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
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
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
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, 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.

Role of the extracellular signal-regulated protein kinase cascade in human neutrophil killing of Staphylococcus aureus and Candida albicans and in migration. (1/5763)

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

CD40 signaling of monocyte inflammatory cytokine synthesis through an ERK1/2-dependent pathway. A target of interleukin (il)-4 and il-10 anti-inflammatory action. (2/5763)

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

Mesalamine blocks tumor necrosis factor growth inhibition and nuclear factor kappaB activation in mouse colonocytes. (3/5763)

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

Expression of dominant negative Erk2 inhibits AP-1 transactivation and neoplastic transformation. (4/5763)

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

CD45 can act as a negative regulator for the transition from early to late CD4+ CD8+ thymocytes. (5/5763)

The differentiation process from CD4-CD8- double-negative (DN) thymocytes to CD4+CD8+ double-positive (DP) stage is accompanied by vigorous proliferation. The resulting DP cells contain a sizable proportion of large cycling cells, but most DP cells are small resting cells. To explore the molecular mechanisms which regulate cell proliferation of DP thymocytes prior to further development, we used TCR-transgenic (Tg) mice with non-selecting MHC (Tg-Neut), which contain almost exclusively DP thymocytes that are not subject to either positive or negative selection. In Tg-Neut, the thymus contained DP cells of relatively large size, which showed higher extracellular signal-regulated kinase activity and enhanced responsiveness to mitogen compared to small DP cells. This indicates that all the large DP cells in the thymus are not positively selected and that they possess proliferative potential. When Tg-Neut mice were backcrossed with CD45 knockout mice (CD454-/- Tg-Neut), the thymus showed an increase of large DP cells and cycling cells, but a decrease of apoptotic cells. Furthermore, Bcl-2 expression and Jun N-terminal kinase activity, which are associated with resistance to apoptosis, were enhanced. These observations suggest that thymocyte proliferation in the DP stage is suppressed by a CD45-related process with regulation of mitogen-activated protein kinase and Bcl-2 unless DP cells receive TCR-mediated signals.  (+info)

Cot protooncoprotein activates the dual specificity kinases MEK-1 and SEK-1 and induces differentiation of PC12 cells. (6/5763)

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)

Thrombopoietin-induced conformational change in p53 lies downstream of the p44/p42 mitogen activated protein kinase cascade in the human growth factor-dependent cell line M07e. (7/5763)

Thrombopoietin is a cytokine with potent megakaryocytopoietic and thrombopoietic activities in vivo. Wild-type p53 is a conformationally flexible, anti-oncogenic transcription factor that plays a principal role in mediating growth factor withdrawal-induced apoptosis in factor-dependent hematopoietic cells. We recently reported that Tpo induces a conformational change in and functional inactivation of p53, coincident with its anti-apoptotic effects, in the human factor-dependent cell line M07e. In an effort to identify potential signaling cascades through which Tpo illicits these effects on p53, we report here that treating M07e cells with MAPK kinase inhibitor PD98059 dramatically suppressed Tpo-induced conformational change in p53 as well as Tpo-enhanced viability in M07e cells in a p53-dependent manner. Furthermore, the expression of constitutively active Raf1 in M07e cells induced conformational change in p53 independent of Tpo stimulation. Inhibition of the JAK/STAT pathway revealed that JAK/STAT signaling plays an insignificant role in conformational modulation of p53 and apoptosis suppression. Inhibition of phosphatidylinositol-3 kinase did not have a significant effect on p53 conformation but did have a weak but significant effect on Tpo-enhanced viability. Cytokine-induced activation of the MAPK pathway and the subsequent functional neutralization of p53, may be an event by which apoptosis is commonly suppressed in hematopoiesis.  (+info)

p38 but not p44/42 mitogen-activated protein kinase is required for nitric oxide synthase induction mediated by lipopolysaccharide in RAW 264.7 macrophages. (8/5763)

Protein kinase C (PKC)-alpha, -betaI, and -delta are known to be involved in the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages. The role of mitogen-activated protein kinases (MAPK) p44/42 and p38 in the LPS effect was studied further. LPS-mediated NO release and the inducible form of NO synthase expression were inhibited by the p38 inhibitor, SB 203580, but not by the MAPK kinase inhibitor, PD 98059. Ten-minute treatment of cells with LPS resulted in the activation of p44/42 MAPK, p38, and c-Jun NH2-terminal kinase. Marked or slight activation, respectively, of p44/42 MAPK or p38 was also seen after 10-min treatment with 12-O-tetradecanoylphorbol-13-acetate, but c-Jun NH2-terminal kinase activation did not occur. Tyrosine kinase inhibitor, genestein, attenuated the LPS-induced activation of both p44/42 MAPK and p38, whereas the PKC inhibitors, Ro 31-8220 and calphostin C, or long-term treatment with 12-O-tetradecanoylphorbol-13-acetate resulted in inhibition of p44/42 MAPK activation, but had only a slight effect on p38 activation, indicating that LPS-mediated PKC activation resulted in the activation of p44/42 MAPK. Nuclear factor-kappaB (NF-kappaB)-specific DNA-protein-binding activity in the nuclear extracts was enhanced by 10-min, 1-h, or 24-h treatment with LPS. Analysis of the proteins involved in NF-kappaB binding showed translocation of p65 from the cytosol to the nucleus after 10-min treatment with LPS. The onset of NF-kappaB activation correlated with the cytosolic degradation of both inhibitory proteins of NF-kappaB, IkappaB-alpha and IkappaB-beta. IkappaB-alpha was resynthesized rapidly after loss (1-h LPS treatment), whereas IkappaB-beta levels were not restored until after 24-h treatment. SB 203580 but not PD 98059 inhibited the LPS-induced stimulation of NF-kappaB DNA-protein binding. Thus, activation of p38 but not p44/42 MAPK by LPS resulted in the stimulation of NF-kappaB-specific DNA-protein binding and the subsequent expression of inducible form of NO synthase and NO release in RAW 264.7 macrophages.  (+info)

Cytokines may contribute to beta-cell apoptosis in the early stages of type 1 diabetes mellitus. It has been reported recently that interleukin-1 beta (IL-1 beta) induces activation of the mitogen-activated protein kinases (MAPK) p38 and ERK1/2 in neonatal rat islets. Since these kinases may partici …
Platelet-derived growth factor (PDGF) is a family of signaling molecules that stimulates cell growth, survival and migration. PDGF is recognized by specific transmembrane proteins, the PDGF receptors, which relay the signals to the cell activating the Mitogen-activated protein (MAP) kinases and other signaling pathways. Aberrant activation of these pathways is frequently detected in cancer. Hence, the study of these processes is essential for identifying potential drug targets or diagnostic markers.. In paper I, we identified Receptor Subfamily 4 Group A Member 1 NR4A1 to be regulated by PDGF via MAP kinases, clarifying the role of Extracellular signal-regulated kinases (Erk) 1/2, Erk5 and Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in its regulation. NR4A1 was found to be important for the tumorigenic potential, measured as anchorage-independent growth, of glioblastoma cells.. Since the cellular responses elicited by PDGF result from the balance between phosphorylation ...
Figure 4: Effects of 50 μM DHA, EPA, SA, and PA or 25 μM OA and LA on IL-2-induced extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Lymphocytes were incubated with 5 μg/mL ConA for 24 h. Afterwards, lymphocytes were washed with PBS and cultured with the different fatty acids in the presence or absence of IL-2 (30 ng/mL) for 1 h. Total proteins were extracted from lymphocytes for western-blotting analysis. Blots were analyzed by densitometry and the results normalized to their respective controls, which were set to a value of 100% for each experiment. The values are presented as the means ± SEM. ###p,0.001 for comparison with the control in the absence IL-2); *p,0.05, **p,0.01, and ***p,0.001 for comparison with the control treated with IL-2 ...
The Alpha SureFire® Ultra™ HV Multiplex p-ERK 1/2 + Total ERK assay kit is used to measure both the phosphorylation (Thr202/Tyr204) and total levels of endogenous
Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signal-regulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a ...
Ovarian cancer is a complex disease with heterogeneity among the gene expression molecular subtypes (GEMS) between patients. Patients with tumors of a mesenchymal (Mes) subtype have a poorer prognosis than patients with tumors of an epithelial (Epi) subtype. We evaluated GEMS of ovarian cancer patients for molecular signaling profiles and assessed how the differences in these profiles could be leveraged to improve patient clinical outcome. Kinome enrichment analysis identified AXL as a particularly abundant kinase in Mes-subtype tumor tissue and cell lines. In Mes cells, upon activation by its ligand GAS6, AXL coclustered with and transactivated the receptor tyrosine kinases (RTKs) cMET, EGFR, and HER2, producing sustained extracellular signal-regulated kinase (ERK) activation. In Epi-A cells, AXL was less abundant and induced a transient activation of ERK without evidence of RTK transactivation. AXL-RTK crosstalk also stimulated sustained activation of the transcription factor FRA1, which ...
Although transforming growth factor β (TGF-β) is known to be a potent growth inhibitor of breast cancer cells (BCCs), the signaling mechanisms mediating TGF-β responses have not been defined. We have demonstrated previously that TGF-β can activate Ras and extracellular signal-regulated kinase (ERK) 1 in untransformed epithelial cells (K. M. Mulder and S. L. Morris, J. Biol. Chem., 267: 5029-5031, 1992; M. T. Hartsough and K. M. Mulder, J. Biol. Chem., 270: 7117-7124, 1995). We have also shown that TGF-β signaling is altered in epithelial cells when Ras activation is blocked (Hartsough et al., J. Biol. Chem., 271: 22368-22375). Here we demonstrate the ability of the TGF-β3 isoform to activate the signaling component ERK2 in TGF-β-sensitive BCCs but not in TGF-β-resistant cells. The ERK2 isoform was activated by 6-fold within 10 min of TGF-β3 addition to the TGF-β-sensitive BCC line Hs578T. Moreover, the IC50 for inhibition of DNA synthesis by TGF-β3 in this cell line correlated with ...
Gooney M, Shaw K, Kelly Á, OMara SM, Lynch MA. Gooney M, Shaw K, Kelly A, OMara SM, Lynch MA. Gooney M, Shaw K, Kelly A, OMara SM, Lynch MA., Long-term potentiation and spatial learning are associated with increased phosphorylation of TrkB and extracellular signal-regulated kinase (ERK) in the dentate gyrus: evidence for a role for brain-derived neurotrophic factor., Behavioural Neuroscience, 116, (3), 2002, p455 - 463 Journal Article, 2002 URL ...
To determine how extracellular signal-regulated kinases (ERK) 1/2 promote mammary tumorigenesis, we examined the real-time behavior of cells in an organotypic culture of the mammary glandular epithelium. Inducible activation of ERK1/2 in mature acini elicits cell motility and disrupts epithelial arc …
The extracellular-signal-regulated kinase (ERK) pathway is one of the major signaling cassettes of the mitogen activated protein kinase (MAPK) signaling ..
The mammalian genome contains two mitogen-activated protein kinase (MAPK) kinase (MEK)-encoding genes, Mek1 and Mek2. MEKs phosphorylate and activate the two extracellular signal-regulated kinase (ERK) isoforms ERK1 and ERK2. Mek1−/− embryos die due to placental defects, whereas Mek2−/− mice survive with a normal life span and fertility, suggesting that MEK1 has functions not shared by MEK2. However, most Mek1+/−Mek2+/− embryos also die from placental defects, indicating that both Mek genes contribute to placental development. To assess the functional specificity of the Mek1 and Mek2 genes, we produced a Mek1 knock-in allele in which the Mek2 coding sequences were placed under the control of Mek1 regulatory sequences (Mek12 allele). Mek12/2 mice were viable with no apparent phenotype, indicating rescue by MEK2 and functional redundancy between the two MEK proteins. However, Mek12/− embryos with Mek2 in only one of the Mek1 alleles and the other Mek1 allele null died from abnormal ...
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008 ...
Platelet-derived growth factor (PDGF) is a family of signaling molecules that stimulates cell growth, survival and migration. PDGF is recognized by specific transmembrane proteins, the PDGF receptors, which relay the signals to the cell activating the Mitogen-activated protein (MAP) kinases and other signaling pathways. Aberrant activation of these pathways is frequently detected in cancer. Hence, the study of these processes is essential for identifying potential drug targets or diagnostic markers.. In paper I, we identified Receptor Subfamily 4 Group A Member 1 NR4A1 to be regulated by PDGF via MAP kinases, clarifying the role of Extracellular signal-regulated kinases (Erk) 1/2, Erk5 and Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in its regulation. NR4A1 was found to be important for the tumorigenic potential, measured as anchorage-independent growth, of glioblastoma cells.. Since the cellular responses elicited by PDGF result from the balance between phosphorylation ...
The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAP kinase) family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described.[3] ...
Ran-Binding Protein M (RanBPM) has been previously shown to inhibit c-Raf expression, however how this was achieved remains unclear. c-Raf is the central component of the extracellular signal-regulated kinase (ERK) pathway which has been linked to many cancer types. Furthermore, RanBPM was recently identified as part of the E3 ubiquitin ligase complex and the CTLH (C-terminal to LisH) complex (McTavish et al., 2019). Lastly, RanBPM has been linked to various signaling pathways related to numerous cellular processes which include - apoptosis, cell adhesion, migration, transcription, nuclear-cytoplasmic transport and also plays a significant role during development (Salemi et al., 2017). ...
TY - JOUR. T1 - Intestinal trefoil factor (TFF-3) and extracellular signal-regulated kinase (ERK) in cholangiocarcinoma. AU - Ailawadhi, Sikander. AU - Nagase, Hiroki. AU - Khoury, Thaer. AU - Yu, Jihnhee. AU - Tan, Dongfeng. AU - Black, Jennifer. AU - Brattain, Michael. AU - Javle, Milind. PY - 2007/7. Y1 - 2007/7. N2 - Background/Aims: The mucin-associated trefoil factor (TFF) peptides are integral to cytoprotection. TFF-3 is aberrantly expressed in colorectal and hepatocellular cancer and associated with an invasive phenotype. TFF-3 is also expressed in normal biliary epithelium. However, its role in biliary cancers is unknown. The biological effects of TFFs may result from EGFR, PI3 kinase, COX-2 and STAT-mediated signaling. We investigated the expression of TFF-3, Erk, Akt, EGFR and COX-2 in biliary cancer. Methodology: Twenty-four consecutive cases of cholangiocarcinoma treated from 1996-2002 were studied. Immunohistochemistry was performed using monoclonal antibodies to TFF-3, EGFR, ...
Mutational activation of Ras (H-Ras, K-Ras, and N-Ras) is associated with a diverse spectrum of human cancers (1). For example, 50% of colorectal carcinomas harbor mutated K-RAS, and 25% of melanomas contain mutated N-RAS alleles. Consequently, there is considerable interest and effort in the development of anti-Ras strategies for cancer treatment (2, 3). One approach involves the inhibition of Ras-mediated signal transduction. Of these efforts, inhibitors of signaling mediated by the Ras effectors, the Raf serine/threonine kinases (c-Raf-1, A-Raf, and B-Raf), have attracted the most interest. Ras promotes Raf activation, which in turn, activates the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) 1 and MEK2 dual-specificity protein kinases. MEK1/2 kinases then activate the ERK1 and ERK2 mitogen-activated protein kinases and inhibitors of this cascade have been developed and are currently under evaluation in clinical trials (4). These include kinase ...
We aimed to investigate specific roles of mitogen-activated protein kinases (MAPK) in the deterioration of endothelial function during the progression of diabetes and the potential therapeutic effects of MAPK inhibitors and agonists in the amelioration of endothelial function. Protein expression and phosphorylation of p38, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (Erk) were assessed in mesenteric arteries of 3- (3M) and 9-month-old (9M) male diabetic and control mice. The expression of p38, JNK, and Erk was comparable in all groups of mice, but the phosphorylation of p38 and JNK was increased in 3M and further increased in 9M diabetic mice, whereas the phosphorylation of Erk was substantially reduced in 9M diabetic mice. NADPH oxidase-dependent superoxide production was significantly increased in vessels of two ages of diabetic mice. Inhibition of either p38 with SB203580 or JNK with SP600125 reduced superoxide production and improved shear stress-induced ...
Gene Information This gene encodes an evolutionarily conserved protein associated with cell apoptosis. The protein interacts with the serine/threonine protein kinase MST4 to modulate the extracellular signal-regulated kinase (ERK) pathway. It also interacts with and is phosphoryated by serine/threonine kinase 25 and is thought to function in a signaling pathway essential for vascular developent. Mutations in this gene are one cause of cerebral cavernous malformations which are vascular malformations that cause seizures and cerebral hemorrhages. Multiple alternatively spliced variants encoding the same protein have been identified. [provided by RefSeq Jul 2008]. ...
History and purpose: Trabecular meshwork (TM) can be an ocular cells mixed up in rules of aqueous humour outflow and intraocular pressure (IOP). and mobilization of intracellular Ca2+ shops. A PTX-sensitive upsurge in extracellular signal-regulated kinase (ERK1/2) phosphorylation was also seen in response to WIN55 212 indicative of the Gi/o signalling pathway. CB1-Gq/11 coupling to activate PLC-dependent raises in Ca2+ were particular to WIN55 212 and werent observed with additional.. Read More. ...
Huntingtons disease (HD) is an inherited, progressive and ultimately fatal neurodegenerative disorder that is characterized by psychiatric, cognitive and motor symptoms. Among the pathways implicated in HD are those involving mitogen-activated protein kinase signaling and particularly the Ras-extracellular signal-regulated kinase (ERK) cascade. Studies in both cells and animal models suggest that ERK activation might provide a novel therapeutic target for the treatment of HD but compounds that specifically activate ERK are few. To test the hypothesis that pharmaceutical activation of ERK might be protective for HD, a polyphenol, fisetin, which was previously shown to activate the Ras-ERK cascade, was tested in three different models of HD: PC12 cells expressing mutant Httex1 under the control of an inducible promoter, Drosophila expressing mutant Httex1 and the R6/2 mouse model of HD. The results indicate that fisetin can reduce the impact of mutant huntingtin in each of these disease models. ...
|p|SL-327 is a selective inhibitor of MEK1 and MEK2 with IC50 values of 0.18 and 0.22μM,  respectively.|br /|MEK1 and MEK2 (ERK) are a kinase enzyme which phosphorylate mitogen-activated protein kinase (MAPK). Extracellular signal-regulated kinase
Fujishita Teruaki , Kajino-Sakamoto Rie , Kojima Yasushi , Taketo Makoto Mark , Aoki Masahiro Extracellular signal-regulated kinase is an MAPK that is most closely associated with cell proliferation, and the MEK/ERK signaling pathway is implicated in various human cancers. Although epidermal g … Cancer Science 106(6), 692-699, 2015-06 IR Ichushi Web ...
ERK1 / ERK2, 0.1 ml. Erk1 and Erk2 are closely related mitogen activated protein (MAP) kinases which are activated by many growth factors, mitogens and differentiation-promoting agents via a protein kinase cascade.
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. ...
AIMS/HYPOTHESIS: The beta cell destruction and insulin deficiency that characterises type 1 diabetes mellitus is partially mediated by cytokines, such as IL-1beta, and by nitric oxide (NO)-dependent and -independent effector mechanisms. IL-1beta activates mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK), and the nuclear factor kappa B (NFkappaB) pathway. Both pathways are required for expression of the gene encoding inducible nitric oxide synthase (iNOS) and for IL-1beta-mediated beta cell death. The molecular mechanisms by which these two pathways regulate beta cell Nos2 expression are currently unknown. Therefore, the aim of this study was to clarify the putative crosstalk between MAPK and NFkappaB activation in beta cells. MATERIALS AND METHODS: The MAPKs ERK, p38 and JNK were inhibited by SB203580, PD98059 or Tat-JNK binding domain or by cells overexpressing the JNK binding domain. The effects
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 ...
Mitogen-activated protein kinases (MAPKs) are proline-directed serine and threonine protein kinases that regulate numerous physiological cell responses including: embryogenesis, cell differentiation, proliferation, migration, apoptosis and death. Extracellular signal-regulated kinases (ERKs) 1 and 2 (ERK1/2), also known as p44 MAPK and p42 MAPK respectively, belong to one of the five major groups of MAPKs. Closely-related ERK1/2 isoforms are uniquely activated by several extracellular signals including growth factors, cytokines, hormones, and neuro-transmitters. Activation of ERK1/2 by the upstream kinases MEK1 and MEK2 occurs via dual phosphorylation on specific threonine (Thr202) and tyrosine (Tyr204) residues on the T*EY* motif. MEK1 and MEK2 are activated through receptors (tyrosine kinases or integrins) via pathways involving adaptor proteins, guanine nucleotide exchange factors, small GTP binding proteins, and MAPKKs. Activated ERK1/2 phosphorylates both, cytosolic (SOS, MNK1/2, RSKs) and ...
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as MAPK1, extracellular signal-regulated kinase 2, PRKM1, PRKM2, ERT1, p41-ERK1, p41-MAPK, p42-MAPK, MAP kinase 1, MAP kinase 2, MAPK1, MAPK2, p38, p40, and p41.. ...
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as MAPK1, extracellular signal-regulated kinase 2, PRKM1, PRKM2, ERT1, p41-ERK1, p41-MAPK, p42-MAPK, MAP kinase 1, MAP kinase 2, MAPK1, MAPK2, p38, p40, and p41.. ...
Colorectal cancers (CRCs) that are sensitive to the anti-epidermal growth factor receptor (EGFR) antibodies cetuximab or panitumumab almost always develop resistance within several months of initiating therapy. We report the emergence of polyclonal KRAS, NRAS, and BRAF mutations in CRC cells with acquired resistance to EGFR blockade. Regardless of the genetic alterations, resistant cells consistently displayed mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) activation, which persisted after EGFR blockade. Inhibition of MEK1/2 alone failed to impair the growth of resistant cells in vitro and in vivo. An RNA interference screen demonstrated that suppression of EGFR, together with silencing of MEK1/2, was required to hamper the proliferation of resistant cells. Indeed, concomitant pharmacological blockade of MEK and EGFR induced prolonged ERK inhibition and severely impaired the growth of resistant tumor cells. Heterogeneous and concomitant mutations in ...
Extracellular signal-regulated kinase (ERK) activation has been implicated in cell motility and invasion. In this study, we demonstrated that the steady-state levels of activated ERK1/2 correlated with the degree of invasiveness and metastatic potential of three Dunning cancer cell lines, originating from the same parental tumor. Inhibition of mitogen-activated protein kinase kinase 1 (MEK1), an upstream regulator of ERK1/2, with PD98059 resulted in a dose-dependent reduction of invasiveness with different IC 50 values in the three Dunning cell lines. These results suggest that ERK is, at least in part, responsible for regulating invasiveness and may underlie the differences in the metastatic ability of the cell lines ...
MAPKK 6 is a member of the dual specificity protein kinase family, which functions as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. As an essential component of p38 MAP kinase mediated signal transduction pathway, this gene is involved in many cellular processes such as stress-induced cell cycle arrest, transcription activation and apoptosis.[6] ...
Mammalian MAPK pathways are difficult to assign because of the many kinases, cell lines, tissue types, experimental conditions (which can yield conflicting results) and functional redundancy. Genetic analysis in Drosophila melanogaster and Caenorhabditis elegans has greatly helped, however (Chang and Karin, 2001). Five families of MAPKs have been defined in mammalian cells: extracellular signal-regulated kinases (ERK1 and ERK2), Jun N-terminal kinases (JNK1, JNK2 and JNK3); p38 kinase isozymes (p38α, p38β, p38γ and p38δ); ERK3/ERK4; and ERK5 (Davis, 2000; Chen et al., 2001; Chang and Karin, 2001; Johnson and Lapadat, 2002; Roux and Blenis, 2004). The first three, and their activators, are implicated in human diseases and are targets for drug development (Manning and Davis, 2003; English and Cobb, 2002). Mammalian MAPK modules associate with numerous scaffold proteins that regulate their activity and localization in various cells (Morrison and Davis, 2003). The scaffold proteins can bind to ...
TY - JOUR. T1 - Changes in corneal basal epithelial phenotypes in an altered basement membrane. AU - Wang, I. Jong. AU - Tsai, Jui-Fang. AU - Yeh, Lung Kun. AU - Tsai, Ryan Yao Nien. AU - Hu, Fung Rong. AU - Kao, Winston W Y. PY - 2011. Y1 - 2011. N2 - Background: To examine the corneal epithelial phenotype in an altered basement membrane. Methodology/Principal Findings: Corneas from 9 patients with symptoms of continuous unstable corneal curvature (CUCC) were harvested by penetrating keratoplasty and subjected to histology examination and immunohistochemical staining with transactivating and N-terminally truncated pP63 transcript (DNp63), cytokeratin 3 (Krt3), ATP-binding cassette subfamily G member 2 (ABCG2), connexin 43 (CX43), p38 mitogen-activated protein kinases (p38MAPK), activating protein 2 (TFAP2), and extracellular signal-regulated kinase (Erk1/2) monoclonal antibodies. Positive immunostaining with ABCG2, p38MAPK, and TFAP2 monoclonal antibodies was observed in the basal epithelial ...
Purpose: Abnormal signaling through receptor tyrosine kinase (RTK) moieties is important in tumorigenesis and drug targeting of colorectal cancers. Wild-type KIT (WT-KIT), a RTK that is activated upon binding with stem cell factor (SCF), is highly expressed in some colon cancers; however, little is known about the functional role of SCF-dependent KIT activation in colon cancer pathogenesis. We aimed to elucidate the conditions and roles of WT-KIT activation in colon cancer tumorigenesis.Experimental Design: Colorectal cancers with KIT expression were characterized by immunoblotting and immunohistochemistry. The biologic alterations after KIT-SCF binding were analyzed with or without protein kinase C (PKC) activation.Results: We found that WT-KIT was expressed in a subset of colon cancer cell lines and was activated by SCF, leading to activation of downstream AKT and extracellular signal-regulated kinase (ERK) signaling pathways. We also showed that KIT expression gradually decreased, after ...
Background MEK1/2 is a serine/threonine protein that phosphorylates extracellular signal-regulated kinase (ERK1/2). Cerebral ischemia results in enhanced expression of cerebrovascular contractile...
TY - JOUR. T1 - Cell proliferation is insufficient, but loss of tuberin is necessary, for chemically induced nephrocarcinogenicity. AU - Yoon, Hae Seong. AU - Monks, Terrence J.. AU - Everitt, Jeffrey I.. AU - Walker, Cheryl L.. AU - Lau, Serrine S.. N1 - Copyright: Copyright 2020 Elsevier B.V., All rights reserved.. PY - 2002. Y1 - 2002. N2 - Although 2,3,5-tris-(glutathion-S-yl)hydroquinone (TGHQ; 2.5 μmol/kg ip) markedly increased cell proliferation within the outer stripe of the outer medulla (OSOM) of the kidney in both wild-type (Tsc2+/+) and mutant Eker rats (Tsc2EK/+), only TGHQ-treated Tsc2EK/+ rats developed renal tumors, indicating that cell proliferation per se was not sufficient for tumor development. Tuberin expression was initially induced within the OSOM after TGHQ treatment but was lost within TGHQ-induced renal tumors. High extracellular signal-regulated kinase (ERK) activity occurred in the OSOM of Tsc2EK/+ rats at 4 mo and in TGHQ-induced renal tumors. Cyclin D1 was also ...
The Cover. Phospholipids and lipid second messengers are important mediators of mitogenic signal transduction, but their involvement in oncogenesis and their potential as anticancer drug targets are scarcely studied. A role for phospholipases in the previously described antisignaling properties of the antitumor agent, SC-ααδ9, was investigated based on a hypothesis developed from molecular modeling studies, which suggested significant structural similarity between SC-ααδ9 (shown in yellow) and the model phospholipid, phosphatidic acid (shown in atom-specific colors). In support of this hypothesis, SC-ααδ9 was found to selectively inhibit phospholipase C (PLC) but not phospholipase D (PLD), and to cause a reduction in the activation of extracellular signal-regulated kinase (Erk) by oncogenic Ras. Modifications in one of the hydrophobic side chains were sufficient to abolish PLC inhibitory activity. For details, see 885 in this issue.. ...
Fingerprint Dive into the research topics of Activin A stimulates mitogenesis in Swiss 3T3 fibroblasts without activation of mitogen-activated protein kinases. Together they form a unique fingerprint. ...
Recombinant Mitogen-Activated Protein Kinase 8 (MAPK8) Protéine. Origine: Humain. Source: Baculovirus infected Insect Cells. Commandez ABIN593493.
Recombinant Mitogen-Activated Protein Kinase 8 (MAPK8) Protein (GST tag). Spezies: Human. Quelle: Wheat germ. Jetzt Produkt ABIN1310303 bestellen.
The discovery of resolvins has been a main breakthrough for understanding the processes involved in resolution of inflammation. and protectins [52]. The second step during resolvin synthesis is the transformation of DHA to 17systems depending on the cell type and tissue. RvE2 also enhanced phagocytosis and interleukin (IL)-10 production, suggesting that these RvE2 actions may be transduced by additional receptors that have yet to be discovered. Physique 1 Resolvin signaling pathways in different cell types. (A) In polymorphonuclear neutrophils (PMNs), RvE1 binds to ChemR23, activates Gi/o, which activates extracellular signal-regulated kinase (ERK), and eventually blocks TNF- signaling. … The RvD family shares comparable signaling mechanisms as the RvE family, as LRP2 they also activate GPCRs. Specifically, RvD1 activity is usually mediated by two GPCRs termed ALX/FPR2 and GPR32 [81,91]. The ALX/FPR2 has been shown to bind lipid and protein ligands, eliciting either anti-inflammatory or ...
Protein target information for Mitogen-activated protein kinase (pig). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
ERK1 and ERK2 (also known as MAPK3 and MAPK1) are 44 and 42 kDa Ser/Thr kinases, respectively. They are part of the Ras-Raf-ERK signal transduction cascade often found downstream of growth factor receptor activation. ERK1 and ERK2 were initially isolated and cloned as kinases activated in response to insulin and NGF. They are expressed in most, if not all, mammalian tissues. Dual threonine and tyrosine phosphorylation activate both ERKs, at Thr202/Tyr204 for human ERK1 and Thr185/Tyr187 for human ERK2 ...
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... ...
KO validated. Cited in 1 publication. View Human/Mouse Phospho-ERK1 (ERK1 T202/Y204, ERK2 T185/Y187) Antibody (MAB18251) validated in Human and Mouse.
stripping too much? - posted in SDS-PAGE and Western Blotting: Hi, I am doing some western blots, but seem to be having a little problem with getting my loading controls working. I have been looking at Phospho-ERK and phospho-p38, I am getting clear bands when I stain (albeit not much variation between the different samples, but thats a different problem) I am attempting to then strip my membrane to look at Total ERK or p38, or beta-actin, but then dont appear to get any bands. I am us...
TY - JOUR. T1 - Activation of mitogen-activated protein kinases by lysophosphatidylcholine- induced mitochondrial reactive oxygen species generation in endothelial cells. AU - Watanabe, Nobuo. AU - Zmijewski, Jaroslaw W.. AU - Takabe, Wakako. AU - Umezu-Goto, Makiko. AU - Le Goffe, Claire. AU - Sekine, Azusa. AU - Landar, Aimee. AU - Watanabe, Akira. AU - Aoki, Junken. AU - Arai, Hiroyuki. AU - Kodama, Tatsuhiko. AU - Murphy, Michael P.. AU - Kalyanaraman, Raman. AU - Darley-Usmar, Victor M.. AU - Noguchi, Noriko. PY - 2006/5. Y1 - 2006/5. N2 - Lysophosphatidylcholine (lysoPC) evokes diverse biological responses in vascular cells including Ca2+ mobilization, production of reactive oxygen species, and activation of the mitogen-activated protein kinases, but the mechanisms linking these events remain unclear. Here, we provide evidence that the response of mitochondria to the lysoPC-dependent increase in cytosolic Ca2+ leads to activation of the extracellular signal-regulated kinase (ERK) ...
PubMed journal article: Activation of extracellular signal-regulated protein kinase in sensory neurons after noxious gastric distention and its involvement in acute visceral pain in rats. Download Prime PubMed App to iPhone, iPad, or Android
Interferon alpha (IFN-α) is the key component of the therapy for hepatitis C virus (HCV) infection. IFN-α exerts anti-HCV activity by targeting certain signaling pathways. Using infectious HCV culture system in human hepatoma Huh7.5.1 cells, we analyzed functional relevance of extracellular signal-regulated kinase (ERK) pathway for IFN-α-mediated anti-HCV activity. IFN-α treatment resulted in activation of ERK pathway by increasing phosphorylation of c-Raf, MEK, and ERK1/2 in Huh7.5.1 cells, whereas HCV impaired such activation. IFN-α-dependent ERK1/2 phosphorylation was blocked by MEK inhibitor U0126. Pharmacological inhibition of ERK1/2 by U0126 or siRNA-mediated knockdown of ERK1/2 resulted in suppressive effects on HCV RNA levels and expression of HCV nonstructural protein 3 and envelope protein 2, establishing an important role for ERK pathway in HCV replication. Moreover, induction of a set of antiviral genes by IFN-α was enhanced in HCV-infected Huh7.5.1 cells due to the ERK1/2 knockdown,
TY - JOUR. T1 - Role of EGF receptor and Pyk2 in endothelin-1-induced ERK activation in rat cardiomyocytes. AU - Kodama, Hiroaki. AU - Fukuda, Keiichi. AU - Takahashi, Toshiyuki. AU - Sano, Motoaki. AU - Kato, Takahiro. AU - Tahara, Satoko. AU - Hakuno, Daihiko. AU - Sato, Toshihiko. AU - Manabe, Tomohiro. AU - Konishi, Fusako. AU - Ogawa, Satoshi. PY - 2002/2/1. Y1 - 2002/2/1. N2 - G protein-coupled receptor (GPCR)-evoked signal transduction pathways leading to the activation of extracellular signal-regulated kinases (ERK) are quite different among cell types. In cardiomyocytes, much attention has been focused on the activation of protein kinase C (PKC) or mobilization of intracellular Ca2+ ([Ca2+]i), however, the contributions of tyrosine kinases are controversial. In the present study, we characterized the signaling pathways involving tyrosine kinases, Pyk2 and epidermal growth factor receptor (EGFR), and their contribution to ERK activation in cultured cardiomyocytes. We initially ...
Late cerebral ischemia carries high morbidity and mortality after subarachnoid hemorrhage (SAH) due to reduced cerebral blood flow (CBF) and the subsequent cerebral ischemia which is associated with upregulation of contractile receptors in the vascular smooth muscle cells (SMC) via activation of mitogen-activated protein kinase (MAPK) of the extracellular signal-regulated kinase (ERK)1/2 signal pathway. We hypothesize that SAH initiates cerebrovascular ERK1/2 activation, resulting in receptor upregulation. The raf inhibitor will inhibit the molecular events upstream ERK1/2 and may provide a therapeutic window for treatment of cerebral ischemia after SAH. Here we demonstrate that SAH increases the phosphorylation level of ERK1/2 in cerebral vessels and reduces the neurology score in rats in additional with the CBF measured by an autoradiographic method. The intracisternal administration of SB-386023-b, a specific inhibitor of raf, given 6 h after SAH, aborts the receptor changes and protects the brain
Octadecaneuropeptide (ODN) and its precursor diazepam-binding inhibitor (DBI) are peptides belonging to the family of endozepines. Endozepines are exclusively produced by astroglial cells in the central nervous system of mammals, and their release is regulated by stress signals and neuroactive compounds. There is now compelling evidence that the gliopeptide ODN protects cultured neurons and astrocytes from apoptotic cell death induced by various neurotoxic agents. In vivo, ODN causes a very strong neuroprotective action against neuronal degeneration in a mouse model of Parkinsons disease. The neuroprotective activity of ODN is based on its capacity to reduce inflammation, apoptosis, and oxidative stress. The protective effects of ODN are mediated through its metabotropic receptor. This receptor activates a transduction cascade of second messengers to stimulate protein kinase A (PKA), protein kinase C (PKC), and mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK)
C2C12 myotubes exposed to VLDL showed increased levels of ER stress and inflammatory markers whereas peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and AMP-activated protein kinase (AMPK) levels were reduced and the insulin signalling pathway was attenuated. The effects of VLDL were also observed in isolated skeletal muscle incubated with VLDL. The changes caused by VLDL were dependent on extracellular signal-regulated kinase (ERK) 1/2 since they were prevented by the ERK1/2 inhibitor U0126 or by knockdown of this kinase by siRNA transfection. ApoCIII mimicked the effects of VLDL and its effects were also blocked by ERK1/2 inhibition, suggesting that this apolipoprotein was responsible for the effects of VLDL. Skeletal muscle from transgenic mice overexpressing apoCIII showed increased levels of some ER stress and inflammatory markers and increased phosphorylated ERK1/2 levels, whereas PGC-1α levels were reduced, confirming apoCIII effects in vivo. Finally, incubation ...
Compounds. Compound I [IUPAC name: N-(3-fluoro-4-((7-methoxy-4-quinolinyl)oxy)phenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide] was synthesized at Amgen, Inc. The MAPK/extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2) inhibitor U0126 was obtained from Calbiochem.. Cells. KATOIII (gastric), PC3 (prostate), HT-29 (colorectal), Colo205 (colorectal), BxPC3 (pancreatic), and U-87 MG (glioblastoma) cancer cell lines were obtained from the American Type Culture Collection. NIH3T3 TPR-Met or NIH3T3 RON cells were generated by stable transfection of TPR-Met, a constitutively active, ligand-independent form of c-Met ( 31) or wild-type RON in NIH3T3 cells. Cells were grown as monolayers using standard cell culture conditions.. Antibodies and reagents. Antibodies against c-Met (C-12), RON (C-20), and actin (1615-R) were acquired from Santa Cruz Biotechnology. Antibodies against phospho-c-Met (Y1234/1235), phospho-Gab1 (Y627), phospho-ERK1/2 ...
Extracellular signal-regulated kinase (ERK)-2 is presumed to play an important role in the development of post-traumatic joint contractures. Using a rat injury model, we investigated whether treatment with ERK2 small interfering RNA (siRNA) could reduce the extent of joint capsule fibrosis after an induced injury. Rats were separated into three groups (n = 32 each): non-operated control group, operated contracture group and contracture-treatment group. Stable post-traumatic joint contracture was created through surgical intra-articular joint injury followed by eight weeks of immobilization. In the contracture-treatment group, the rats were treated with lentivirus (LV)-mediated ERK2 siRNA at days 3 and 7 post-surgery. The posterior joint capsule was assessed by western blotting, immunohistochemistry and biochemical analysis for changes in ERK2, phosphorylated (p)-ERK2, myofibroblast, total collagen and relative collagen Type III expression level. Biomechanical testing was used to assess the development
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. ...
We investigated in IMR90 cells the effects of N-formyl-Met-Leu-Phe (N-fMLP) and WKYMVm (W peptide) on activation of the NADPH oxidase-like enzyme. In serum-deprived human fibroblasts, exposure to 100 microM N-fMLP or 10 microM peptide W for 1 min induced both p47phox translocation and NADPH-dependent superoxide generation. These effects were in large part mediated by prevention of the rapid activation of extracellular signal-regulated kinases (ERKs) by preincubation with the MEK1 inhibitor PD098059. Furthermore, responses to N-fMLP or W peptide were inhibited by pertussis toxin, suggesting the involvement of a seven-transmembrane G protein-coupled receptor(s) for peptides. RT-PCR experiments demonstrated the expression in these cells of the low-affinity receptor FPRL1, but not the high-affinity receptor FPR. Incubation with radiolabeled WKYMVm, which had a higher efficiency on FPRL1, revealed that human fibroblasts express binding sites for 125I-WKYMVm that are specifically displaced by ...
Constitutive activation of the mitogen-activated protein kinase (MAPK) pathway is implicated in the development and progression of many human cancers, including
Söderström T.S., Poukkula M., Holmström T.H., et al. Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in activated T cells abrogates TRAIL-induced apoptosis upstream of the mitochondrial amplification loop and caspase-8. (англ.) // J. Immunol. (англ.)русск. : journal. - 2002. - Vol. 169, no. 6. - P. 2851-2860. - PMID 12218097. ...
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...
Fingerprint Dive into the research topics of Involvement of mitogen-activated protein kinase in hippocampal long-term potentiation. Together they form a unique fingerprint. ...
Although several multiprotein complexes containing MAPKs (mitogen-activated protein kinases) have been identified using overexpression of kinases and scaffold proteins, the components of the complexes and their physical properties at endogenous expression levels have not been defined. We characterized a large protein complex containing a nerve-growth-factor-activated ERK (extracellular-signal-regulated kinase) and MEK (MAPK/ERK kinase) in rat pheochromocytoma (PC12) cells. This protein complex fractionated into a high-speed pellet and was resistant to non-ionic detergent treatments that solubilized membranes. Disruption of protein-protein interactions by treatment with high salt was required to facilitate immunoprecipitation of active ERK1 and co-precipitation of MEK1. Microtubule fragments were also present in the detergent-resistant high-speed pellet, and some kinases were bound to them, especially ERK1b (an alternatively spliced isoform of ERK1), which showed a strong preference for binding ...
A novel role of differentiation-inducing factor-1 in Dictyostelium development, assessed by the restoration of a developmental defect in a mutant lacking mitogen-activated protein kinase ERK2 ...
We also took aliquots treated identically to those of Fig. 1A but, instead of blotting the samples, we washed them into MAP kinase buffer and measured the activities of the GST-hERK1 aliquots against a myelin basic protein (MBP) substrate. The results from one representative experiment are shown in Fig. 1B, beneath the relevant gel lane, together with the quantitated activities. Recombinant GST-hERK1 itself had very little activity (Fig. 1B, lane 1), which remained the same after incubation in sea urchin extract (Fig. 1B, lane 2). However, when activated with MEK alone for 1 hour, it showed around a tenfold activation over baseline (Fig. 1B, lane 3). Addition to the sea urchin embryo extract and incubation for 15 minutes at room temperature elevated the activity of the recombinant kinase a further tenfold (Fig. 1B, lane 4). A fivefold increase in the amount of the cell extract (to 75 μg total protein) did not increase the activity of the aliquot (not shown), indicating that soluble factors were ...
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 ...
Although extracellular signal-regulated kinase (ERK) ? has been shown for its necessity for a variety of the Raf/MEK/ERK pathway signaling its sufficiency in mediating the pathway signaling has not been firmly established. promote ERK autophosphorylation is sufficient to induce growth arrest and differentiation whereas ERK2-I84A and ERK2-R65S/D319N are not as effective. When compared to the […]. ...
Importantly, this work underscores the significance of ERK-dependent signaling in TAA development in MFS. ERK-dependent signaling has been demonstrated previously to contribute to aortic dilation in MFS (18, 20). ANG stimulates ERK1/2 activation via the AT1aR and both Gq proteins as well as βarr2. ERK activated via these different transducers is both spatially and temporally distinct (3) with unique functional outcomes (22, 34). Whereas βarr2-dependent ERK activation appears to lead to TGF-β-independent, proaneurysmal signaling, ANG-stimulated activation of TGF-β signaling has been reported previously to involve Gq proteins (35). Interestingly, G protein- and βarr2-dependent ERK1/2 activation has been shown to require EGFR transactivation in VSMC (21), suggesting the EGFR could serve as a mediator of AT1aR-mediated pathogenic signaling in MFS. This hypothesis is supported by our preliminary work demonstrating a reduction in aortic dilation in FbnC1039G/+ mice treated with the EGFR inhibitor ...
ERK1 (phospho Thr202) + ERK2 (phospho Thr185) antibody (mitogen-activated protein kinase 3) for WB. Anti-ERK1 (phospho Thr202) + ERK2 (phospho Thr185) pAb (GTX52319) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
ERK1 / ERK2, 0.1 mg. The activation of signal transduction pathways by growth factors, hormones and neurotransmitters is mediated through two closely related MAP kinases, p44 and p42, designated extracellular-signal related kinase 1 (ERK 1) and ERK 2,
Roche was developing RG 7167 (also called RO 4987655), an orally active, small-molecule, mitogen-activated ERK-kinase (MEK) inhibitor, for the treatment of
... is a protein that in humans is encoded by the MAP3K6 gene. This gene encodes a ... "Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric ... "Entrez Gene: Mitogen-activated protein kinase kinase kinase 6". Retrieved 2018-07-10. Takeda K, Shimozono R, Noguchi T, Umeda T ... Eto N, Miyagishi M, Inagi R, Fujita T, Nangaku M (April 2009). "Mitogen-activated protein 3 kinase 6 mediates angiogenic and ...
Barr AJ, Marjoram R, Xu J, Snyderman R (2002). "Phospholipase C-beta 2 interacts with mitogen-activated protein kinase kinase 3 ... "Phospholipase C-beta 2 interacts with mitogen-activated protein kinase kinase 3". Biochem. Biophys. Res. Commun. 293 (1): 647- ... Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11, as well as G-beta gamma subunits. PLCB2 has been ...
Signal transduction MAP kinase kinase MAP kinase kinase kinase MAP kinase kinase kinase kinase MAPK1 (ERK2) MAPK3 (ERK1) MAPK7 ... MAP Kinase Resource . Table of names for mitogen-activated kinases. MAPK cascade picture Mitogen-Activated+Protein+Kinases at ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ... Extracellular signal-regulated kinases (ERKs) c-Jun N-terminal kinases (JNKs) p38 mitogen-activated protein kinases (p38s) ...
... is an enzyme that in humans is encoded by the MAPK9 gene. The protein encoded by this gene ... "The JIP group of mitogen-activated protein kinase scaffold proteins". Molecular and Cellular Biology. 19 (10): 7245-54. doi: ... "Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3". Molecular and Cellular ... "Entrez Gene: MAPK9 mitogen-activated protein kinase 9". Saleem A, Datta R, Yuan ZM, Kharbanda S, Kufe D (Dec 1995). " ...
The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAP kinase) family. MAP kinases, also ... Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the MAPK3 gene. ... "Entrez Gene: MAPK3 mitogen-activated protein kinase 3". Buggele WA, Johnson KE, Horvath CM (2012). "Influenza A virus infection ... Meloche S, Pouysségur J (2007). "The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S- ...
... -21 promotes hepatocellular carcinoma HepG2 cell proliferation through repression of mitogen-activated protein kinase- ... binding protein], PACT (protein activator of the interferon-induced protein kinase), the SMN complex, fragile X mental ... HMGA proteins (HMGA1a, HMGA1b and HMGA2) are implicated in cancer, and expression of these proteins is regulated by microRNAs. ... HMGA2 protein specifically targets the promoter of ERCC1, thus reducing expression of this DNA repair gene. ERCC1 protein ...
... family of proteins that regulate growth factor-induced activation of the MAP kinase cascade. GRCh38: Ensembl release 89: ... Sprouty-related, EVH1 domain-containing protein 3 also known as Spread-3 is a protein that in humans is encoded by the SPRED3 ... kinase activation in hematopoietic cells". The Journal of Biological Chemistry. 279 (50): 52543-51. doi:10.1074/jbc.M405189200 ... Spread-3 is a member of the Sprouty (see SPRY1/SPRED) ... "Eve-3: a liver enriched suppressor of Ras/MAPK signaling". ...
"Betacellulin induces angiogenesis through activation of mitogen-activated protein kinase and phosphatidylinositol 3'-kinase in ... activates nuclear factor-kappaB through IkappaBalpha kinase-independent but EGF receptor-kinase dependent tyrosine 42 ... Betacellulin is a protein that in humans is encoded by the BTC gene located on chromosome 4 at locus 4q13-q21. Betacellulin was ... As results, nuclear factor-kappaB (NF-κB), a major mediator of resistance in GBM, is also activated. Inhibition of STAT3 and ...
The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade. ... SPRED-1 is a member of the Sprouty family of proteins and is phosphorylated by tyrosine kinase in response to several growth ... Sprouty-related, EVH1 domain-containing protein 1 (Spread-1) is a protein that in humans is encoded by the SPRED1 gene located ... Human proteins, Proteins, Hematopathology, Neuro-cardio-facial-cutaneous syndromes). ...
Signal transduction MAP kinase MAP kinase kinase kinase MAP kinase kinase kinase kinase Dérijard B, et al. (1995). "Independent ... Mitogen-activated protein kinase kinase (also known as MAP2K, MEK, MAPKK) is a dual-specificity kinase enzyme which ... Mitogen-Activated+Protein+Kinase+Kinases at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology ... phosphorylates mitogen-activated protein kinase (MAPK). MAP2K is classified as EC There are seven genes: MAP2K1 (a.k. ...
... 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 ...
Its activation also induces mitogen-activated protein kinases (MAPK) activation along with phosphoinositide 3-kinase activation ...
"A protein factor for ras p21-dependent activation of mitogen-activated protein (MAP) kinase through MAP kinase kinase". ... "MAP kinase-kinase", thus qualifying as a "MAP kinase kinase kinase". The MAP kinase-kinase, which activates ERK, was named " ... Mitogen-activated protein kinase 1 (MAPK1) is also known as extracellular signal-regulated kinase 2 (ERK2). Two similar protein ... Ras activates c-Raf, followed by mitogen-activated protein kinase kinase (abbreviated as MKK, MEK, or MAP2K) and then MAPK1/2 ( ...
This gene encodes a member of the mitogen-activated protein kinase kinase kinase kinase family. The encoded protein activates ... Mitogen-activated protein kinase kinase kinase kinase 3 is a protein that in humans is encoded by the MAP4K3 gene. ... "Entrez Gene: Mitogen-activated protein kinase kinase kinase kinase 3". Retrieved 2017-09-22. Lam D, Dickens D, Reid EB, Loh SH ... "The kinase GLK controls autoimmunity and NF-κB signaling by activating the kinase PKC-θ in T cells". Nat. Immunol. 12 (11): ...
"Sequential phosphorylation by mitogen-activated protein kinase and glycogen synthase kinase 3 represses transcriptional ... a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase ... The genes activated by HSF1 under heat shock conditions have been recently shown to differ from those activated in malignant ... transcription factor 1 binds selectively in vitro to Ku protein and the catalytic subunit of the DNA-dependent protein kinase ...
"Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase ... The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase ... "Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated ...
Mitogen-activated protein kinase kinase kinase 7-interacting protein 3 is an enzyme that in humans is encoded by the MAP3K7IP3 ... "Entrez Gene: MAP3K7IP3 mitogen-activated protein kinase kinase kinase 7 interacting protein 3". Bouwmeester T, Bauch A, Ruffner ... and the similar and functionally redundant protein MAP3K7IP2/TAB2, forms a ternary complex with the protein kinase MAP3K7/TAK1 ... Cheung PC, Nebreda AR, Cohen P (Feb 2004). "TAB3, a new binding partner of the protein kinase TAK1". Biochem J. 378 (Pt 1): 27- ...
The noncanonical signaling pathway includes mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase thymoma ... January 2001). "Interferon-tau activates multiple signal transducer and activator of transcription proteins and has complex ... The canonical pathway involves Janus kinase-signal transducer and activator of transcription-interferon regulatory factor (JAK- ... CS1 French-language sources (fr), Protein pages needing a picture, Antiviral drugs). ...
... a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase". ... "Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and ... They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are ... "Mitogen-activated protein kinase phosphatase-3 (MKP-3) in the surgical wound is necessary for the resolution of postoperative ...
... and the mitogen-activated protein kinase (MAPK) docking motif. There are several predicted protein kinase c phosphorylation ... C12orf29 protein was not found in bacteria, fungi, and viruses. There is no paralog for C12orf29 protein. The mutation rate of ... "uncharacterized protein C12orf29 [Homo sapiens] - Protein - NCBI". Retrieved 2021-09-26. "SAPS < Sequence ... C12orf29 protein has 325 amino acids. The molecular weight is 37.5 kD, and the isoelectric point is 6.6 pH. It is not a ...
Protein kinase D1, and Protein kinase Mζ. Model organisms have been used in the study of ADAP1 function. A conditional knockout ... 5-trisphosphate-binding protein that is functionally homologous to the yeast ADP-ribosylation factor (ARF) GTPase-activating ... Arf-GAP with dual PH domain-containing protein 1 is a protein that in humans is encoded by the ADAP1 gene. Centaurin, alpha 1 ... "Identification of casein kinase Ialpha interacting protein partners". FEBS Letters. 517 (1-3): 167-71. doi:10.1016/s0014-5793( ...
Involvement of activation of stress protein kinases (stress-activated protein kinase and p38 mitogen-activated protein kinase) ... a new member of the TNF family activates nuclear factor-kappa B and c-Jun N-terminal kinase and modulates cell growth". ... is protein that in humans is encoded by the TNFSF15 gene. VEGI is an anti-angiogenic protein. It belongs to tumor necrosis ... The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is ...
Other names for CXCR3 are G protein-coupled receptor 9 (GPR9) and CD183. There are three isoforms of CXCR3 in humans: CXCR3-A, ... CXCR3 is expressed primarily on activated T lymphocytes and NK cells, and some epithelial cells. CXCR3 and CCR5 are ... Binding of CXCL9, CXCL10, and CXCL11 to CXCR3 is able to elicit increases in intracellular Ca2++ levels and activate ... Chemokine receptor CXCR3 is a Gαi protein-coupled receptor in the CXC chemokine receptor family. ...
... mitogen-activated protein kinase, Ras, and Wnt signaling. Activated Twist upregulates N-cadherin and downregulates E-cadherin, ... Twist-related protein 1 (TWIST1) also known as class A basic helix-loop-helix protein 38 (bHLHa38) is a basic helix-loop-helix ... proteins is the novel target for direct inhibition by another bHLH protein, Twist". Molecular and Cellular Biology. 17 (11): ... The protein encoded by this gene is a bHLH transcription factor and shares similarity with another bHLH transcription factor, ...
... kinase and mitogen-activated protein (MAP) kinase pathways". J. Leukoc. Biol. 78 (4): 1016-23. doi:10.1189/jlb.0105056. PMID ... and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain ... "Extracellular HIV-1 Tat protein induces a rapid and selective activation of protein kinase C (PKC)-alpha, and -epsilon and - ... 1998). "Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat ...
... and Mitogen-activated Protein Kinase Can Regulate Epithelial Cell Proliferation". Mol. Biol. Cell. 10 (2): 259-70. doi:10.1091/ ... "HIV-protein-mediated alterations in T cell interactions with the extracellular matrix proteins and endothelium". Arch. Immunol ... The protein encoded by this gene is the alpha-3 chain of laminin 5, which is a complex glycoprotein composed of three subunits ... "Bone morphogenetic protein 1 is an extracellular processing enzyme of the laminin 5 gamma 2 chain". J. Biol. Chem. 275 (30): ...
... particularly to the activity of mitogen-activated protein kinase kinase-1 (MEK1). Studies have demonstrated that inhibition of ... "SMAD3 expression is regulated by mitogen-activated protein kinase kinase-1 in epithelial and smooth muscle cells". Cellular ... The expression of SMAD3 has been related to the mitogen-activated protein kinase (MAPK/ERK pathway), ... The SMAD proteins are homologs of both the Drosophila protein "mothers against decapentaplegic" (MAD) and the C. elegans ...
Jensen LE, Whitehead AS (2003). "Pellino2 activates the mitogen activated protein kinase pathway". FEBS Lett. 545 (2-3): 199- ... Protein pellino homolog 1 is a protein that in humans is encoded by the PELI1 gene. GRCh38: Ensembl release 89: ENSG00000197329 ... Butler MP, Hanly JA, Moynagh PN (2007). "Kinase-active interleukin-1 receptor-associated kinases promote polyubiquitination and ... direct evidence for PELLINO proteins being ubiquitin-protein isopeptide ligases". J. Biol. Chem. 282 (41): 29729-29737. doi: ...
Jensen LE, Whitehead AS (2003). "Pellino2 activates the mitogen activated protein kinase pathway". FEBS Lett. 545 (2-3): 199- ... Protein pellino homolog 2 is a protein that in humans is encoded by the PELI2 gene. GRCh38: Ensembl release 89: ENSG00000139946 ... 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. ... for the Pelle adaptor protein Pellino to mouse chromosomes 11 and 14 and human chromosomes 2p13.3 and 14q21, respectively, by ...
"Docking sites on mitogen-activated protein kinase (MAPK) kinases, MAPK phosphatases and the Elk-1 transcription factor compete ... Wu, J. J.; Zhang, L.; Bennett, A. M. (16 May 2005). "The Noncatalytic Amino Terminus of Mitogen-Activated Protein Kinase ... Wu, J. J.; Zhang, L.; Bennett, A. M. (16 May 2005). "The Noncatalytic Amino Terminus of Mitogen-Activated Protein Kinase ... MAPK phosphatases (MKPs) are the largest class of phosphatases involved in down-regulating Mitogen-activated protein kinases ( ...
"Entrez Gene: MAPK8IP3 mitogen-activated protein kinase 8 interacting protein 3". Matsuura, Hiroshi; Nishitoh Hideki; Takeda ... "Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3". Mol Cell Biol. 20 (3): 1030 ... MAPK8IP3 has been shown to interact with ASK1, C-Raf, PTK2, MAPK10, Mitogen-activated protein kinase 9, MAPK8, MAP2K1, KLC2, ... 2002). "A scaffold protein in the c-Jun N-terminal kinase signaling pathway is associated with focal adhesion kinase and ...
... mitogen-activated protein kinase and nuclear factor-κB". Int. J. Mol. Med. 30 (2): 344-50. doi:10.3892/ijmm.2012.1000. PMID ... Phylogenetic relationships of Sparassis inferred from nuclear and mitochondrial ribosomal DNA and a protein-coding gene (rpb2 ... 28 (3): 560-5. doi:10.1016/j.peptides.2006.10.004. PMID 17113195. S2CID 7912537. Hu (2016). "Mitochondria Related Pathway Is ... Ohno (2000). "Antitumor 1,3-β-glucan from cultured fruit body of Sparassis crispa". Biol. Pharm. Bull. 23 (7): 866-72. doi: ...
Type I IFNs further activate p38 mitogen-activated protein kinase (MAP kinase) to induce gene transcription. Antiviral and ... PI3K activates P70-S6 Kinase 1, an enzyme that increases protein synthesis and cell proliferation; phosphorylates ribosomal ... cells produce large amounts of an enzyme known as protein kinase R (PKR). This enzyme phosphorylates a protein known as eIF-2 ... Production of protein kinase R, for example, can be disrupted in cells infected with JEV. Some viruses escape the anti-viral ...
... signals through ouabain-triggered protein phosphorylation events include activation of the mitogen-activated protein kinase ( ... However, upon subsequent ouabain binding, the Src kinase domain is released and then activated. Based on this scenario, NaKtide ... Protein-protein interactions play a very important role in Na⁺-K⁺ pump-mediated signal transduction. For example, the Na⁺-K⁺ ... this membrane protein can also relay extracellular ouabain-binding signalling into the cell through regulation of protein ...
But MyD88 also activates mitogenactivated protein kinases (MAPKs). However, several strains of lactic acid bacteria have been ... Toll-like receptor 6 is a protein that in humans is encoded by the TLR6 gene. TLR6 is a transmembrane protein, member of toll- ... It is also known that TLR2/6 binds some viral products, among them hepatitis C core and NS3 protein from the hepatitis C virus ... TLR6 has also been designated as CD286 (cluster of differentiation 286). The protein encoded by this gene is a member of the ...
Akt and a p38 mitogen-activated protein kinases pathways to inhibit the actions of pro-inflammatory cytokines and/or the ... H-Ras: 15-Deoxy-Δ12,14-PGJ2 forms a covalent bond with cysteine 184 on H-ras thereby activating this signaling protein and ... The PGJ2 series of cyclopentenone PGs bind to and activate the G protein-coupled receptor, Prostaglandin DP2 receptor, with 15- ... These PGJ2's also bind and activate a second G protein-coupled receptor, Prostaglandin DP1 receptor, but require high ...
... mitogen-activated protein kinase) cascade that is itself a kinase. RSK2 phosphorylates cellular proteins (including histone H3 ... RSK2 is normally activated by the ERK MAP kinase. Mutated RSK2 may be deficient for activation by ERK, or its kinase activity ... Mutations in the RPS6KA3 gene can result in expression of an RSK2 protein (ribosomal S6 kinase 2) with reduced or absent kinase ... The protein RSK2 which is encoded by the RPS6KA3 gene is a kinase which phosphorylates some substrates like CREB and histone H3 ...
"Adaptor proteins Grb2 and Crk couple Pyk2 with activation of specific mitogen-activated protein kinase cascades". J. Biol. Chem ... involves the Src homology 2 domain of v-Crk and sustained activation of the Ras/mitogen-activated protein kinase pathway". J. ... The name Crk is from "CT10 Regulator of Kinase" where CT10 is the avian virus from which was isolated a protein, lacking kinase ... related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins". ...
Navas TA, Baldwin DT, Stewart TA (November 1999). "RIP2 is a Raf1-activated mitogen-activated protein kinase kinase". The ... of mitogen-activated protein kinase and NF-kappaB pathways by a Kaposi's sarcoma-associated herpesvirus K15 membrane protein". ... "Human cytomegalovirus IE1 protein activates AP-1 through a cellular protein kinase(s)". The Journal of General Virology. 80 ( ... Many of these stimuli activate the c-Jun N-terminal kinases (JNKs) leading to the phosphorylation of Jun proteins and enhanced ...
Involvement of Mitogen-Activated Protein Kinases and Gene Expression". Annals of the New York Academy of Sciences. 1053 (1): 84 ... "Heterologous Upregulation of Nerve Growth Factor-TrkA Receptors in PC12 Cells by Pituitary Adenylate Cyclase-Activating ... 62 (3): 270-277. doi:10.1097/FJC.0b013e3182982de7. PMID 23644989. S2CID 601556. Mirshahi, P; Rafii, A; Vincent, L; Berthaut, A ... 54 (3): 574-585. doi:10.1007/s12031-014-0388-2. PMID 25078264. S2CID 1620005. "Professor Philip Lazarovici". medicine.ekmd.huji ...
... and mitogen-activated protein kinase (MAPK) as well as increases in concentrations of signaling molecules like calcium and ... The anti-ER (SP1) antibody targets the ER alpha protein (ERα) located in the nucleus of ER positive normal and neoplastic cells ... Both of these are nuclear receptors activated by the sex hormone, estrogen, and encoded by the ESR1 (Estrogen Receptor 1) gene ... Immunohistochemistry (IHC) techniques involve the selective identification of antigen proteins by exploiting these antigen- ...
... of FOXC1 stability and transcriptional activity by an epidermal growth factor-activated mitogen-activated protein kinase ... Rho kinase inhibitors, such as ripasudil, work by inhibition of the actin cytoskeleton, resulting in the morphological changes ... Plain English summary Wang SK, Chang RT (2014). "An emerging treatment option for glaucoma: Rho kinase inhibitors". Clinical ... the pressure results from the accumulation of microscopic granular protein fibers, which can block normal drainage of the ...
Mitogen-activated protein kinase kinase kinase 7-interacting protein 2 is an enzyme that in humans is encoded by the MAP3K7IP2 ... "Entrez Gene: MAP3K7IP2 mitogen-activated protein kinase kinase kinase 7 interacting protein 2". Thienpont B, Zhang L, Postma AV ... activates TAK1 mitogen-activated protein kinase kinase kinase through a signaling complex containing RANK, TAB2, and TRAF6". ... Human TGF-beta-activated kinase 1 and MAP3K7-binding protein 2) at the PDBe-KB. Overview of all the structural information ...
NF-κB and MAP kinases of MAPK3, MAPK1, and mitogen-activated protein kinase kinase). He was responsible for the codiscovery of ... 3 February 1998. Weissmann, Gerald (2 August 2007). Written at The Marine Biological Laboratory, Woods Hole, Massachusetts. " ...
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 ...
... and on the positive strand is the gene Mitogen-activated protein kinase, kinase 3 (MAP2K3). Microarray and EST data indicates ... "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957-68. doi:10.1016/j.cell ... Other proteins interacting with DHRS7B have only been identified through text mining. Conservation of the DHRS7B protein ... DHRS7B encodes a protein that is predicted to function in steroid hormone regulation. A deletion in the chromosomal region ...
"The role of mitogen-activated protein (MAP) kinase in breast cancer". February 2002, The Journal of Steroid Biochemistry and ... mechanism of action of a mitogen is that it triggers signal transduction pathways involving mitogen-activated protein kinase ( ... Mitogen-activated protein kinase (MAPK) pathways can induce enzymes such as the COX-2 enzyme. MAPK pathways may also play a ... Second, cancer cells can have mutated cell-surface receptors for mitogens. The protein kinase domain found on mitogenic ...
"Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proceedings of the National ... Dual-specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene. MAP2K4 ... mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes". The Journal of Experimental Medicine. 186 (6): 941- ... Chen Z, Cobb MH (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". The ...
1998). "The exchange factor Ras-GRF2 activates Ras-dependent and Rac-dependent mitogen-activated protein kinase pathways". Curr ... "Dematin interacts with the Ras-guanine nucleotide exchange factor Ras-GRF2 and modulates mitogen-activated protein kinase ... 2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi: ... Ras-specific guanine nucleotide-releasing factor 2 is a protein that in humans is encoded by the RASGRF2 gene. RAS (MIM 190020 ...
A mitogen-activated protein kinase (MAPK) called pmk1 is genetically close to one necessary for mating and cell morphology in ... Infection of rice induces phosphorylation of the light-harvesting complex II protein LHCB5 . LHCB5 is required for a reactive ... "A single fungal MAP kinase controls plant cell-to-cell invasion by the rice blast fungus". Science. 359 (6382): 1399-1403. ... doi:10.1007/978-3-319-76162-6. ISBN 978-3-319-76161-9. ISSN 2213-7114. S2CID 199492358. Rice Blast Archived 2010-07-31 at the ...
"LSP1 is the major substrate for mitogen-activated protein kinase-activated protein kinase 2 in human neutrophils". J. Biol. ... Harrison RE, Sikorski BA, Jongstra J (2005). "Leukocyte-specific protein 1 targets the ERK/MAP kinase scaffold protein KSR and ... Lymphocyte-specific protein 1 is a protein that in humans is encoded by the LSP1 gene. This gene encodes an intracellular F- ... 2004). "Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel ...
Downstream effectors of Ras include three mitogen-activated protein kinases Raf a MAP Kinase Kinase Kinase (MAPKKK), MEK a MAP ... half of the protein). The unregulated expression of this protein activates other proteins that are involved in cell cycle and ... Receptor tyrosine kinases add phosphate groups to other proteins in order to turn them on or off. Receptor kinases add ... the MAPK-activated protein kinases". Microbiology and Molecular Biology Reviews. 75 (1): 50-83. doi:10.1128/MMBR.00031-10. PMC ...
... is a CREB kinase under dominant control of p38alpha mitogen-activated protein kinase (p38alphaMAPK)". J Biol Chem. 273 (45): ... Deak M, Clifton AD, Lucocq LM, Alessi DR (Sep 1998). "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly ... 2007). "Dimethylfumarate specifically inhibits the mitogen and stress-activated kinases 1 and 2 (MSK1/2): possible role for its ... This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non- ...
Guan has made seminal contributions in the fields of protein tyrosine phosphatase, Mitogen-Activated Protein (MAP) kinase, and ... In contrast, TORC2 phosphorylates and activates AKT, a key kinase involved in cell growth and apoptosis. Guan and his team are ... TSC1 and TSC2 proteins form a physical and functional complex. Recent studies from Guan's laboratory demonstrate that TSC1/TSC2 ... For example, TORC1 phosphorylates the ribosomal S6 kinase (S6K), thereby regulating translation and cell growth. ...
"An SH3 domain-containing GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase". Molecular and ... This cytosolic kinase has been implicated in diverse cellular roles including cell locomotion, mitogen response and cell ... PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by ... Lineage for Protein: Focal adhesion kinase 1 Q00944 "Entrez Gene: PTK2 PTK2 protein tyrosine kinase 2". Guan JL, Shalloway D ( ...
23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway". The Journal of ... Fibroblast growth factor 23 (FGF23) is a protein that in humans is encoded by the FGF23 gene. FGF23 is a member of the ... This putative protein was known as phosphatonin. Several types of effects were described including impairment of sodium ... Mutations in FGF23 that render the protein resistant to proteolytic cleavage leads to increased activity of FGF23 and the renal ...
... factor-stimulated neuronal gene expression by protein phosphatases SHP-1 and SHP-2 through mitogen-activated protein kinase- ... receptor by mitogen-activated protein kinase and the regulation of LIF receptor function by heterologous receptor activation". ... "Stimulation of leukemia inhibitory factor receptor degradation by extracellular signal-regulated kinase". The Journal of ... 93 (3): 804-15. doi:10.1182/blood.V93.3.804. PMID 9920829. S2CID 39078004. Knight DA, Lydell CP, Zhou D, Weir TD, Robert ...
... c-src kinase, tyrosine kinase 2 mitogen-activated protein kinase kinase, tyrosine kinase 2, c-jun, JNK1, Janus kinase 1, TNF-a ... Thioredoxin is a protein crucial to the reduction-oxidation reactions involved in metabolism within a cell, and is often found ... The expression of H19 in these cells is also independent of the tumor suppressor protein p53 and the cell cycle marker Ki-67. ... The ovarian cancer patient experienced a 50% decline in the amount of the ovarian cancer marker protein CA-125 in her blood as ...
PI3-kinase) inhibitors. The p38 mitogen-activated protein (MAP) kinase was activated at 0.5 to 3 h after SAAD, followed by ... showing that PI3-kinase is not involved in the activation of p38 MAP kinase. Data showed that PI3-kinase plays an essential ... Electrophoretic mobility shift assay revealed that the ARE complex, consisting of Nrf-1/2 and Maf proteins, was activated 12 to ... which activates the p38 MAP kinase and leads to rGSTA2 induction. ... The activation of p38 MAP kinase, however, failed to be ...
Medical Mitogen-activated protein kinases (MAPK) Research. anti- Phospoho CDK, MAPK, GSK3, CLK, ERK1/2, JNK ... Mitogen-activated protein kinase (MAPK) pathway performs numerous roles in organic processes however its function in ... Resume The immunomodulatory proteins present in garlic have recently been shown to be identical to the garlic lectins ASA I and ... Identification of Potential Kinase Inhibitors within the PI3K/AKT Pathway of Leishmania Species. *. Lieven ...
... domain-containing proteins. In this paper, we identified membrane-associated guanylate kinase inverted-3 (MAGI-3) as a novel ... Membrane Proteins / metabolism* * Mitogen-Activated Protein Kinase 1 / metabolism* * Mitogen-Activated Protein Kinase 3 / ... domain-containing proteins. In this paper, we identified membrane-associated guanylate kinase inverted-3 (MAGI-3) as a novel ... Our data also demonstrated that beta2AR-stimulated extracellular signal-regulated kinase-1/2 (ERK1/2) activation was ...
Many of the same genes were activated in both species, but genetic regulation shifted towards defense in lemon, together with ... Functional analysis of the differentially expressed genes (DEGs) indicated that genes involved in the mitogen activated protein ... kinase (MAPK) signaling pathway were highly upregulated in rough lemon. MAPK induces the transcription of WRKY and other ... hypothetical protein; JAZ1: JASMONATE-ZIM-DOMAIN PROTEIN; MPK3: MITOGEN-ACTIVATED PROTEIN KINASE 3; WRKY70: WRKY transcription ...
HBX protein-induced downregulation of microRNA-18a is responsible for upregulation of connective tissue growth factor in hbv ... Histone deacetylases activate hepatocyte growth factor signaling by repressing microRNA-449 in hepatocellular carcinoma cells. ... Janus kinase/signal transducer; PI3K/MAPK, phosphoinositide 3-kinase/mitogen-activated protein kinase; WNT/β-Catenin, wingless- ... Hepatitis B virus X protein represses miRNA-148a to enhance tumorigenesis. J Clin Invest. (2013) 123:630-45. doi: 10.1172/ ...
... protein geranylgeranyltransferase type I) inhibitor - Ontology Report - Rat Genome Database ... mitogen activated protein kinase 1. multiple interactions. EXP. GGTI-2133 inhibits the reaction [Smoke analog results in ... mitogen activated protein kinase 3. multiple interactions. EXP. GGTI-2133 inhibits the reaction [Smoke analog results in ... protein geranylgeranyltransferase type I (EC inhibitors; protein geranylgeranyltransferase type I inhibitor; protein ...
Mitogen-activated protein kinase kinase 3. Predicted locationi All transcripts of all genes have been analyzed regarding the ... HUMAN BRAIN PROTEIN LOCATIONi The Human brain protein data is based on curated and manually selected Tissue Atlas data. The ... HUMAN PROTEIN ATLAS INFORMATION. Tissue specificityi The RNA specificity category is based on mRNA expression levels in the ... The Human Protein Atlas project is funded. by the Knut & Alice Wallenberg Foundation. ...
... mitogen-activated protein kinase 6 [MAPK6])-MAPK-activated protein kinase 5 signaling complex regulates septin function and ... is an atypical member of the mitogen-activated protein (MAP) kinase family of serine/threonine kinases. The human ERK3 protein ... The catalytic activity of the mitogen-activated protein kinase extracellular signal-regulated kinase 3 is required to sustain ... MAPK6 (mitogen-activated protein kinase 6). 2017-03-01 Simon Mathien , Sylvain Meloche Affiliation Institute of Research in ...
TargetMitogen-activated protein kinase 14(Homo sapiens (Human)). Boehringer Ingelheim Pharmaceuticals Inc. Curated by ChEMBL. ... Affinity DataKon: 0.0000380M-1s-1Assay Description:Binding affinity for Mitogen-activated protein kinase p38 alphaMore data for ... TargetMitogen-activated protein kinase 14(Homo sapiens (Human)). Boehringer Ingelheim Pharmaceuticals Inc. Curated by ChEMBL. ... TargetMitogen-activated protein kinase 14(Homo sapiens (Human)). Boehringer Ingelheim Pharmaceuticals Inc. Curated by ChEMBL. ...
Publications] Hida M., et al.: Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase are required for ... Publications] Mariko Hida 他: Extracellular・signal-regulated kinase-and p38 mitogen-activated protein kinase are required for ... Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase are required for rat renal developmentKidney ... We investigated the role of mitogen-activated protein kinase (MAPK) family, a critical enzyme in cellular signaling, in normal ...
Mitogen-Activated Protein Kinase 3 regulates seed dormancy in barley. Curr. Biol. 26 (2016) 775-781. ... A barley ROP GTPase ACTIVATING PROTEIN associates with microtubules and regulates entry of the barley powdery mildew fungus ... The nucleoid-associated protein WHIRLY1 is required for the coordinate assembly of plastid and nucleus-encoded proteins during ... PROTEIN DISULFIDE ISOMERASE LIKE 5-1 is a susceptibility factor to plant viruses. Proc. Natl. Acad. Sci. U.S.A. 111 (2014) 2104 ...
The mitogen-activated protein kinase (MAPK) signaling pathway is an important signal transduction pathway, consisting of p38 ... mitogen-activated protein kinase (MAPK), transcriptional factor nuclear factor-κB (NF-κB), and transforming growth factor beta ... The first module contained 31 target proteins and 381 protein interaction edges, with an MCODE score of 25.4, while the second ... STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide ...
... and mitogen-activated protein kinase (MAPK) pathways. IL-4 treatment of human B cells results in the dephosphorylation of ... In addition to triggering TRAF associations, engagement of CD40 activates protein tyrosine kinases (PTKs), which play an ... The B cell-specific activator protein BSAP (Pax 5) also binds to the Iε promoter, and has been implicated in activating Cε- ... The switch recombinase may include the DNA repair enzyme DNA-dependent protein kinase (DNA-PK), which is defective in severe ...
Mitogen-Activated Protein Kinase 1/metabolism, Mitogen-Activated Protein Kinase 3/metabolism, Neoplasms, Hormone-Dependent/ ... KW - Mitogen-Activated Protein Kinase 1/metabolism. KW - Mitogen-Activated Protein Kinase 3/metabolism ... Mitogen-Activated Protein Kinase 1/metabolism. *Mitogen-Activated Protein Kinase 3/metabolism ... Proto-Oncogene Proteins c-akt/metabolism, Proton Pump Inhibitors/toxicity, Receptor, ErbB-2/metabolism, Signal Transduction", ...
protein coding gene. Chr4:132965290-132980240 (+). 129S1/SvImJ MGP_129S1SvImJ_G0028889. protein coding gene. Chr4:135475570- ... protein coding gene. Chr4:144001082-144013134 (+). DBA/2J MGP_DBA2J_G0028700. protein coding gene. Chr4:130230935-130242988 (+) ... protein coding gene. Chr4:133492776-133504830 (+). BALB/cJ MGP_BALBcJ_G0028871. protein coding gene. Chr4:130431492-130443541 ... protein coding gene. Chr4:133744389-133756443 (+). C57BL/6NJ MGP_C57BL6NJ_G0029313. protein coding gene. Chr4:140346661- ...
... and by the mitogen-activated protein kinase (MAPK) inhibitor, U0126. Propolis inhibited the activity of GSK3α and β via the ... Involvement of Non-Protein Thiols, Mitochondrial Dysfunction, Reactive Oxygen Species and p53 in Honey-Induced Apoptosis. ... Activation of ERK, Akt, p38 MAP kinase (MAPK), and caspase 3 proteins was evaluated by western blotting. Results ... The concentrate acts like an "orchestra leader" to set into motion and activate the combination of these mechanisms that ...
... the mitogen-activated protein kinase p38, and caspase-3, molecules highly expressed in the CNS and implicated in recent studies ... mitogen-activated protein kinase), and caspase-3 inhibitors. Comparing retinal and sensory axons of different developmental ... mitogen-activated protein kinase) inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580 ... Goldberg DJ, Wu DY (1995) Inhibition of formation of filopodia after axotomy by inhibitors of protein tyrosine kinases. J ...
Mitogen-Activated Protein Kinase 3 Medicine & Life Sciences 18% View full fingerprint ... MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and normal T cells. In: Journal of Leukocyte Biology. ... MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and normal T cells. Journal of Leukocyte Biology. 2005 ... Mukherjee, P., Tinder, T. L., Basu, G. D., & Gendler, S. J. (2005). MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat ...
Regulations of mitogen-activated protein kinase (MAPK) pathways by RSF in 5637 cells. To investigate the effects of RSF on MAPK ... 9 and regulated the activations of mitogen-activated protein kinases (MAPKs). In addition, RSF increased intracellular reactive ... Maslinic acid induced apoptosis in bladder cancer cells through activating p38 MAPK signaling pathway. Mol Cell Biochem. 2014; ... Quercetin-induced growth inhibition in human bladder cancer cells is associated with an increase in Ca2+-activated K+ channels ...
... an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 kinase. Clinical Cancer Research, 15 ... an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 kinase, Clinical Cancer Research, ... an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 kinase. In: Clinical Cancer Research ... an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 kinase. Clinical Cancer Research. ...
Apoptosis, downregulation of protein kinases, histone deacetylases and heat-shock proteins. (41). ... The RASAL2 gene that encodes for Ras-GTPase-activating protein 2 is also upregulated through promoter hypomethylation in ... have proven the role of HDACs in the regulation of p21 protein (97). p21 Protein is a cyclin-dependant kinase inhibitor which ... receptor tyrosine kinase signalling, histone deacetylases (HDAC1-4, 6-8 and 11), protein kinases, phosphatases, growth factors ...
The mitogen-activated protein 2 kinase (MAP2K1) inhibitor PD98059 also prevented heat-induced maturation, but this effect was ... The AMP-activated protein kinase (PRKA) inhibitors compound C and Ara-A each blocked the meiosis-stimulating effects of heat. ... Adenosine 5′ monophosphate-activated protein kinase (AMPK) is involved in metformin action in various cell types. We ... Meiotic Induction by Heat Stress in Mouse Oocytes: Involvement of AMP-Activated Protein Kinase and MAPK Family Members ...
p38 mitogen-activated protein kinase mediates bid cleavage, mitochondrial dysfunction, and caspase-3 activation during ... A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye ... OBJECTIVE: To research the effect of fluorine on the expression of Fas protein, then study the mechanism of male reproductive ... Fluoride-induced histopathology and synthesis of stress protein in liver and kidney of mice. Arch. Toxicol. 85: 327-335 ...
... if they identify a mitogen-activated protein (MAP) kinase abnormality or phosphoinositide (PI)-3 kinase abnormality-which are ... phase 3 trial for patients who were human epidermal growth factor receptor 2 (HER2)-negative and, indeed, had residual disease ...
The study demonstrated that EGCG acts directly or on downstream of ErbB signaling such as mitogen-activated protein kinase ( ... 13-acetate-induced invasion and migration of human hepatoma cells through inactivating mitogen-activated protein kinase and ... linked to protein kinase C (PKC) and MAPK signaling pathways [38]. In our previous study, we have shown that BITC induces ... ribosomal protein S6 kinase (RSK)-2 has been established as a novel molecular target of EGCG using computational docking ...
... involvement of calcineurin and mitogen-activated protein kinase signalings. Eur J Pharmacol 2009;608(1-3):42-7. View abstract. ... Anti-inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide-stimulated microglia: critical role of the protein kinase ... Lee Y, Jin Y, Lim W, Ji S, Choi S, Jang S, Lee S. A ginsenoside-Rh1, a component of ginseng saponin, activates estrogen ... Lee S, Jung J, and Cho D. Ginseng application on the skin enhances synthesis of extracellular matrix proteins:217. The Journal ...
... including the mitogen-activated protein kinase (MAPK) pathway and phosphoinositide 3-kinase (PI3K) pathway. ... and by GTPase-activating proteins (GAPs) such as neurofibromin 1 (NF1), which promote the formation of RAS-GDP. ... RAS proteins, including KRAS, switch between an inactive or "off" state to an active or "on" state by binding to guanosine ... When activated by external stimuli, the inactive RAS-GDP converts to active RAS-GTP and promotes activation of many signaling ...
... and mitogen-activated protein kinase pathways. Previous studies demonstrate that Ras guanyl nucleotide-releasing protein ( ... Consequently, activation of Akt, PIP3-dependent kinase, and protein kinase C delta was defective. Expression of a ... Cross-linking of the FcepsilonRI activates the phosphatidyl inositol 3 kinase (PI3K) ...
Mitogen-activated protein kinase kinase 3 (MKK3), also known as MEK3, and the closely related MKK6 are activated by ... Both MKK3 and MKK6 are dual specificity protein kinases, phosphorylating and activating the p38 MAP kinases at Thr and Tyr ... Activation occurs through phosphorylation by several upstream MAPK kinase kinases, including ASK1 and TAK1. ...
Dex down-regulated MKP-1 expression and attenuated an OGD-induced change in the mitogen activated protein kinase 3 (MAPK3) ... The relative expressions of mitogen-activated protein kinase phosphatase 1 (MKP-1) and related genes were detected by ... which suppressed the synthesis level of Beclin1 and light chain 3 proteins. ... Dex down-regulated MKP-1 expression and attenuated an OGD-induced change in the mitogen activated protein kinase 3 (MAPK3) ...
  • Nuclear ARE activation and rGSTA2 mRNA increase were both completely inhibited by wortmannin or LY294002, the phosphatidylinositol 3-kinase (PI3-kinase) inhibitors. (
  • However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. (
  • Exposure to asphalt fumes activates activator protein-1 through the phosphatidylinositol 3-Kinase/Akt signaling pathway in mouse epidermal cells. (
  • It activated phosphatidylinositol 3-kinase and induced phosphorylation of Akt at Ser-473/Thr-308, and concurrently activated downstream p70 S6 kinase as well as glycogen synthase kinase-3. (
  • Further study indicated that blockage of phosphatidylinositol 3-kinase activation eliminated asphalt fume-stimulated AP-1 activation and formation of anchorage-independent colonies in soft agar. (
  • The most frequently hyperactivated pathways in this form of cancer are the mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3-kinase (PI3K) pathway . (
  • The researchers' goal was to test signaling molecules and pathways of AVP and OXT, as well as RAS-MAPK (mitogen-activated protein kinase) and P13K (phosphatidylinositol 3-kinase)-AKT and then test the "translational utility" of their preclinical findings in a small cohort of pediatric patients with ASD. (
  • Caveolin-1 interacts with and negatively regulates the EGFR, PDGFR, and Neu tyrosine kinases, Ha-Ras, c-Src, and phosphatidylinositol 3-kinase. (
  • Functional analysis of the differentially expressed genes (DEGs) indicated that genes involved in the mitogen activated protein kinase (MAPK) signaling pathway were highly upregulated in rough lemon. (
  • The extracellular signal-regulated kinase 3 (mitogen-activated protein kinase 6 [MAPK6])-MAPK-activated protein kinase 5 signaling complex regulates septin function and dendrite morphology. (
  • We investigated the role of mitogen-activated protein kinase (MAPK) family, a critical enzyme in cellular signaling, in normal and abnormal renal development. (
  • Extracellular signal-regulated kinase (ERK), p38 MAPK (p38), and MAPK phosphatase-1 (MKP-1) are strongly expressed in the developing kidney, and JNK is detected predominantly in the adult kidney. (
  • Furthermore, OME induced the phosphorylation of MAPK-ERK1/2, PI3K/Akt and GSK-3β, and blunted the expression and activity of cellular prostatic acid phosphatase. (
  • Similar inhibition of growth cone formation was observed on addition of target of rapamycin (TOR), p38 MAPK (mitogen-activated protein kinase), and caspase-3 inhibitors. (
  • Collectively, these findings suggest that local protein synthesis and degradation, controlled by various TOR-, p38 MAPK-, and caspase-dependent pathways, underlie growth cone initiation after axotomy. (
  • Activation occurs through phosphorylation by several upstream MAPK kinase kinases, including ASK1 and TAK1. (
  • These pathways include the nuclear factor kappa beta (NFkB), activating protein-1 (AP-1), mitogen-activating protein kinase (MAPK), and phosphotidyl inositol-3 kinase (PI3K) pathways. (
  • 11 , 12 IL-17 also activates mitogen-activated protein kinases (MAPK), including the extracellular signal-regulated kinase (ERK)1/2, p38, and c-Jun N-terminal kinase (JNK1/2/3) pathways. (
  • We show that the two Pnt protein forms are activated in a sequential manner within the EGFR signaling pathway: MAPK phosphorylates and activates PntP2, which in turn induces pntP1 transcription. (
  • They also measured gene expression of oxytocin receptor (OXTR) and arginine vasopressin receptor V1a (AVPRV1a) in peripheral blood mononuclear cells (PBMCs), as well as the ratios of phosphorylated/total extracellular signal-regulated kinase, PTEN, and AKT (components of the RAS-MAPK and PI3K-AKT signaling pathways) in PBMCs. (
  • The pathways involve a triple kinase core cascade comprising of the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). (
  • The induction of apoptosis and decrease in GSH/GSSG ratio was also accompanied by sustained phosphorylation and activation of p38 mitogen activated protein kinase (MAPK). (
  • KIAA1549-BRAF fusion is the most common genetic event in pilocytic astrocytoma (PA), and leads to activation of the mitogen activated protein kinase (MAPK) signaling pathway. (
  • Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein (MAP) kinase family of serine/threonine kinases. (
  • ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. (
  • ATM serine/threonine kinase [Source:HGNC Sy. (
  • Rochat-Steiner V, Becker K, Micheau O, Schneider P, Burns K, Tschopp J: FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits fas-mediated Jun NH(2)-terminal kinase activation. (
  • PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. (
  • The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. (
  • mTOR, a serine/threonine kinase, is thought to play a central role in regulating cell growth, proliferation, cellular metabolism and angiogenesis [ 7 ]. (
  • This cilia in the life of the serine by receptor fusion kinases of the Src neddylation( 1). (
  • Our data also demonstrated that beta2AR-stimulated extracellular signal-regulated kinase-1/2 (ERK1/2) activation was substantially retarded by MAGI-3 expression. (
  • The catalytic activity of the mitogen-activated protein kinase extracellular signal-regulated kinase 3 is required to sustain CD4+ CD8+ thymocyte survival. (
  • Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase are required for rat renal development'Kidney Int. (印刷中). (
  • These include reduction in Ca 2+ influx and extracellular signal-regulated kinase 1/2 phosphorylation, leading to a decrease in CD69 expression, proliferation, and interleukin-2 production. (
  • We investigated the effects of AZD6244 (ARRY-142886), an inhibitor of MAP kinase/extracellular signal-regulated kinase 1/2, on radiation response. (
  • We found that the high-glucose-induced Ca 2+ increase activates the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 (ERK1/2). (
  • Asphalt fumes transiently activated c-Jun NH2-terminal kinases without affecting extracellular signal-regulated kinases and p38 mitogen-activated protein kinases. (
  • Here, we examine the role of extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase/ERK signaling cascade, which is crucial for adult memory, in the consolidation and reconsolidation of an early memory using a conditioned taste aversion paradigm in 3-day-old rat pups. (
  • The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. (
  • infected bisecting proteins re-enter endosomal body chains to promote with the SAMM50 regulator and extracellular plasma metazoans to have with the TIMM22 superpathway. (
  • Neither missense is IP7 to the convergent reaction as IL7R assembles produced by the MSH2 for wide extracellular complex( TSLP) while IL2RG activates involved with the residues for IL2, IL4, IL9, IL15 and IL21. (
  • Cross-linking of the FcepsilonRI activates the phosphatidyl inositol 3 kinase (PI3K) and mitogen-activated protein kinase pathways. (
  • Phphatidylinositol 3 kinase (PI3K)/Akt and mammalian target of rapamycin (mTOR) are activated in 30% and 60% of human gastric carcinoma, respectively [ 5 , 6 ]. (
  • 2010, Discovery of 3-(2-aminoethyl)-5-(3-phenyl-propylidene)-thiazolidine-2,4-dione as a dual inhibitor of the Raf/MEK/ERK and the PI3K/Akt signaling pathways. (
  • It shares 50% sequence identity with EGFR protein, but involves different signaling pathways. (
  • The CCL2 in MAC-T cells attenuates endoplasmic reticulum stress induced by tunicamycin, suggesting that CCL2 regulates intracellular synthesis of proteins and lipids and prevents activation of apoptotic pathways initiated in response to endoplasmic reticulum stress. (
  • ERK3 is a highly unstable protein, with a half-life of less than one hour, that is constitutively degraded by the ubiquitin-proteasome pathway. (
  • Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway. (
  • Through the method of network pharmacology, the present study constructed bioactive component-relative targets and protein-protein interaction network of the LQHBG and implemented gene function analysis and pathway enrichment of targets, discussing the mechanisms of traditional Chinese medicine LQHBG in treating DR. (
  • Purpose: The mitogen-activated protein (MAP) kinase pathway is important for cell proliferation, survival, and differentiation, and is frequently up-regulated in cancers. (
  • The MAP kinase pathway is also activated after exposure to ionizing radiation. (
  • Dex down-regulated MKP-1 expression and attenuated an OGD-induced change in the mitogen activated protein kinase 3 (MAPK3) signaling pathway. (
  • βA1-42 results from hydrolysis of the amyloid precursor protein by β-secretase in a process known as the amyloidogenic pathway. (
  • 7 The polyubiquitinated TRAF6 activates transforming growth factor-β-activated kinase 1 (TAK1) and then IκB kinase (IKK) complex, which subsequently activates the NF-κB pathway to initiate transcription of a variety of chemokines, cytokines, and growth factor, such as C-X-C motif ligand 1 (CXCL1), IL-6, and vascular endothelial growth factor (VEGF). (
  • The Smad pathway is thought to be the major TGF-β signal transduction pathway [ 3 ]. (
  • Caveolin-1 links integrin subunits to the tyrosine kinase FYN, an initiating step in coupling integrins to the Ras-ERK pathway. (
  • Application of protein synthesis inhibitors (cycloheximide and anisomycin) to cut axons, including axons whose cell bodies were removed, or proteasome inhibitors (lactacystin and N -acetyl-Nor-Leu-Leu-Al) all result in a reduction in the proportion of transected axons able to reform growth cones. (
  • Inhibitors of programmed cell death 1 (PD-1) protein and its ligands PD-L1 and PD-L2, are first-line agents in patients with metastatic urothelial carcinoma who are not candidates for platinum-containing chemotherapy, and second-line agents for those with disease progression despite cisplatin-based chemotherapy. (
  • Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. (
  • Both MKK3 and MKK6 are dual specificity protein kinases, phosphorylating and activating the p38 MAP kinases at Thr and Tyr positions within the phosphoacceptor sequence Thr-Gly-Tyr. (
  • To test the specificity of the staining, negative controls using protein block reagent in replacement of the lectin, and isotype-matched control in replacement of the primary antibody were included. (
  • Catalytic domain of Plant dual-specificity MAP kinase kinases and similar proteins. (
  • non-methyl-alkyl or aryl transferase) inhibitor that interferes with the action of protein geranylgeranyltransferase type I (EC (
  • von Drathen T, Ure EM, Kirschner S, Roth A, Meier L, Woolhouse AD, Cameron SA, Knippschild U , Peifer C, Luxenburger A. C5-Iminosugar modification of casein kinase 1δ lead 3-(4-fluorophenyl)-5-isopropyl-4-(pyridin-4-yl)isoxazole promotes enhanced inhibitor affinity and selectivity. (
  • The drug is an oral, brain-penetrant, highly selective type II pan-RAF kinase inhibitor. (
  • Pimasertib is an oral, highly selective small-molecule inhibitor of mitogen-activated protein kinases 1 and 2 (MEK-1/-2). (
  • cyclin dependent kinase inhibitor 1B [Sourc. (
  • We show that intraperitoneal injection of SL327, the upstream mitogen-activated protein kinase kinase inhibitor, impairs both consolidation and reconsolidation of early memory, leaving short-term memory after acquisition and after reactivation intact. (
  • As non-coding small endogenous RNAs with ~22 nucleotides, miRNAs silence genes by binding to the 3' untranslated region (3' UTR) of messenger RNAs (mRNAs) and triggering mRNA degradation or translational repression ( 4 - 6 ). (
  • The relative expressions of mitogen-activated protein kinase phosphatase 1 (MKP-1) and related genes were detected by quantitative polymerase chain reaction and western blotting. (
  • 1 It binds to a heterodimer of IL-17 receptor A (IL-17RA) and IL-17 receptor C (IL-17RC) complex, and subsequently activates nuclear factor-κB (NF-κB) activator 1 (Act1) through a similar expression to fibroblast growth factor genes, IL-17 receptors, and the Toll-IL-1R (SEFIR) domain. (
  • Sequential ETS-protein recruitment therefore allows sustained induction of target genes, beyond the transient activation of EGFR. (
  • This domain occurred 443 times on human genes ( 1020 proteins). (
  • We performed correlation analyses between expression levels of kinase genes and response for capecitabine plus RAD001. (
  • In subgroups with response for capecitabine plus RAD001, there is significant overexpression of 6 genes among 519 kinase gene such as EPHA2 (P = 0.0025), PIM1 (P = 0.0031), KSR1 (P = 0.0033), and EIF2AK4 (P = 0.0046) that are related to the activation of mTOR signalling. (
  • PTI is mediated by pattern-recognition receptors (PRRs) that recognize PAMPs, whereas effector-triggered immunity is mediated by resistance (R) proteins that recognize pathogen effectors. (
  • Archived formalin-fixed, paraffin-embedded human adult normal duodenal and colonic biopsy tissues obtained from 6 persons (3 duodenal and 3 colonic, all without influenza infection) were used for virus receptors distribution study. (
  • Plasma kallikrein promotes epidermal growth factor receptor transactivation and signaling in vascular smooth muscle through direct activation of protease-activated receptors. (
  • Its activity is directed by intracellular signals mediated by various types of receptors such as G protein-coupled receptors. (
  • reabsorption chaperones via precursor virus Protease Activated Receptors( PARs). (
  • 8 - 10 Some previous studies have demonstrated that IL-17 can stabilize downstream CXCL1 messenger (m)RNA through an inducible kinase IKKi-dependent Act1-TRAF2-TRAF5 complex, which binds to splicing factor 2 (SF2) (also named alternative splicing factor [ASF]) and prevents SF2/ASF-mediated mRNA degradation. (
  • Encodes a mitogen-activated kinase whose mRNA levels increase in response to touch, cold, salinity stress and chitin oligomers.Also functions in ovule development. (
  • Vutrisiran targets and silences the mRNA linked to the production of TTR proteins. (
  • Suppressing S1P₁ activity with its functional antagonist, AUY954 (5 mg/kg, p.o.), attenuated mRNA upregulation of M1 polarization markers in post-ischemic brain at 1 day and 3 days after tMCAO challenge. (
  • The uncleaved receptor can also be activated by the N-terminal peptide present on the activated THROMBIN RECEPTOR and by small synthetic peptides that contain the unmasked N-terminal sequence. (
  • Comparing retinal and sensory axons of different developmental stages, levels of ribosomal protein P0 and phosphorylated translation initiation factor are high in sensory axons, lower in embryonic axons, and absent in adult retinal axons. (
  • ribosomal protein S6 kinase B1 [Source:HGNC. (
  • The p38 mitogen-activated protein (MAP) kinase was activated at 0.5 to 3 h after SAAD, followed by sustained diminished activation up to 12 h. (
  • The activation of p38 MAP kinase, however, failed to be inhibited by wortmannin or LY294002, showing that PI3-kinase is not involved in the activation of p38 MAP kinase. (
  • These data suggest that MAGI-3 regulates beta2AR-mediated ERK activation through the physical interaction between beta2AR and MAGI-3. (
  • Mechanisms of mitogen-activated protein kinase activation in experimental diabetes'J.Am.Soc.Nephrol. (
  • These results suggest a regulatory role of MUC1 in modulating proximal signal transduction events through its interaction with proteins of the activation complex. (
  • Previous studies demonstrate that Ras guanyl nucleotide-releasing protein (RasGRP)1 is essential in T cell receptor-mediated Ras-Erk activation. (
  • Consequently, activation of Akt, PIP3-dependent kinase, and protein kinase C delta was defective. (
  • Yu, T, Jhun, BS & Yoon, Y 2011, ' High-glucose stimulation increases reactive oxygen species production through the calcium and mitogen-activated protein kinase-mediated activation of mitochondrial fission ', Antioxidants and Redox Signaling , vol. 14, no. 3, pp. 425-437. (
  • The Son of Sevenless (Sos) proteins control receptor-mediated activation of Ras by catalyzing the exchange of guanosine diphosphate for guanosine triphosphate on Ras. (
  • The tandem DH-PH domain of Sos (DH-PH-Sos) was defective in Rac activation but regained Rac stimulating activity when it was coexpressed with activated Ras. (
  • Biochemical analyses revealed ERK hyperphosphorylation in the amygdala but not the hippocampus following acquisition, suggesting functional activation of the amygdala as early as post-natal day 3, although there was no clear evidence for amygdalar ERK activation after reactivation. (
  • Particularly, NF-κB activation was observed in activated microglia of post-ischemic brain and markedly attenuated by AUY954, indicating that M1 polarization through S1P₁ in post-ischemic brain mainly occurred in activated microglia. (
  • By measuring the levels of heat shock proteins as well as the activation of mitogen activated protein kinases (MAPKs), we could not detect any differences upon RF exposure. (
  • A treatment with 5%(v/v) coffee extract and more than 2.5 μM pyrocatechol inhibited the LPS-induced activation of NF-κB and also significantly activated Nrf2, which acts as a negative regulator in LPS-induced inflammation. (
  • Activation of Rho proteins through release of bound GDP and subsequent binding of GTP, is catalysed by guanine nucleotide exchange factors (GEFs) in the Dbl family. (
  • Combining MRTX849 with therapeutics that target receptor tyrosine kinases, mTOR, or cell cycle molecules resulted in enhanced tumor responses in many tumor models, including those resistant to MRTX849 alone. (
  • HER2 is a member of the human epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. (
  • This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. (
  • In vitro kinase assays showed that ERK1/2 is capable of phosphorylating dynamin-like protein 1. (
  • Once activated, caspases -3 and -7 cleave downstream proteins. (
  • The beta-2 adrenergic receptor (beta2AR) has a carboxyl terminus motif that can interact with PSD-95/discs-large/ZO1 homology (PDZ) domain-containing proteins. (
  • Another region with homology to the MAP kinase ERK4 (C34 domain) has been identified after the kinase domain. (
  • The proteins encoded by members of the Dbl family share a common domain, presented in this entry, of about 200 residues (designated the Dbl homology or DH domain) that has been shown to encode a GEF activity specific for a number of Rho family members. (
  • It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. (
  • These small molecules mimic pro-death B-cell lymphoma-2 (Bcl-2) Homology 3 (BH3) domain-only proteins. (
  • Activated p38 and ERK may med … More iate hyperproliferation of dysplastic tubules resulting in cyst formation/whereas downregulated JNK expression may be the cause or the result of an undifferentiated state of dysplastic epithelia. (
  • Expression of mitogen-activated protein kinase family in rat renal development'Kidney Int. 58. (
  • Expression of mitogen-activated protein kinases in human renal dysplasia'Kidney Int. 61. (
  • Decrease of interleukin (IL)17a gene expression in leucocytes and in the amount of IL-17a protein in CD4+ T cells in children with Down syndrome. (
  • synthesis VI is the most PLK1 s expression signaling circulation browser, an migration defined from its breast with the FcRI protein pro-IL1B. (
  • Expression of PIM1 protein in chronic lymphocytic leukemia/small lymphocytic lymphoma. (
  • Our results showed that all dosages induced no significant alterations in growth parameters and the seric levels of total protein, albumin, globulin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides and activities of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase and lactate dehydrogenase, when compared to the control group. (
  • Glycoprotein E2 is the Isomalt most immunodominant protein and induces the production of neutralizing antibodies in infected pigs [21]. (
  • Axotomy in vitro leads to a fourfold to sixfold increase in 3 H-leucine incorporation in both neurones and axons, starting within 10 min and peaking 1 h after axotomy. (
  • Conditioning lesions, which increase the regenerative ability of sensory axons, lead to increases in intra-axonal protein synthetic and degradative machinery both in vitro and in vivo . (
  • Dex significantly reduced in vitro apoptosis of MSCs under OGD, which suppressed the synthesis level of Beclin1 and light chain 3 proteins. (
  • Thus, the principle of protein or peptide haptenation could be used in in vitro assays to predict the sensitization potential of a new chemical entity. (
  • As a result, the 3-D in vitro bloodstream vessel model may be used to understand radiation-induced endothelial accidents. (
  • Atypical mitogen-activated protein kinases: structure, regulation and functions. (
  • RSF‑induced cell death was associated with the down-regulation of B‑cell lymphoma 2 (Bcl‑2) and the up-regulation of Bcl‑2 X‑associated protein (Bax). (
  • Interacting with various cellular proteins, E6 and E7 influence fundamental cellular functions like cell cycle regulation, telomere maintenance, susceptibility to apoptosis, intercellular adhesion and regulation of immune responses. (
  • The Rho family of GTP-binding proteins has been implicated in the regulation of various cellular functions including actin cytoskeleton-dependent morphological change. (
  • The guanine nucleotide exchange factor (GEF) Dbl targets Rho family proteins thereby stimulating their GDP/GTP exchange, and thus is believed to be involved in receptor-mediated regulation of the proteins. (
  • About 13 percent of non-small cell lung cancers (NSCLC) and about 3 percent of colorectal cancers are known to have KRAS mutations. (
  • ERK4 and ERK3 define a distinct subfamily of MAP kinases. (
  • Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, Plant MAPKKs and similar proteins, catalytic (c) domain. (
  • Electrophoretic mobility shift assay revealed that the ARE complex, consisting of Nrf-1/2 and Maf proteins, was activated 12 to 48 h after sulfur amino acid deprivation (SAAD). (
  • Smirlis D, Dingli F, Sabatet V, Roth A, Knippschild U , Loew D, Späth GF, Rachidi N. Identification of the Host Substratome of Leishmania -Secreted Casein Kinase 1 Using a SILAC-Based Quantitative Mass Spectrometry Assay. (
  • Identification of the host substratome of Leishmania-secreted casein kinase 1 using a SILAC-based quantitative mass spectrometry assay. (
  • Results indicated that curcumin induced cell toxicity (light microscopy and MTT assay) and apoptosis (AnnexinV-FITC/PI labeling and caspase-3 activity) in these cells. (
  • An nCounter assay of 519 kinase panels has been used. (
  • Description: A sandwich quantitative ELISA assay kit for detection of Mouse Tubulin Polymerization Promoting Protein (TPPP) in samples from tissue homogenates or other biological fluids. (
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Tubulin Polymerization Promoting Protein (TPPP) in tissue homogenates, cell lysates and other biological fluids. (
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Tubulin Polymerization Promoting Protein (TPPP) in samples from tissue homogenates, cell lysates and other biological fluids with no significant corss-reactivity with analogues from other species. (
  • Impact of that time period between Positive PCR Outcomes and Serum Test Acquisition Significance for higher odds of discovering positive indicators after extended duration around 3 weeks between your first documented positive PCR result and serum acquisition was computed for everyone IgG-specific assays and Roches immunoglobulin class-overarching assay. (
  • In cells, the association of full-length beta2AR with MAGI-3 occurs constitutively and is enhanced by agonist stimulation of the receptor. (
  • Using the Jurkat T cell lymphoma cell line and normal human T cells, we demonstrate that MUC1 is not only expressed in these cells but is also phosphorylated upon T cell receptor (TCR) ligation and associates with the Src-related T cell tyrosine kinase, p56 lck . (
  • Further experiments showed that if a protein receptor that detects the Semaphorins was deleted, the nerve cells stopped responding to the signal, and their axons did not collapse. (
  • IL-21 is principally composed by activated T cells which facilitate IL-21 to modulate the acquired and innate immunity [ 10 ]. (
  • CD95 counts in the 3 types of white blood cells were significantly higher in PEM infants and showed improvement after nutritional rehabilitation yet not reaching the control values. (
  • We found that, unlike sporadic colorectal cancer and control patients, patients with CAC show activated VEGFR2 on intestinal epithelial cells (IECs). (
  • On the other hand, addition of N-acetyl cysteine (NAC), an antioxidant, blocked the curcumin-induced ROS production and rescued malignant cells from curcumin-induced apoptosis through caspase-3 deactivation. (
  • The vascular endothelium is formed by a sheet of endothelial cells tethered together by junctional proteins such as tight and adherens junctions. (
  • Caveolin-2 has the same tissue distribution as and co-localizes with Caveolin-1, whereas Caveolin-3 is expressed only in cardiac, skeletal, and smooth muscle cells. (
  • The small intestines allows properly digested fats, proteins and starches to pass through the cells in order to be used by the body while providing a barrier to keep out foreign substances, large undigested molecules and bacterial products. (
  • Wikimedia Commons has cells removed to Lipid kinases. (
  • We show that this ability to regenerate a new growth cone depends on local protein synthesis and degradation within the axon. (
  • the present study examines the hypothesis that local protein synthesis and proteasome-mediated degradation are critical to the ability of an amputated axon to remodel its tip into a new growth cone. (
  • Fluoride-induced histopathology and synthesis of stress protein in liver and kidney of mice. (
  • Liver qi is involved in the processing of macronutrients into molecules to fuel energy metabolism in brain neurons, as well as the synthesis of plasma proteins that maintain blood circulation to the brain, thereby enabling these fuel molecules to be delivered to the brain. (
  • Following signaling, proteins that activate transcription replace the inhibitory proteins, generating a bi-stable switch. (
  • Detection and quantification of fecal influenza A viral RNA were performed by quantitative real-time reverse transcription PCR (RT-PCR) specific for the viral matrix-gene as described ( 1 - 3 ). (
  • Bombesin-receptor-subtype-3 (BRS-3) is an orphan G-protein-coupled receptor of the bombesin (Bn) family whose natural ligand is unknown and which does not bind any natural Bn-peptide with high affinity. (
  • The receptor is activated by TRYPSIN, which cleaves off the N-terminal peptide from the receptor. (
  • 2 - 6 Act1 is an E3 ubiquitin ligase, which activates tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) through lysine-63-linked ubiquitination. (
  • Fas ligand is a transmembrane protein part of the tumor necrosis factor (TNF) family. (
  • The tumor was positive for OLIG2 and GFAP and negative for BRAF V600E and IDH1 R132H mutant protein immunostains. (
  • CONTEXTO CLÍNICO: El melanoma es un tumor maligno que surge de células melanocíticas y principalmente involucra la piel.1 En Argentina, cada año se diagnostican aproximadamente 1.400 nuevos casos y mueren 550 personas.2,3 La mayoría de los casos (90%) se diagnostican en estádios tempranos siendo la. (
  • Inhibition of p38 MAP kinase by SB203580 prevented the ARE-mediated rGSTA2 induction. (
  • XIII" YMR047C 3 13 3 YMR047C "Nuclear pore complex protein that is member of GLFG repeat-containing family of nucleoporins and is,XIII" YMR049C 3 13 4 YMR049C "Ymr049cp,XIII" YMR051C 3 13 5 YMR051C "TyA Gag protein. (
  • Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP [ ( PUBMED:1898771 ) ] in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. (
  • This is the first report showing that exposure to asphalt fumes can activate AP-1 and intracellular signaling that may promote skin tumorigenesis, thus providing important evidence on the potential involvement of exposure to asphalt fumes in skin carcinogenesis. (
  • An intracellular-signaling kinase that plays a role in regulating APOPTOSIS . (
  • Recent studies suggest a potential involvement of the kinase in the control of cell differentiation, cytoskeletal remodelling, cell migration and invasion, DNA repair, and immune response. (
  • In this paper, we identified membrane-associated guanylate kinase inverted-3 (MAGI-3) as a novel binding partner of beta2AR. (
  • HER2 can heterodimerize with EGFR protein or homodimerize when it is present in high concentrations. (
  • Tian X, Traub B, Shi J, Huber N, Schreiner S, Chen G, Zhou S, Henne-Bruns D, Knippschild U , Kornmann M. c-Jun N-terminal kinase 2 suppresses pancreatic cancer growth and invasion and is opposed by c-Jun N-terminal kinase 1. (
  • involved PARs cyanide via G effectiveness histone( 4) and via the metabolism: system fructose of the G-protein( 5). (
  • RSF also activated caspase‑3 and -9 and regulated the activations of mitogen-activated protein kinases (MAPKs). (
  • Taurine reverses sodium fluoride-mediated increase in inflammation, caspase-3 activity, and oxidative damage along the brain-pituitary-gonadal axis in male rats. (
  • Moreover, taurine reversed NaF-induced elevation in inflammatory biomarkers and caspase-3 activity as well as histological damage in the brain, testes, and epididymis of the treated rats. (
  • Fas ligand binds to the receptor and forms the death-inducing signalling complex, including the Fas-associated death domain, death-domain associated protein, and caspase-10. (
  • Caspase-8 is an initiator caspase that is activated in response to pro-apoptotic stimulus and causes a cascade of further caspase activity by cleaving and activating effector caspases, like caspases -3 and -7. (
  • In the present study, we demonstrate that seminal vesicle protein secretion 2 (SVS2), which is a 40-kDa basic protein and a major component of the copulatory plug, enters the uterus and interacts with ejaculated sperm heads after copulation. (
  • Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM: FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. (
  • ADP interacts P2Y1 and P2Y12, which have via both the download Финансовый анализ and stress: immune characteristics of the inactive G-protein( Hirsch et al. (
  • It is also a negative regulator of the Ras-p42/44 mitogen-activated kinase cascade. (
  • 3 Since no toxins, cell wall degrading enzymes or specialized secretion systems have been identified in the C Las genome, it is believed that the disease symptoms are the result of host metabolic imbalances brought about by nutrient depletion or interference with nutrient transport. (
  • Smad proteins mediate the cellular effects of the TGF-β protein family, with BMPs and GDFs acting through Smad1, Smad5, and Smad8, whereas other members of the TGF-β family act through Smad2 and Smad3 [ 2 ]. (
  • Caveolin-1 is intricately involved in caveolar functioning and has been found to be a key regulator of some of signaling proteins. (