for fast and simple kinase inhibitor profiling. (promega.com)
  • Among the latter group, more recent attention has focused on the bicyclic pyridinyl imidazole class of compounds, which are potent inhibitors of TNF and IL-1 synthesis ( 20 , 21 , 22 , 23 ). (jimmunol.org)
  • The lack of readily available selective MKP-1 inhibitors has severely limited interrogation of its biological role and was one rationale for using a recently described tricyclic pyrrole-2-carboxamide library in our screening efforts. (aspetjournals.org)
  • Two of the pyrrole carboxamides, PSI2106 and MDF2085, were especially notable in vitro inhibitors of recombinant human MKP-1 enzyme activity with IC 50 values of 8.0 ± 0.9 and 8.3 ± 0.8 μM, respectively. (aspetjournals.org)
  • 7 Administration of glial metabolic inhibitors, cytokine antagonists, antiinflammatory cytokine interleukin (IL)-10, or IL-1 receptor antagonist IL-1ra has been shown to attenuate the development of opioid tolerance and to prevent hyperalgesia and allodynia. (asahq.org)
  • Further evidence for Ras involvement came from the observation that IL-1 caused a rapid activation of Ras in the cells and from the inhibitory effects of the Ras inhibitors manumycin A and damnacanthal. (tcd.ie)
  • Firm adhesion was inhibited by blocking E-selectin, L- selectin, or PSGL-1 with Abs and by inhibitors to the mitogen-activated protein kinases. (elsevier.com)
  • The Kinase Enzyme Systems allow you to easily screen and profile kinase inhibitors. (promega.com)
  • Therefore, recently cloned dual-specificity protein tyrosine phosphatases (PTPases), which exhibit dual-catalytic activity toward phosphotyrosine and phosphothreonine in substrate proteins, may play a pivotal role in the regulation of MAP kinase-signaling pathways. (ahajournals.org)
  • 15 16 Furthermore, the kinetics of gene expression and the cellular localization are consistent with a role for MKP-1 in the compensatory inactivation of stimulated MAP kinase-signaling pathways. (ahajournals.org)
  • The up-regulation of SRPK1 in multiple cancers and its ability to regulate multiple relevant signaling pathways provide support for developing agents to inhibit this kinase for possible broad application to treat epithelial cancers. (aacrjournals.org)
  • Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review). (semanticscholar.org)
  • The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. (nih.gov)
  • The effects of interleukin 1 (IL-1) are mediated by the activation of protein kinase signalling pathways, which have been well characterized in cultured cells. (ox.ac.uk)
  • We have investigated the activation of these pathways in rabbit liver and other tissues after the systemic administration of IL-1α. (ox.ac.uk)
  • We conclude that IL-1α might activate a more restricted set of signalling pathways in tissues in vivo than it does in cultured cells, where ERK and JNK3 activation are often observed. (ox.ac.uk)
  • FSS induced MKP-1 via ERK and protein kinase A (PKA) pathways. (uconn.edu)
  • These results suggest that activation of MAP kinases secondary to stimulation of the ET B receptor with ET-1 in rat primary cultured astrocytes was mediated through two independent signalling pathways, PKC-dependent pathway and PTX-sensitive G protein-mediated pathway. (elsevier.com)
  • Introduction Studies of innate immunity in phylogenetically diverse organisms have revealed the conservation of important signaling pathways mediating pathogen defense [1],[2]. (bcl-2-protein.com)
  • Sustained activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase pathways by hepatitis B virus X protein mediates apoptosis via induction of Fas/FasL and tumor necrosis factor (TNF) receptor 1/TNF-alpha expression. (qxmd.com)
  • Collectively, these results support the hypothesis that IGF-II coordinately activates multiple cell signaling pathways critical to survival, growth, and differentiation of the ovine conceptus during early pregnancy. (elsevier.com)
  • Serine/threonine kinase which responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating downstream targets. (uniprot.org)
  • We have recently shown overexpression of a core splice regulatory protein, serine-arginine protein kinase 1 (SRPK1), in dysplastic and neoplastic pancreatic ductular cells. (aacrjournals.org)
  • We recently reported the elevation of a kinase [serine-arginine protein kinase (SRPK) 1] in pancreatic carcinoma cells that is critical for the regulation of various mRNA splicing factors ( 1 ). (aacrjournals.org)
  • The serine/threonine kinase Raf-1 functions downstream of Rats in a signal transduction cascade which transmits mitogenic stimuli from the plasma membrane to the nucleus. (asm.org)
  • Ras recruits the serine/threonine kinase Raf to the plasma membrane, where it is then able to phosphorylate and activate mitogen-activated protein kinase kinases (MEK) 1 and 2, which are dual specificity protein kinases that phosphorylate serine/threonine and tyrosine residues. (aacrjournals.org)
  • MAP2K1 is a protein serine/threonine kinase that is an upstream activator of the extracellular signal-regulated kinases (ERKs) which are activated in response to numerous growth factors and cytokines. (creativebiomart.net)
  • Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. (rcsb.org)
  • Amino Acid Sequence CDC2 Protein Kinase/ metabolism Hela Cells Humans MAP Kinase Kinase 1 MAP Kinase Kinase 2 Mitogen-Activated Protein Kinase Kinases Molecular Sequence Data Peptide Mapping Peptides/chemistry Phosphothreonine/metabolism Protein-Serine-Threonine Kinases/ metabolism Protein-Tyrosine Kinase/ metabolism Recombinant Proteins Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. (cshl.edu)
  • Therefore, MAP kinase phosphatase-1 (MKP-1), a dual-specificity protein tyrosine phosphatase that exhibits catalytic activity toward both regulatory sites on MAP kinases, is suggested to be responsible for the downregulation of extracellular signal-regulated kinase (ERK), stress-activated protein kinase (SAPK), and p38 MAP kinase. (ahajournals.org)
  • The vaccina H-1 gene product (VH-1) was the first phosphatase shown to effectively hydrolyze both phosphotyrosine and phosphoserine/phosphothreonine. (ahajournals.org)
  • 10 Recently, MAP kinase phosphatase-1 (MKP-1), a mammalian VH-1-like dual-specificity PTPase, has been isolated. (ahajournals.org)
  • To test the hypothesis that mitogen-activated protein kinase phosphatase (MKP)-1 is actively involved in atherogenesis. (scialert.net)
  • Glucocorticoids induce rapid up-regulation of mitogen-activated protein kinase phosphatase-1 and dephosphorylation of extracellular signal-regulated kinase and impair proliferation in human and mouse osteoblast cell lines. (ox.ac.uk)
  • Mitogen-activated protein kinase phosphatase 1/dual specificity phosphatase 1 mediates glucocorticoid inhibition of osteoblast proliferation. (ox.ac.uk)
  • In the present study, we investigated the role of mitogen-activated kinase phosphatase-1 (MKP-1) in dipyridamole's anti-inflammatory effects. (elsevier.com)
  • Lee, Horng M. / Dipyridamole activation of mitogen-activated protein kinase phosphatase-1 mediates inhibition of lipopolysaccharide-induced cyclooxygenase-2 expression in RAW 264.7 cells . (elsevier.com)
  • 3 MEK, the specific activator of ERK, is a dual-specificity protein kinase that phosphorylates both threonine and tyrosine regulatory sites in ERK. (ahajournals.org)
  • Insulin regulates the activity of the AP-1 (activator protein-1) transcriptional complex in several cell types. (biochemj.org)
  • We find that ATF-7 functions as a transcriptional regulator of PMK-1 MAPKCmediated innate immunity, functioning as a repressor of immune gene expression that undergoes a switch to an activator upon activation by PMK-1. (bcl-2-protein.com)
  • Moreover, BDB decreased the expression levels of c-Fos and phospho-c-Jun and the binding of activator protein-1 to the MMP-1 promoter induced by UVB irradiation. (mdpi.com)
  • Activator protein-1 (AP-1) is a nuclear transcription factor complex that acts as a key mediator for UV-induced MMPs and the degradation of extracellular matrix proteins. (mdpi.com)
  • TNF is a potent inducer of activator protein-1 (AP-1), and flavopiridol abrogated this activation in a dose- and time-dependent manner. (qxmd.com)
  • Flavonoids inhibit tumor necrosis factor-alpha-induced up-regulation of intercellular adhesion molecule-1 (ICAM-1) in respiratory epithelial cells through activator protein-1 and nuclear factor-kappaB: structure-activity relationships. (qxmd.com)
  • Cell signaling analysis showed that the activation of extracellular signal-regulated protein kinase (ERK) in response to PMA strongly induced miR-34a expression by transactivation via the activator protein-1 binding site in the upstream region of the miR-34a gene. (elsevier.com)
  • The loss of IL-1β message was due mainly to inhibition of transcription, since nuclear run-off analysis showed an ∼80% decrease in specific IL-1 RNA synthesis. (jimmunol.org)
  • In contrast, inhibition of p38 MAP kinase had no effect on the stimulated surface expression of the intercellular cell adhesion molecule (ICAM)-1. (nih.gov)
  • We have also examined the effect of selective inhibition of this kinase on cancer-relevant processes. (aacrjournals.org)
  • The direct interaction with caveolin-1 results in the inhibition of a number of signaling molecules, such as G-protein α subunit, Ras, nitric oxide synthase, protein kinase C, and protein kinase A ( 2 , 7 , 10 , 16 - 25 ). (aacrjournals.org)
  • including potent inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-1, and suppression of the activation of NF-κB and AP-1 in various cells. (aspetjournals.org)
  • The inhibition of p38 and the induction of MKP-1 by dexamethasone occurred with similar dose dependence and kinetics. (asm.org)
  • This inhibitory effect involves direct interactions of the glucocorticoid receptor with transcription factors such as NF-κB and AP-1, resulting in the inhibition of their function (reviewed in references 1 and 47 ). (asm.org)
  • c-Jun NH2-terminal kinase activating kinase 1/mitogen-activated protein kinase kinase 4-mediated inhibition of SKOV3ip.1 ovarian cancer metastasis involves growth arrest and p21 up-regulation. (semanticscholar.org)
  • 4 Phosphorylated and activated ERK migrates to the nucleus, where it phosphorylates several transcription factors. (ahajournals.org)
  • Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. (nih.gov)
  • VCAM-1 mRNA accumulation induced by TNFalpha was not affected by SB203580, suggesting that the p38 MAP kinase signalling cascade regulates the endothelial expression of VCAM-1 at the post-transcriptional level. (nih.gov)
  • Surprisingly, the precise determinants of its substrate specificity remain uncertain ( Wu and Bennett, 2005 ), although it regulates cytokine and mitogen response. (aspetjournals.org)
  • These observations suggest that MKP-1 participates in a negative-feedback loop which regulates p38 function and that dexamethasone may inhibit proinflammatory gene expression in part by inducing MKP-1 expression. (asm.org)
  • It regulates cellular biological processes through the ubiquitin critical proteins. (springer.com)
  • RAF1 then further activates the dual-specificity protein kinases MAP2K1 /MEK1 and MAP2K2 /MEK2. (rcsb.org)
  • The ability of ARRY-142886 to inhibit purified MEK1 as well as other kinases was evaluated. (aacrjournals.org)
  • Here, we demonstrate that acetylation of the mitogen-activated protein kinase kinase-1 (MEK1) stimulates its kinase activity, and that acetylated MEK1 is under the regulatory control of the sirtuin family members SIRT1 and SIRT2. (uncg.edu)
  • These results reveal that muscarinic receptors activate Egr-1 through a signaling cascade primarily encompassing protein kinase C, MEK1/2, and ERK1/2 and that valproate substantially inhibits Egr-1 DNA branding activity stimulated by carbachol or protein kinase C. (elsevier.com)
  • The MAP2K1 gene provides instructions for making a protein known as MEK1 protein kinase. (medlineplus.gov)
  • MEK1 protein kinase appears to be essential for normal development before birth and for survival after birth. (medlineplus.gov)
  • Each mutation changes a single protein building block (amino acid) in MEK1 protein kinase. (medlineplus.gov)
  • The known mutations change single amino acids in MEK1 protein kinase. (medlineplus.gov)
  • The identified MAP2K1 gene mutation is a germline mutation that replaces the amino acid glutamic acid with the amino acid glycine at position 102 (written as Glu102Gly or E102G) in MEK1 protein kinase. (medlineplus.gov)
  • Reporter gene assays identified mitogen-activated protein kinase kinase 1 (MEK1) as a direct target of miR-34a and c-fos as a direct target of miR-221/222. (elsevier.com)
  • Although overexpression of the three miRNAs had little effect on cell differentiation, overexpression of miR-34a significantly repressed the proliferation of K562 cells with a concomitant reduction in MEK1 protein expression. (elsevier.com)
  • Taken together, the results show that PMA activates the MEK-ERK pathway and strongly induces miRNA-34a expression, which in turn inhibits cell proliferation by repressing the expression of MEK1. (elsevier.com)
  • MAP2K1 is also known as MEK1 (see Mitogen-activated protein kinase kinase ). (wikipedia.org)
  • MEK1 is a meiotic chromosome-axis-associated kinase that is thought to slow down, but not entirely block, sister chromatid recombination . (wikipedia.org)
  • In addition, PD 098059, an antagonist of MEK (MAP kinase/ERK kinase), the upstream kinase of ERK, significantly reduced the PDGF-induced activation of ERK and potently inhibited the expression of MKP-1 after stimulation with PDGF, thereby demonstrating the induction of MKP-1 in response to activation of the ERK signaling cascade. (ahajournals.org)
  • The cytokine tumor necrosis factor (TNF) alpha was found to stimulate the p38 mitogen activated protein (MAP) kinase signalling cascade in human umbilical vein endothelial cells. (nih.gov)
  • The signaling cascade is initiated by the binding of peptide growth factors to their tyrosine kinase receptors at the plasma membrane. (aacrjournals.org)
  • This pathway is composed of a protein kinase cascade in which RAF, MEK, and ERK are in a sequential order. (pubmedcentralcanada.ca)
  • Component of a protein kinase signal transduction cascade. (nih.gov)
  • They participate also in a signaling cascade initiated by activated KIT and KIT LG/SCF. (rcsb.org)
  • Component of a protein kinase signal transduction cascade (PubMed:9808624). (genecards.org)
  • However, the MAP kinase signaling cascade has never been studied in fungi with respect to in aspirin-induced apoptosis. (idhinhibitor.com)
  • Mitogen-activated protein kinase kinase 1 (MKK1), a dual-specificity tyrosine/threonine protein kinase, has been shown to be phosphorylated and activated by the raf oncogene product as part of the mitogen-activated protein kinase cascade. (cshl.edu)
  • Gene array for 23 genes associated with members of the mitogenic pathway cascade and immediate early genes revealed that the expression of early growth response 1 and c-raf-1 was increased. (elsevier.com)
  • Abstract -Mitogen-activated protein (MAP) kinase cascades are major signaling systems by which cells transduce extracellular cues into intracellular responses. (ahajournals.org)
  • ERK1/2 proteins translocate to the nucleus where they phosphorylate and activate effector proteins and transcription factors, resulting in diverse cellular responses, including proliferation. (aacrjournals.org)
  • The overexpression and/or mutation of epidermal growth factor (EGF) receptor (EGFR), erbB2, platelet-derived growth factor receptor, RET, and other growth factor receptors have been observed in many types of cancer and have been associated with elevated levels of phospho-ERK1/2 ( 1 - 4 ). (aacrjournals.org)
  • We report that glucose (10 mM) induces an increase in cytosolic calcium concentration that leads to cAMP-induced protein kinase A (PKA) activation, promoting nuclear translocation of activated ERK1/2. (nih.gov)
  • Valproate treatment reduced carbachol-stimulated Egr-1 DNA binding activity by 60% but did not alter carbachol-induced activation of ERK1/2 or p38 or increases in Egr-1 protein levels. (elsevier.com)
  • The first mitogen-activated protein kinase to be discovered was ERK1 ( MAPK3 ) in mammals. (wikipedia.org)
  • Thus the role of mammalian ERK1/2 kinases as regulators of cell proliferation is not a generic, but a highly specialized function. (wikipedia.org)
  • In the case of classical MAP kinases, the activation loop contains a characteristic TxY (threonine-x-tyrosine) motif (TEY in mammalian ERK1 and ERK2 , TDY in ERK5 , TPY in JNKs , TGY in p38 kinases ) that needs to be phosphorylated on both the threonine and the tyrosine residues in order to lock the kinase domain in a catalytically competent conformation. (wikipedia.org)
  • Norway rat protein-coding gene Mapk1. (nih.gov)
  • The tomato Mi-1 gene confers resistance to root-knot nematodes ( Meloidogyne spp. (apsnet.org)
  • This gene encodes a member of the mitogen-activated protein (MAP) kinase family. (antibodies-online.com)
  • Here, we show that subcytotoxic oxidative stress generated by hydrogen peroxide application promotes premature senescence and stimulates the activity of a (−1,296) caveolin-1 promoter reporter gene construct in fibroblasts. (aacrjournals.org)
  • This study delineates for the first time the molecular mechanisms that modulate caveolin-1 gene transcription upon oxidative stress and brings new insights into the redox control of cellular senescence in both normal and cancer cells. (aacrjournals.org)
  • The caveolin gene family consists of three members: caveolin-1, caveolin-2, and caveolin-3 ( 3 , 4 , 8 ). (aacrjournals.org)
  • Finally, endogenous MSK1 levels concomitantly increased to regulate MOR gene expression during neuronal differentiation of P19 cells, suggesting a conserved role of this kinase in the epigenic activation of MOR in neurons. (aspetjournals.org)
  • Here we demonstrate that insulin stimulates the activity of a fra-1 promoter linked to a luciferase reporter gene, indicating that the ability of insulin to induce expression of Fra-1 mRNA is due, at least in part, to an increase in gene transcription. (biochemj.org)
  • Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene. (nih.gov)
  • In the present investigation, we studied regulatory mechanisms of CD38 gene expression in astrocytes activated with HIV-1-relevant stimuli. (biomedcentral.com)
  • Cultured human astrocytes were transfected with HIV-1 YU-2 proviral clone and levels of CD38 mRNA and protein were measured by real-time PCR gene expression assay, western blot analysis and immunostaining. (biomedcentral.com)
  • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) is a Protein Coding gene. (genecards.org)
  • Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity . (genecards.org)
  • Insights into function and regulation of small heat shock protein 25 (HSPB1) in a mouse model with targeted gene disruption. (qxmd.com)
  • We report here that cultured airway smooth muscle cells contain transcripts of endothelial differentiation gene 1 (EDG-1), a prototypical orphan Gi-coupled receptor whose natural ligand is sphingosine 1-phosphate (S1P). (strath.ac.uk)
  • Mutation analysis of mitogen activated protein kinase 1 gene in Indian cases of 46,XY disorder of sex development. (bvsalud.org)
  • Recently, mitogen activated protein kinase kinase kinase 1 (MAP3K1) gene was found to be associated with 46, XY disorders of sex development (DSD). (bvsalud.org)
  • Siah E3 ubiquitin protein ligase 1 (Siah1) has been identified as a tumor suppressor gene and plays an important role in the development of malignant tumors. (springer.com)
  • Siah E3 ubiquitin protein ligase 1, also known as Siah1, is a human homolog of Drosophila seven in absentia (sina) gene. (springer.com)
  • Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the MAP2K1 gene . (wikipedia.org)
  • The protein encoded by this gene is a member of the dual-specificity protein kinase family that acts as a mitogen-activated protein (MAP) kinase kinase . (wikipedia.org)
  • This protein has been shown to prevent MAPK8 mediated activation of transcription factors, and to decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. (nih.gov)
  • IB1/JIP-1 controls JNK activation and increased during prostatic LNCaP cells neuroendocrine differentiation. (nih.gov)
  • Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. (rcsb.org)
  • by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2 - BRAF dimerization and BRAF activation (PubMed:29433126). (rcsb.org)
  • These data suggest the induction of MKP-1, not only after stimulation of the cell growth-promoting ERK pathway but also in response to activation of stress-responsive MAP kinase signaling cascades. (ahajournals.org)
  • 8 9 Interestingly, the mechanism involved in the activation of SAPK and p38 MAP kinase is similar to that involved in the activation of ERK. (ahajournals.org)
  • The results ( 26 , 28 ) demonstrated that both proximal and distal NFIL-6 regulatory elements play an important role in the activation of IL-1β transcription. (jimmunol.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)
  • Furthermore, macrophages isolated from MKP-1-null mice showed dramatic defects in their spreading/migration and impairment in extracellular signal-regulated kinase, but not c-Jun N-terminal kinase and p38, pathway activation. (scialert.net)
  • The hydrogen peroxide-mediated activation of both Cav-1 (−244/−222) and Cav-1 (−124/−101) was prevented by the antioxidant quercetin. (aacrjournals.org)
  • Consistent with this idea, we have previously shown that overexpression of caveolin-1 is sufficient to arrest mouse embryonic fibroblasts in the G 0 -G 1 phase of the cell cycle, reduce their proliferative life span, and promote premature cellular senescence through activation of a p53/p21-dependent pathway ( 33 , 34 ). (aacrjournals.org)
  • In HeLa cells treated with IL-1 or IL-1 and dexamethasone, the dynamics of p38 activation mirrored the expression of MKP-1. (asm.org)
  • this spinal microglia activation and increasing of cytokine tumor necrosis factor-α (TNFα), IL-1β, and IL-6 expression were also suppressed by the amitriptyline coinfusion. (asahq.org)
  • Mechanism of mitogen-activated protein kinase activation by gonadotropin-releasing hormone in the pituitary of alphaT3-1 cell line: differential roles of calcium and protein kinase C. (semanticscholar.org)
  • Cell arrest was dependent on application of shear and activation of Mac-1 and LFA- 1 to bind ICAM-1. (elsevier.com)
  • We conclude that neutrophils rolling on E-selectin undergo signal transduction leading to activation of cell arrest through β 2 integrins binding to ICAM-1. (elsevier.com)
  • Reflecting this, we show that the activation of the p38 mitogen-activated protein (MAP) kinase is increased only by LASS1/CerS1, and not by LASS4/CerS4 or LASS5/CerS5. (illinois.edu)
  • Activation of muscarinic receptors in human neuroblastoma SH-SY5Y cells with carbachol stimulated a rapid and large increase in early growth response-1 (Egr-1, also called zif268 and NGF1-A) protein levels and DNA binding activity. (elsevier.com)
  • Grimes, CA & Jope, RS 1999, ' Cholinergic stimulation of early growth response-1 DNA binding activity requires protein kinase C and mitogen-activated protein kinase kinase activation and is inhibited by sodium valproate in SH-SY5Y cells ', Journal of neurochemistry , vol. 73, no. 4, pp. 1384-1392. (elsevier.com)
  • Significant JNK3 activity was detectable only in the brain, although little activation of the JNK pathway in response to IL-1α was observed in this tissue. (ox.ac.uk)
  • This activation was potently inhibited by pretreatment of the cells with phorbol 12-myristate 13-acetate (PMA) which leads to protein kinase C (PKC) down-regulation and was slightly inhibited by pretreatment with pertussis toxin (PTX). (elsevier.com)
  • Activation of MAP kinases was also induced by 0.1 nM ET-1, which hardly stimulated phosphoinositide hydrolysis. (elsevier.com)
  • Activating BRAF mutations are found clustered within the P-loop (exon 11) and activation segment (exon 15) of the kinase domain, and a single point mutation, V600E, accounts for approximately 90% of cases ( 12 , 14 ). (aacrjournals.org)
  • Structural analysis of the V600E mutation suggests that it disrupts the interaction between the P-loop and the activation segment, which normally locks the kinase in the inactive conformation ( 15 ). (aacrjournals.org)
  • BDB significantly impeded MMP-1 activation and expression, and abrogated the activation of mitogen-activated protein kinases and intracellular Ca 2+ level in UVB-irradiated HaCaT cells. (mdpi.com)
  • Activation was blocked by EGTA and by a potent blocker of calcium release-activated Ca ++ (CRAC) channels, but was insensitive to pertussis toxin (PTX), implicating CRAC-mediated extracellular Ca ++ influx but not Gα i protein-dependent mechanisms. (ashpublications.org)
  • YUHSpace: Diphenyleneiodonium inhibits the activation of mitogen-activated protein kinases and the expression of monocyte chemoattractant protein-1 in Helicobacter pylori-infected gastric epithelial AGS cells. (yonsei.ac.kr)
  • S1P might also function as a co-mitogen with PDGF, producing a more robust activation of a common permissive signal transduction pathway linked to DNA synthesis. (strath.ac.uk)
  • Flavopiridol also suppressed AP-1 activation induced by various carcinogens and inflammatory stimuli. (qxmd.com)
  • It is noteworthy that this flavone also suppressed TNF-induced activation of Akt, a cell survival kinase, and expression of various antiapoptotic proteins, such as IAP-1, IAP-2, XIAP, Bcl-2, Bcl-xL, and TRAF-1. (qxmd.com)
  • Cannabinoid-1 receptor activation induces reactive oxygen species-dependent and -independent mitogen-activated protein kinase activation and cell death in human coronary artery endothelial cells. (unil.ch)
  • P-ERK, P-JNK, and P-p38 were activated in SCLC and NSCLC, but the degree of their activation was variable. (unav.edu)
  • JNK activation associated with T(1-2) and early stage, whereas ERK activation correlated with late stages and higher T and N. Neither JNK nor ERK activation were independent prognostic factors when studied for patient survival. (unav.edu)
  • It is also recognized that the innate immune system can be perturbed during sepsis, as reflected by extensive activation of the inflammatory, complement, and clotting systems, together with the appearance in plasma of cytokines and chemokines ( 1 , 4 ). (jimmunol.org)
  • This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon activation by a wide variety of extra- and intracellular signals. (wikipedia.org)
  • Surprisingly, the archetypal cAMP-dependent protein kinase was apparently not responsible for ERK 1/2 activation. (aspetjournals.org)
  • JNK interacting protein 1 (JIP-1) protects LNCaP prostate cancer cells from growth arrest and apoptosis mediated by 12-0-tetradecanoylphorbol-13-acetate (TPA). (nih.gov)
  • In contrast to ERK, more recently described MAP kinases such as stress-activated protein kinase (SAPK), also referred to as c-Jun N-terminal kinase (JNK), and p38 MAP kinase are suggested to inhibit cellular proliferation and to induce apoptosis. (ahajournals.org)
  • Finally, we show that oxidative stress induces p38-mediated up-regulation of caveolin-1 and premature senescence in normal human mammary epithelial cells but not in MCF-7 breast cancer cells, which do not express caveolin-1 and undergo apoptosis. (aacrjournals.org)
  • Intensive Dimethylenastron studies have been conducted to uncover how aspirin induce apoptosis in mammals and these have targeted p38 MAP kinase [40]. (idhinhibitor.com)
  • The novel triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) potently enhances apoptosis induced by tumor necrosis factor in human leukemia cells. (qxmd.com)
  • Indomethacin induces apoptosis in 786-O renal cell carcinoma cells by activating mitogen-activated protein kinases and AKT. (qxmd.com)
  • The JNK interacting protein JIP-1 and insulin like growth factor II genes are co-expressed in human embryonic tumours. (nih.gov)
  • The TIR-1-NSY-1-SEK-1-PMK-1 Nitrarine 2HCl pathway serves cell autonomously in the intestine to modify innate immunity in mutants lacking in PMK-1 pathway activity provides identified several PMK-1-dependent applicant effector genes, including C-type lectins and putative antimicrobial peptides, a lot of that are induced by pathogen. (bcl-2-protein.com)
  • A series of genes such as SRY, steroidogenic factor‑1 (SF1), AR, SRD5 α, Desert hedgehog (DHH) etc., have been reported to have a significant role in development of sex in the fetus and secondary sexual characteristics at the time of puberty . (bvsalud.org)
  • Extracellular stimuli such as platelet-derived growth factor (PDGF), 12-O-tetradecanoylphorbol 13-acetate (TPA), and angiotensin II, which activated ERK but not SAPK/p38 MAP kinase, induced a transient induction of MKP-1 mRNA and its intracellular protein. (ahajournals.org)
  • Mitogen-activated protein (MAP) kinases are important mediators involved in the intracellular network of interacting proteins that transduce extracellular cues to intracellular responses. (ahajournals.org)
  • Finally, the effect of A 2A R blockade on glutamate-induced intracellular calcium, in the presence or absence of IL-1β, was studied using single-cell calcium imaging. (biomedcentral.com)
  • The role of IL-1 in normal physiological processes is poorly understood, but it appears to play an assortment of roles in many tissues, including wound repair in skin ( 1 ), parturition ( 2 ), fat metabolism ( 3 , 4 ), and α brain wave formation ( 5 ), to name a few. (jimmunol.org)
  • The stress-activated protein kinase p38 stabilizes a number of mRNAs encoding inflammatory mediators, such as cyclooxygenase 2 (Cox-2). (asm.org)
  • The Global Dual Specificity Mitogen Activated Protein Kinase Kinase 1 Market report has a mention of the industrial chain, sourcing strategy, and downstream buyers. (whatech.com)
  • BRAF mutations are found, with rare exceptions, in a mutually exclusive pattern with RAS mutations, suggesting that these genetic alterations activate common downstream effectors of transformation. (aacrjournals.org)
  • Owing to huge tissue mass and relatively high energy demand, skeletal muscle plays a critical role in energy expenditure in humans and most rodents ( 1 , 2 ). (diabetesjournals.org)
  • Adiponectin mRNA and blood protein levels are inversely associated with obesity ( 7 ), which is a common cause of insulin resistance in humans. (diabetesjournals.org)
  • The compounds inhibited MKP-1 reversibly but displayed mixed kinetics. (aspetjournals.org)
  • IL-1 also activated Rap in the cells, but with slower kinetics than Ras. (tcd.ie)
  • Furthermore, anisomycin, a potent stimulus of SAPK and p38 MAP kinase, also induced MKP-1 mRNA expression. (ahajournals.org)
  • IL-1 is a potent inflammatory cytokine that is produced by, and affects, a variety of tissues. (jimmunol.org)
  • Better understood is the role of IL-1 as a potent inflammatory cytokine in a variety of diseases, such as arthritis ( 6 , 7 , 8 ), atherosclerosis ( 9 ), and diabetes mellitus ( 10 ). (jimmunol.org)
  • LPS is a potent stimulator of IL-1 in the macrophage/monocyte cell lineage, and these processes play a major role in sepsis and subsequent endotoxic shock ( 11 ). (jimmunol.org)
  • Alternatively spliced versions of androgen ( 6 ) and estrogen ( 7 ) receptors have been found in mammary carcinomas, and expression of the ESR1Δexon3 isoform has proven more potent in activating vascular endothelial growth factor than wild-type receptor ( 8 ), linking this variant to angiogenesis of breast tumors. (aacrjournals.org)
  • They are part of complex protein kinase cascades. (humbio.ru)
  • Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. (rcsb.org)
  • In the present study, we examined the role of these MAP kinases in the induction of MKP-1 in vascular smooth muscle cells (VSMCs). (ahajournals.org)
  • The inappropriate retention of intron 4 during processing of cyclin D1 transcripts results in production of a variant protein termed cyclin D1b that serves as a nuclear oncogene ( 3 ), whereas expression of CD44 isoforms containing variable exon 6 increases metastatic propensity of pancreatic carcinoma cells ( 4 , 5 ). (aacrjournals.org)
  • However, the molecular mechanisms underlying caveolin-1 up-regulation in senescent cells remain unknown. (aacrjournals.org)
  • Caveolin-1 and caveolin-2 are coexpressed in many cell types, including adipocytes, endothelial cells, epithelial cells, and fibroblasts ( 9 ). (aacrjournals.org)
  • In addition, E6201 cream inhibited the 1-fluoro-2,4-dinitrobenzene-induced contact hypersensitivity reaction mediated by T cells in mice. (aspetjournals.org)
  • One component of the AP-1 complex is the transcription factor Fra-1 ( fos -related antigen-1), and we have demonstrated previously that insulin stimulates the expression of Fra-1 mRNA in CHO.T cells [Griffiths, Black, Culbert, Dickens, Shaw, Gillespie and Tavaré (1998) Biochem. (biochemj.org)
  • Honokiol causes the p21WAF1-mediated G(1)-phase arrest of the cell cycle through inducing p38 mitogen activated protein kinase in vascular smooth muscle cells. (semanticscholar.org)
  • A - C ) Cells were subjected to detect the protein levels of pro-/cleaved-caspase3 in ( A ) bcl-2 and bax in ( B ) and pro-/cleaved-caspase7, 9 in ( C ) by western blot. (aging-us.com)
  • Neutrophils were introduced into a parallel plate flow chamber having as a substrate an L cell monolayer coexpressing E-selectin and ICAM-1 (E/I). At shears ≥0.1 dyne/cm 2 , neutrophils rolled on the E/I. A step increase to 4.0 dynes/cm 2 revealed that ~60% of the interacting cells remained firmly adherent, as compared with ~10% on L cells expressing E-selectin or ICAM-1 alone. (elsevier.com)
  • MAP3K1 protein expression level in breast cancer cells was higher than that in normal mammary gland cells. (nih.gov)
  • Activated autoreactive B cells and T cells as well as increased levels of pro-inflammatory cytokines drive chronic inflammation of the exocrine glands, associated with loss of function ( 4 ). (frontiersin.org)
  • Mitogen-activated protein kinases (MAP kinases) in the cells were activated by 10 nM ET-1, a dose that maximally stimulated phosphoinositide hydrolysis. (elsevier.com)
  • Pretreatment of the cells with PMA plus PTX completely inhibited the ET-1-augmented MAP kinase activity. (elsevier.com)
  • One of the central regulators of growth factor-induced cell proliferation and survival in both normal and cancer cells is the RAS protein. (aacrjournals.org)
  • This study uses TS cell culture to detect proteins with differential expression in proliferating and differentiating TS cells in order to identify proteins with potential roles in the differentiation process. (qxmd.com)
  • In mononuclear trophectoderm cells isolated from d-15 conceptuses, IGF-II increased the abundance of p-pyruvate dehydrogenase kinase 1, p-protooncogenic protein kinase 1, p-glycogen synthase kinase 3B, p-FK506 binding protein 12-rapamycin associated protein 1, and p-ribosomal protein S6 kinase protein within 15 min, and the increase was maintained for 90 min. (elsevier.com)
  • This system can be rapidly activated via cells (the phagocytic cell system) or by plasma components (complement proteins, coagulation factors, etc.) ( 1 , 2 , 3 ). (jimmunol.org)
  • Small numbers (e.g. 1 in 100,000) of circulating nucleated blood cells bearing this t(14:18)q32:q21) translocation are found in 50-67% of otherwise healthy individuals. (wikipedia.org)
  • Addition of SB203580 30 min before stimulation of monocytes with LPS inhibited IL-1β protein and steady state message in a dose-dependent manner in both RAW264.7 and J774 cell lines. (jimmunol.org)
  • Sphingosine 1-phosphate stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle. (strath.ac.uk)
  • This action of S1P is consistent with the stimulation of EDG-1 receptors. (strath.ac.uk)
  • the purpose of this study was therefore to determine whether A 3 adenosine receptor stimulation with reperfusion modulates expression of the different mitogen-activated protein kinases. (springer.com)
  • Raf-1 integrates signals coming from extracellular factors and, in turn, activates its substrate, MEK kinase. (asm.org)
  • They provide all the optimized components (enzyme, preferred substrate, required cofactors, buffer) that you need to generate a kinase selectivity profile for a compound. (promega.com)
  • however, little is known about the role of their counterparts: the protein phosphatases. (scialert.net)
  • Both showed some selectivity for MKP-1 over the closely related phosphatases MKP-3, Cdc25B, VHR, and PTP1B. (aspetjournals.org)
  • No other known p38 phosphatases were induced by dexamethasone, and other cell types which failed to express MKP-1 also failed to inhibit p38 in response to dexamethasone. (asm.org)
  • Fluid shear stress (FSS), which is used to model the stresses generated in vivo by loading of bone, induces COX-2 expression in osteoblasts via extracellular signal-regulated kinase (ERK). (uconn.edu)
  • FSS also induces MKP-1, and MKP-1 can dephosphorylate ERK. (uconn.edu)
  • Moreover, UVB irradiation stimulates the generation of reactive oxygen species (ROS) and induces the overexpression of MMP-1, -3, and -9 in human fibroblasts, resulting in the destruction of collagen that leads to wrinkle formation and sagging, characteristics of aging skin [ 5 , 6 , 7 ]. (mdpi.com)
  • We suggest that this pattern of MKP-1 induction may be a negative feedback mechanism in the control of MAP kinase activity in VSMCs. (ahajournals.org)
  • Combination of electrophoretic mobility shift studies, chromatin immunoprecipitation analysis, Sp1 overexpression experiments, as well as promoter mutagenesis identifies enhanced Sp1 binding to two GC-boxes at −238/−231 and −118/−106 as the core mechanism of oxidative stress-triggered caveolin-1 transactivation. (aacrjournals.org)
  • We used the MIN6 beta cell line and isolated rat islets to clarify the signaling mechanism(s) used by glucose to activate cAMP-responsive element binding protein (CREB), a transcription factor crucial for beta cell biology, and to evaluate the possible downregulation of this mechanism mediated by long-term hyperglycemia. (nih.gov)
  • Therefore, MKP-1 up-regulation provides a novel and rapid mechanism, whereby GCs inhibit osteoblast proliferation. (ox.ac.uk)
  • Regulation of ERK by MKP-1 provides a novel mechanism for control of osteoblast proliferation by GCs. (ox.ac.uk)
  • A likely candidate mechanism for this neuroprotection is the control of neuroinflammation, which contributes to the amplification of neurodegeneration, mainly through the abnormal release of pro-inflammatory cytokines such as interleukin(IL)-1β. (biomedcentral.com)
  • MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. (nih.gov)
  • To examine the translocation of activated ERKs, fluorescein isothiocyanate-conjugated secondary antibody was used to detect the distribution of total and phosphorylated ERKs. (elsevier.com)
  • MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. (wikipedia.org)
  • Transcriptional activity is independent of kinase activity. (nih.gov)
  • One study also suggests that this protein acts as a transcriptional repressor independent of its kinase activity. (nih.gov)
  • Extracellular signal-regulated kinase (ERK) remains the best characterized mammalian MAP kinase. (ahajournals.org)
  • In contrast to the V600E mutant, these mutations activate the pathway in a RAF1-dependent manner ( 16 ). (aacrjournals.org)
  • Click on any enzyme for additional information (such as Applications Note, the Catalog Page, or the NCBI Database entry) for that kinase. (promega.com)
  • Mekk1 mediates p53 protein stability in the presence of Mdm2 and reduces p53 ubiquitination, suggesting an interference with Mdm2-mediated degradation of p53 by the ubiquitin-proteasome pathway. (nih.gov)
  • Studies have also reported that adiponectin increases PGC-1α expression followed by mitochondrial biogenesis and fatty acid oxidation ( 16 - 18 ). (diabetesjournals.org)
  • Immuno-histochemical analysis revealed that MKP-1 expression was enriched in macrophage-rich areas versus smooth muscle cell regions of the atheroma. (scialert.net)
  • Whereas the expression of the antiapoptotic protein survivin is grossly elevated in many cancers, the survivin2B splice variant has a growth-inhibitory effect and is lost in late-stage breast ( 10 ) and colonic cancers ( 11 ). (aacrjournals.org)
  • The proinflammatory cytokine interleukin 1 (IL-1) induced MKP-1 expression in a p38-dependent manner and acted synergistically with dexamethasone to induce MKP-1 expression. (asm.org)
  • MKP-1, but not MKP-3, mRNA expression was 10-fold up-regulated in both mouse and human osteoblast cell lines within 30 min of Dex treatment and remained elevated for 24 h. (ox.ac.uk)
  • We also reported an increase in CD38 expression in interleukin (IL)-1β-activated astrocytes. (biomedcentral.com)
  • HIV-1 YU-2 -transfection effectively induced HIV-1 p 24 protein expression and activated astrocytes to upregulate CCL2, CXCL8 and CD38. (biomedcentral.com)
  • Next, we investigated the role of MKP-1 in the regulation of COX-2 expression in ulnar loading in vivo . (uconn.edu)
  • We subjected 16 wk-old female MKP-1 WT and KO mice to 30 s of unlar loading and measured COX-2 mRNA expression 1 h after loading. (uconn.edu)
  • COX-2 expression was stimulated by loading and tended to be higher in MKP-1 KO ulnae than in WT ulnae. (uconn.edu)
  • We speculate that MKP-1 may play an important role in limiting loading-induced COX-2 expression in bone. (uconn.edu)
  • Intraperitoneal injection of TNFα significantly increased MKP-1 mRNA expression in paraventricular and arcuate nuclei in the hypothalamus. (fujita-hu.ac.jp)
  • The ERK pathway contains a classical feedback loop in which the expression of feedback elements such as SPRY and DUSP family proteins are regulated by the level of ERK activity. (aacrjournals.org)
  • UVB is known to induce the expression of MMP-1, -3, and -9 in the normal human epidermis in vivo [ 4 ]. (mdpi.com)
  • We identified four proteins with differential expression: dimethylarginine dimethylaminohydrolase1 (DDAH1), keratin 8, keratin 18, and HSPB1 (also known as heat shock protein 25, HSP25). (qxmd.com)
  • mRNA expression of MCP-1 was analyzed by reverse transcription-polymerase chain reaction. (yonsei.ac.kr)
  • RESULTS: In the cell lines, CL100/MKP-1 expression was substantially higher in NSCLC than in SCLC. (unav.edu)
  • In univariate analysis, no relationship was found among CL100/MKP-1 expression and P-ERK, P-JNK, or P-p38. (unav.edu)
  • Interestingly, high CL100/MKP-1 expression levels independently predicted improved survival in multivariate analysis. (unav.edu)
  • We show that dipyridamole inhibited interleukin-6 and monocyte chemoattractant protein-1 secretion, inducible nitric oxide synthase protein expression, nitrite accumulation, and cyclooxygenase-2 (COX-2) induction in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. (elsevier.com)
  • The receptor kinases are activated and through the recruitment of the growth factor receptor binding protein 2/son of sevenless complex to autophosphorylated sites on the receptors, the G protein Ras is induced to its active GTP-bound state. (aacrjournals.org)
  • Human immunodeficiency virus type 1 (HIV-1) uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry. (ashpublications.org)
  • The protein encoded by MAPK1/3 is a member of the MAP kinase family. (antibodies-online.com)
  • The report analyses the pipeline products from therapy areas Oncology and Musculoskeletal Disorders under development targeting Mitogen Activated Protein Kinase 1 (ERT1 or MAP Kinase Isoform p42 or Extracellular Signal Regulated Kinase 2 or Mitogen Activated Protein Kinase 2 or MAPK1 or EC 2.7.11.24). (globalmarketsdirect.com)
  • X-ray structure of the ERK2 MAP kinase in its active form. (wikipedia.org)
  • Although in vivo adiponectin overexpression reduced MKP1 protein levels, the stimulative effects of adiponectin on mitochondrial biogenesis vanished in skeletal muscle of PGC-1α knockout mice. (diabetesjournals.org)
  • however, both MKP-1 +/- and MKP-1 -/- mice had significantly less aortic root atherosclerotic lesion formation than MKP-1 +/+ mice. (scialert.net)
  • Less en face lesion was observed in 8-month-old MKP-1 -/- mice. (scialert.net)
  • In addition, MKP-1-null mice had higher levels of plasma stromal cell-derived factor-1a, which negatively correlated with atherosclerotic lesion size. (scialert.net)
  • Finally, transplantation of MKP-1-intact bone marrow into MKP-1-null mice fully rescued the wild-type atherosclerotic phenotype. (scialert.net)
  • The levels of creatine kinase (CK) and lactate dehydrogenase (LDH) in plasma from mice were assayed. (aging-us.com)
  • We also examined the skeletal phenotype of MKP-1 WT and KO mice. (uconn.edu)
  • In addition, the results showed that both the CCAAT/enhancer binding protein (C/EBP)β 3 and C/EBPδ transcription factors bound to these sites. (jimmunol.org)
  • Several approaches have been initiated to control IL-1 and other proinflammatory cytokines. (jimmunol.org)
  • These compounds, termed cytokine suppressive antiinflammatory drugs (CSAID), have a marked specificity for cytokines with no generalized effects on total RNA and protein synthesis. (jimmunol.org)
  • The encoded protein is a p38 MAP kinase and is activated by proinflammatory cytokines and cellular stress. (antibodies-online.com)
  • It is highly similar to JIP-1, a mouse protein known to be a regulator of c-Jun amino-terminal kinase (Mapk8). (nih.gov)
  • Increases in phosphorylated c-Jun amino-terminal protein kinase (JNK), p38, and extracellular signal-regulated kinase (ERK)1/2 levels were observed by the end of reperfusion compared with controls. (springer.com)
  • As an essential component of the MAP kinase signal transduction pathway , this kinase is involved in many cellular processes such as proliferation , differentiation , transcription regulation and development. (wikipedia.org)
  • Our laboratory has identified and characterized cis -acting elements and nuclear DNA-binding proteins that regulate murine IL-1β transcription in the murine macrophage cell line RAW264.7 ( 25 , 26 , 27 , 28 , 29 ). (jimmunol.org)
  • Caveolin acts as a scaffolding protein to concentrate and functionally regulate signaling molecules ( 1 - 7 ). (aacrjournals.org)
  • Owing to the possibility of mismatching between antigens from another resource and antibodies used in this supplier's kits (e.g., antibody targets conformational epitope rather than linear epitope), some native or recombinant proteins from other manufacturers may not be recognized by this supplier's products. (antikoerper-online.de)