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.

Nitric oxide stimulates the stress-activated protein kinase p38 in rat renal mesangial cells. (1/7444)

Nitric oxide (NO) has gained increased attention as a diffusible universal messenger that plays a crucial role in the pathogenesis of inflammatory and autoimmune diseases. Recently, we reported that exogenous NO is able to activate the stress-activated protein kinase (SAPK) cascade in mesangial cells. Here, we demonstrate that exposure of glomerular mesangial cells to compounds releasing NO, including spermine-NO and (Z)-1- (N-methyl-N-[6-(N-methylammoniohexyl)amino]diazen)-1-ium-1,2-diolate (MAHMA-NO), results in an activation of the stress-activated p38-mitogen-activated protein kinase (p38-MAPK) cascade as measured by the phosphorylation of the activator of transcription factor-2 (ATF2) in an immunocomplex kinase assay. Activation of the p38-MAPK cascade by a short stimulation (10 min) with the NO donor MAHMA-NO causes a large increase in ATF2 phosphorylation that is several times greater than that observed after stimulation with interleukin-1beta, a well-known activator of the p38-MAPK pathway. Time course studies reveal that MAHMA-NO causes rapid and maximal activation of p38-MAPK after 10 min of stimulation and that activation declines to basal levels within 60 min. The longer-lived NO donor spermine-NO causes a comparable rapid activation of the p38-MAPK pathway; however, the increased activation state of p38-MAPK was maintained for several hours before control values were reattained after 24 h of stimulation. Furthermore, the NO donors also activated the classical extracellular signal-regulated kinase (ERK) p44-MAPK cascade as shown by phosphorylation of the specific substrate cytosolic phospholipase A2 in an immunocomplex kinase reaction. Both MAHMA-NO and spermine-NO cause a rapid activation of p44-MAPK after 10 min of stimulation. Interestingly, there is a second delayed peak of p44-MAPK activation after 4-24 h of stimulation with NO donors. These results suggest that there is a differential activation pattern for stress-activated and mitogen-activated protein kinases by NO and that the integration of these signals may lead to specific cell responses.  (+info)

A low-affinity serum response element allows other transcription factors to activate inducible gene expression in cardiac myocytes. (2/7444)

Hypertrophic growth of cardiac muscle cells is induced by a variety of physiological and pathological stimuli and is associated with a number of changes, including activation of genes such as atrial natriuretic factor. We found that two serum response element (SRE)-like DNA elements, one of which does not meet the consensus sequence and binds serum response factor (SRF) with low affinity, regulate the activity of this promoter. Surprisingly, the ability to induce the promoter by two different physiologic stimuli, as well as various activated transcription factors, including SRF-VP16, was primarily dependent upon the nonconsensus rather than the consensus SRE. This SRE controls the induction of gene expression via an unusual mechanism in that it is required to allow some, but not all, active transcription factors at unrelated sites on the promoter to stimulate gene expression. Thus, in addition to regulation of SRF activity by growth stimuli, regulation of a low-affinity SRE element controls inducible gene expression by modulating the ability of other transcription factors to stimulate the transcription machinery.  (+info)

p38 mitogen-activated protein kinase can be involved in transforming growth factor beta superfamily signal transduction in Drosophila wing morphogenesis. (3/7444)

p38 mitogen-activated protein kinase (p38) has been extensively studied as a stress-responsive kinase, but its role in development remains unknown. The fruit fly, Drosophila melanogaster, has two p38 genes, D-p38a and D-p38b. To elucidate the developmental function of the Drosophila p38's, we used various genetic and pharmacological manipulations to interfere with their functions: expression of a dominant-negative form of D-p38b, expression of antisense D-p38b RNA, reduction of the D-p38 gene dosage, and treatment with the p38 inhibitor SB203580. Expression of a dominant-negative D-p38b in the wing imaginal disc caused a decapentaplegic (dpp)-like phenotype and enhanced the phenotype of a dpp mutant. Dpp is a secretory ligand belonging to the transforming growth factor beta superfamily which triggers various morphogenetic processes through interaction with the receptor Thick veins (Tkv). Inhibition of D-p38b function also caused the suppression of the wing phenotype induced by constitutively active Tkv (TkvCA). Mosaic analysis revealed that D-p38b regulates the Tkv-dependent transcription of the optomotor-blind (omb) gene in non-Dpp-producing cells, indicating that the site of D-p38b action is downstream of Tkv. Furthermore, forced expression of TkvCA induced an increase in the phosphorylated active form(s) of D-p38(s). These results demonstrate that p38, in addition to its role as a transducer of emergency stress signaling, may function to modulate Dpp signaling.  (+info)

Activation of stress-activated protein kinase/c-Jun NH2-terminal kinase and p38 kinase in calphostin C-induced apoptosis requires caspase-3-like proteases but is dispensable for cell death. (4/7444)

Apoptosis was induced in human glioma cell lines by exposure to 100 nM calphostin C, a specific inhibitor of protein kinase C. Calphostin C-induced apoptosis was associated with synchronous down-regulation of Bcl-2 and Bcl-xL as well as activation of caspase-3 but not caspase-1. The exposure to calphostin C led to activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) and p38 kinase and concurrent inhibition of extracellular signal-regulated kinase (ERK). Upstream of ERK, Shc was shown to be activated, but its downstream Raf1 and ERK were inhibited. The pretreatment with acetyl-Tyr-Val-Ala-Asp-aldehyde, a relatively selective inhibitor of caspase-3, or benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD.fmk), a broad spectrum caspase inhibitor, similarly inhibited calphostin C-induced activation of SAPK/JNK and p38 kinase as well as apoptotic nuclear damages (chromatin condensation and DNA fragmentation) and cell shrinkage, suggesting that caspase-3 functions upstream of SAPK/JNK and p38 kinase, but did not block calphostin C-induced surface blebbing and cell death. On the other hand, the inhibition of SAPK/JNK by transfection of dominant negative SAPK/JNK and that of p38 kinase by SB203580 induced similar effects on the calphostin C-induced apoptotic phenotypes and cell death as did z-VAD.fmk and acetyl-Tyr-Val-Ala-Asp-aldehyde, but the calphostin C-induced PARP cleavage was not changed, suggesting that SAPK/JNK and p38 kinase are involved in the DNA fragmentation pathway downstream of caspase-3. The present findings suggest, therefore, that the activation of SAPK/JNK and p38 kinase is dispensable for calphostin C-mediated and z-VAD.fmk-resistant cell death.  (+info)

Acetyl-CoA:1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase is directly activated by p38 kinase. (5/7444)

Acetyl-CoA:1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase, along with phospholipase A2, is a key regulator of platelet-activating factor biosynthesis via the remodeling pathway. We have now obtained evidence in human neutrophils indicating that this enzyme is regulated by a specific member of the mitogen-activated protein kinases, namely the p38 kinase. We earlier demonstrated that tumor necrosis factor-alpha (TNF-alpha) as well as N-formyl-methionyl-leucyl-phenylalanine treatment leads to increased phosphorylation and activation of p38 kinase in human neutrophils. Strikingly, in the present study these stimuli increased the catalytic activity of acetyltransferase up to 3-fold, whereas 4-phorbol 12-myristate 13-acetate, which activates the extracellular-regulated kinases (ERKs) but not p38 kinase, had no effect. Furthermore, a selective inhibitor of p38 kinase, SB 203580, was able to abolish the TNF-alpha- and N-formyl-methionyl-leucyl-phenylalanine-induced activation of acetyltransferase. The same effect was not observed in the presence of an inhibitor that blocked ERK activation (PD 98059). Complementing the findings in intact cells, we have shown that recombinant, activated p38 kinase added to microsomes in the presence of Mg2+ and ATP increased acetyltransferase activity to the same degree as in microsomes obtained from TNF-alpha-stimulated cells. No activation of acetyltransferase occurred upon treatment of microsomes with either recombinant, activated ERK-1 or ERK-2. Finally, the increases in acetyltransferase activity induced by TNF-alpha could be ablated by treating the microsomes with alkaline phosphatase. Thus acetyltransferase appears to be a downstream target for p38 kinase but not ERKs. These data from whole cells as well as cell-free systems fit a model wherein stimulus-induced acetyltransferase activation is mediated by a phosphorylation event catalyzed directly by p38 kinase.  (+info)

Raf-1 is activated by the p38 mitogen-activated protein kinase inhibitor, SB203580. (6/7444)

SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imi dazole) is widely used as a specific inhibitor of p38 mitogen-activated protein kinase (MAPK). Here, we report that SB203580 activates the serine/threonine kinase Raf-1 in quiescent smooth muscle cells in a dose-dependent fashion. The concentrations of SB203580 required lie above those necessary to inhibit p38 MAPK and we were unable to detect basal levels of active p38 MAPK. SB203580 does not directly activate Raf-1 in vitro, and fails to activate Ras, MEK, and ERK in intact cells. In vitro, however, SB203580-stimulated Raf-1 activates MEK1 in a coupled assay. We conclude that activation of Raf-1 by SB203580 is not mediated by an inhibition of p38 MAPK, is Ras-independent, and is uncoupled from MEK/ERK signaling.  (+info)

An inhibitor of p38 mitogen-activated protein kinase protects neonatal cardiac myocytes from ischemia. (7/7444)

Cellular ischemia results in activation of a number of kinases, including p38 mitogen-activated protein kinase (MAPK); however, it is not yet clear whether p38 MAPK activation plays a role in cellular damage or is part of a protective response against ischemia. We have developed a model to study ischemia in cultured neonatal rat cardiac myocytes. In this model, two distinct phases of p38 MAPK activation were observed during ischemia. The first phase began within 10 min and lasted less than 1 h, and the second began after 2 h and lasted throughout the ischemic period. Similar to previous studies using in vivo models, the nonspecific activator of p38 MAPK and c-Jun NH2-terminal kinase, anisomycin, protected cardiac myocytes from ischemic injury, decreasing the release of cytosolic lactate dehydrogenase by approximately 25%. We demonstrated, however, that a selective inhibitor of p38 MAPK, SB 203580, also protected cardiac myocytes against extended ischemia in a dose-dependent manner. The protective effect was seen even when the inhibitor was present during only the second, sustained phase of p38 MAPK activation. We found that ischemia induced apoptosis in neonatal rat cardiac myocytes and that SB 203580 reduced activation of caspase-3, a key event in apoptosis. These results suggest that p38 MAPK induces apoptosis during ischemia in cardiac myocytes and that selective inhibition of p38 MAPK could be developed as a potential therapy for ischemic heart disease.  (+info)

Cot protooncoprotein activates the dual specificity kinases MEK-1 and SEK-1 and induces differentiation of PC12 cells. (8/7444)

Mitogenic signals initiated at the plasma membrane are transmitted to the nucleus through an intricate signalling network. We identified the protooncoprotein Cot as a new component of mitogenic signalling cascades, which activates both the classic cytoplasmic cascade and the SAPK stress pathway. Wildtype and activated Cot phosphorylate and activate MEK-1 and SEK-1 in vitro. These findings are consistent with the sequence homology between Cot and the rat gene Tpl-2. Expression of oncogenic Cot in 293, NIH3T3 and PC12 cells leads to in vivo phosphorylation of endogenous c-Jun and Erk-1/2 suggesting that the serine/threonine kinase Cot functions beside c-Raf-1 and Mos as a direct activator of MEK-1. Furthermore, we have examined the biological effects of Cot on the phenotype of fibroblastic and neuronal cells. In order to test a potential c-Raf-1 dependency of Cot transformation, the effect of oncogenic Cot on Raf revertant CHP25 cells was determined. Cot could restore the transformed phenotype indicating that Cot transformation is not dependent on active c-Raf-1 and that Cot is not a target for the putative Raf inhibitor, which is presumably active in the revertant cell line. Expression of oncogenic versions of Raf as well as v-Mos leads to differentiation of PC12 cells. Cot also induces neurite outgrowth of PC12 cells. These data are consistent with the role of Cot in the classic mitogenic cascade and suggest that the simultaneously activated JNK/SAPK stress pathway has no antagonistic effects in this context.  (+info)

A tetracycline-regulated reporter system was used to investigate the regulation of cyclooxygenase 2 (Cox-2) mRNA stability by the mitogen-activated protein kinase (MAPK) p38 signaling cascade. The stable beta-globin mRNA was rendered unstable by insertion of the 2, 500-nucleotide Cox-2 3 untranslated region (3 UTR). The chimeric transcript was stabilized by a constitutively active form of MAPK kinase 6, an activator of p38. This stabilization was blocked by SB203580, an inhibitor of p38, and by two different dominant negative forms of MAPK-activated protein kinase 2 (MAPKAPK-2), a kinase lying downstream of p38. Constitutively active MAPKAPK-2 was also able to stabilize chimeric beta-globin-Cox-2 transcripts. The MAPKAPK-2 substrate hsp27 may be involved in stabilization, as beta-globin-Cox-2 transcripts were partially stabilized by phosphomimetic mutant forms of hsp27. A short (123-nucleotide) fragment of the Cox-2 3 UTR was necessary and sufficient for the regulation of mRNA stability by the p38
A series of 3-(4-fluorophenyl)-2-(4-pyridyl)-chromone derivs. were synthesized and evaluated as p38 MAP kinase inhibitors. Introduction of an amino group in the 2-position of the pyridyl moiety gave p38 inhibitors with IC50 values in the low nanomolar range (e.g. 8a; IC50 = 17 nm). Addnl., the inhibitors (8a and 8e) demonstrate an excellent selectivity profile towards the p38 kinase among other kinases, as well as inhibition (8e) of p38 signaling in human breast cancer cells. [on SciFinder(R)]. ...
p38 MAPK inhibitors (inhibiting targets of signaling pathways) used for various assays, some have entered clinical trials, which would be new cancer therapies.
CMPD-1 is a non-ATP-competitive, selective inhibitor of p38α-mediated MK2a (mitogen-activated protein kinase-2a) phosphorylation (apparent Ki = 330 nM).
Dilmapimod,SB-681323,p38 MAPK Inhibitor。CAS 番号:444606-18-2,純度:99.56%。東京倉庫。溶解度:DMSO。高品質な生理・薬理活性化合物。Dilmapimod製品詳細ページです。
Monocef Sb in Punjabi - ਵਰਤੋਂ, ਖੁਰਾਕ, ਬੁਰੇ ਪ੍ਰਭਾਵ, ਲਾਭ, ਪਰਸਪਰ ਪ੍ਰਭਾਵ ਅਤੇ ਚੇਤਾਵਨੀ ਦੇਖੋ
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. ...
1. Raman M, Chen W, Cobb M.H. Differential regulation and properties of MAPKs. Oncogene. 2007;26(22):3100 2. Iñesta-Vaquera F, Sabio G, Kuma Y, Cuenda A. Alternative p38 Pathways MAPK. Stress-Activated Protein Kinases. Heidelberg: Springer Berlin. 2008:17 3. Adams R.H. et al. Essential role of p38alpha MAP kinase in placental but not embryonic cardiovascular development. Mol Cell. 2000;6(1):109 4. Allen M. et al. Deficiency of the stress kinase p38alpha results in embryonic lethality: characterization of the kinase dependence of stress responses of enzyme-deficient embryonic stem cells. J Exp Med. 2000;191(5):859 5. Mudgett J.S. et al. Essential role for p38alpha mitogen-activated protein kinase in placental angiogenesis. Proc Natl Acad Sci U S A. 2000;97(19):10454 6. Tamura K. et al. Requirement for p38alpha in erythropoietin expression: a role for stress kinases in erythropoiesis. Cell. 2000;102(2):221 7. Zarubin T, Han J. Activation and signaling of the p38 MAP kinase pathway. Cell Res. ...
TY - JOUR. T1 - bHLH-zip transcription factor Spz1 mediates mitogen-activated protein kinase cell proliferation, transformation, and tumorigenesis. AU - Hsu, Shih Hsien. AU - Hsieh-Li, Hsiu Mei. AU - Huang, Hsin Yi. AU - Huang, Pei Hsin. AU - Li, Hung. PY - 2005/5/15. Y1 - 2005/5/15. N2 - BHLH-zip proteins usually play important regulatory roles in cell growth and differentiation. In this study, we show that Spz1, a bHLH-zip transcription factor, acts downstream of mitogen-activated protein kinase (MAPK, extracellular signal-regulated kinase 1/2) to up-regulate cell proliferation and tumorigenesis. In addition, through an interaction with proliferating cell nuclear antigen (PCNA) promoter, Spz1 induced cell proliferation concomitant with an increase in PCNA gene expression. Spz1-transfected cells formed colony foci on soft agar and developed fibrosarcoma tumors in nude mice. MAPK directly interacted and phosphorylated Spz1 protein, which increased PCNA transcription and cell tumorigenic ...
Delayed cytoprotection (preconditioning) occurs 24h after sublethal simulated ischaemia and reperfusion (SI/R) in neonatal rat ventricular cardiomyocytes. SI/R was used to investigate the role of activation of mitogen-activated protein kinases (MAPKs), stress-activated protein kinases (SAPKs) and phosphoinositide 3-kinase-dependent protein kinase B (PKB)/Akt in cytoprotection. SI resulted in transient dual (Thr/Tyr) phosphorylation of p42/p44-MAPK and p38-MAPK, weak phosphorylation of p46/p54-SAPK, but no phosphorylation of PKB. Reperfusion caused further transient phosphorylation of p38-MAPK, but sustained phosphorylation of p42/p44-MAPK (lasting 4h) and of Ser473 of PKB (lasting 2h). Furthermore, SI/R (24h) induced delayed protection against lethal SI, as determined by an increase in cell viability {bioreduction of MTT [3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide]} and a decrease in cell injury (release of creatine kinase). Both protection and phosphorylation of ...
Background Mitogen-activated protein kinases (MAPKs) are signalling transduction molecules that have different functions and diverse behaviour in cancer. phosphorylated protein except p-ERK1/2 which showed both nuclear and cytoplasmic expression. The total/unphosphorylated forms showed cytoplasmic expression. All MAPKs PIK-293 proteins showed an equivocal expression in normal breast tissue, DCIS and BC tissue included within the TMA cores at varying degrees ranging from unfavorable to strong positivity (Online Resource). Cut-off of positivity was chosen for each marker to assess its association with other variables. There were positive correlations between different members of MAPKs using continuous data as well as dichotomised variables (Online Resource). The association between MAPKs and clinicopathological variables Expression of MAPK proteins showed positive correlations with clinicopathological features characteristic of good prognosis including lower grade, early stage, smaller tumour ...
Constitutive activation of the mitogen-activated protein kinase (MAPK) pathway is implicated in the development and progression of many human cancers, including
Investigation of T-helper type 2 cytokines and the mitogen-activated protein kinase pathway in the modulation of bronchial hyperresponsiveness, airway inflammation and remodelling ...
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 ...
p38alpha MAP kinase is activated in response to many cellular stresses and also regulates the differentiation and/or survival of various cell types in vitro, including skeletal muscle cells and cardiomyocytes. Here we show that targeted inactivation of the mouse p38alpha gene results in embryonic le …
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...
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 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. ...
Recombinant Mitogen-Activated Protein Kinase 8 (MAPK8) Protéine. Origine: Humain. Source: Baculovirus infected Insect Cells. Commandez ABIN593493.
Recombinant Mitogen-Activated Protein Kinase 8 (MAPK8) Protein (GST tag). Spezies: Human. Quelle: Wheat germ. Jetzt Produkt ABIN1310303 bestellen.
SB203580 is a pyridinyl imidazole inhibitor widely used to elucidate the roles of p38 mitogen-activated protein (MAP) kinase.. SB203580 inhibits also the phosphorylation and activation of protein kinase B (PKB, also known as Akt). Both kinases are involved in a wide array of signaling pathways, including the TLR signaling pathway. Moreover, several studies suggest that p38 MAPKs regulate distinct phases of autophagy. p38 can elicit autophagy via Beclin1. Contrarily, p38α has also been reported to inhibit autophagy by interfering with the trafficking of Atg9.
Direct evidence that Gi-coupled receptor stimulation of mitogen-activated protein kinase is mediated by G beta gamma activation of p21ras.
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. ...
TY - JOUR. T1 - NHP6A and NHP6B, which encode HMG1-like proteins, are candidates for downstream components of the yeast SLT2 mitogen-activated protein kinase pathway. AU - Costigan, Christine. AU - Kolodrubetz, David J. AU - Snyder, Michael. PY - 1994/4. Y1 - 1994/4. N2 - The yeast SLK1 (BCK1) gene encodes a mitogen-activated protein kinase (MAPK) activator protein which functions upstream in a protein kinase cascade that converges on the MAPK Slt2p (Mpk1p). Dominant alleles of SLK1 have been shown to bypass the conditional lethality of a protein kinase C mutation, pkc1-Δ, suggesting that Pkc1p may regulate Slk1p function. Slk1p has an important role in morphogenesis and growth control, and deletions of the SLK1 gene are lethal in a spa2-Δ mutant background. To search for genes that interact with the SLK1-SLT2 pathway, a synthetic lethal suppression screen was carried out. Genes which in multiple copies suppress the synthetic lethality of slk1-1 spa2-Δ were identified, and one, the NHP6A ...
TY - JOUR. T1 - Chromatin-tethered MAPKs. AU - Klein, Aileen M.. AU - Zaganjor, Elma. AU - Cobb, Melanie H.. PY - 2013. Y1 - 2013. N2 - Mitogen-activated protein kinases (MAPKs) are a family of protein kinases that are essential nodes in many cellular regulatory circuits including those that take place on DNA. Most members of the four MAPK subgroups that exist in canonical three kinase cascades - extracellular signalregulated kinases 1 and 2 (ERK1/2), ERK5, c-Jun N-terminal kinases (JNK1-3), and p38 (α, β, γ, and δ) families - have been shown to perform regulatory functions on chromatin. This review offers a brief update on the variety of processes that involve MAPKs and available mechanisms garnered in the last two years.. AB - Mitogen-activated protein kinases (MAPKs) are a family of protein kinases that are essential nodes in many cellular regulatory circuits including those that take place on DNA. Most members of the four MAPK subgroups that exist in canonical three kinase cascades - ...
Supplementary Materials Figure S1. in Shape ?Figure4B.4B. (C) No significant adjustments (p? ?0.003) in RNA following Wilcoxon Signed Rank check with Bonferroni multiple tests modification, n = 3C6. Shape S7. (A) The suggest and regular deviation in the fifty percent\existence of MYC\Venus in MCF10A cells after 16?h treatment with CHIR99021 and DMSO while positive and negative settings, or Dorsomorphin Belizatinib in the identified focus of 10 previously?M, is plotted. **p? ?0.01. College student t\check with Bonferroni multiple tests modification, n = 3. (B) Consultant immunoblots for cells expressing MYC\Venus treated using the indicated medication for 16 hours and 10?g/ml cycloheximide was added and cells were processed and harvested in the indicated timepoints. (C) The reported percentage of kinase activity staying following treatment using the indicated focus of either C1651 or GW851052 when compared with the automobile control. CYTO-97-363-s001.tiff (41M) ...
The mitogen-activated protein kinase (MAPK) pathway is the canonical signaling pathway for many receptor tyrosine kinases, such as the Epidermal Growth Factor Receptor. Downstream of the receptors, this pathway involves the activation of a kinase cascade that culminates in a transcriptional response and affects processes, such as cell migration and adhesion. In addition, the strength and duration of the upstream signal also influence the mode of the cellular response that is switched on. Thus, the same components can in principle coordinate opposite responses, such as proliferation and differentiation. In recent years, it has become evident that MAPK signaling is regulated and fine-tuned by proteins that can bind to several MAPK signaling proteins simultaneously and, thereby, affect their function. These so-called MAPK scaffolding proteins are, thus, important coordinators of the signaling response in cells. In this review, we summarize the recent advances in the research on MAPK/extracellular signal
The mitogen-activated protein kinase (MAPK) pathway is the canonical signaling pathway for many receptor tyrosine kinases, such as the Epidermal Growth Factor Receptor. Downstream of the receptors, this pathway involves the activation of a kinase cascade that culminates in a transcriptional response and affects processes, such as cell migration and adhesion. In addition, the strength and duration of the upstream signal also influence the mode of the cellular response that is switched on. Thus, the same components can in principle coordinate opposite responses, such as proliferation and differentiation. In recent years, it has become evident that MAPK signaling is regulated and fine-tuned by proteins that can bind to several MAPK signaling proteins simultaneously and, thereby, affect their function. These so-called MAPK scaffolding proteins are, thus, important coordinators of the signaling response in cells. In this review, we summarize the recent advances in the research on MAPK/extracellular signal
Leukotactin(Lkn)-1 is a CC chemokine and is upregulated in macrophages in response to Mycobacterium tuberculosis (MTB) infection. We investigated whether mitogen-activated protein kinases (MAPKs) are involved in MTB-induced expression of Lkn-1. The up-regulation of Lkn-1 by infection with MTB was inhibited in cells treated with inhibitors specific for JNK (SP600125) or p38 MAPK (SB202190). Since the up-regulation of Lkn-1 by MTB has been reported to be mediated by the PI3-K/PDK1/Akt signaling, we examined whether JNK and/or p38 MAPK are also involved in this signal pathway. MTB-induced Akt phosphorylation was blocked by treatment with JNK- or p38 MAPK-specific inhibitors implying that p38 and JNK are upstream of Akt. In addition, treatment with the PI3-K-specific inhibitor inhibited MTB-stimulated activation of JNK or p38 MAPK implying that PI3-K is upstream of JNK and p38 MAPK. These results collectively suggest that JNK and p38 MAPK are involved in the signal pathway responsible for ...
TY - JOUR. T1 - Systematic review of p38 mitogen-activated kinase and its functional role in reproductive tissues. AU - Sheller-Miller, Samantha. AU - Richardson, Lauren. AU - Martin, Laura. AU - Jin, Jin. AU - Menon, Ramkumar. PY - 2018/1/1. Y1 - 2018/1/1. N2 - Oxidative stress (OS) plays a role in uterine tissue remodeling during pregnancy and parturition. While p38 MAPK is an OS-response kinase, a precise functional role is unknown. Therefore, we conducted a systematic review of literature on p38 MAPK expression, activation, and function in reproductive tissues throughout pregnancy and parturition, published between January 1980 and August 2017, using four electronic databases (Web of Science, PubMed, Medline, and CoCHRANE). We identified 418 reports; 108 were selected for full-text evaluation and 74 were included in final review. p38 MAPK was investigated using feto-maternal primary or immortalized cells, tissue explants, and animal models. Western blot was most commonly used to report ...
arabidopsis, polyclonal, antibody, mpk6, mapk6, map kinase 6, mitogen activated protein kinase 6, MAP kinase induced by pathogens, ethylene biosynthesis, oxidative stress and osmotic stress
Kit Component:- KN206583G1, MAPK11 gRNA vector 1 in pCas-Guide vector- KN206583G2, MAPK11 gRNA vector 2 in pCas-Guide vector- KN206583D, donor vector…
Preconditioning, the phenomenon whereby brief episodes of ischemia or pharmacological agents protect the myocardium against subsequent ischemic injury, consists of an early and a late phase.1 The early phase develops immediately and disappears within 1 to 2 hours of ischemic preconditioning stimulus, whereas the late phase, also known as the second window of protection, becomes manifest after 12 to 24 hours and lasts for 3 to 4 days. An understanding of the signaling mechanisms that trigger and mediate this cardioprotective phenomenon would have vast physiological and pathological implications. Accordingly, many recent studies have focused on the characterization and delineation of the signal transduction pathways (molecules) underlying the development and manifestation of both the early and late phases of preconditioning. The general hypothesis is that the preconditioning stimulus will induce the activation of a cascade of stress-responsive kinases, which in turn transduce the stress signal ...
Opens the Highlight Feature Bar and highlights feature annotations from the FEATURES table of the record. The Highlight Feature Bar can be used to navigate to and highlight other features and provides links to display the highlighted region separately. Links in the FEATURES table will also highlight the corresponding region of the sequence. More... ...
Gut stem cell aging is driven by mTORC1 via a p38 MAPK-p53 pathway - posted in BioscienceNews: . F U L L T E X T S O U R C E : nature Abstract Nutrients are absorbed solely by the intestinal villi. Aging of this organ causes malabsorption and associated illnesses, yet its aging mechanisms remain unclear. Here, we show that aging-caused intestinal villus structural and fun...
Detail záznamu - Plasma-Activated Polyvinyl Alcohol Foils for Cell Growth - Detailní zobrazení záznamu - Knihovna Akademie věd České republiky
As previously reported, recombinant xEIAP/XLX is rapidly degraded by at least two distinct, consecutively acting proteolytic systems [11, 14]. Within 2 h incubation, xEIAP/XLX is significantly degraded in both CSF-arrested and interphase egg extracts in a C-terminal RING finger-dependent manner. Subsequently, spontaneous cytochrome c-induced caspase activation begins after 4 h incubation in interphase egg extracts (apoptotic egg extracts), and the remaining xEIAP/XLX is cleaved by the activated caspases at yet unidentified site(s). This caspase activation is delayed or suppressed in CSF-arrested egg extracts by a p42MAPK-dependent pathway [7-11]. We found that the electrophoretic mobilities of recombinant 6XHis-tagged (6XHis-FL) and MBP-tagged (MBP-FL) xEIAP/XLX slightly decreased during incubation in CSF-arrested but not interphase egg extracts (Fig. 1B), whereas those of other BIR family proteins (xSurvivin1/xBIR1, xSurvivin2/SIX, and xXIAP) did not (data not shown). However, the rapid ...
Cells use a network of mitogen-activated protein kinases (MAPKs) to coordinate responses to diverse extracellular signals. Here, we examine the role of docking interactions in determining connectivity of the yeast MAPKs Fus3 and Kss1. These closely related kinases are activated by the common upstrea …
Fibronectin stabilization and Fibronectin-Integrin signaling via MAPK are required in L-Glutamine-mediated protection against gut injury
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MAPKAPK5-AS1 - (untagged)-Homo sapiens, clone MGC:15178 IMAGE:4122851, complete cds available for purchase from OriGene - Your Gene Company.
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A method for inhibiting proliferation of a PPAR .gamma.-responsive hyperproliferative cell which comprises the step of contacting the cell with (I) an inhibitory amount of a PPAR.gamma. agonist and (II) a MAP kinase inhibitor is disclosed. A method for treating or prophylactically ...
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Protein kinases have become central in the efforts to understand the nature of various diseases, and a lot is invested into creating effective therapeutic strategies and finding effective and selective protein kinase inhibitors. In order to succeed it is also important to focus on the structure of the kinases, their exact biological role, and how they interact and cooperate in the signaling. The exact structure of MAPKAPK5 is still unknown, and selective inhibitors are yet to be identified. Even though some of its biological roles are starting to emerge more work is required, including searching for selective inhibitors, analyzing its structure and interactions with its interaction partners. In order to analyze the structure of MAPKAPK5, homology models were generated and their ability to discriminate between binders and non-binders were analyzed. Based on the results, one model was found satisfactory and may be used as a working tool for further experimental studies and possibly structure aided ...
Following denervation skeletal muscles change their functional and structural properties. Some changes resemble conditions in developing muscles and may be important for reinnervation. Due to inactivity following denervation most skeletal muscles loose muscle mass and become atrophic. The hemidiaphragm muscle, however, undergoes a phase of transient hypertrophy following denervation, gaining weight during the first 6-10 days followed by a decrease in weight. In this thesis the expression (mRNA, protein and protein phosphorylations) of potential factors involved in the regulation of muscle mass were examined in denervated hind-limb and hemidiaphragm muscles.. NIFK is a protein that associates with Ki67, a protein expressed predominantly in proliferating cells. The mRNA expression of NIFK was upregulated in denervated atrophic muscles but unaltered in denervated hypertrophic muscles, suggesting a potential role in the regulation of skeletal muscle mass (Paper I). p38 MAPK has previously been ...
PGC-1α-dependent irisin, a novel myokine, is derived from cleaving Fndc5 protein. Irisin promotes brown fat-like development and thermogenesis in WAT both in vitro and in vivo. The discovery of irisin has created an opportunity to further understand the role of adipocytes in obesity, diabetes, and other associated metabolic disorders (12,13,26,27). However, the molecular mechanisms and cellular signaling pathways responsible for the browning effect of irisin have not been elucidated.. In this study, we successfully constructed the yeast expression plasmid containing a synthesized optimal codon usage, human irisin-coding sequence and generated pure human recombinant irisin protein in P. pastoris with high yield that is fully biologically functional. The P. pastoris system is widely used for heterogenic protein expression, with the capacity to generate posttranslational modified proteins (28). The human recombinant irisin protein expressed in yeast showed a predominant band of ∼22 kDa, which is ...
Protein kinase B (PKB) isoforms became activated [and glycogen synthase kinase-3 (GSK3) became inhibited] when mouse Swiss 3T3 fibroblasts were exposed to oxidative stress (H2O2) or heat shock, but not when they were exposed to osmotic shock (0.5 M sorbitol or 0.7 M NaCl), chemical stress (sodium arsenite), the protein-synthesis inhibitor anisomycin, or UV radiation. In contrast, all seven stimuli activated mitogen-activated protein kinase-activated protein kinase-2 (MAPKAP-K2). The activation of MAPKAP-K2 was suppressed by the drug SB 203580, but not by inhibitors of phosphoinositide (phosphatidylinositide, PI) 3-kinase. In contrast, the activation of PKB isoforms and the inhibition of GSK3 by oxidative stress or heat shock were prevented by inhibitors of PI 3-kinase, but not by SB 203580. Thus the activation of PKB by oxidative stress or heat shock is mediated by PI 3-kinase and not by MAPKAP-K2. PKBα and PKBγ were also activated by heat shock and oxidative stress in human embryonic kidney ...
PRAK antibody [N3C3] (mitogen-activated protein kinase-activated protein kinase 5) for ICC/IF, WB. Anti-PRAK pAb (GTX107938) is tested in Human samples. 100% Ab-Assurance.
Saccharomyces cerevisiae is the micro-organism of choice for the conversion of fermentable sugars during beverage or bioethanol fermentations. These fermentations are characterised by high osmotic stress on a yeast cell, with selected brewing fermentations beginning at 20-25% fermentable sugars and bioethanol fermentations at 13% fermentable sugars. RCK2 encodes for a MAPKAP (MAPK-activated protein kinase) enzyme and was identified on a locus by QTL analysis in yeast cells under osmotic stress, RCK2 expression was placed under a tetracycline regulatable vector and rescued glucose, sorbitol or glycerol induced osmotic stress in an rck2 null strain. A strain overexpressing RCK2 had significantly faster fermentation rates when compared
Stimulation of hemopoietic cells with IL-3, IL-4, IL-5, granulocyte-macrophage-CSF and Steel factor-(SLF) induced tyrosine phosphorylation of a number of protein substrates. Two of these proteins, designated p42 and p44, were tyrosine phosphorylated rapidly in response to treatment with IL-3, IL-5, granulocyte-macrophage-CSF and SLF, but not IL-4. We demonstrate that these common substrates are members of the mitogen-activated protein kinase (MAP kinase) family of protein serine/threonine kinases. Ion-exchange chromatography yielded a peak of MAP kinase activity eluting at 0.3 to 0.32 M NaCl. Immunoblotting of column fractions with antiphosphotyrosine antibodies showed coelution of the peak of MAP kinase enzyme activity with the p42 and p44 tyrosine phosphorylated species, and with two proteins of 42 and 44 kDa which were immunoreactive with anti-MAP kinase antibodies. Moreover, a characteristic shift in mobility of the p42 and p44 species was observed after factor treatment. Time-course ...
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 ...
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.
TY - JOUR. T1 - Attenuation of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice. AU - Sari, Flori R.. AU - Widyantoro, Bambang. AU - Thandavarayan, Rajarajan A.. AU - Harima, Meilei. AU - Lakshmanan, Arun. AU - Zhang, Shaosong. AU - Muslin, Anthony J.. AU - Suzuki, Kenji. AU - Kodama, Makoto. AU - Watanabe, Kenichi. PY - 2011/6/27. Y1 - 2011/6/27. N2 - Background/Aims: Pressure overload stimulation is known to elicit disturbances in the endoplasmic reticulum (ER), which leads to ER stress (ERS). p38 mitogen-activated protein kinase (MAPK) plays an important role in mediating apoptotic processes, however, the roles of this kinase in activating ERS-initiated apoptosis in pressure-overloaded hearts are largely unknown. Methods: We clarified the role of p38α MAPK in ERS-associated apoptosis by subjecting transgenic mice displaying cardiac specific dominant negative (DN) mutant p38α MAPK over-expression to seven day pressure ...
MAP kinase-activated protein kinase 2 (MAPKAPK2) is an enzyme that in humans is encoded by the MAPKAPK2 gene. MAPKAP kinase-2 (MK2) is originally identified by its phosphorylation of glycogen synthase at serine-7 and the corresponding serine in a peptide (GS peptide-1) modelled after the N-terminus of glycogen synthase.. MAPKAP kinase-2 is a novel protein kinase activated by mitogen-activated protein kinase. This MAP kinase activated protein kinase, termed MAPKAP kinase-2, is distinguished from S6 kinase-II (MAPKAP kinase-1) by its response to inhibitors, lack of phosphorylation of S6 peptides and amino acid sequence.. ...
MAPK (mitogen-activated proteins kinase) pathways constitute major regulators of cellular transcriptional programmes. multiple ErbB ligands, vascular endothelial growth element and PHRP (parathyroid hormone-related protein). PHRP is the main mediator of humoral hypercalcaemia of malignancy, and has been implicated in metastasis to bone. We demonstrate that PHRP is definitely secreted by MEK1EE-expressing cells. This secretion is definitely inhibited by PD184352, but not by ErbB inhibitors. Our results suggest that, in addition to anti-proliferative properties, MEK1,2 inhibitors may be anti-angiogenic Tyrosine kinase inhibitor manufacture and possess restorative energy in the treatment of PHRP-positive tumours. transcription reagents (Enzo Diagnostics; Affymetrix, #900182), resulting in approx.?100-fold amplification of RNA. The biotin-labelled cRNA probes were purified and fragmented in fragmentation buffer (Affymetrix, #900371) by incubation at 95?C for 35?min. Hybridization to Affymetrix U95A ...
TY - JOUR. T1 - The p38 mitogen-activated protein kinase pathway and its role in interferon signaling. AU - Platanias, Leonidas C.. PY - 2003/5/1. Y1 - 2003/5/1. N2 - Interferons (IFNs) are pleiotropic cytokines that exhibit multiple biological effects on cells and tissues. IFN receptors are expressed widely in mammalian cells and virtually all different cell types express them on their surface. The Type I IFN receptor has a multichain structure, composed of at least two distinct receptor subunits, IFNαR1 and IFNαR2. Two Jak-kinases, Tyk-2 and Jak-1, associate with the different receptor subunits and are activated in response to IFNα or IFNβ to regulate engagement of multiple downstream signaling cascades. These include the Stat-pathway, whose function is essential for transcriptional activation of IFN-sensitive genes, and the insulin receptor substrate pathway, which regulates downstream activation of the phosphatidyl-inositol-3′ kinase. Members of the Map family of kinases are also ...
View mouse Mapkapk5 Chr5:121525038-121545905 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
LOC100996792 (dual specificity mitogen-activated protein kinase kinase 3), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
The phosphorylation of the human estrogen receptor (ER) serine residue at position 118 is required for full activity of the ER activation function 1 (AF-1). This Ser118 is phosphorylated by mitogen-activated protein kinase (MAPK) in vitro and in cells treated with epidermal growth factor (EGF) and insulin-like growth factor (IGF) in vivo. Overexpression of MAPK kinase (MAPKK) or of the guanine nucleotide binding protein Ras, both of which activate MAPK, enhanced estrogen-induced and antiestrogen (tamoxifen)-induced transcriptional activity of wild-type ER, but not that of a mutant ER with an alanine in place of Ser118. Thus, the activity of the amino-terminal AF-1 of the ER is modulated by the phosphorylation of Ser118 through the Ras-MAPK cascade of the growth factor signaling pathways.. ...
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. ...
Growth factors and various cellular stresses are known to activate mitogen-activated protein (MAP) kinase, which plays a role in conveying signals from the cytosol to the nucleus. The phosphorylation of MAP kinase is thought to be a prerequisite for translocation. Here, we investigate the translocation and activation of MAP kinase during ischaemia and reperfusion in perfused rat heart. Ischaemia (0-40 min) induces the translocation of MAP kinase from the cytosol fraction to the nuclear fraction. Immunohistochemical observation shows that MAP kinase staining in the nucleus is enhanced after ischaemia for 40 min. Unexpectedly, tyrosine phosphorylation of MAP kinase is unchanged in the nuclear fraction during ischaemia, indicating that unphosphorylated MAP kinase translocates from the cytosol to the nucleus. During reperfusion (0-30 min), after ischaemia for 20 min, tyrosine phosphorylation of MAP kinase in the nuclear fraction is increased with a peak at 10 min of reperfusion. The activation is ...
TY - JOUR. T1 - Effect of p38 MAPK inhibition on corticosteroid suppression of cytokine release in severe asthma. AU - Bhavsar, Pankaj K.. AU - Khorasani, N.. AU - Hew, M.. AU - Chung, K F. PY - 2010/4. Y1 - 2010/4. N2 - Patients with severe asthma respond less well to corticosteroids than those with non-severe asthma. Increased p38 mitogen-activated protein kinase (MAPK) activation in alveolar macrophages (AMs) from severe asthma patients has been associated with a reduced inhibition of cytokine release by dexamethasone. We determined whether p38 MAPK inhibitors would modulate corticosteroid suppression of cytokine release from AMs and peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from venous blood and AMs by bronchoalveolar lavage in severe and non-severe asthma patients. PBMCs and AMs were exposed to lipopolysaccharide (LPS) with and without the p38 MAPK inhibitor, SD282, or dexamethasone. We determined the concentrationdependent effects of another p38 MAPK inhibitor, GW-A, ...
Background The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour. Methods We performed primary SHIRPA observations during background breeding into the C57BL/6 background and assessed the behaviour of the background-bred animals on the elevated plus maze and in the light-dark test. Our results were analyzed using Chi-square tests and homo- and heteroscedatic T-tests; Results Female transgenic mice displayed increased amounts of head dips and open arm time on the maze, compared to littermate controls. In ...
Mitogen-activated protein kinase involved in a signal transduction pathway that is activated by changes in the osmolarity of the extracellular environment. Controls osmotic regulation of transcription of target genes (By similarity).
Mitogen-activated protein kinase 13 (MAPK 13), also known as stress-activated protein kinase 4 (SAPK4), is an enzyme that in humans is encoded by the MAPK13 gene. The protein encoded by this gene is a member of the MAP kinase family. MAP kinases 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. This kinase is closely related to p38 MAP kinase, both of which can be activated by proinflammatory cytokines and cellular stress. MAP kinase kinases 3, and 6 can phosphorylate and activate this kinase. Transcription factor ATF2, and microtubule dynamics regulator stathmin have been shown to be the substrates of this kinase. GRCh38: Ensembl release 89: ENSG00000156711 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000004864 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Entrez Gene: mitogen-activated protein kinase 13. ...
Fingerprint Dive into the research topics of Involvement of mitogen-activated protein kinase in hippocampal long-term potentiation. Together they form a unique fingerprint. ...
p42 MAP Kinase (Mitogen-Activated Protein Kinase, MAPK), also known as Erk2 (Extracellular signal-regulated kinase 2) is one of two isoforms of MAP kinase family. It is a serine/threonine protein kinase
This study identifies PKR as an essential mediator for several forms of stress-induced apoptosis. Specifically, our results implicate PKR in a signaling pathway that is responsive not only to dsRNA, but also to TNF-α and LPS. While the activation of PKR by dsRNA has been well studied (8), the mechanism of activation by these other stimuli is presently unclear. One possibility could involve the phosphorylation of PKR by an upstream kinase that is activated by one of the above stimuli [for example, the TNF-receptor-associated kinase, RIP (27), or a TNF-α/LPS-activated MAP kinase (4)]. Regardless of the activation mechanisms involved, our data show that PKR is required for regulating the DNA-binding ability of IRF-1 in response to stress-related stimuli. Previous studies have suggested that expression of IRF-1 protein in cells is insufficient to manifest any functional activity unless a phosphorylation signal is provided, potentially by PKR (28). While the mechanistic details of the interaction ...
Presentation Research Lines Group Members Ana Cuenda Group Leader Contact Research summary The aim of our group is to understand the role of p3...
MK5 (mitogen-activated protein kinase [MAPK]-activated protein kinase 5), also designated PRAK (p38-regulated and -activated kinase), was deleted from mice by homologous recombination. Although no MK5 full-length protein and kinase activity was detected in the MK5 knockout mice, the animals were viable and fertile and did not display abnormalities in tissue morphology or behavior. In addition, these mice did not show increased resistance to endotoxic shock or decreased lipopolysaccharide-induced cytokine production. Hence, MK5 deletion resulted in a phenotype very different from the complex inflammation-impaired phenotype of mice deficient in MK2, although MK2 and MK5 exhibit evolutional, structural, and apparent extensive functional similarities. To explain this discrepancy, we used wild-type cells and embryonic fibroblasts from both MK2 and MK5 knockout mice as controls to reexamine the mechanism of activation, the interaction with endogenous p38 MAPK, and the substrate specificity of both ...
What cellular and molecular properties of neurons in the T-SWR support a 45 min spacing interval for two-trial LTM? Studies of the patterning requirements for the induction of long-term facilitation (LTF) of the tail SN-motor neuron (MN) synapse parallel those for sensitization memory in the T-SWR (Mauelshagen et al., 1996, 1998). For example, four spaced (ISI of 15 min) pulses of exogenous 5-HT are required to induce LTF at tail SN-MN synapses (Mauelshagen et al., 1996). If 5-HT release within the CNS is a critical signaling event initiated by TS, an important experimental question is whether two spaced 5-HT pulses (ISI of 45 min) can induce LTF or whether additional 5-HT signaling (provided by additional pulses) is required.. The analysis of repeated trial learning in Aplysia has identified several critical molecular requirements for LTM induction downstream of 5-HT. These include the signaling kinases protein kinase A (PKA), MAPK, the transcription factor CREB1, and CRE-mediated transcription ...
Quantitative sandwich enzyme immunoassay (EIA) systems, that can distinguish between active-form subtypes of mitogen-activated protein kinases (p44 and p42 MAP kinase, also called ERK1 and ERK2), were developed employing subtype-specific antibodies a
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 ». ...
This trial aims to evaluate the efficacy of fulvestrant +/- selumetinib [AZD6244] in patients with advanced stage breast cancer progressing after aromatase
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BioAssay record AID 327182 submitted by ChEMBL: Inhibition of JNK1 in rat H9c2 cells assessed as inhibition of anisomycin-induced cJun phosphorylation after 30 mins.
Appropriate regulation of the Hog1 mitogen-activated protein kinase (MAPK) pathway is essential for cells to survive osmotic stress. Here, we show that the two sensing mechanisms upstream of Hog1 display different signaling properties. The Sho1 branch is an inducible nonbasal system, whereas the Sln1 branch shows high basal signaling that is restricted by a MAPK-mediated feedback mechanism. A two-dimensional mathematical model of the Snl1 branch, including high basal signaling and a Hog1-regulated negative feedback, shows that a system with basal signaling exhibits higher efficiency, with faster response times and higher sensitivity to variations in external signals, than would systems without basal signaling. Analysis of two other yeast MAPK pathways, the Fus3 and Kss1 signaling pathways, indicates that high intrinsic basal signaling may be a general property of MAPK pathways allowing rapid and sensitive responses to environmental changes.. ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. 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.
Sigma-Aldrich offers abstracts and full-text articles by [Lili Zhao, Guoyuan Lu, Qing Zhao, Mingyi Zhang, Mengxing Chen, Jiansheng Zhang, Kesheng Dai].
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 ...
Cocaethylene (CE) is an active metabolite of cocaine and ethanol and is a toxicant of physiological relevance due to the high rate of cocaine and ethanol co-exposure (~80%) in cocaine abusers. It has prolonged action and ...
The MAPK (mitogen-activated protein kinase) pathway is one of the most important and intensively studied signalling pathways. It is at the heart of a molecular-signalling network that governs the growth, proliferation, differentiation and survival of many, if not all, cell types. It is de-regulated in various diseases, ranging from cancer to immunological, inflammatory and degenerative syndromes, and thus represents an important drug target. Over recent years, the computational or mathematical modelling of biological systems has become increasingly valuable, and there is now a wide variety of mathematical models of the MAPK pathway which have led to some novel insights and predictions as to how this system functions. In the present review we give an overview of the processes involved in modelling a biological system using the popular approach of ordinary differential equations. Focusing on the MAPK pathway, we introduce the features and functions of the pathway itself before comparing the ...
Figure 6. Effect of MAPK inhibition on MET and EGFR signaling. A and B, A549 cells were incubated with selumetinib (1 μmol/L, 24 hours) and then treated with HGF (A) or EGF (B) at 25 ng/mL for indicated hours. C and D, A549 cells were incubated with MAPK inhibitors (1 μmol/L, 24 hours) and then treated with HGF (C) or EGF (D) at 25 ng/mL for 30 minutes. DM, DMSO; LY, LY3009120 (pan-RAFi); AZD, AZD6244 (MEKi); GDC, GDC0623 (MEKi); SCH, SCH772984 (ERKi); Vem, vemurafenib. E and F, H23 cells were treated as described above. G and H, A549 cells were incubated with selumetinib (1 μmol/L, 24 hours), and then endogenous MET (G) or integrin β4 (H) was immunoprecipitated (IP). Coimmunoprecipitated integrin β4 (G) or MET (H) was detected by Western blotting. ...
SEK1 / MKK4 (phospho Ser80) antibody (mitogen-activated protein kinase kinase 4) for ICC/IF, IHC-P, WB. Anti-SEK1 / MKK4 (phospho Ser80) pAb (GTX55115) is tested in Human samples. 100% Ab-Assurance.
Reaktivität: Affe - Probe: Serum, Cell Culture Supernatant. | Mitogen-Activated Protein Kinase 1/3 (MAPK1/3) ELISA Kit (ABIN1057202).
IL-17A is a pro-inflammatory cytokine and a member of the IL-17 family of cytokines. It is produced by activated T cells and acts through its receptor, IL-17R. This cytokine regulates the activities of NF-kappaB and mitogen-activated protein kinases.
reference: Specificity of linear motifs that bind to a common mitogen-activated protein kinase docking groove., Garai A, Zeke A, Gogl G, Toro I, Fordos F, Blankenburg H, Barkai T, Varga J, Alexa A, Emig D, Albrecht M, Remenyi A, Sci Signal. 2012 Oct 9;5(245):ra74. doi: 10.1126/scisignal.2003004. PMID: 23047924 ...
1H-Imidazole, 5-bromo-1-methyl-. CAS Number: 1003-21-0. Catalog Number: AA0001EW. MDL Number: MFCD01632218. Molecular Formula: C4H5BrN2. Molecular Weight: 160.9999. AA Blocks.
Yang TT, Xiong Q, Enslen H, Davis RJ, Chow CW (Jun 2002). "Phosphorylation of NFATc4 by p38 mitogen-activated protein kinases ... Nuclear factor of activated T-cells, cytoplasmic 4 is a protein that in humans is encoded by the NFATC4 gene. The product of ... NFATC4+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text ... Other members of this family of nuclear factors of activated T cells also participate in the formation of this complex. The ...
Yang SH, Galanis A, Sharrocks AD (June 1999). "Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors ... Yang SH, Galanis A, Sharrocks AD (1999). "Targeting of p38 Mitogen-Activated Protein Kinases to MEF2 Transcription Factors". ... with a mitogen-activated protein kinase, ERK5/BMK1". Nucleic Acids Res. 26 (20): 4771-7. doi:10.1093/nar/26.20.4771. PMC 147902 ... "Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins". Nucleic Acids Res. 29 (3): 732-42. doi: ...
Yang SH, Galanis A, Sharrocks AD (Jun 1999). "Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors ... with a mitogen-activated protein kinase, ERK5/BMK1". Nucleic Acids Research. 26 (20): 4771-7. doi:10.1093/nar/26.20.4771. PMC ... with a mitogen-activated protein kinase, ERK5/BMK1". Nucleic Acids Research. 26 (20): 4771-7. doi:10.1093/nar/26.20.4771. PMC ... "Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation". Nature. 386 (6622): 296-9. doi:10.1038/ ...
It is a p38 mitogen-activated protein kinase inhibitor. A phase II trial for treatment of ovarian cancer has completed. Patnaik ... March 2016). "A First-in-Human Phase I Study of the Oral p38 MAPK Inhibitor, Ralimetinib (LY2228820 Dimesylate), in Patients ... January 2020). "A randomized, double-blind, placebo-controlled phase 1b/2 study of ralimetinib, a p38 MAPK inhibitor, plus ...
... "p38 Mitogen-activated protein kinase stabilizes SMN mRNA through RNA binding protein HuR". Human Molecular Genetics. 18 (21): ... Survival of motor neuron 2 (SMN2) is a gene that encodes the SMN protein (full and truncated) in humans. The SMN2 gene is part ... Chen HH, Chang JG, Lu RM, Peng TY, Tarn WY (November 2008). "The RNA binding protein hnRNP Q modulates the utilization of exon ... Yong J, Wan L, Dreyfuss G (May 2004). "Why do cells need an assembly machine for RNA-protein complexes?". Trends in Cell ...
The authors found that KOR activates p38, a member of the mitogen-activated protein kinase (MAPK) family, through ... "Stress-Induced p38 Mitogen-Activated Protein Kinase Activation Mediates κ-Opioid-Dependent Dysphoria". J. Neurosci. 27 (43): ... causes an increase in phosphorylated p38 mitogen-activated protein kinase (MAPK) in microglia in the dorsal horn of the spinal ... "Prostaglandin E2 release evoked by intrathecal dynorphin is dependent on spinal p38 mitogen activated protein kinase". ...
Stein B, Yang MX, Young DB, Janknecht R, Hunter T, Murray BW, Barbosa MS (1997). "p38-2, a novel mitogen-activated protein ... mitogen-activated protein kinase". J. Biol. Chem. 272 (7): 4219-24. doi:10.1074/jbc.272.7.4219. PMID 9020136. Janknecht R, ... Kamakura S, Moriguchi T, Nishida E (1999). "Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. ... The protein encoded by this gene is phosphorylated by the kinases, MAPK1 and MAPK8. Several transcript variants have been ...
"Independent regulation of JNK/p38 mitogen-activated protein kinases by metabolic oxidative stress in the liver". Proc. Natl. ... "Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions". Mol. Cell. Biol. 17 (6): 3094-102 ... JUNB+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ... Fuchs SY, Xie B, Adler V, Fried VA, Davis RJ, Ronai Z (1998). "c-Jun NH2-terminal kinases target the ubiquitination of their ...
These include extracellular signal-regulated kinase, p38 mitogen-activated protein kinases, and c-Jun N-terminal kinases. The ... evidence for the involvement of protein kinase C and the mitogen-activated protein kinase signaling cascade". Journal of ... "Stress-induced p38 mitogen-activated protein kinase activation mediates kappa-opioid-dependent dysphoria". The Journal of ... and recent work also implicates the mitogen-activated protein kinase cascade and pCREB in KOR-dependent behaviors. While the ...
"Voltage-gated sodium channel Nav1.6 is modulated by p38 mitogen-activated protein kinase". The Journal of Neuroscience. 25 (28 ... Sodium channels are modulated by protein kinase A and protein kinase C (PKC) phosphorylation, which reduce peak sodium currents ... However, NaV1.6 channels lacks adequate protein kinase sites. Phosphorylation sites at amino acid residues Ser573 and Ser687 ... "Activation of Go-proteins by membrane depolarization traced by in situ photoaffinity labeling of galphao-proteins with [ ...
... mitogen-activated protein kinase)-dependent pathway. Usually, the p38 within the dendritic cell expresses TLR 4 (toll-like ... This causes the p38 MAPK to be phosphorylated. This phosphorylation activates the p38 MAPK to begin producing IL-10 and IL-12. ... for proteins involved in mitochondrial respiration and for cytoskeleton-related proteins. Morphine has long been known to act ... Morphine is a phenanthrene opioid receptor agonist - its main effect is binding to and activating the μ-opioid receptor (MOR) ...
November 2001). "Trophic factor withdrawal: p38 mitogen-activated protein kinase activates NHE1, which induces intracellular ... Yan W, Nehrke K, Choi J, Barber DL (August 2001). "The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 ... It is inhibited by the non-specific diuretic drug amiloride and activated by a variety of signals including growth factors, ... Pang T, Su X, Wakabayashi S, Shigekawa M (May 2001). "Calcineurin homologous protein as an essential cofactor for Na+/H+ ...
... induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases". ... C-C motif chemokine 11 also known as eosinophil chemotactic protein and eotaxin-1 is a protein that in humans is encoded by the ... The effects of CCL11 are mediated by its binding to a G-protein-linked receptor known as a chemokine receptor. Chemokine ... Jinquan T, Quan S, Feili G, Larsen CG, Thestrup-Pedersen K (Apr 1999). "Eotaxin activates T cells to chemotaxis and adhesion ...
... hormone induces Fas ligand production and apoptosis in PC12 cells via activation of p38 mitogen-activated protein kinase". The ... PC12 cells treated with CRH (1-10 nM) showed increased numbers of apoptotic cells and upregulation of the Fas ligand via p38 ... receptor antagonist blocks activating and 'anxiogenic' actions of CRF in the rat". Brain Research. 369 (1-2): 303-6. doi: ...
... are upregulated following injury and the increase in purinergic signaling activates p38-mitogen-activated protein kinase (p38 ... and release of brain-derived neurotrophic factor in microglia is dependent on calcium and p38-mitogen-activated protein kinase ... have shown that they are activated by diverse stimuli but they are dependent on activation of mitogen-activated protein kinase ... When activated by HIV-1 or viral proteins, they secrete or induce other cells to secrete neurotoxic factors; this process is ...
2000). "Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase". J. ... This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. This gene is widely ... Serine/threonine-protein kinase VRK1 is an enzyme that in humans is encoded by the VRK1 gene. ... This protein also phosphorylates histone, casein, and the transcription factors ATF2 (activating transcription factor 2) and C- ...
"The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced ... The SOCS3 protein can bind to JAK2 kinase, and inhibits the activity of JAK2 kinase. SOCS3 has been shown to interact with: ... "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase ... "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase ...
... prevents synaptotoxicity and memory dysfunction caused by beta-amyloid peptides via p38 mitogen-activated protein kinase ... brain damage and activation of p38 MAPK in rat focal cerebral ischemia". Brain Research. 1073-1074: 470-80. doi:10.1016/j. ... "Antagonism of adenosine A2A receptors underlies the behavioural activating effect of caffeine and is associated with reduced ...
de 2000). «Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase». J ... de 1997). «Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase». Proc. Natl. Acad. Sci. ... Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase ... de 1999). «Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors». Mol. Cell. Biol. (UNITED STATES) ...
2018). "The p38 mitogen activated protein kinase inhibitor losmapimod in chronic obstructive pulmonary disease patients with ... It selectively inhibits enzymes p38α/β mitogen-activated protein kinases (MAPKs), which are modulators of DUX4 expression and ... September 2012). "Effects of p38 mitogen-activated protein kinase inhibition on vascular and systemic inflammation in patients ... September 2014). "Losmapimod, a novel p38 mitogen-activated protein kinase inhibitor, in non-ST-segment elevation myocardial ...
... roles of cyclic AMP and p38 mitogen-activated protein kinase". World J. Gastroenterol. 11 (17): 2557-63. doi:10.3748/wjg.v11. ... The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in ... Fatty acid-CoA ligase 4 (FACL4), the protein encoded by the ACSL4 gene, is an acyl-CoA synthetase, which is an essential class ... ASCL4 encodes a 74.4 kDa protein, FACL4, which is composed of 670 amino acids; 17 peptides have been observed through mass ...
... 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 ... Calcium/calmodulin-dependent protein kinases Laube B, Hirai H, Sturgess M, Betz H, Kuhse J (March 1997). "Molecular ... Yu XM, Askalan R, Keil GJ, Salter MW (January 1997). "NMDA channel regulation by channel-associated protein tyrosine kinase Src ...
... which then activates the downstream kinases, Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), ... of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice". ... Those processes are mainly regulated by three factors: protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating ... proteins in the ER activates the integrated stress response through protein kinase RNA-like endoplasmic reticulum kinase (PERK ...
The anti-inflammatory effects of CO are attributed to activation of the p38 mitogen-activated protein kinase (MAPK) pathway. ... Heme oxygenase (HO) is a heme-containing member of the heat shock protein (HSP) family identified as HSP32. Three isoforms of ... While CO commonly interacts with the iron atom of heme in a hemoprotein, it has been demonstrated that CO activates calcium- ... CO has an inhibitory effect on numerous proteins including cytochrome P450 and cytochrome c oxidase CO is a modulator of ion ...
... encodes p38α mitogen-activated protein kinase (MAPK) which is the prototypic member of the p38 MAPK family. p38 MAPKs ... Johnson GL, Lapadat R (Dec 2002). "Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases". ... "Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase". The Journal ... "Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase ...
Fu XB, Xing F, Yang YH, Sun TZ, Guo BC (September 2003). "Activation of phosphorylating-p38 mitogen-activated protein kinase ... Below is a list of genes/protein products that can be used to identify various types of stem cells, or functional assays that ... Stahl J, Wobus AM, Ihrig S, Lutsch G, Bielka H (September 1992). "The small heat shock protein hsp25 is accumulated in P19 ... Stem cell markers are genes and their protein products used by scientists to isolate and identify stem cells. Stem cells can ...
... mycotoxins trigger a ribotoxic stress response that activates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase ... Activated c-jun acts as a transcription factor in the cell nucleus for proteins important for facilitating the downstream ... p53 is a protein responsible for controlling the cell cycle, but an increase in the activity of this protein also leads to ... Protein synthesis occurs in both the cytoplasm of the cell as well as in the luminal space of mitochondria, the cytoplasmic ...
... lacks the ability to inhibit the cAMP-dependent pathway but gained the ability to induce P38 mitogen-activated protein kinases ...
... trigger a proinflammatory response in human monocyte-derived macrophages through the p38α mitogen-activated protein kinase ... Fim C, D, and E accessory components associate with the main FimA protein and have a role in binding with matrix proteins and ... The genome of P. gingivalis was described in 2003 revealing 1,990 open reading frames (i.e. protein-coding sequences), encoded ... Lys- gingipains (Kgp) can bind to immobilized matrix proteins fibrinogen and fibronectin and may have a role in host ...
"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 ...
"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 ...
"Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways ... "Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... 1998). "Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway". J ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. ...
P38 mitogen-activated protein *MAPK11. *MAPK13. *MAPK14. MAP3K (EC 2.7.11.25). *MAP kinase kinase kinases *MAP3K1 ... 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 ...
... enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2 ... p38, and c-Jun NH2-terminal kinase. Correlation with its inhibitory effect on tumor necrosis factor-alpha production". J. Biol ... 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 ...
"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 ...
"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] ...
The activators of p38 (MKK3 and MKK6), JNK (MKK4 and MKK7), and ERK (MEK1 and MEK2) define independent MAP kinase signal ... Mitogen-activated protein kinase kinase (also known as MAP2K, MEK, MAPKK) is a kinase enzyme which phosphorylates mitogen- ... Mitogen-Activated+Protein+Kinase+Kinases at the US National Library of Medicine Medical Subject Headings (MeSH) ... Retrieved from "https://en.wikipedia.org/w/index.php?title=Mitogen-activated_protein_kinase_kinase&oldid=921615706" ...
... p38 mitogen-activated protein kinases (p38 Mpk), and cAMP response element-binding protein (CREB) which when activated ... activating prostanoids. classification[5]. G protein linkage[2]. pathways[2] Prostaglandin DP1 receptor. DP1. PGD2,,PGE2,PGF2α, ... cell signaling agents and for activating protein kinase C (PKC) secondary messengers; and Extracellular signal-regulated ... G proteins types to which they link and activate, i.e. those containing the Gs alpha subunit, Gi alpha subunit, Gq alpha ...
1997). „Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S ... 2001). „Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions". ... 1997). „Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. ENGLAND. 16 (8): 1909- ... 2003). „The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 ...
P38 mitogen-activated protein *MAPK11. *MAPK13. *MAPK14. MAP3K (EC 2.7.11.25). *MAP kinase kinase kinases *MAP3K1 ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... protein kinase activity. • PDZ domain binding. • SH3 domain binding. • scaffold protein binding. • metal ion binding. • kinase ... protein serine/threonine kinase activity. • GO:0001948 protein binding. • ATP binding. • Rho GTPase binding. ...
Mitogen-activated protein kinase (MAPK) signaling pathways includes three pathways: the classical MAPK/ERK pathway, p38 MAPK ... For example, miR-27a up-regulates P-gp expression by suppressing Raf kinase inhibitor protein (RKIP);[27] alternatively, miR- ... The protein belongs to the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules ... P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ...
P38 mitogen-activated protein *MAPK11. *MAPK13. *MAPK14. MAP3K (EC 2.7.11.25). *MAP kinase kinase kinases *MAP3K1 ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ... Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ...
de 2000). «Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase». J ... de 2001). «Mapping of the interaction domain of the protein kinase CKII beta subunit with target proteins». Mol. Cells (Korea ( ... de 1999). «Interactions of protein kinase CK2beta subunit within the holoenzyme and with other proteins». Mol. Cell. Biochem. ( ... de 1998). «Characterization of protein interaction among subunits of protein kinase CKII in vivo and in vitro». Mol. Cells ( ...
... and increases mitogen-activated protein kinase (MAP kinase) concentration. Alternatively, in some rare cases CB1 receptor ... protein kinase C (PKC), Raf-1, ERK, JNK, p38, c-fos, c-jun, and others.[15] ... which are activated by cAMP-dependent interaction with such molecules as protein kinase A (PKA), ... Cannabinoid receptor type 1 (CB1), also known as cannabinoid receptor 1, is a G protein-coupled cannabinoid receptor that in ...
... mitogen-activated protein kinases) such as ERK and JNK, bring about an increase in the synthesis of inflammatory factors that ... In this chronic signaling pathway, p38 is activated as a result of IL-1β signaling, and there is a presence of chemokines that ... astrocytes were generated by exposing human glial precursor cells to bone morphogenetic protein (Bone morphogenetic protein is ... A 2012 study[54] of the effects of marijuana on short term memories found that THC activates CB1 receptors of astrocytes which ...
Bandyopadhyay, G (2004). "Chlorogenic acid inhibits Bcr-Abl tyrosine kinase and triggers p38 mitogen-activated protein kinase- ... "The Tyrosine Kinase c-Abl Responds to DNA Damage by Activating the Homeodomain-interacting Protein Kinase 2". Journal of ... The BCR-ABL tyrosine kinase activates Ras via phosphorylation of the GAB2 protein, which is dependent on BCR-located ... Tyrosine kinase inhibitors[edit]. Crystal structure of Abl kinase domain (blue) in complex with 2nd generation tyrosine kinase ...
Type I IFNs further activate p38 mitogen-activated protein kinase (MAP kinase) to induce gene transcription.[17] Antiviral and ... PI3K activates P70-S6 Kinase 1, an enzyme that increases protein synthesis and cell proliferation; phosphorylates of ribosomal ... cells produce large amounts of an enzyme known as protein kinase R (PKR). This enzyme phosphorylates a protein known as eIF-2 ... to prevent the activity of RNA-dependent protein kinases; this is the mechanism reovirus adopts using its sigma 3 (σ3) protein ...
P38 mitogen-activated protein *MAPK11. *MAPK13. *MAPK14. MAP3K (EC 2.7.11.25). *MAP kinase kinase kinases *MAP3K1 ... kinase activity. • protein binding. • ATP binding. • protein serine/threonine kinase activity. • protein kinase activity. ... Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by the second ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ...
P38 mitogen-activated protein *MAPK11. *MAPK13. *MAPK14. MAP3K (EC 2.7.11.25). *MAP kinase kinase kinases *MAP3K1 ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... protein kinase activity. • protein serine/threonine kinase activity. • protein binding. • ATP binding. • magnesium ion binding ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ...
AMP-activated protein kinase,. (3-metil-2-oksobutanoat dehidrogenaza (prenos acetila)) (EC 2.7.11.4) ... vezivanje mitogen-aktivirane proteinske kinaze kinaze. • vezivanje metalnog jon. • aktivnost proteinske heterodimerizacije. ... P38 mitogenom-aktivirani protein (MAPK11, MAPK13, MAPK14) ... Protein kinaza C (EC 2.7.11.13). Protein kinaza C, Protein ... Receptor protein serin/treonin kinaza (EC 2.7.11.30). Koštani morfogenetski proteinski receptori (BMPR1, BMPR1A, BMPR1B, BMPR2 ...
"Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6". The ... "Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 (MAPKK 6) or MAPK/ERK kinase 6 is ... protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • protein ...
... "p38α Isoform Mxi2 Binds to Extracellular Signal-Regulated Kinase 1 and 2 Mitogen-Activated Protein Kinase and Regulates Its ... protein tyrosine kinase activity. • nucleotide binding. • MAP kinase kinase activity. • protein kinase activity. • protein ... MAP2K1 is also known as MEK1 (see Mitogen-activated protein kinase kinase). MEK1 is a meiotic chromosome-axis-associated kinase ... "Entrez Gene: MAP2K1 mitogen-activated protein kinase kinase 1".. *^ a b Goldfarb T, Lichten M (2010). "Frequent and efficient ...
mitogen-activated protein kinase p38 binding. • FK506 binding. • transcriptional activator activity, RNA polymerase II distal ... Nuclear factor of activated T-cells, cytoplasmic 1 is a protein that in humans is encoded by the NFATC1 gene.[5] ... Porter CM, Havens MA, Clipstone NA (Feb 2000). "Identification of amino acid residues and protein kinases involved in the ... NFATC1, NF-ATC, NFAT2, NFATc, NF-ATc1.2, nuclear factor of activated T-cells 1, nuclear factor of activated T cells 1. ...
... there are three p38-type kinases in Drosophila, Mpk2(p38a), p38b and p38c). The single ERK5 protein appears to fill a very ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ... MAP kinase kinase kinase (MAP3K or MKKK). *MAP kinase kinase kinases *MAP3K1 ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ...
P38 mitogen-activated protein *MAPK11. *MAPK13. *MAPK14. MAP3K (EC 2.7.11.25). *MAP kinase kinase kinases *MAP3K1 ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... kinase activity. • protein binding. • RNA polymerase II carboxy-terminal domain kinase activity. • ATP binding. • protein ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ...
Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH (2001). "Mitogen-activated protein (MAP) kinase ... Aktivatori p38 (MKK3 i MKK6), JNK (MKK4 i MKK7), i ERK (MEK1 i MEK2) kinaza definišu nezavisne MAP kinazne puteve prenosa ... Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 izd.). Wiley- ... Nicholas C. Price, Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins ( ...
Mitogen-activated protein kinases (MAPKs). respond to extracellular stimuli (mitogens) and regulate various cellular activities ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... kinases function as mitogen-activated kinases downstream from cell surface receptors that activate phosphoinositide 3-kinase. ... Protein kinase C ('PKC'). is actually a family of protein kinases consisting of ~10 isozymes. They are divided into three ...
P38 mitogen-activated protein *MAPK11. *MAPK13. *MAPK14. MAP3K (EC 2.7.11.25). *MAP kinase kinase kinases *MAP3K1 ... protein kinase activity. • cAMP-dependent protein kinase activity. • ADP binding. • AMP-activated protein kinase activity. • ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... protein binding. • cAMP-dependent protein kinase regulator activity. • protein kinase binding. • ATP binding. • adenyl ...
p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress ... p38+Mitogen-Activated+Protein+Kinases at the US National Library of Medicine Medical Subject Headings (MeSH) P38mapkPathway p38 ... MKK3 and SEK activate p38 MAP kinase by phosphorylation at Thr-180 and Tyr-182. Activated p38 MAP kinase has been shown to ... a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity". The Journal of ...
B) All four p38 MAP kinase isoforms phosphorylate NFATc4 in vitro. Four different p38 MAP kinase isoforms (p38α, p38β2, p38γ, ... Here we demonstrate that NFATc4 is phosphorylated by p38 mitogen-activated protein (MAP) kinase but not by JNK. The p38 MAP ... Phosphorylation of NFATc4 by p38 mitogen-activated protein kinases.. Yang TT1, Xiong Q, Enslen H, Davis RJ, Chow CW. ... Immune complex kinase assays were performed by using p38α MAP kinase activated with (+) and without (−) the MKK6-Glu mutant. ...
The structure of mitogen-activated protein (MAP) kinase p38 has been solved at 2.1-Å to an R factor of 21.0%, making p38 the ... The structure of mitogen-activated protein kinase p38 at 2.1-Å resolution. Zhulun Wang, Paul C. Harkins, Richard J. Ulevitch, ... mitogen-activated protein;. MEK,. MAP/ERK kinase;. JNK,. c-Jun N-terminal kinase. ... The structure of mitogen-activated protein kinase p38 at 2.1-Å resolution ...
p38 Mitogen-activated protein kinase regulates chamber-specific perinatal growth in heart. ... p38 Mitogen-activated protein kinase regulates chamber-specific perinatal growth in heart. ... This chamber-specific growth pattern was associated with a selective activation of p38 mitogen-activated protein kinase (MAPK) ... Whole-genome rVISTA analysis of the differentially expressed genes in the P1 and P3 p38-cdKO RV vs. the control RV. The top 20 ...
Find out what is the full meaning of p38 mitogen-activated protein kinases on Abbreviations.com! Protein Kinase C is one ... Looking for the definition of p38 mitogen-activated protein kinases? ... What does p38 mitogen-activated protein kinases mean?. p38 Mitogen-Activated Protein Kinases. A mitogen-activated protein ... Know what is p38 mitogen-activated protein kinases? Got another good explanation for p38 mitogen-activated protein kinases? ...
MITOGEN-ACTIVATED PROTEIN KINASE 111,2-Ethanediol4-methyl-n-[3-(4-methyl-1h-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4- ... 3GP0: Crystal Structure Of Human Mitogen Activated Protein Kinase 11 (p38 Beta) In Complex With Nilotinib. ...
p38α, p38β, p38γ, and p38δ are four isoforms of p38 mitogen-activated protein (MAP) kinase (MAPK) involved in multiple cellular ... The family of p38 mitogen-activated protein (MAP) kinases (MAPKs) include p38α, β, δ, and γ isoforms. The four p38 MAPK ... Differentiation stage-specific activation of p38 mitogen-activated protein kinase isoforms in primary human erythroid cells. ... Differentiation stage-specific activation of p38 mitogen-activated protein kinase isoforms in primary human erythroid cells ...
Human serotonin transporter variants display altered sensitivity to protein kinase G and p38-mitogen-activated protein kinase. ... 1998) Extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases regulate inducible nitric ... Previous reports demonstrated that SB203580 does not inhibit protein kinase A, protein kinase C, or other mitogen-activated ... 2001) The p38 mitogen-activated protein kinase is involved in associative learning in rabbits. J Neurosci 21:5513-5519. ...
Jin SX, Zhuang ZY, Woolf CJ, Ji RR (2003) p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in ... c-Jun N-terminal kinase, p38, and ERK5/big mitogen-activated protein kinase 1] are abundant in signal transduction pathways and ... Protein kinase modulation of dendritic K+ channels in hippocampus involves a mitogen-activated protein kinase pathway. J ... Voltage-Gated Sodium Channel Nav1.6 Is Modulated by p38 Mitogen-Activated Protein Kinase. Ellen K. Wittmack, Anthony M. Rush, ...
It will look,in particular, at a protein enzyme called p38 mitogenactivated protein kinase (p38 MAPK for short)which controls ... p38 MitogenActivated Protein Kinase (MAPK) and Steroid Insensitivity in Asthma. The safety and scientific validity of this ... We also wish to find out whether any specific inhibitors of p38 MAPK can improve severe asthma by improving the effects of ... 1. Differences in activity and downstream activity of the p38 MAPK activity in macrophages or PBMCs between those from severe ...
Furthermore, STS stimulation induced phosphorylation of p38 mitogen-activated protein kinase (MAPK). Inhibition of p38 MAPK ... Staurosporine Induces Platelet Apoptosis Through p38 Mitogen-Activated Protein Kinase Signaling Pathway.. [Lili Zhao, Guoyuan ... These data indicate that STS induces platelet apoptosis via the p38 MAPK signaling pathway. These findings suggest that ...
... huge efforts have been made to develop inhibitors of p38 MAPK with the intent to modu … ... Since the identification of the p38 mitogen-activated protein kinase (MAPK) as a key signal-transducing molecule in the ... The p38 mitogen-activated protein kinase signaling cascade in CD4 T cells Arthritis Res Ther. 2006;8(2):205. doi: 10.1186/ ... Since the identification of the p38 mitogen-activated protein kinase (MAPK) as a key signal-transducing molecule in the ...
Selective activation and functional significance of p38α mitogen-activated protein kinase in lipopolysaccharide-stimulated ... Selective activation and functional significance of p38α mitogen-activated protein kinase in lipopolysaccharide-stimulated ... We investigated the MAPk kinase (MKK) that activates p38 MAPk in response to LPS, the p38 MAPk isoforms that are activated as ... Of p38 MAPk isoforms studied, only p38α and p38δ were detected in neutrophils. LPS stimulation selectively activated p38α. ...
EFFECT OF N-ACETYLCYSTEINE ON HYPEROXIA-INDUCED LUNG INJURY AND ITS INTERACTION WITH P38 MITOGEN-ACTIVATED PROTEIN KINASE ... EFFECT OF N-ACETYLCYSTEINE ON HYPEROXIA-INDUCED LUNG INJURY AND ITS INTERACTION WITH P38 MITOGEN-ACTIVATED PROTEIN KINASE ... EFFECT OF N-ACETYLCYSTEINE ON HYPEROXIA-INDUCED LUNG INJURY AND ITS INTERACTION WITH P38 MITOGEN-ACTIVATED PROTEIN KINASE ... EFFECT OF N-ACETYLCYSTEINE ON HYPEROXIA-INDUCED LUNG INJURY AND ITS INTERACTION WITH P38 MITOGEN-ACTIVATED PROTEIN KINASE ...
Crystal Structure of Human Mitogen Activated Protein Kinase 11 (p38 beta) in complex with Nilotinib. *DOI: 10.2210/pdb3GP0/pdb ... Crystal Structure of Human Mitogen Activated Protein Kinase 11 (p38 beta) in complex with Nilotinib. Filippakopoulos, P., Barr ... Mitogen-activated protein kinase 11. A. 348. Homo sapiens. Mutation(s): 0 Gene Names: MAPK11, PRKM11, SAPK2, SAPK2B. EC: 2.7. ...
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. ... The Role of p38 Mitogen-Activated Protein Kinase in IL-1β Transcription ...
TNFalpha increased the activity of the p38 substrate MAP kinase-activated-protein (MAPKAP) kinase 2 and the subsequent ph … ... alpha was found to stimulate the p38 mitogen activated protein (MAP) kinase signalling cascade in human umbilical vein ... p38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level Biochem Biophys ... The cytokine tumor necrosis factor (TNF) alpha was found to stimulate the p38 mitogen activated protein (MAP) kinase signalling ...
We hypothesize that p38 pathway is altered in w-fb.MethodsW-fb were isolated from venous ulcers and n-fb from the ipsilateral ... W-fb treated with bFGF demonstrated decreased p38. TNF-α and IL-1β significantly increase p38 expression.ConclusionsMAPK p38 is ... p38 inhibitor). Fibroblasts were treated with bFGF, TNF-a, and IL-1 and p38 expression analyzed.ResultsPhosphorylated p38 ... Regulation of w-fb proliferation is influenced by p38. Altering the p38 pathway in vivo with growth factors or cytokine ...
The phosphorylation of p38 MAPK was assessed by western blotting. The results showed that AME was not toxic to macrophages. The ... These effects may be mediated by p38 MAPK and the NF-κB pathway. The results suggest that AME can inhibit AGE-induced ... inflammatory cytokine production to down-regulate macrophage-mediated inflammation via p38 MAPK and NF-κB signaling pathways ... Astragalus membranaceus Inhibits Inflammation via Phospho-P38 Mitogen-Activated Protein Kinase (MAPK) and Nuclear Factor (NF)- ...
We previously showed that H5N1/97 hyperinduces tumor necrosis factor (TNF)-alpha through p38 mitogen activated protein kinase ( ... We investigated the roles of protein phosphatases including MAPK phosphatase-1 (MKP-1) and protein phosphatase type 2A (PP2A) ... We demonstrate that H9N2/G1 virus activated p38MAPK and hyperinduced TNF-alpha production in PBMac when compared with H1N1 ... Here we hypothesize that protein phosphatases are involved in the regulation of cytokine expressions during influenza virus ...
P. A. Detmers, D. Zhou, E. Polizzi et al., "Role of stress-activated mitogen-activated protein kinase (p38) in β2- integrin- ... S. Zhang, M. Rahman, S. Zhang et al., "p38 Mitogen-activated protein kinase signaling regulates streptococcal M1 protein- ... kinase, and p38 mitogen-activated protein kinase in Fc receptor-mediated signaling of chicken heterophil degranulation," ... S. L. Pan, K. Y. Tao, J. H. Guh et al., "The p38 mitogen-activated protein kinase pathway plays a critical role in PAR2-induced ...
The p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and ... two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. Expression of activated MKK3 and MKK6 in cultured cells ... MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway.. ... The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the ...
If patients could recognise themselves, or anyone else could recognise a patient from your description, please obtain the patients written consent to publication and send them to the editorial office before submitting your response [Patient consent forms] ...
... mitogen-activated protein kinases (c-Jun N-terminal kinases and p38 mitogen-activated protein kinases) in the myocardium. Circ ... induction of p38 mitogen-activated protein kinase activation and Hsp27 phosphorylation via a tyrosine kinase- and protein ... Role of p38 Mitogen-Activated Protein Kinases in Preconditioning. A Detrimental Factor or a Protective Kinase?. Peipei Ping, ... In this context, the p38 mitogen-activated protein kinases (MAPKs), a family of stress-activated MAPKs,2 3 have been examined ...
Influence of electroacupuncture on p38-mitogen activated protein kinase in substantia nigra cells of rats with Parkinson ... To explore the role of inflammatory reaction mediated by p38-mitogen activated protein kinase (p38-MAPK) signal path on ... To explore the role of inflammatory reaction mediated by p38-mitogen activated protein kinase (p38-MAPK) signal path on ... p38 Mitogen-Activated Protein Kinases. Pub Type(s). English Abstract. Journal Article. Research Support, Non-U.S. Govt. ...
... protein kinase A; PKC, protein kinase C; MAPK, mitogen-activated protein kinase; CREB, CRE-binding protein; ATF, activating ... The Involvement of Tyrosine Kinases, Cyclic AMP/Protein Kinase A, and p38 Mitogen-Activated Protein Kinase in IL-13-Mediated ... The Involvement of Tyrosine Kinases, Cyclic AMP/Protein Kinase A, and p38 Mitogen-Activated Protein Kinase in IL-13-Mediated ... The Involvement of Tyrosine Kinases, Cyclic AMP/Protein Kinase A, and p38 Mitogen-Activated Protein Kinase in IL-13-Mediated ...
... p38 mitogen-activated protein kinase inhibition improves cardiac function and attenuates left ventricular remodeling following ... The aim of this study was to examine the effect of the p38 mitogen-activated protein kinase (MAPK) inhibitor, RWJ-67657 (RWJ), ... TY - JOUR T1 - p38 mitogen-activated protein kinase inhibition improves cardiac function and attenuates left ventricular ... p38 mitogen-activated protein kinase inhibition improves cardiac function and attenuates left ventricular remodeling following ...
Irisin Stimulates Browning of White Adipocytes Through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase ... Irisin Stimulates Browning of White Adipocytes Through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase ... Irisin Stimulates Browning of White Adipocytes Through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase ... Irisin Stimulates Browning of White Adipocytes Through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase ...
... and p38 MAPK.35 The p38 MAPK group consists of four isoforms: p38α, p38β, p38γ, and p38δ, with p38α and p38β expressed ... Hongo A, Okumura N, Nakahara M, Kay EP, Koizumi N. The effect of a p38 Mitogen-activated protein kinase inhibitor on cellular ... Iwasa H, Han J, Ishikawa F. Mitogen-activated protein kinase p38 defines the common senescence-signalling pathway. Genes Cells ... Effect of a p38 Mitogen-Activated Protein Kinase Inhibitor on Corneal Endothelial Cell Proliferation ...
Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for activation of p38α and p38δ MAPK isoforms by TGF-β1 in ... p38 Mitogen-activated protein kinase mediates cell death and p21-activated kinase mediates cell survival during ... We identify mitogen-activated protein kinase (MAPK) kinase 3 (MKK3) as a key activator of p38 MAPK in glioma; MKK3 activation ... MAP-ing glioma invasion: Mitogen-activated protein kinase kinase 3 and p38 drive glioma invasion and progression and predict ...
  • Persistent activation of the p38 MAPK pathway in muscle satellite cells (muscle stem cells) due to ageing, impairs muscle regeneration. (wikipedia.org)
  • Similar to the SAPK/JNK pathway, p38 MAP kinase is activated by a variety of cellular stresses including osmotic shock, inflammatory cytokines, lipopolysaccharides (LPS), Ultraviolet light, and growth factors. (wikipedia.org)
  • KOR activation of a MAPK pathway is one possible mechanism for the long-lasting effects of repeated stress, and in the present study, we directly assessed the role of p38 MAPK activation in mediating these behavioral responses to KOR activation. (jneurosci.org)
  • Staurosporine Induces Platelet Apoptosis Through p38 Mitogen-Activated Protein Kinase Signaling Pathway. (sigmaaldrich.com)
  • These data indicate that STS induces platelet apoptosis via the p38 MAPK signaling pathway. (sigmaaldrich.com)
  • We investigated the MAPk kinase (MKK) that activates p38 MAPk in response to LPS, the p38 MAPk isoforms that are activated as part of this pathway, and the functional responses affected by p38 MAPk activation. (jci.org)
  • These findings support a pathway by which LPS stimulation of neutrophils results in activation of MKK3, which in turn activates p38α MAPk, ultimately regulating adhesion, NF-κB activation, enhanced gene expression of TNF-α, and regulation of TNF-α synthesis. (jci.org)
  • We hypothesize that p38 pathway is altered in w-fb. (ovid.com)
  • Altering the p38 pathway in vivo with growth factors or cytokine inhibition may improve fibroblast proliferation and venous ulcer healing. (ovid.com)
  • These effects may be mediated by p38 MAPK and the NF-κB pathway. (mdpi.com)
  • MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. (uniprot.org)
  • The p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and environmental stress. (uniprot.org)
  • These data demonstrate that the nucleus is one target of the p38 MAP kinase signal transduction pathway. (uniprot.org)
  • The role of the p38 MAPK signaling pathway in the early phase of preconditioning has been more extensively investigated. (ahajournals.org)
  • However, inhibition of p38 MAPK had no effect on either the IL-13-increased intracellular cAMP or the exogenous cAMP-induced arginase activation, suggesting that p38 MAPK signaling is parallel to the cAMP/PKA pathway. (jimmunol.org)
  • The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription. (uniprot.org)
  • The MKK3/6 pathway is reported as the major activator of p38α and has been described to be autoactivated through interaction with TAB1 in mouse embryonic fibroblasts ( 8 ). (aacrjournals.org)
  • In breast cancer, the MKK3/6 pathway, activated through H-Ras, induces the invasive phenotype. (aacrjournals.org)
  • Collectively, our results indicate that transcriptional activation of Nrf2/ARE is critical in sulforaphane-mediated induction of HO-1, which can be modulated in part by the blockade of p38 MAPK signaling pathway. (aacrjournals.org)
  • These observations identify Rit as a downstream target of IFNγ and suggest that a novel IFNγ-Rit-p38 signaling pathway contributes to dendritic retraction and may, therefore, represent a potential therapeutic target in diseases with a significant neuroinflammatory component. (ovid.com)
  • However, glucocorticoids also posttranscriptionally repress a number of proinflammatory genes, several of which are known targets of the p38 pathway ( 3 , 26 , 48 , 60 , 67 ). (asm.org)
  • Activation and inhibition experiments demonstrated that protein kinase A and p38 participate sequentially upstream of the NHE1 in regulating the paclitaxel-induced apoptotic pathway. (aacrjournals.org)
  • To investigate intracellular pathway transducing RAGE activation by Aβ, we used inhibitors of stress activated kinases. (ku.edu)
  • In this study, we show that sphingosine induces death receptor-independent caspase-8 activation and apoptotic cell death via p38 mitogen-activated protein kinase (MAPK) activation and that suppression of the MAPK/extracellular signal-regulated kinase (ERK) kinase/ERK pathway by protein phosphatase 2A (PP2A) is required for p38 MAPK activation. (aacrjournals.org)
  • For instance, sphingosine treatment results in complete inhibition of extracellular signal-regulated kinase (ERK) activity in leukemic and solid cancer cells ( 5 - 7 ), indicating that suppression of this pathway is required for sphingosine-induced apoptosis. (aacrjournals.org)
  • A close relationship exists between the ERK pathway and the p38 MAPK or JNK pathway in a variety of eukaryotic cells ( 8 - 11 ). (aacrjournals.org)
  • Interestingly, deprivation of neurotrophic factors or UV irradiation not only activates stress kinase cascades but also leads to dramatic inhibition of the ERK pathway ( 12 ). (aacrjournals.org)
  • Thus, it seems that the cell fate (i.e., death or survival) is decided by a critical balance between the ERK pathway and the JNK or p38 MAPK pathway. (aacrjournals.org)
  • Lipopolysaccharide (LPS) activated the p38 MAPK signaling pathway in BMM phi by sequential phosphorylation of MAPK kinase 3/6, p38 MAPK, and activating transcription factor-2. (semanticscholar.org)
  • Our findings thus suggest that the p38 MAPK signaling pathway plays a key role in H. pylori lipopolysaccharide-induced gastric mucosal inflammatory responses leading to up-regulation of apoptotic events and induction of NOS-2 expression. (brillonline.com)
  • It has been suggested that all triggers are linked to a common final pathway, for example, activation of protein kinase C (PKC) and/or the mitogen-activated kinases (MAPKs), in particular p38 MAPK. (sun.ac.za)
  • These include the Stat-pathway, whose function is essential for transcriptional activation of IFN-sensitive genes, and the insulin receptor substrate pathway, which regulates downstream activation of the phosphatidyl-inositol-3′ kinase. (northwestern.edu)
  • The p38 Map kinase pathway appears to play a very important role in the induction of IFN responses. (northwestern.edu)
  • Extensive studies have shown that p38 plays a critical role in Type I IFN-dependent transcriptional regulation, without modifying activation of the Stat-pathway. (northwestern.edu)
  • As Type I IFNs regulate gene expression for proteins with antiviral properties, it is not surprising that pharmacological inhibition of the p38 pathway blocks induction of IFNα-antiviral responses. (northwestern.edu)
  • Inhibition of breast cancer cell invasion by melatonin is mediated through regulation of the p38 mitogen-activated protein kinase signaling pathway. (greenmedinfo.com)
  • These data suggested that insulin's effects on neuronal survival are mediated by inhibition of a p38-mediated apoptotic pathway. (elsevier.com)
  • PD98059 did not influence insulins ability to block apoptosis, indicating that the extracellular signal-regulated kinase pathway does not mediate insulin's survival effects. (elsevier.com)
  • These data further support the role of p38 in cellular apoptosis and support the hypothesis that insulin promotes cell survival, at least in part, by inhibiting the p38 pathway. (elsevier.com)
  • These results suggested that PI3K/p38 MAPK/Rac pathway was present in the activation of NADPH oxidase in bovine neutrophils. (elsevier.com)
  • 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)
  • 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)
  • Recent studies from the PMK-1 pathway are suggestive of a job for proteins kinase C-dependent signaling upstream of TIR-1 [19],[20]. (bcl-2-protein.com)
  • The p38 mitogen-activated protein kinase (MAPK) pathway plays an integral role in pathological glial activation and neuroinflammatory responses. (boothampitheatre.com)
  • However, involvement of the p38 MAPK pathway in cPLA 2 activation and of reactive oxygen species in expression of p38 MAPK/cPLA 2 after ischemia-reperfusion injury in the brain remains unclear. (elsevier.com)
  • These findings suggest that the p38 MAPK/cPLA 2 pathway may promote BBB disruption with secondary vasogenic edema and that superoxide anions can stimulate this pathway after ischemia-reperfusion injury. (elsevier.com)
  • 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. (mindunwindart.com)
  • Our findings reveal a unique cellular pathway involving the p38 mitogen-activated protein kinase (p38MAPK)-mediated phosphorylation of ERα at Ser-294 that specifies its turnover by the SCF(Skp2) proteasome complex. (semanticscholar.org)
  • The involvement of AU-rich element-binding proteins in p38 mitogen-activated protein kinase pathway-mediated mRNA stabilisation. (ox.ac.uk)
  • The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in the post-transcriptional regulation of inflammatory genes. (ox.ac.uk)
  • AREs act as mRNA instability determinants but also confer stabilisation of the mRNA by the p38 pathway. (ox.ac.uk)
  • The p38 mitogen-activated protein kinase (MAPK) signaling pathway regulates a wide range of inflammatory responses in many different cells. (elsevier.com)
  • Teng, Che M. / The p38 mitogen-activated protein kinase pathway plays a critical role in PAR2-induced endothelial IL-8 production and leukocyte adhesion . (elsevier.com)
  • For example, the mitogen-activated protein kinase (MAPK) p38 pathway mediates stabilization of tumor necrosis factor alpha (TNF-alpha) mRNA in myeloid cells stimulated with bacterial lipopolysaccharide (LPS). (ox.ac.uk)
  • The p38 pathway is required for the induction of TNF-alpha RNA-binding activity and for the expression of TTP protein and mRNA. (ox.ac.uk)
  • Our findings demonstrate a direct link between a specific signal transduction pathway and a specific RNA-binding protein, both of which are known to regulate TNF-alpha gene expression at a posttranscriptional level. (ox.ac.uk)
  • In these experiments, we looked at the effect of Ang-II on the production of VEGF, and investigated whether VEGF production depends on the p38 mitogen activated protein kinase (MAPK) pathway in cultured mouse podocytes. (elsevier.com)
  • Taken together, these results suggest that Ang-II stimulates the synthesis of VEGF in podocytes and the production of VEGF induced by Ang-II is mediated, in part, through the activation of the p38 MAPK pathway. (elsevier.com)
  • The p38 MAPK pathway has been implicated to play an important role in endothelial cell migration because inhibiting p38 MAPK activity down-regulates vascular endothelial growth factor (VEGF)-stimulated migration. (elsevier.com)
  • Currently, the signaling components in the p38 MAPK activation pathway and especially the mechanisms responsible for p38 MAPK-regulated endothelial cell migration are not well understood. (elsevier.com)
  • By using dominant negative forms of signaling components in the p38 MAPK pathway, we identified that a regulatory pathway consisting of MKK3-p38α/γ-MAPK-activated protein kinase 2 participated in VEGF-stimulated migration. (elsevier.com)
  • These results thus suggest that the p38 MAPK pathway participates in endothelial cell migration by regulating uPA expression. (elsevier.com)
  • It was concluded that the p38 MAPK pathway predominantly regulates deadenylation, rather than decay of the mRNA body, and this provides an explanation for why p38 MAPK regulates mRNA stability in some situations and translation in others. (ox.ac.uk)
  • These results indicate that NF-kappaB and p38 MAPK play an important role in TNF-activated signalling pathway regulating eotaxin release by eosinophils. (edu.hk)
  • Inhibition of NF-κB activation by SB203580-induced inhibition of p38α MAPk. (jci.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)
  • 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)
  • 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)
  • This stimulation was blocked almost completely by the specific p38 MAP kinase inhibitor SB203580. (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)
  • The relation between p38 and w-fb proliferation was assessed with SB203580 (p38 inhibitor). (ovid.com)
  • The induction of arginase was abolished by a protein kinase A (PKA) inhibitor, KT5720, and was down-regulated by tyrosine kinase inhibitors and a p38 MAPK inhibitor, SB203580. (jimmunol.org)
  • Inhibition of the p38 MAPK by SB203580 and ERK by U0126 abolished the upregulatory effect of irisin on UCP-1. (diabetesjournals.org)
  • Thus, the p38 MAPK inhibitor SB203580 and SB202190 abolished insulin activation of NE transport yet failed to impact basal NET activity. (aspetjournals.org)
  • This stabilization was blocked by SB203580, an inhibitor of p38, and by two different dominant negative forms of MAPK-activated protein kinase 2 (MAPKAPK-2), a kinase lying downstream of p38. (asm.org)
  • Phosphorylation of ERα on Ser-118 was due to p38 MAP kinase (p38 MAPK) as, it was inhibited by SB203580 and overexpression of dominant-negative p38α MAPK. (ahajournals.org)
  • Superoxide production was induced by stimulation with serum-opsonized zymosan (OZ) and attenuated by p38 MAPK inhibitor, SB203580. (elsevier.com)
  • Furthermore, SB203580 abolished the OZ-elicited activation of Rac, which was assessed by detecting the GTP-bound form of this protein. (elsevier.com)
  • The effect on cells viability and Caspase-3 activity of SB203580, a specific inhibitor of p38 MAPK , were also examined. (bvsalud.org)
  • Both PAR2-AP and the endogenous PAR2 activator trypsin caused concentration- and time-dependent increase in endothelial IL-8 production, and this effect was concentration dependency and selectively attenuated by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. (elsevier.com)
  • In addition, to investigate the role of p38 MAPK in Ang-II-induced VEGF synthesis, podocytes were pretreated with or without the p38 MAPK inhibitor, SB203580 for 24 h to observe whether Ang-II-mediated VEGF synthesis was inhibited by blocking p38 MAPK. (elsevier.com)
  • The addition of SB203580 led to a marked inhibition of the increased VEGF mRNA and protein production induced by Ang-II in a dose-dependent manner. (elsevier.com)
  • In further studies, we showed that a minimum of a 10-h treatment with SB203580 (specific p38 MAPK inhibitor) was needed to block VEGF-stimulated migration, suggesting an indirect role of p38 MAPK in this cellular event. (elsevier.com)
  • These studies demonstrated the involvement of Jak/Stat, Shc/Grb2/Ras, Gab1/2, extracellular response kinase (ERK), and phosphatidylinositol 3-kinase (PI3-kinase)/protein kinase B (PKB) pathways in the regulation of proliferation and cell viability ( 16 - 22 ). (pnas.org)
  • It will look,in particular, at a protein enzyme called p38 mitogen−activated protein kinase (p38 MAPK for short)which controls the activation of several important pathways in the cell. (clinicaltrials.gov)
  • The intracellular target of these compounds is the p38 MAPK ( 22 ), a key component in stress-induced signal transduction pathways. (jimmunol.org)
  • The results suggest that AME can inhibit AGE-induced inflammatory cytokine production to down-regulate macrophage-mediated inflammation via p38 MAPK and NF-κB signaling pathways and indicate that AME could be an immunoregulatory agent against AGE-induced inflammation in diabetes. (mdpi.com)
  • The data are compatible with the hypothesis that p38 MAPKs may mediate the protective signaling pathways or function as protective kinases during the late phase of pharmacological preconditioning. (ahajournals.org)
  • This effect was possibly mediated by irisin-induced phosphorylation of the p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-related kinase (ERK) signaling pathways. (diabetesjournals.org)
  • In summary, our data suggest that irisin can potentially prevent obesity and associated type 2 diabetes by stimulating expression of WAT browning-specific genes via the p38 MAPK and ERK pathways. (diabetesjournals.org)
  • We identified distinct phosphatidylinositol 3-OH kinase (PI3K)-linked pathways supporting basal and insulin-triggered NE transport in the human noradrenergic neuroblastoma, SK-N-SH. (aspetjournals.org)
  • Our findings establish two distinct pathways for regulation of NE uptake involving PI3K, one linked to transporter trafficking and a second linked to Ca 2+ -dependent, p38 MAPK phosphorylation that promotes activation of cell surface NETs. (aspetjournals.org)
  • To investigate the influence of p38 MAPK inhibition on acute phase protein (APP) production, which is dependent on both JAK/STAT and p38 MAPK pathways. (bmj.com)
  • In particular, whereas the MAP kinase and PKA pathways have been examined in several studies, no clear interaction has been yet been established between them for paclitaxel-induced apoptosis. (aacrjournals.org)
  • In this study, we tested the hypothesis that mitogen-activated protein kinase (MAPK) signaling pathways are involved in this process. (aspetjournals.org)
  • These results indicate that extracellular adenosine can regulate ERK, c-Jun N-terminal kinase, and p38 MAPK signaling cascades and that activation of ERK and p38 MAPK pathways are essential steps in adenosine A 2B receptor-dependent stimulation of IL-8 production in HMC-1. (aspetjournals.org)
  • Our findings clearly imply that activation of p38 MAPK promotes death receptor-independent activation of caspase-8 and apoptotic cell death pathways, thus providing a novel cellular mechanism for the anticancer activity of sphingolipid metabolites. (aacrjournals.org)
  • and involved p38 and c-Jun amino-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, as further confirmed by OCP crystal-induced p38 and JNK MAPK phosphorylation. (inserm.fr)
  • Taken together, our data suggest that the transcriptional inducible NOS response to OCP crystals involved both the p38 and the JNK MAPK pathways, probably under the control of activator protein-1. (inserm.fr)
  • Here, using bovine neutrophils we examined the role of p38 mitogen-activated protein kinase (p38 MAPK) in the signaling pathways of the NADPH oxidase activation. (elsevier.com)
  • We transfected hSERT or 10 hSERT coding variants and examined total and surface protein expression, antagonist recognition, and transporter modulation by posttranslational, regulatory pathways. (meta.org)
  • Nonetheless important differences exist among the four members of the p38 group of enzymes, and thus each may have highly specific, individual contributions to biologic events involving activation of the p38 pathways. (scripps.edu)
  • 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. (mindunwindart.com)
  • Vaccinia virus encodes a number of proteins that inhibit and manipulate innate immune signaling pathways that also have a role in virulence. (ul.ie)
  • 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)
  • 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)
  • IL-1beta, an immediate early protein secreted by activated microglia, induces iNOS/NO in C6 astrocytoma cells through p38 MAPK and NF-kappaB pathways. (qxmd.com)
  • Different roles of spinal p38 and c-Jun N-terminal kinase pathways in bee venom-induced multiple pain-related behaviors. (qxmd.com)
  • p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell differentiation, apoptosis and autophagy. (wikipedia.org)
  • Inactivation of p38 activity led to a marked increase in cardiomyocyte proliferation and hypertrophy but diminished cardiomyocyte apoptosis, specifically in the RV. (jci.org)
  • p38α, p38β, p38γ, and p38δ are four isoforms of p38 mitogen-activated protein (MAP) kinase (MAPK) involved in multiple cellular functions such as cell proliferation, differentiation, apoptosis, and inflammation response. (pnas.org)
  • Moreover, our data indicate that activation of p38α does not induce apoptosis or promote proliferation of erythroid progenitors. (pnas.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)
  • Biochemical studies have shown that cell cycle arrest by sulforaphane occurred through an irreversible G 2 -M phase arrest with a reduction of key G 2 -M-regulating proteins ( 7 ), whereas overexpression of Bax, down-regulation of Bcl-2, and activation of caspase-8 and caspase-9 were implicated in sulforaphane-mediated apoptosis ( 8 ). (aacrjournals.org)
  • In MDA-MB-435 cells, paclitaxel treatment stimulated the activity of both protein kinase A and p38, and inhibited the activity of the Na + /H + exchanger isoform 1 (NHE1) with similar IC 50 concentrations as for its activation of apoptosis. (aacrjournals.org)
  • Accumulating evidence suggests a role of mitogen-activated protein kinase (MAPK) in sphingosine-induced apoptosis. (aacrjournals.org)
  • p38 is a member of the mitogen-activated protein (MAP) kinase superfamily activated by stress signals and implicated in cellular processes involving inflammation and apoptosis. (elsevier.com)
  • To better understand the relationship between p38 activity and cell survival, we induced apoptosis in two cell lines and examined the ability of insulin or a specific p38 inhibitor (a pyridinyl imidazole compound PD169316) to block p38 activity and cell death. (elsevier.com)
  • After the removal of serum for 16 h, p38 activity was markedly elevated, and apoptosis increased by 14-16-fold. (elsevier.com)
  • Both insulin and PD169316 markedly blocked the increase in p38 activity and apoptosis. (elsevier.com)
  • The MAP kinase inhibitor, PD98059, had no effect on apoptosis in Rat. (elsevier.com)
  • Kummer, JL, Rao, PK & Heidenreich, KA 1997, ' Apoptosis induced by withdrawal of trophic factors is mediated by p38 mitogen-activated protein kinase ', Journal of Biological Chemistry , vol. 272, no. 33, pp. 20490-20494. (elsevier.com)
  • SNP is really a nitric oxide donor popular to induce neuronal apoptosis, and p38 activation provides previously been implicated to advertise nitric oxide induced neuronal harm (Ghatan et al. (boothampitheatre.com)
  • Furthermore, this study investigated whether p38 MAPK inhibition would cause widespread suppression of the cytokine network in vivo or uncontrolled apoptosis. (ox.ac.uk)
  • In the in vitro study, the p38 MAPKalpha/beta inhibitor reduced production of MCP-1 and IL-6 by TNF-alpha-or IL-1beta-stimulated mesangial cells without any effect on cell viability or apoptosis. (ox.ac.uk)
  • p38 mitogen-activated protein kinase (MAPK) plays an important role in mediating apoptotic processes, however, the roles of this kinase in activating ERS-initiated apoptosis in pressure-overloaded hearts are largely unknown. (elsevier.com)
  • Methods: We clarified the role of p38α MAPK in ERS-associated apoptosis by subjecting transgenic mice displaying cardiac specific dominant negative (DN) mutant p38α MAPK over-expression to seven day pressure overload. (elsevier.com)
  • Interestingly, increased myocardial apoptosis and the up-regulation of CCAAT/enhancer binding protein homology protein (CHOP) expression compared with those in the sham mice were found in the aortic-banded WT mice, but not in the DN p38α mice. (elsevier.com)
  • To explore the function of Caspase-3 and p38 MAPK in MMT-induced apoptosis in PC-3M cells . (bvsalud.org)
  • Caspase-3 and p38 MAPK are involved in MMT-induced PC-3M cells apoptosis . (bvsalud.org)
  • p38 MAPK also mediates T-cell differentiation and apoptosis by regulating gamma interferon production (27, 34). (mindunwindart.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)
  • 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)
  • Indomethacin induces apoptosis in 786-O renal cell carcinoma cells by activating mitogen-activated protein kinases and AKT. (qxmd.com)
  • Role of antisense oligodeoxynucleotide of inducible nitric oxide synthase in the apoptosis and p-p38 MAPK signal transduction in rat neurons after spinal cord injury]. (qxmd.com)
  • The family of p38 mitogen-activated protein (MAP) kinases (MAPKs) include p38α, β, δ, and γ isoforms. (pnas.org)
  • Mitogen-activated protein kinases (MAPKs) are expressed in neurons and are activated after injury, for example, after sciatic nerve transection and hypoxia. (jneurosci.org)
  • However, despite the coexpression of mitogen-activated protein kinases (MAPKs) and voltage-gated sodium channels in neurons, phosphorylation and modulation of these channels by MAP kinases have not been investigated. (jneurosci.org)
  • In this context, the p38 mitogen-activated protein kinases (MAPKs), a family of stress-activated MAPKs, 2 3 have been examined as the candidate kinases during preconditioning. (ahajournals.org)
  • If activation of p38 MAPKs is a necessary signaling event for the protection to manifest on day 2, then inhibition of this kinase will lead to the abrogation of late preconditioning. (ahajournals.org)
  • 5 6 7 8 9 10 11 However, the published observations are inconsistent, and the role of p38 MAPKs in early preconditioning seems to be controversial. (ahajournals.org)
  • The two lines of studies performed thus far have sought to determine (1) whether preconditioning induces the activation of p38 MAPKs and (2) whether inhibition of p38 MAPKs abrogates the cardioprotective effect. (ahajournals.org)
  • In the first line of studies, it remains uncertain whether ischemia/reperfusion induces sustained activation of p38 MAPKs. (ahajournals.org)
  • Ischemia stimulus has been shown to induce activation of p38 MAPKs. (ahajournals.org)
  • Several studies 7 12 13 have reported that activation of p38 MAPKs during ischemia is transient and does not correlate with the preconditioning effect, thereby questioning the functional significance of this observation. (ahajournals.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)
  • Regulation of MAPKs involves dynamic interplay between kinases and phosphatases. (aacrjournals.org)
  • 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)
  • However, hereditary evaluation of transcription aspect goals of p38 and JNK MAPKs continues to be tied to lethality of knockouts and feasible redundancy [8], and therefore the id and characterization from the physiologically relevant goals of MAPK signaling in innate immunity continues to be a major problem [9]. (bcl-2-protein.com)
  • This reveals a molecular mechanism whereby poxviruses manipulate TRAF6 to activate MAPKs (which can be proviral) without stimulating antiviral NF B activation. (ul.ie)
  • p38 mitogen-activated proteins kinases (MAPKs) are crucial for innate immune signaling and subsequent cytokine expression in periodontal inflammation and bone tissue destruction. (bio2009.org)
  • p38 MAPK, among three specific classes of MAPKs, is definitely a nexus for sign transduction, playing an essential role in various inflammatory-driven pathological procedures including periodontitis. (bio2009.org)
  • We found that inhibition of p38 MAPK blocked the dynorphin-mediated enhancement of swim stress-induced immobility and blocked the conditioned place aversion induced by κ agonist administration. (jneurosci.org)
  • Inhibition of p38 MAPK activation significantly reduced ΔΨm depolarization and PS exposure in platelets stimulated with STS. (sigmaaldrich.com)
  • Before the role of p38 MAPK in late preconditioning can be definitely established, it is necessary to show that the inhibition of p38 MAPK blocks the protection. (ahajournals.org)
  • Inhibition of p38 MAPK was shown to completely block the cardioprotective phenomenon in several studies, 5 6 8 indicating that activation of p38 MAPK is an essential signaling event in the genesis of preconditioning. (ahajournals.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)
  • Silencing of Rit by RNA interference suppressed IFNγ-elicited activation of p38 MAPK in pheochromacytoma cells, and pharmacological inhibition of p38 MAPK significantly attenuated the dendrite-inhibiting effects of IFNγ in cultured sympathetic and hippocampal neurons without altering signal transducer and activator of transcription 1 activation. (ovid.com)
  • Inhibition of p38 MAPK led to the marked suppression of death receptor-independent caspase-8 activation and subsequent cell death induced by sphingosine. (aacrjournals.org)
  • In addition, to evaluate the role of p38 MAPK in PC protection, the effect of inhibition of p38 MAPK activation, by 8B203580, was determined in adult isolated rat cardiomyocytes as well as in isolated perfused rat hearts. (sun.ac.za)
  • Inhibition of p38 MAPK, but not ERK-1,2, in endothelial cells completely abrogated the stimulation of the mesenchymal stem cell adhesion by von Willebrand factor. (biomedcentral.com)
  • Inhibition of p38 MAPK in mice prevented the progression of collagen-induced arthritis (13) and resulted in a significant decrease in LPS-induced ZLN005 tumor necrosis element (TNF-) launch and neutrophil infiltration into the lungs (37). (mindunwindart.com)
  • Inhibition of p38 MAPK before exposing a cell to stress stimuli has profound anti-inflammatory effects, but little is known about the effects of p38 MAPK inhibition on ongoing inflammatory responses. (elsevier.com)
  • We found that phosphorylation of p38α, MAPK kinase kinase 3/6 and MAPKAP-2 occurs only upon growth factor withdrawal in primary erythroid progenitors. (pnas.org)
  • Furthermore, STS stimulation induced phosphorylation of p38 mitogen-activated protein kinase (MAPK). (sigmaaldrich.com)
  • The phosphorylation of p38 MAPK was assessed by western blotting. (mdpi.com)
  • PI3K activation was found to support phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). (aspetjournals.org)
  • Kinome analysis of PBMCs revealed that HNA1 induced the phosphorylation of p38 mitogen-activated protein kinase, the inhibition of which blocked HNA1-induced cytokine and COX-2 induction. (snfge.org)
  • The aim of the present study was to investigate whether phosphorylation of p38 (p-p38) also mediates mechanical allodynia and thermal hyperalgesia induced by plantar incision. (asahq.org)
  • In this course , the phosphorylation of p38 MAPK could be observed. (bvsalud.org)
  • Western blotting analysis showed that PAR2-AP induced phosphorylation of p38 MAPK and its upstream protein kinase MAPK kinase 3/6 (MKK3/6) in a time-dependent manner. (elsevier.com)
  • Furthermore, stimulation of the cells with Ang-II increased both phosphorylation of p38 MAPK and MAP kinase kinase 3/6 (MKK3/6). (elsevier.com)
  • To investigate whether the phosphorylation of p38 in cerebral ischemia occurs via angiotensin II receptor type 1a (AT1a), we examined the time course of phosphorylation of p38 and proline-rich tyrosine kinase 2 in AT1a knock-out mouse striatal neurons during middle cerebral artery occlusion (MCAO) and reperfusion. (elsevier.com)
  • We demonstrated a delay of phosphorylation of p38 in the reperfusion model of the AT1a knock-out mouse, and detected microglia in the striatum on the ischemic side that were phosphorylated-p38-positive after 71 h of reperfusion in both animals. (elsevier.com)
  • Furthermore, TNF was shown to induce phosphorylation of p38 MAPK time-dependently but not extracellular signal-regulated kinases (ERK). (edu.hk)
  • We show that p38α and p38γ transcripts are expressed in early hematopoietic progenitors as well as in late differentiating erythroblasts, whereas p38δ mRNA is only expressed and active during the terminal phase of erythroid differentiation. (pnas.org)
  • Inhibition of p38α MAPk resulted in a transient decrease in TNF-α mRNA accumulation but persistent loss of TNF-α synthesis. (jci.org)
  • Results showed that IL-13 increased arginase activity through de novo synthesis of the arginase I mRNA and protein. (jimmunol.org)
  • The effects of p38 MAPK inhibition on APP production and mRNA expression in four human hepatoma cell lines was investigated, after stimulation with interleukin (IL)6 and/or IL1β or tumour necrosis factor α. (bmj.com)
  • Production and mRNA expression of CRP and fibrinogen, but not SAA production and mRNA expression, were significantly inhibited by p38 MAPK specific inhibitor in hepatoma cell lines. (bmj.com)
  • A tetracycline-regulated reporter system was used to investigate the regulation of cyclooxygenase 2 (Cox-2) mRNA stability by the mitogen-activated protein kinase (MAPK) p38 signaling cascade. (asm.org)
  • A short (123-nucleotide) fragment of the Cox-2 3′ UTR was necessary and sufficient for the regulation of mRNA stability by the p38 cascade and interacted with a HeLa protein immunologically related to AU-rich element/poly(U) binding factor 1. (asm.org)
  • In a variety of cells treated with different inducing agents, specific inhibitors of p38 block the accumulation of Cox-2 mRNA ( 21 , 29 , 33 , 41 , 43 , 45 ). (asm.org)
  • In HeLa cells stimulated with interleukin 1 (IL-1) and in primary human monocytes stimulated with bacterial lipopolysaccharide inhibition of p38 results in a rapid and specific destabilization of Cox-2 mRNA but has little effect upon Cox-2 transcription ( 12 , 44 ). (asm.org)
  • In the present study, we found that activation of p38 MAPK by anisomycin potentiated induction of CYP2B6 mRNA by CAR ligand in HepG2 cells to levels observed in ligand-treated human primary hepatocytes. (aspetjournals.org)
  • siRNA knockdown of p38 MAPK abrogated the ability of anisomycin to synergistically induce CYP2B6 mRNA. (aspetjournals.org)
  • In HeLa cells the anti-inflammatory glucocorticoid dexamethasone destabilizes Cox-2 mRNA by inhibiting p38 function. (asm.org)
  • Human proximal tubular cells (HK-2) were incubated with human serum albumin (HSA), which induced a dose-dependent increase in fractalkine mRNA associated with increased levels of both membrane-bound and soluble forms of the protein. (asnjournals.org)
  • Similarly, when cells were infected with the recombinant adenovirus expressing dominant negative mutant of the IkB kinase 2, a 55% inhibition of fractalkine mRNA was achieved. (asnjournals.org)
  • To directly test the inflammatory effects of HNA1 and HNA2 on leukocytes, these oxidized albumin forms were prepared ex vivo and their posttranslational modifications monitored by liquid chromatography (LC)-quadrupole time-of-flight/mass spectrometry (MS). HNA1, but not HNA2, increased IL-1β, IL-6, and TNF-α mRNA and protein expression in leukocytes from both healthy volunteers and patients with cirrhosis. (snfge.org)
  • Human umbilical vein endothelial cell lines (ECV304) were cultured in normoxic or hypoxic conditions for 12 approximately 24 h and harvested for determination of VEGF mRNA expression and phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase (p38 MAPK) by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. (docphin.com)
  • One mechanism by which MAPKAPK2 induces TNF- production is usually by stabilizing TNF- mRNA via phosphorylation of the zinc finger protein tristetraprolin (24). (mindunwindart.com)
  • However, it is unclear which protein is responsible for mRNA stabilisation by p38. (ox.ac.uk)
  • This review gives an overview of the major ARE-binding proteins and discusses reasons for and against their involvement in p38-mediated mRNA stabilisation. (ox.ac.uk)
  • Mitogen-activated protein kinase p38 controls the expression and posttranslational modification of tristetraprolin, a regulator of tumor necrosis factor alpha mRNA stability. (ox.ac.uk)
  • The zinc finger protein tristetraprolin (TTP) is expressed in response to LPS and regulates the stability of TNF-alpha mRNA. (ox.ac.uk)
  • Incubation of podocytes with Ang-II induced a rapid increase in VEGF mRNA expression and protein synthesis as well as its transcriptional activity in an Ang-II dose-dependent manner. (elsevier.com)
  • Prior treatment with losartan significantly inhibited VEGF mRNA and protein synthesis induced by Ang-II, which suggests that the AT1 receptor is involved in Ang-II-mediated VEGF synthesis. (elsevier.com)
  • 1999). One essential mechanism where MK2 increases appearance of proinflammatory mediators is normally via concentrating on AU-rich components (ARE) situated in the Rabbit Polyclonal to ADRB2 3 untranslated area from the mRNA via phosphorylation of RNA stability-regulating proteins such as for example tristetraprolin (TTP) (Carballo et al. (bio2009.org)
  • The regulation of deadenylation by p38 MAPK was found to be specific because deadenylation of the beta-globin reporter mRNA either lacking an ARE or containing the c-Myc 3'-untranslated region (which is not p38 MAPK-responsive) was unaffected by p38 MAPK. (ox.ac.uk)
  • Expression was measured at the level of mRNA by reverse-transcriptase PCR and protein by Western blot analysis. (antibody-antibodies.com)
  • p38gamma protein was not detected in any cell type, although p38gamma mRNA was present in endothelial cells. (antibody-antibodies.com)
  • While MAP kinases are selective in their interactions with activators and substrates, they share a common regulatory mechanism, being activated 100- to 1000-fold or more ( 21 - 23 ) by dual phosphorylation on a conserved threonine and a conserved tyrosine residue in the phosphorylation Lip (residues Leu-171-Val-183) near the active site ( 24 ). (pnas.org)
  • The increased p38 MAPK activity was completely abolished when the infarct-sparing effect of CCPA was abrogated by either the protein kinase C (PKC) inhibitor chelerythrine or the tyrosine kinase inhibitor lavendustin A. This is a very provocative study, and it is also the first to demonstrate activation of the p38 MAPK 24 hours after preconditioning. (ahajournals.org)
  • The expression of tyrosine hydroxylase (TH), phosphorylated p38-MAPK, cyclooxygenase-2 (COX-2) in the substantia nigra were detected with immunohistochemical method. (unboundmedicine.com)
  • The activation of arginase was preceded by a transient increase in intracellular cAMP, tyrosine kinase phosphorylation, and p38 mitogen-activated protein kinase (MAPK) activation. (jimmunol.org)
  • Together, these data demonstrate for the first time that IL-13 down-regulates NO production through arginase induction via cAMP/PKA, tyrosine kinase, and p38 MAPK signalings and underline the importance of arginase in the immunosuppressive activity of IL-13 in activated macrophages. (jimmunol.org)
  • Basal and insulin-modulated NET activities were reduced by the tyrosine kinase inhibitor genistein and the PI3K inhibitors wortmannin and LY-294002, but not by the PKC inhibitor staurosporine. (aspetjournals.org)
  • Effects of tyrosine kinase and PI3K inhibitors on basal NET uptake appear to arise from a loss of cell surface NET protein, whereas the p38 MAPK-dependent enhancement of NE transport occurs without a detectable enhancement of surface NET. (aspetjournals.org)
  • This kinase is activated by phosphorylation at threonine and tyrosine residues, catalyzed by the dual-specificity kinase MAPK kinase 6 (MKK6) ( 11 , 23 , 42 ). (asm.org)
  • ERKs are activated by phosphorylation of both conserved threonine and tyrosine residues and inactivated on dephosphorylation by tyrosine and serine-threonine phosphatases ( 15 - 20 ). (aacrjournals.org)
  • p38 is rapidly activated during engagement of the Type I IFN receptor, and such an activation is regulated by the small G-protein Rac1, which functions as its upstream effector in a tyrosine kinase-dependent manner. (northwestern.edu)
  • MKK3 and SEK activate p38 MAP kinase by phosphorylation at Thr-180 and Tyr-182. (wikipedia.org)
  • Phosphorylation of serine and threonine residues by MAPK kinase (MKK) 6 and MKK3 (β isoform is not activated by MKK3), activates all four isoforms leading to transcriptional activation of ATF-2 ( 3 - 5 ). (pnas.org)
  • Although MKK3, MKK4, and MKK6 all activated p38 MAPk in experimental models, only MKK3 was found to activate recombinant p38 MAPk in LPS-treated neutrophils. (jci.org)
  • To test this hypothesis, we constructed expression vectors for activated MKK3 and MKK6, two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. (uniprot.org)
  • Expression of activated MKK3 and MKK6 in cultured cells caused a selective increase in p38 MAP kinase activity. (uniprot.org)
  • MKK3 activation is strongly correlated with p38 activation in vitro and in vivo . (aacrjournals.org)
  • Our findings therefore argue that interference with MKK3 signaling through a novel treatment combination of p38 inhibitor plus temozolomide heightens the vulnerability of glioma to chemotherapy. (aacrjournals.org)
  • For the first time, we report mitogen-activated protein kinase (MAPK) kinase 3 (MKK3) to be up-regulated with glioma invasion in vitro and in vivo . (aacrjournals.org)
  • Among the upstream kinases, although MKK3 was not involved in suppression of ARE by any of p38 MAPK isoforms, MKK6 selectively suppressed ARE by p38γ or p38δ, but not by p38α or p38β. (aacrjournals.org)
  • Importantly, sulforaphane not only activated MAP/extracellular signal-regulated kinase (ERK) kinases 1/2 and ERK1/2, but also strongly suppressed anisomycin-induced activation of p38 MAPK isoforms by blocking phosphorylation of upstream kinases, MKK3/6. (aacrjournals.org)
  • p38delta can be activated by MKK3 and MKK6, known activators of the other isoforms. (scripps.edu)
  • Furthermore, introduction of dominant-negative vectors targeting p38 MAPK, MKK3, and MKK6 abolished PAR2-AP-mediated IL-8 production and cell adhesion function. (elsevier.com)
  • 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)
  • We applied the animal model of H. pylori -induced gastritis to study the effect of a specific inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), SB 203580, on the mucosal apoptotic processes, and the expression of inducible nitric oxide synthase (NOS-2) activity and soluble tumor necrosis factor- α (TNF- α ). (brillonline.com)
  • VX-745 is a potent and selective inhibitor of p38 with IC50 of 10 nM, 22-fold greater selectivity versus p38 and no inhibition to p38. (csnpharm.com)
  • SKF-86002 is a potent inhibitor of p38 MAP kinase with IC50 of 0.5-1 M and inhibits LPS-induced IL-1 and TNF- production in human monocytes (IC50 1 M). (csnpharm.com)
  • SD-169 is an orally active ATP-competitive inhibitor of p38α MAPK, with an IC50 of 3.2 nM. (csnpharm.com)
  • SB202190, an inhibitor of p38 MAPK was able to blunt the hypoxia-induced increase in VEGF biosynthesis. (docphin.com)
  • To determine the effect of p38 inhibition on LG secretion, PD 169316, a general p38 inhibitor, and SB 239063, an inhibitor of p38α and β, were added to the cells prior to secretion measurements. (diva-portal.org)
  • On the olher hand, an inactive inhibitor of p38 MAPK did not augment LPS-induced vacuole formation. (fujita-hu.ac.jp)
  • Here, we examined whether IL-13 up-regulates arginase and thus reduces NO production from LPS-activated macrophages. (jimmunol.org)
  • The constitutive active/androstane receptor (CAR) regulates hepatic drug metabolism by activating genes, such as cytochrome P450, and certain transferases. (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)
  • The activated form of p38 regulates downstream activation of other serine kinases, notably MapKapK-2 and MapKapK-3, indicating the existence of Type I IFN-dependent signaling cascades activated downstream of p38. (northwestern.edu)
  • In this study we demonstrate that vWF stimulates p38 MAPK that regulates EC adhesiveness for hMSCs. (biomedcentral.com)
  • In conclusion, PAR2 via p38 MAPK signaling regulates IL-8 production and thereby mediates cell adhesion. (elsevier.com)
  • Epitope-tagged JNK1 and p38α MAP kinases were activated by coexpression with (+) and without (−) MLK3 and MKK6-Glu mutant, respectively. (nih.gov)
  • Four different p38 MAP kinase isoforms (p38α, p38β2, p38γ, and p38δ) were expressed in COS cells in the presence (+) and absence (−) of the MKK6-Glu mutant. (nih.gov)
  • Immune complex kinase assays were performed by using p38α MAP kinase activated with (+) and without (−) the MKK6-Glu mutant. (nih.gov)
  • Conversely, constitutively active MKK6 induced p38 MAPK activation that recapitulated the effects of polyphenols by inducing ERα phosphorylation and downstream activation of Akt, and eNOS. (ahajournals.org)
  • B) All four p38 MAP kinase isoforms phosphorylate NFATc4 in vitro. (nih.gov)
  • On the other hand, under steady-state culture conditions, both p38α and p38δ isoforms are increasingly phosphorylated activated in the terminal phase of differentiation. (pnas.org)
  • Taken together, our data demonstrate that both p38α and δ isoforms function to promote the late-stage differentiation of primary erythroid progenitors and are likely to be involved in functions related to erythrocyte membrane remodeling and enucleation. (pnas.org)
  • The four p38 MAPK isoforms are defined by the common TGY motif and has significant homology with each other at the amino acid level ( 1 , 2 ). (pnas.org)
  • The p38α and p38β isoforms are expressed in most tissues, but expression of p38γ is limited to the skeletal muscle ( 6 - 11 ). (pnas.org)
  • Moreover, expression and activation of the other three-kinase isoforms has not been examined in Epo-dependent cell lines or in primary erythroid progenitors. (pnas.org)
  • Of p38 MAPk isoforms studied, only p38α and p38δ were detected in neutrophils. (jci.org)
  • Overexpression of individual p38 mitogen-activated protein (MAP) kinase (MAPK) isoforms also suppressed constitutive as well as sulforaphane- or Nrf2-induced ARE-dependent gene expression. (aacrjournals.org)
  • Finally, we found that stimulation of p38 MAPK isoforms phosphorylated purified Nrf2 protein and caused an increase in the interaction between Nrf2 and Keap1 in vitro and the suppression of Nrf2 translocation into the nucleus. (aacrjournals.org)
  • Stimulation of HMC-1 with the stable adenosine analog NECA (5′-N-ethylcarboxamidoadenosine) activated p21 ras and both p42 and p44 isoforms of extracellular signal-regulated kinase (ERK). (aspetjournals.org)
  • Western blotting was used to determine the phosphorylation status of p38 and p42/44 and determine expression of p38 isoforms. (diva-portal.org)
  • Sequence comparisons revealed that p38delta is approximately 60% identical to the other three p38 isoforms but only 40-45% to the other mitogen-activated protein kinase family members. (scripps.edu)
  • It contains the TGY dual phosphorylation site present in all p38 group members and is activated by a group of extracellular stimuli including cytokines and environmental stresses that also activate the other three known p38 isoforms. (scripps.edu)
  • However, unlike the other p38 isoforms, the kinase activity of p38delta is not blocked by the pyridinyl imidazole, 4-(4-fluorophenyl)-2-2(4-hydroxyphenyl)-5-(4-pyridyl)-imidazole (identicalto SB202190). (scripps.edu)
  • Once activated, MAP kinases phosphorylate a variety of proteins and relay signals downstream, often ending in activation of transcriptional factors ( Cano and Mahadevan, 1995 ). (jneurosci.org)
  • We investigated the roles of protein phosphatases including MAPK phosphatase-1 (MKP-1) and protein phosphatase type 2A (PP2A) in modulating p38MAPK activation and downstream TNF-alpha expressions in primary human monocyte-derived macrophages (PBMac) infected with H9N2/G1 or H1N1 influenza virus. (mdpi.com)
  • 5 6 Furthermore, ischemic preconditioning activates MAPKAPK2, the downstream signaling substrate of p38 MAPK, 5 6 demonstrating that activation of the p38 MAPK signaling cascade, not just one element of the MAPK module, is part of the signaling events involved in preconditioning. (ahajournals.org)
  • MAPK12 is activated by environmental stress and pro-inflammatory cytokines, in turn phosphorylating downstream targets. (thefreedictionary.com)
  • Both these cyclic nucleotides transiently activate the downstream stress kinase, p38 MAPK, which may trigger further downstream adaptive processes. (sun.ac.za)
  • Two Jak-kinases, Tyk-2 and Jak-1, associate with the different receptor subunits and are activated in response to IFNα or IFNβ to regulate engagement of multiple downstream signaling cascades. (northwestern.edu)
  • It also activated inositol-requiring enzyme (Ire)-1α and its downstream molecule, tumor necrosis factor receptor (TNFR)-associated factor (TRAF)2 in the WT and DN p38α mice compared with the sham mice. (elsevier.com)
  • p38 Mitogen-activated protein kinase mediates hypoxia-induced vascular endothelial growth factor release in human endothelial cells. (docphin.com)
  • In conclusion, p38 activation mediates secretion in cholinergic stimulation of rabbit LG cells. (diva-portal.org)
  • 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)
  • Sphingosine-1-phosphate mediates ICAM-1-dependent monocyte adhesion through p38 MAPK and p42/p44 MAPK-dependent Akt activation. (qxmd.com)
  • 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 purpose of this study was to investigate the usefulness of a p38 MAPK inhibitor for promoting proliferation of human corneal endothelial cells (HCECs). (arvojournals.org)
  • Corneal endothelial wounds were created in a rabbit model, and p38 MAPK was applied in eye drop form, followed by evaluation of cell proliferation in the corneal endothelium by Ki67-immunostaining. (arvojournals.org)
  • HNE increased TF procoagulant activity but not TF antigen of both activated monocytic and endothelial cells. (ahajournals.org)
  • Black tea has been shown to improve endothelial function in patients with coronary artery disease and recent data indicate the polyphenol fraction of black tea enhances endothelial nitric oxide synthase (eNOS) activity through p38 MAP kinase (p38 MAPK) activation. (ahajournals.org)
  • These findings suggest p38 MAP kinase-mediated eNOS activation requires ERα and these data uncover a new mechanism of ERα activation that has broad implications for NO bioactivity and endothelial cell phenotype. (ahajournals.org)
  • We used Affymetrix DNA microarrays, human protein phospho-MAPK array, Western blot, cell-based ELISA and flow cytometry analysis to study the activation of endothelial cells by von Willebrand factor. (biomedcentral.com)
  • Cell adhesion assay and protein kinase inhibitors were used to evaluate the role of mitogen-activated protein kinases in the regulation of endothelial cell adhesiveness for mesenchymal stem cell. (biomedcentral.com)
  • Treatment of endothelial cells with von Willebrand factor activated ERK-1,2 and p38 MAPK without an effect on gene or cell surface expression of E-selectin, P-selectin, VCAM1 and ICAM1. (biomedcentral.com)
  • Activation of p38 MAPK in endothelial cells by von Willebrand factor is responsible for the regulation of endothelial cell adhesiveness for mesenchymal stem cells. (biomedcentral.com)
  • These dada provide the first direct evidence for a role of p38 MAPK in mediating hypoxia-induced increase in VEGF biosynthesis in human endothelial cells. (docphin.com)
  • A member of a new subfamily of G protein-coupled receptors, protease-activated receptor 2 (PAR2), is highly expressed on endothelial cells and plays an important role in inflammation. (elsevier.com)
  • We observed that PAR2-activating peptide (PAR2-AP) significantly increase peripheral blood mononuclear cells adhere to endothelial cells. (elsevier.com)
  • In the present study, we found that p38 MAPK activity is required for endothelial cell migration stimulated by both VEGF and nongrowth factor stimulants, sphingosine 1-phosphate and soluble vascular cell adhesion molecule. (elsevier.com)
  • IL-1beta activated p38alpha and p38beta in endothelial cells. (antibody-antibodies.com)
  • We evaluated the mitogen-activated protein kinase (MAPK)-dependent, GLP-1-independent, anti-inflammatory effects of linagliptin in lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) which do not secrete GLP-1. (biomedcentral.com)
  • Although the role of MAPK in signal transduction and in injury-induced regulation of gene expression is well established, the ability of these kinases to phosphorylate and modulate voltage-gated sodium channels has not been reported. (jneurosci.org)
  • Activation of leukocytes by proinflammatory stimuli selectively initiates intracellular signal transduction via sequential phosphorylation of kinases. (jci.org)
  • The kinase p38 has important signal transduction functions, e.g. in gene transcription, but has previously not been known to modulate exocrine secretion. (diva-portal.org)
  • We also wish to find out whether any specific inhibitors of p38 MAPK can improve severe asthma by improving the effects of corticosteroids on these cells. (clinicaltrials.gov)
  • Since the identification of the p38 mitogen-activated protein kinase (MAPK) as a key signal-transducing molecule in the expression of the proinflammatory cytokine tumor necrosis factor (TNF) more than 10 years ago, huge efforts have been made to develop inhibitors of p38 MAPK with the intent to modulate unwanted TNF activity in diseases such as autoimmune diseases or sepsis. (nih.gov)
  • Specific inhibitors of p38α MAPk blocked LPS-induced adhesion, nuclear factor-kappa B (NF-κB) activation, and synthesis of tumor necrosis factor-α (TNF-α). (jci.org)
  • Abnormal activity (higher or lower than physiological) of p38 has been implicated in pathological stresses in several tissues, that include neuronal, bone, lung, cardiac and skeletal muscle, red blood cells, and fetal tissues. (wikipedia.org)
  • Nuclear factor of activated T cells (NFAT) is implicated in multiple biological processes, including cytokine gene expression, cardiac hypertrophy, and adipocyte differentiation. (nih.gov)
  • Phosphorylation provides a fast posttranslational modification of proteins that has been shown to regulate the acute response of cells to a variety of stimuli. (jneurosci.org)
  • In particular, p38 MAPK has a multifaceted role in CD4 T cells that have been implicated in initiating and driving sustained inflammation in autoimmune diseases, such as rheumatoid arthritis or systemic vasculitis. (nih.gov)
  • Here we review recent advances in the understanding of the role of the p38 MAPK signaling cascade in CD4 T cells and the consequences that its inhibition provokes in T cell functions in vitro and in vivo. (nih.gov)
  • The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the nucleus. (uniprot.org)
  • Exposure of sulforaphane to HepG2 cells increased heme oxygenase-1 (HO-1) expression by activating antioxidant response element (ARE) through induction of Nrf2 and suppression of Kelch-like ECH-associated protein 1 (Keap1). (aacrjournals.org)
  • HNE treatment generated reactive oxygen species, activated p38 mitogen-activated protein kinase, and increased the exposure of phosphatidylserine at the outer leaflet in THP-1 cells. (ahajournals.org)
  • Conclusions- HNE increases TF coagulant activity in monocytic cells through a novel mechanism involving p38 mitogen-activated protein kinase activation that leads to enhanced phosphatidylserine exposure at the cell surface. (ahajournals.org)
  • p38 Mitogen-activated protein kinase (MAPK) is highly activated in human primary hepatocytes but barely in human hepatoma cell lines including HepG2 cells. (aspetjournals.org)
  • Because of our unexpected finding that p38 MAPK is present but not activated in HepG2 cells, we investigated the role of p38 MAPK in CAR-mediated transcriptional activation of the CYP2B6 gene. (aspetjournals.org)
  • In the present study, we used human primary hepatocytes, hepatoma-derived cell lines (HepG2, FLC7, and Huh 7), and HepG2 ectopically expressing mouse and human CAR (called Ym17 and Yh18 cells, respectively) to demonstrate the role of p38 MAPK in the CAR-mediated activation of CYP2B6 gene. (aspetjournals.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)
  • Paclitaxel is known to modulate PKA 3 (6 , 7 , 8 , 9) and the various MAP kinases (10 , 11 , 12 , 13 , 14 , 15 , 16) in normal and cancer human breast cells. (aacrjournals.org)
  • Protein overload is a promoter of fractalkine gene induction mediated by NF-κB and p38 activation in proximal tubular cells. (asnjournals.org)
  • Among cellular mechanisms that may underlie interstitial inflammation, it has been suggested that abnormally filtered proteins may have intrinsic renal toxicity and may serve as an early fosterer in tubular cells by activating the synthesis of vasoactive and proinflammatory substances ( 2 ). (asnjournals.org)
  • In resting cells, NF-κB exists in an inactive form in the cytoplasm bound to the inhibitory protein IkBα. (asnjournals.org)
  • Evidence in chronic nephropathy induced by renal mass reduction and in passive Heymann nephritis in rats revealed that excess uptake of plasma proteins in proximal tubular cells precedes because the early stage is subsequently associated with an inflammatory reaction ( 12 ). (asnjournals.org)
  • Treatment of cells with sphingosine induced suppression of ERK and activation of p38 MAPK. (aacrjournals.org)
  • Here we further investigated the role of p38 MAPK in the function and differentiation of mouse bone marrow macrophages (BMM phi), common precursors of osteoclasts and dendritic cells. (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)
  • 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)
  • IL-1 also activated Rap in the cells, but with slower kinetics than Ras. (tcd.ie)
  • p38 is also activated during IFNα-treatment of primary leukemia cells from patients with chronic myelogenous leukemia. (northwestern.edu)
  • ECs show limited adhesiveness for cells circulating in the bloodstream, however, they became activated after exposure to inflammatory or stress factors. (biomedcentral.com)
  • Bars indicate the percentages of cells expressing the activated forms of (a) p38 mitogen-activated protein kinase (MAPK)α, (b) extracellular signal-regulated kinase (ERK) and (c) c-Jun amino-terminal kinase (JNK) after treatment with vehicle (phosphate-buffered saline [PBS]), anti-tumour necrosis factor (aTNF), osteoprotegerin (OPG) and IL-1 receptor antagonist (IL-1ra). (biomedcentral.com)
  • The aim of the current study was to investigate the role of p38 in carbachol (Cch)-induced LG secretion in LG acinar cells in vitro. (diva-portal.org)
  • The p38δ isoform was shown to have robust expression both by Western blotting of acinar cells and immunofluorescence of the whole gland. (diva-portal.org)
  • The role of p38 mitogen-activated protein kinase (MAPK) on vacuole formation in lipopolysaccharide (LPS)-stimulaled RAW 264.7 cells was examine. (fujita-hu.ac.jp)
  • LPS definitely induced the formation of vacuoles in RAW 264.7 cells and SB202190 as a p38 specific inhibitor also induced slight vacuole formation. (fujita-hu.ac.jp)
  • Recent studies have implicated the activation of stress-activated mitogen-activated protein kinase (MAPK) p38 in spinal microglial cells for development of neuropathic and inflammatory pain. (asahq.org)
  • After rats received a plantar incision surgery, mechanical allodynia and thermal hyperalgesia were determined by von Frey filaments and radiant heat, respectively, and the number of p-p38 immunoreactive cells in the dorsal horn was quantified to determine p38 activation at different time points after incision. (asahq.org)
  • A significant increase in number of p-p38 immunoreactive cells was observed in the ipsilateral L4-5 spinal dorsal horn from 1 h to 3 days after the incision. (asahq.org)
  • p38 MAPK is usually triggered in macrophages, neutrophils, and T cells by several extracellular mediators of swelling, including chemoattractants, cytokines, chemokines, and bacterial lipopolysaccharide (LPS) (examined in research 31). (mindunwindart.com)
  • Interestingly, by the knockdown of Skp2 or the inhibition of p38MAPK, we restored functional ERα protein levels and the control of gene expression and proliferation by estrogen and antiestrogen in ERα-negative breast cancer cells. (semanticscholar.org)
  • 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)
  • We measured on Northern gels the migration of reporter mRNAs isolated from cells transfected only with reporter plasmid or co-transfected with an active mutant of MAPK kinase-6, and treated either with or without the p38 MAPK inhibitor SB 203580. (ox.ac.uk)
  • To understand the role of p38 family members in inflammation, we determined their relative expression in cells that participate in the inflammatory process. (antibody-antibodies.com)
  • Cell viability was checked when the tested cells were cultured with inhibitors of ERK, JNK and p38 to discern the possible signalling cascade involved in the proliferative effect of the SMF on the DPSCs. (elsevier.com)
  • Nuclear factor of activated T-cells, cytoplasmic 4 is a protein that in humans is encoded by the NFATC4 gene. (wikipedia.org)
  • The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. (wikipedia.org)
  • Other members of this family of nuclear factors of activated T cells also participate in the formation of this complex. (wikipedia.org)
  • Immune complex kinase assays were performed with recombinant NFATc3 and NFATc4 as the substrates. (nih.gov)
  • None of the other cytoplasmic loops and termini of the channel are phosphorylated by activated p38α in these assays. (jneurosci.org)
  • Nonetheless, in-gel kinase assays provide evidence for additional activators. (scripps.edu)
  • Activity assays showed that both p38 MAPK and cPLA 2 activation markedly increased 1 day after reperfusion. (elsevier.com)
  • However, p38alpha was the more activated form based on kinase assays and phosphorylation analysis. (antibody-antibodies.com)
  • Unbiased transcriptome analysis revealed that IRE1α/XBP1-mediated gene regulation contributed to p38 MAPK-dependent regulation of neonatal cardiomyocyte proliferation and binucleation. (jci.org)
  • Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1. (uniprot.org)
  • Several proinflammatory treatments which induce Cox-2 gene expression also stimulate the mitogen-activated protein kinase (MAPK) p38. (asm.org)
  • 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)
  • The synthetic glucocorticoid dexamethasone was demonstrated to inhibit p38 activity in a manner requiring ongoing, glucocorticoid receptor-mediated gene expression ( 40 ). (asm.org)
  • Here the link between dexamethasone, p38 activity, and proinflammatory gene expression is investigated in further detail. (asm.org)
  • A gene on chromosome 22q13.33 that encodes a member of the MAP kinase family, which integrate multiple biochemical signals and are involved in cell proliferation, differentiation, transcription, regulation and development. (thefreedictionary.com)
  • It is now well established that the function of p38 is essential for gene transcription via ISRE or GAS elements, but has no effects on the phosphorylation of Stat-proteins, the formation of Stat-complexes, and their binding to the promoters of IFN-sensitive genes. (northwestern.edu)
  • A model presented for substrate and activator interactions has implications for the evolution of protein kinase cascades. (pnas.org)
  • Role of p38 MAP kinase in LPS-induced airway inflammation in the rat," British Journal of Pharmacology , vol. 132, no. 8, pp. 1715-1724, 2001. (hindawi.com)
  • Objectives This study sought to determine the effects of a p38 mitogen-activated protein kinase inhibitor, losmapimod, on vascular inflammation, by 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography imaging. (onlinejacc.org)
  • Oxidized Albumin Triggers a Cytokine Storm in Leukocytes Through P38 Mitogen-Activated Protein Kinase: Role in Systemic Inflammation in Decompensated Cirrhosis. (snfge.org)
  • Activation of p38 mitogen-activated protein kinase (MAPK) is known to be important in cytokine production and cell survival in inflammation. (ox.ac.uk)
  • A murine model of acute LPS-induced lung inflammation was used to study the effect of p38 MAPK inhibition in ongoing pulmonary inflammation. (elsevier.com)
  • These findings support the feasibility of p38 MAPK inhibition as a selective intervention to reduce neutrophilic inflammation. (elsevier.com)
  • Inhibition of spinal constitutive NOS-2 by 1400W attenuates tissue injury and inflammation-induced hyperalgesia and spinal p38 activation. (qxmd.com)
  • They have also provided a biochemical basis for the potential of using specific inhibitors of NF-kappaB and p38 MAPK for treating allergic inflammation. (edu.hk)
  • This increased phosphorylation/activity was accompanied by up-regulation of heat shock protein 27 phosphorylation. (pnas.org)
  • In this study, we investigated the association of MAP kinase p38 with Na v 1.6 in brain tissue and examined the regulation by MAP kinase p38 of the Na v 1.6 sodium current. (jneurosci.org)
  • One possible reason for this paradox might relate to the fact that the p38 MAPK signaling cascade is involved in the functional regulation of several different cell types that all contribute to the complex pathogenesis of human autoimmune diseases. (nih.gov)
  • Regulation of w-fb proliferation is influenced by p38. (ovid.com)
  • Here we hypothesize that protein phosphatases are involved in the regulation of cytokine expressions during influenza virus infection. (mdpi.com)
  • A novel mechanism for TNF- α regulation by p38 MAPK: involvement of NF- κ B with implications for therapy in rheumatoid arthritis," Journal of Immunology , vol. 173, no. 11, pp. 6928-6937, 2004. (hindawi.com)
  • We observed an up-regulation of inducible nitric oxide synthase (iNOS), prepro endothelin-1 (preproET-1) and phosphorylated p38-MAPK in thoracic aorta and kidney cortex but not in kidney medulla in 28-days diabetes group. (ebscohost.com)
  • Small interfering RNA targeting of PP2A effectively attenuated sphingosine-induced p38 MAPK activation through restoration of ERK activity, suggesting PP2A-mediated opposing regulation of ERK and p38 MAPK. (aacrjournals.org)
  • Our data indicate the regulation from the ATF2/ATF7/CREB5 category of transcriptional regulators by p38 MAPK as a historical conserved system for the control of innate immunity in metazoans, and suggest that ATF2/ATF7 may function in a similar manner in the regulation of mammalian innate immunity. (bcl-2-protein.com)
  • Our data point to the regulation of the ATF2/ATF7/CREB5 family of transcriptional regulators by p38 MAPK as an ancient conserved mechanism for the control of innate immunity in metazoans and suggests a mechanism by which the protean effects of p38 MAPK around the mammalian innate immune response may be mediated. (bcl-2-protein.com)
  • Regulation of Mediator Secretion in Human Basophils by p38 Mitogen-Activated Protein Kinase: Phosphorylation is Sensitive to the Effects of Phosphatidylinositol 3-Kinase Inhibitors and Calcium Mobilization. (kent.ac.uk)
  • Intrathecal IL-1beta leads to a time-dependent up-regulation of phosphorylated p38 (p-p38) MAPK protein expression in the spinal cord 30-240 min following IL-1beta injection (i.t. (qxmd.com)
  • The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens. (abbreviations.com)
  • Finally, we demonstrate that tumor necrosis factor α, an inflammatory cytokine that is modulated by p38α, is expressed by differentiating erythroblasts and inhibition of p38α or tumor necrosis factor α results in reduction in differentiation. (pnas.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)
  • 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)
  • Recently, a Th2 cell-derived cytokine IL-13 was found to be a potent suppressor of NO production in activated macrophages ( 10 , 11 , 12 ). (jimmunol.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)
  • The report provides comprehensive information on the Mitogen Activated Protein Kinase 14 (Cytokine Suppressive Anti Inflammatory Drug Binding Protein or Mitogen Activated Protein Kinase p38 Alpha or MAP Kinase MXI2 or MAX Interacting Protein 2 or Stress Activated Protein Kinase 2a or MAPK14 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. (marketresearch.com)
  • Additionally, the report provides an overview of key players involved in Mitogen Activated Protein Kinase 14 (Cytokine Suppressive Anti Inflammatory Drug Binding Protein or Mitogen Activated Protein Kinase p38 Alpha or MAP Kinase MXI2 or MAX Interacting Protein 2 or Stress Activated Protein Kinase 2a or MAPK14 or EC 2.7.11.24) targeted therapeutics development and features dormant and discontinued projects. (marketresearch.com)
  • p38 Mitogen-activated protein kinase is crucially involved in osteoclast differentiation but not in cytokine production, phagocytosis, or dendritic cell differentiation of bone marrow macrophages. (semanticscholar.org)
  • 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)
  • PD169316 is a potent, cell-permeable and selective p38 MAP kinase inhibitor (IC50 89 nM). (csnpharm.com)
  • Intrathecal administration of either selective p38 MAPK, or JNK, or ERK inhibitor alone did not affect the thermal nociceptive threshold or iNOS protein expression in the spinal cord. (qxmd.com)
  • The activation of these protein kinases leads to diverse regulatory events, particularly proliferation and differentiation. (pnas.org)
  • Activation of p38 MAPK signaling due to culture stress might suppress the proliferation of HCECs, whereas a p38 MAPK inhibitor can counteract this activation and enable efficient in vitro HCEC expansion. (arvojournals.org)
  • 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)
  • This effect may activate p38 mitogen-activated protein kinase signalling, and thus reorganize the cytoskeleton, which contributes to the increased cell proliferation of the DPSCs. (elsevier.com)
  • TNF-α and IL-1β significantly increase p38 expression. (ovid.com)
  • Finally, IL-13 significantly inhibited NO production from LPS-activated macrophages, and this effect was reversed by an arginase inhibitor, l -norvaline. (jimmunol.org)
  • CRP production was significantly inhibited by the p38 MAPK specific inhibitor RWJ 67657 at 1 μmol/l, which is pharmacologically relevant. (bmj.com)
  • Even though KO neurons were slightly less vunerable to SNP toxicity in comparison to WT neurons, the degrees of neuron loss of life/neurite harm between WT and p38 KO neurons weren't significantly different. (boothampitheatre.com)
  • Intrathecal pretreatment of FR167653 attenuated incision-induced mechanical allodynia from 1 h to day 2 and significantly reduced activation of p38 in the dorsal horn 1 day after plantar incision. (asahq.org)
  • The basal activity of p38 significantly increased in both the liver and brain of old rats as compared with young rats. (elsevier.com)
  • Linagliptin significantly inhibited LPS-stimulated IL-6 production, intranuclear p65 expression, and p38 MAPK phosphorylation. (biomedcentral.com)
  • However, pretreatment with a p38 MAPK inhibitor significantly reduced the IL-1beta-induced p-p38 MAPK expression by 38-49%, and nearly completely blocked the subsequent iNOS expression (reduction by 86.6%), NO production, and thermal hyperalgesia. (qxmd.com)
  • Existence of extracellular signal-related kinase (ERK) and p38 mitogen activated protein kinse (MAPK) in the rat corpus luteum (CL). (edu.au)
  • however, the upstream activator(s) of p38 MAPk is unknown, and consequences of p38 MAPk activation remain largely undefined. (jci.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)
  • Using human HO-1 promoter reporter plasmids and ChIP assay, we have identified that sulforaphane transcriptionally activated the upstream ARE-rich enhancer region, located at −9.0 kb upstream human HO-1 promoter. (aacrjournals.org)
  • The upstream components of polyphenol-mediated eNOS activation are not well described and the precise signals linking p38 MAPK to eNOS activation are largely unknown. (ahajournals.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)
  • Octacalcium phosphate crystals directly stimulate expression of inducible nitric oxide synthase through p38 and JNK mitogen-activated protein kinases in articular chondrocytes. (inserm.fr)
  • Intrathecal interleukin-1beta administration induces thermal hyperalgesia by activating inducible nitric oxide synthase expression in the rat spinal cord. (qxmd.com)
  • The chimeric transcript was stabilized by a constitutively active form of MAPK kinase 6, an activator of p38. (asm.org)
  • Furthermore, constitutively active Rap1AV12 inhibited p38 MAPK activation by IL-1, consistent with Rap antagonizing Ras function. (tcd.ie)
  • We show in this study that sodium channels and p38 MAP kinase colocalize in rat brain tissue and that activated p38α phosphorylates L1 of Na v 1.6, specifically at serine 553 (S553), in vitro . (jneurosci.org)
  • and IL-1β is upregulated after stroke and in vitro inhibits BDNF effects on neuronal/synaptic plasticity via induction of p38 MAPK (Tong, 2012). (neurology.org)
  • VX-745 is an investigational clinical stage brain penetrant specific chemical antagonist of p38 MAPKα that in vitro inhibits IL-1β production and signaling (Alam, 2015). (neurology.org)
  • In vitro anti-osteoclastogenic activity of p38 inhibitor doramapimod via inhibiting migration of pre-osteoclasts and NFATc1 activity. (semanticscholar.org)
  • We developed a functional proteomic approach using a combination of in vitro MAPKAPK2 phosphorylation of neutrophil lysate, separation of phosphorylated proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and phosphoprotein recognition by peptide mass fingerprinting using ZLN005 matrix-assisted laser beam desorption ZLN005 ionization mass spectrometry (MALDI-MS) and protein database analysis. (mindunwindart.com)
  • 2006). Inside the periodontal microenvironment, different cell types need p38 MAPK signaling as an intrinsic element in the rules of manifestation of proinflammatory cytokines and enzymes induced by inflammatory and infectious indicators in vitro, including IL-6, matrix metalloproteinase-13, and receptor activator of NF-B ligand (Patil et al. (bio2009.org)
  • MAP kinase p38 ( 1 - 4 ) is activated by proinflammatory cytokines and environmental stresses such as osmotic shock and UV light, and is essential for the lipopolysaccharide-induced translation of tumor necrosis factor in monocytes. (pnas.org)
  • Activation of p38 in the neuronal ND7/23 cell line transfected with Na v 1.6 leads to a significant reduction in the peak Na v 1.6 current amplitude, without a detectable effect on gating properties. (jneurosci.org)
  • Together, our results indicate that Aβ impairs LTP in the entorhinal cortex through neuronal RAGE-mediated activation of p38 MAPK. (ku.edu)
  • but that p38 within the neuron contributes quantitatively towards the neuronal dysfunction replies. (boothampitheatre.com)
  • Like the results with L-glutamate, inhibition of p38 by MW-181 or MW-108 remedies of WT neurons considerably decreased SNP-induced neuronal loss of life (Fig.?3a), and protected neurons against neurite degeneration (Fig.?3b, c). (boothampitheatre.com)
  • neuronal loss of life both in p38 KO and WT neurons, without significant differences between your genotypes. (boothampitheatre.com)
  • LPS stimulation selectively activated p38α. (jci.org)
  • p38 mitogen-activated protein kinase activation is required for human neutrophil function triggered by TNF- α or FMLP stimulation," Journal of Immunology , vol. 160, no. 4, pp. 1982-1989, 1998. (hindawi.com)
  • Two out of four cell lines produced C reactive protein (CRP), especially after combined IL6 and IL1β stimulation. (bmj.com)
  • The results revealed activation of p38 mediated by Cch stimulation and inhibition of Cch-induced secretion as a result of p38 inhibition. (diva-portal.org)
  • Remarkably, five variants (Thr4Ala, Gly56Ala, Glu215Lys, Lys605Asn, and Pro612Ser) demonstrated no capacity for 5-HT uptake stimulation after acute protein kinase G (PKG)/p38 mitogen-activated protein kinase (MAPK) activation. (meta.org)
  • Fibroblasts were analyzed for phosphorylated p38 using immunoblot. (ovid.com)
  • Fibroblasts were treated with bFGF, TNF-a, and IL-1 and p38 expression analyzed. (ovid.com)
  • In addition, pharmacological inhibition of p38 abrogates the suppressive effects of Type I IFNs on normal human hematopoietic progenitors, indicating a critical role for this signaling cascade in the induction of the regulatory effects of Type I IFNs on hematopoiesis. (northwestern.edu)
  • Phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002, blocked not only p38 MAPK activation but also Rac activation. (elsevier.com)
  • The stress-activated protein kinase p38 stabilizes a number of mRNAs encoding inflammatory mediators, such as cyclooxygenase 2 (Cox-2). (asm.org)
  • The stress-activated protein kinases (SAPKs), c-Jun NH 2 -terminal kinases (JNKs) and p38 mitogen-activated protein kinases, were evaluated in the liver and brain of young and old rats in response to a direct-acting alkylating agent, methyl methanesulfonate (MMS). (elsevier.com)
  • While p38 antagonists in pre-clinical studies are neuroprotective when administered up to 12 hours after stroke induction, effects of p38 antagonists when administered outside the neuroprotection window are unknown. (neurology.org)
  • These new data suggest that p38 MAPK inhibitors may elicit several unwanted effects in human autoimmune diseases but may be useful for the treatment of allergic disorders. (nih.gov)
  • Our results suggest that p38 activation in spinal microglia play a role in incision-induced mechanical allodynia in rats. (asahq.org)
  • Our results suggest that p38 MAPK plays a pivotal role in i.t. (qxmd.com)
  • Activated p38 MAP kinase has been shown to phosphorylate and activate MAPKAP kinase 2 and to phosphorylate the transcription factors ATF2, Mac and MEF2. (wikipedia.org)
  • The protein product of proto-oncogene RAS can increase activity of p38, and thereby cause excessively high activity of transcription factor NF-κB. (wikipedia.org)
  • Dysregulated NF-κB activity can activate genes that cause cancer cell survival, and can also activate genes that facilitate cancer cell metastasis to other tissues. (wikipedia.org)
  • The structure of mitogen-activated protein (MAP) kinase p38 has been solved at 2.1-Å to an R factor of 21.0%, making p38 the second low activity MAP kinase solved to date. (pnas.org)
  • Here we describe the structure of unphosphorylated, low activity p38 at 2.1-Å resolution. (pnas.org)
  • This chamber-specific growth pattern was associated with a selective activation of p38 mitogen-activated protein kinase (MAPK) activity in the RV and simultaneous inactivation in the LV. (jci.org)
  • Cardiomyocyte-specific deletion of both the Mapk14 and Mapk11 genes in mice resulted in loss of p38 MAPK expression and activity in the neonatal heart. (jci.org)
  • Chamber-specific p38 activity was associated with differential expression of dual-specific phosphatases (DUSPs) in neonatal hearts, including DUSP26. (jci.org)
  • IRE1α/XBP1 and p38 MAPK activity in cardiomyocytes. (jci.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)
  • Twenty-four hours after the transient activation of the adenosine A 1 receptor, the myocardium exhibited a significant rise in the activity of p38 MAPK. (ahajournals.org)
  • For p38 MAPK inhibitor treatment in RA SAA might be a better marker of disease activity than CRP and fibrinogen, because SAA is not directly affected by p38 MAPK inhibition. (bmj.com)
  • Blockade of p38 mitogen-activated protein kinase activation inhibited HNE-induced phosphatidylserine exposure and increased TF activity. (ahajournals.org)
  • We present experimental data to characterize p38 MAPK as a regulatory cell signal in CAR activation and propose the hypothesis that CAR requires cellular signaling, such as p38 MAPK, to fully confer its transactivation activity in response to xenobiotic exposures. (aspetjournals.org)
  • Scopoletin has important anti-inflammatory activity by inhibiting the phosphorylation of NF-B and p38 MAPK. (csnpharm.com)
  • Unlike the extracellular signal- regulated kinases (p42 and p44 MAP kinases), which are stimulated by insulin in many cell types, p38 activity is inhibited by insulin in postmitotic fetal neurons for which insulin is a potent survival factor (Heidenreich, K. A., and Kummer, J. L. (1996) J. Biol. (elsevier.com)
  • Notably, the increased loss of PMK-1 p38 MAPK activity in on nonpathogenic bacterias. (bcl-2-protein.com)
  • A large body of evidence shows that p38 MAPK activity is critical to immune and inflammatory responses. (mindunwindart.com)
  • We showed recently that MAPKAPK2 phosphorylates and activates PKB/Akt in human being neutrophils, providing an antiapoptotic activity (19, 33). (mindunwindart.com)
  • Phosphorylation by p38 mitogen-activated protein kinase promotes estrogen receptor α turnover and functional activity via the SCF(Skp2) proteasomal complex. (semanticscholar.org)
  • Additionally, Ang-II enhanced the DNA binding activity to cAMP response element binding protein (CREB) and phosphorylation of CREB. (elsevier.com)
  • Suh, Y 2001, ' Age-specific changes in expression, activity, and activation of the c-Jun NH 2 -terminal kinase and p38 mitogen-activated protein kinases by methyl methanesulfonate in rats ', Mechanisms of Ageing and Development , vol. 122, no. 15, pp. 1797-1811. (elsevier.com)
  • Inhibition of NF-kappaB activation and p38 MAPK activity decreased the TNF-induced release of eotaxin from eosinophils. (edu.hk)
  • MAP kinase p38 phosphorylates and activates both nuclear transcription factors ATF2 ( 12 ) and GADD153 ( 13 ), and protein kinase targets such as MAPKAP kinases 2 and 3 ( 3 , 4 , 14 ). (pnas.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • J. Kaur, R. C. Woodman, and P. Kubes, "P38 MAPK: critical molecule in thrombin-induced NF- κ B-dependent leukocyte recruitment," American Journal of Physiology , vol. 284, no. 4, pp. (hindawi.com)
  • Conclusion: Partial inhibition of p38α protein blocked the activation of CHOP-mediated apoptotic processes during pressure overload by partially inhibiting signaling from the Ire-1α/TRAF2 to its down-stream molecule, CHOP. (elsevier.com)
  • In vivo data claim that p38 signaling is necessary for LPS-induced alveolar bone tissue reduction because small-molecule p38 inhibitors had been effective in reducing periodontitis in rodent versions (Kirkwood et al. (bio2009.org)
  • p38 MAPK inhibitors have already been been shown to be efficacious in various other small pet inflammatory disease versions, but the advancement of small-molecule inhibitor therapeutics continues to be hampered by several negative effects, such as for example dermatoses and neurotoxicity, PF-562271 in scientific trials. (bio2009.org)
  • The tole of p38 MAPK in the vacuole formation in LPS-stimulated macrophages is discussed. (fujita-hu.ac.jp)
  • Both early and late treatment with p38 MAPK inhibitor reduced renal monocyte chemoattractant protein-1 (MCP-1) levels, the number of glomerular macrophages, the severity of tissue injury, and proteinuria compared with the vehicle group. (ox.ac.uk)
  • Results Phosphorylated p38 expression was increased in w-fb (AU%=233.5±59.7, P=0.039) compared to n-fb (AU%=99.9±14.6). (ovid.com)
  • The expression of UCP-1 is regulated by several transcriptional factors, including peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α), which can be induced by cold exposure and/or β-adrenergic signaling ( 9 ). (diabetesjournals.org)
  • It has been shown that PGC-1α and exercise upregulate the expression of fibronectin type III domain containing 5 (Fndc5), a type I transmembrane protein of skeletal muscle. (diabetesjournals.org)
  • Western blot analysis showed a significant increase in expression of phospho-p38 MAPK and phospho-cPLA 2 in rat brain cortex after tFCI. (elsevier.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)
  • An increase in the basal expression of p38 was detected in the brain but not in the liver of old rats. (elsevier.com)
  • GENTAUR antibody-antibodies.com The Marketplace for Antibodies : Differential expression and activation of p38 mitogen-activated protein kinase alpha, beta, gamma, and delta in inflammatory cell lineages. (antibody-antibodies.com)
  • Differential expression and activation of p38 mitogen-activated protein kinase alpha, beta, gamma, and delta in inflammatory cell lineages. (antibody-antibodies.com)
  • The iNOS and MAPK protein expression in the spinal cord dorsal horn were examined by western blot. (qxmd.com)
  • These data are in keeping with our prior results of the vital need for microglia p38 in comparison to p38, and continue steadily to support selective concentrating on from the p38 isoform being a potential healing strategy. (boothampitheatre.com)
  • p-p38 was found predominantly in microglia. (asahq.org)
  • Abs specific for mono- and dual-phophorylated forms of p38 suggested that LPS induces dual phosphorylation of p38alpha, but primarily mono-phosphorylation of p38delta. (antibody-antibodies.com)
  • The results explain why MAP kinases are specific for different activating enzymes, substrates, and inhibitors. (pnas.org)
  • Each MAP kinase is characterized by the substrates it phosphorylates and by the distinct MAP/ERK kinases (MEKs) by which it is preferentially activated. (pnas.org)
  • MAP kinases also share a common specificity for substrates containing proline in the P+1 position ( 25 , 26 ). (pnas.org)
  • The structure is compared with that of ERK2, which we solved previously ( 27 ) to understand how the common mechanism of activation by dual phosphorylation and the common specificity for proline is integrated with the unique specificity of these kinases for their activating enzymes, substrates, and inhibitors. (pnas.org)
  • Activation of substrates of p38 MAPK and cell cycle regulatory proteins were evaluated by western blotting. (arvojournals.org)
  • Western blotting showed activation of ATF2 and HSP27 (substrates of p38 MAPK), and upregulation of cyclin D and downregulation of p27 were induced by inhibiting p38 MAPK. (arvojournals.org)
  • In turn, activated p38 phosphorylates numerous substrates which include kinases such as MAPK-activated protein kinase 2 (MAPKAPK-2) and -3 ( 18 , 34 , 49 ). (asm.org)
  • Substrates of MAPKAPK-2 and -3 include the small heat shock protein hsp27, an abundant cytoplasmic protein of uncertain function ( 15 , 18 , 53 ). (asm.org)
  • Warmth shock protein 27 (Hsp27), leukocyte-specific protein 1 (LSP1), and 5-lipoxygenase (5-LO) were recognized previously as MAPKAPK2 substrates in neutrophils (12, 28, 40). (mindunwindart.com)
  • Sites of activation were visualized using phosphoselective antibodies against activated κ receptors (KOR-P) and against phospho-p38 MAPK. (jneurosci.org)
  • p38 MAPK activation was also assessed by Western blotting, using dual phospho-p38 MAPK (Thr180ITyr182) antibody as well as activating transcription factor 2 (ATF2) activation. (sun.ac.za)
  • p38 also has been shown to phosphorylate post-transcriptional regulating factors like TTP. (wikipedia.org)
  • It is strongly induced by mitogenic and proinflammatory stimuli, superinduced by inhibitors of protein synthesis, and acutely regulated at both transcriptional and posttranscriptional levels ( 17 , 37-39 , 46 , 47 ). (asm.org)
  • Hereditary evaluation of MK2 knockout mice is normally suggestive of a job for p38 MAPK legislation of MK2 in the post-transcriptional legislation of TNF- creation [7]. (bcl-2-protein.com)
  • The general hypothesis is that the preconditioning stimulus will induce the activation of a cascade of stress-responsive kinases, which in turn transduce the stress signal into the generation of a protective protein or activation of a protective kinase. (ahajournals.org)
  • A52-M65E although capable of interacting with TRAF6, was unable to cause either TRAF6 self-association, induce the TRAF6-TAK1 association, or activate p38 MAPK. (ul.ie)
  • These findings establish an obligatory role of DUSP/p38/IRE1α signaling in cardiomyocytes for chamber-specific growth in the postnatal heart. (jci.org)
  • Although phosphorylation of sodium channels has been shown to produce rapid modulation of sodium currents, these studies have been primarily focused on investigating the role of cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) (for review, see Cantrell and Catterall, 2001 ). (jneurosci.org)
  • To explore the role of inflammatory reaction mediated by p38-mitogen activated protein kinase (p38-MAPK) signal path on prevention and treatment of Parkinson disease (PD) model rats by electroacupuncture (EA). (unboundmedicine.com)
  • RWJ-67657 treatment post-MI had beneficial effects on LV remodeling and dysfunction, supporting a key role for p38 MAPK in pathologic cell signaling in these processes and its inhibition as a novel therapy. (unboundmedicine.com)
  • Background The p38 mitogen-activated protein kinase cascade plays an important role in the initiation and progression of inflammatory diseases, including atherosclerosis. (onlinejacc.org)
  • C) establish the role of p38 MAPK in ischaemie PC: trigger or mediator involvement (Chapter 6). (sun.ac.za)
  • Here, we show that the members of the sphingosine kinase (SphK1 and SphK2) and dihydroceramide synthase (LASS1/CerS1, LASS4/CerS4, and LASS5/CerS5) enzyme families each have a unique role in regulating sensitivity to cisplatin and other drugs. (illinois.edu)
  • The p38 inhibitor FR167653 was administered intrathecally 30 min before hind paw plantar incision to determine the role of p38 in postoperative pain. (asahq.org)
  • This study further examines the role of mitogen-activated protein kinase (MAPK) in i.t. (qxmd.com)
  • Nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPK) have been found to play an essential role for the eotaxin-mediated eosinophilia. (edu.hk)