An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Agents that inhibit PROTEIN KINASES.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Substances that stimulate mitosis and lymphocyte transformation. They include not only substances associated with LECTINS, but also substances from streptococci (associated with streptolysin S) and from strains of alpha-toxin-producing staphylococci. (Stedman, 25th ed)
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Established cell cultures that have the potential to propagate indefinitely.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The rate dynamics in chemical or physical systems.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Proteins isolated from the roots of the pokeweed, Phytolacca americana, that agglutinate some erythrocytes, stimulate mitosis and antibody synthesis in lymphocytes, and induce activation of plasma cells.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.
Proteins prepared by recombinant DNA technology.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
A group of phenyl benzopyrans named for having structures like FLAVONES.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.
The relationship between the dose of an administered drug and the response of the organism to the drug.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
Elements of limited time intervals, contributing to particular results or situations.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
Cell surface proteins that bind eicosanoids with high affinity and trigger intracellular changes influencing the behavior of cells. Among the eicosanoid receptors are receptors for the prostaglandins, thromboxanes, and leukotrienes.
A cell line derived from cultured tumor cells.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.
Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
The phosphoric acid ester of serine.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
Transport proteins that carry specific substances in the blood or across cell membranes.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.
Four carbon unsaturated hydrocarbons containing two double bonds.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
A family of calcium/calmodulin-dependent PROETIN-SERINE-THREONINE KINASES. They are ubiquitously expressed in adult and embryonic mammalian tissues, and their functions are tightly related to the early stages of eukaryotic programmed cell death.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A cyclic GMP-dependent protein kinase subtype that is expressed in SMOOTH MUSCLE tissues and plays a role in regulation of smooth muscle contraction. Two isoforms, PKGIalpha and PKGIbeta, of the type I protein kinase exist due to alternative splicing of its mRNA.
Compounds of four rings containing a nitrogen. They are biosynthesized from reticuline via rearrangement of scoulerine. They are similar to BENZYLISOQUINOLINES. Members include chelerythrine and sanguinarine.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A regulatory calcium-calmodulin-dependent protein kinase that specifically phosphorylates CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 1; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 2; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 4; and PROTEIN KINASE B. It is a monomeric enzyme that is encoded by at least two different genes.
Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture.
A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.
A structurally-diverse family of intracellular-signaling adaptor proteins that selectively tether specific protein kinase A subtypes to distinct subcellular sites. They play a role in focusing the PROTEIN KINASE A activity toward relevant substrates. Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A mitogen-activated protein kinase kinase with specificity for a subset of P38 MITOGEN-ACTIVATED PROTEIN KINASES that includes MITOGEN-ACTIVATED PROTEIN KINASE 12; MITOGEN-ACTIVATED PROTEIN KINASE 13; and MITOGEN-ACTIVATED PROTEIN KINASE 14.
A genus of trees in the Lamiaceae family containing assorted flavonoids with possible analgesic and antineoplastic properties. The fruit of these trees is used in herbal preparations.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
The sum of the weight of all the atoms in a molecule.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 48 and 54 KD exist due to multiple ALTERNATIVE SPLICING.
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A 110-kDa extracellular signal-regulated MAP kinase that is activated in response to cellular stress and by GROWTH FACTOR RECEPTORS-mediated pathways.
A 38-kDa mitogen-activated protein kinase that is abundantly expressed in a broad variety of cell types. It is involved in the regulation of cellular stress responses as well as the control of proliferation and survival of many cell types. The kinase activity of the enzyme is inhibited by the pyridinyl-imidazole compound SB 203580.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.
Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.
A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.
Compounds or factors that act on a specific enzyme to increase its activity.
A monomeric calcium-calmodulin-dependent protein kinase subtype that is primarily expressed in neuronal tissues; T-LYMPHOCYTES and TESTIS. The activity of this enzyme is regulated by its phosphorylation by CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A type I cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIBETA SUBUNIT.
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.
Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.
Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions.
An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
An imidazole derivative which is a metabolite of the antineoplastic agents BIC and DIC. By itself, or as the ribonucleotide, it is used as a condensation agent in the preparation of nucleosides and nucleotides. Compounded with orotic acid, it is used to treat liver diseases.
An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
A specific inhibitor of phosphoserine/threonine protein phosphatase 1 and 2a. It is also a potent tumor promoter. (Thromb Res 1992;67(4):345-54 & Cancer Res 1993;53(2):239-41)
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

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 ...
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) ...
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
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 ...
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 ... This protein is a ligand for the EGF receptor. As a typical EGFR ligand, betacellulin is expressed by a variety of cell types ... Betacellulin is a protein that in humans is encoded by the BTC gene located on chromosome 4 at locus 4q13-q21. Betacellulin, is ...
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 ... This mutation may result in a truncated nonfunctional protein. Blast cells analysis displayed the same abnormality as germline ...
"Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 (MAPKK 6) or MAPK/ERK kinase 6 is ... protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • protein ... the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase ...
Its activation also induces mitogen-activated protein kinases (MAPK) activation along with phosphoinositide 3-kinase activation ...
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". CS1 maint: discouraged ... 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- ... promoter sequences of genes and biological activity of protein products". Endocrinology. 142 (7): 2906-15. doi:10.1210/endo. ...
... 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 ...
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 ...
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( ...
... 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, ...
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. ...
... 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): ...
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 ( ...
... and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase ... Mitogen-activated protein kinase kinase kinase 3 is an enzyme that in humans is encoded by the MAP3K3 gene, which is located on ... "Entrez Gene: MAP3K3 mitogen-activated protein kinase kinase kinase 3". Gilmore PM, McCabe N, Quinn JE, Kennedy RD, Gorski JJ, ... "BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". ...
protein binding. • protein kinase binding. Cellular component. • membrane. • plasma membrane. • caveola. • cytosol. • cell ... The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade.[5] ... negative regulation of protein kinase activity. • negative regulation of angiogenesis. • regulation of MAPK cascade. • negative ... protein serine/threonine kinase inhibitor activity. • phosphatase binding. • stem cell factor receptor binding. • ...
... 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 ...
... and Ras/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal ... The natural human glycoprotein exists in two forms, a 174- and 177-amino-acid-long protein of molecular weight 19,600 grams per ... Loop mobility in a four-helix-bundle protein". Biochemistry. 33 (28): 8453-63. doi:10.1021/bi00194a009. PMID 7518249. Corcione ... G-CSF regulates them using Janus kinase (JAK)/signal transducer and activator of transcription (STAT) ...
Through the receptor tyrosine kinases, signals are sent to the nucleus through the mitogen-activated protein kinase (MAPK/ERK) ... "Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase". Science. 270 (5241): 1491-4. ... Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone ... 17β-Estradiol has been shown to activate the G protein-coupled receptor GPR30. However the subcellular localization and role of ...
... translocation induces cell survival mediated by mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt/mTOR ... The resulting chimeric protein contains the N-terminal leucine-rich region of this encoded protein fused to the catalytic ... This gene encodes a largely hydrophilic protein postulated to be a leucine-rich protein family member. A t(6;8)(q27;p11) ... Yan X, Habedanck R, Nigg EA (February 2006). "A complex of two centrosomal proteins, CAP350 and FOP, cooperates with EB1 in ...
... cells involves Smad7-dependent activation of p38 by TGF-beta-activated kinase 1 and mitogen-activated protein kinase kinase 3 ... Erk-family MAP kinases, the Ca2+ /calmodulin-dependent protein kinase II (CamKII) and protein kinase C (PKC). Smad7 does not ... contains important regulatory peptide motifs including potential phosphorylation sites for mitogen-activated protein kinases( ... Yakymovych I, Ten Dijke P, Heldin CH, Souchelnytskyi S (March 2001). "Regulation of Smad signaling by protein kinase C". FASEB ...
"The neuropeptide substance P activates p38 mitogen-activated protein kinase resulting in IL-6 expression independently from NF- ... "Metalloproteinases and transforming growth factor-alpha mediate substance P-induced mitogen-activated protein kinase activation ... "Substance P induces rapid and transient membrane blebbing in U373MG cells in a p21-activated kinase-dependent manner". PLOS ONE ... The molecule, which is rapidly inactivated (or at times further activated by peptidases) is rapidly released - repetitively and ...
Mijelin protein nula • Osteonektin • Protein C • Protein S • Proteoglikan • Serum amiloid P komponenta • Sialoglikoprotein ( ... Shu HB, Hu WH, Johnson H (May 1999). "TALL-1 is a novel member of the TNF family that is down-regulated by mitogens". J. Leukoc ... 1999). "Identification and characterization of a novel cytokine, THANK, a TNF homologue that activates apoptosis, nuclear ... factor-kappaB, and c-Jun NH2-terminal kinase.". J. Biol. Chem. 274 (23): 15978-81. PMID 10347144. doi:10.1074/jbc.274.23.15978. ...
... mitogen-activated protein kinase) cascade that is itself a kinase. RSK2 phosphorylates cellular proteins (including histone H3 ... RSK2 is normally activated by the ERK MAP kinase. Mutated RSK2 may be deficient for activation by ERK, or its kinase activity ... Mutations in the RPS6KA3 gene can result in expression of an RSK2 protein (ribosomal S6 kinase 2) with reduced or absent kinase ... The protein RSK2 which is encoded by the RPS6KA3 gene is a kinase which phosphorylates some substrates like CREB and histone H3 ...
"Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... Deacon K, Blank JL (1997). "Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. ... "Entrez Gene: MAP2K4 mitogen-activated protein kinase kinase 4". Marti, A; Luo Z; Cunningham C; Ohta Y; Hartwig J; Stossel T P; ...
Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... The ligands interact with the two tyrosine kinase receptor monomers, PDGFRα (PDGFRA) and -Rβ (PDGFRB).[6] The PDGF family also ... PDGF[1][2] is a potent mitogen for cells of mesenchymal origin, including fibroblasts, smooth muscle cells and glial cells. In ... There are five different isoforms of PDGF that activate cellular response through two different receptors. Known ligands ...
Mitogen-activated protein kinase (EC 2.7.11.24). *Extracellular signal-regulated *MAPK1. *MAPK3 ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene ...
GHB inhibits mitogen activated protein (MAP) kinase action via the GABAB receptor mechanism. MAP kinase is imperative for ... Ren, X.; Mody, I. (2003). "Gamma-hydroxybutyrate reduces mitogen-activated protein kinase phosphorylation via GABAB receptor ... GABA acts via binding to its receptors which include the ligand gated ion channels, GABAA and GABAC and the G-protein couple ... Taurine is a non-protein sulfur amino acid that is found in high concentrations in human milk. It has been shown to have ...
... mitogen-activated protein kinase) kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) ... mitogen-activated protein kinase) kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) ... The β chain of IL-15R recruits and also activates protein tyrosine kinases of the Src family including Lck, Fyn and Lyn kinase ... Upon binding IL-15β subunit activates Janus kinase 1 (Jak1) and γc subunit Janus kinase 3 (Jak3), which leads to ...
JUN kinase binding. • mitogen-activated protein kinase kinase binding. • mitogen-activated protein kinase kinase kinase binding ... "Entrez Gene: MAPK8IP1 mitogen-activated protein kinase 8 interacting protein 1".. *^ a b c d e f Yasuda, J; Whitmarsh A J; ... MAP-kinase scaffold activity. • protein kinase inhibitor activity. • protein binding. • kinesin binding. • protein kinase ... MAPK8IP1, IB1, JIP-1, JIP1, PRKM8IP, mitogen-activated protein kinase 8 interacting protein 1. ...
kinase binding. • mitogen-activated protein kinase kinase binding. • guanylate kinase activity. • protein binding. • protein ... SAP97 is a mammalian MAGUK-family member protein that is similar to the Drosophila protein Dlg1 (the protein is alternatively ... brain-enriched guanylate kinase-associated protein), a novel neuronal PSD-95/SAP90-binding protein". The Journal of Biological ... protein kinase binding. • L27 domain binding. • ligand-gated ion channel activity. • potassium channel regulator activity. • ...
... factor depends on heparan sulfate proteoglycans and sustained phosphorylation of mitogen-activated protein kinases p42/44". The ... protein heterodimerization activity. • growth factor activity. • serine-type endopeptidase activity. • protein tyrosine kinase ... positive regulation of protein kinase B signaling. • positive regulation of protein phosphorylation. • cytokine-mediated ... regulation of tau-protein kinase activity. • proteolysis. • positive chemotaxis. • MAPK cascade. • peptidyl-tyrosine ...
... and/or 271 by Mitogen-activated protein kinases, S6 kinase, protein kinase A (PKA), protein kinase C, Cdc2, and/or a Ca2+/ ... This chemotactic factor stimulation concurrently causes the activation of mitogen-activated protein kinases (MAPK) which in ... ALOX5 binds with the F actin-binding protein, coactin-like protein. Based on in vitro studies, this protein binding serves to ... "5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes". J. ...
... cyclin-dependent kinases, and other cell cycle proteins. The phases follow one another in strict order and there are " ... the motor activates, using energy from ATP to "crawl" up the tube toward the originating centrosome. This motor activity, ... Mitogen. *Mitosis Promoting Factor. *Mitotic bookmarking. *Motor protein. References[edit]. *^ "Cell division and growth". ... Generation of pressure is dependent on formin-mediated F-actin nucleation[71] and Rho kinase (ROCK)-mediated myosin II ...
Hardie DG, Hawley SA (December 2001). "AMP-activated protein kinase: the energy charge hypothesis revisited". Bioessays 23 (12 ... Pri vseh adenozinskih receptorjih opazimo aktivacijo najmanj ene poddružine mitogen - aktiviranih proteinskih kinaz. Učinek ... Lin X, Ayrapetov M, Sun G (2005). "Characterization of the interactions between the active site of a protein tyrosine kinase ... Scheeff E, Bourne P (2005). "Structural evolution of the protein kinase-like superfamily". PLoS Comput Biol 1 (5): e49. doi: ...
... and gp130-mediated stimulation of mitogen-activated protein kinase. Evidence for participation of multiple signaling pathways ... Mijelin protein nula • Osteonektin • Protein C • Protein S • Proteoglikan • Serum amiloid P komponenta • Sialoglikoprotein ( ... Glikoprotein 130 (takođe poznat kao gp130, IL6ST, IL6-beta ili CD130) je transmembranski protein. On je osnivački član klase ... 2000). „Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines.". ...
... synaptic NMDA excitation caused a decrease in the intracellular concentration of p38 mitogen-activated protein kinase (p38MAPK ... which contain residues that can be directly modified by a series of protein kinases and protein phosphatases, as well as ... The NMDA receptor is a glutamate and ion channel protein receptor that is activated when glycine and glutamate bind to it.[2] ... Yu XM, Askalan R, Keil GJ, Salter MW (January 1997). "NMDA channel regulation by channel-associated protein tyrosine kinase Src ...
... enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2 ... Galyov EE, Håkansson S, Forsberg A, Wolf-Watz H (1993). "A secreted protein kinase of Yersinia pseudotuberculosis is an ... "En Ladant, Daniel; Alouf, Joseph E.; Popoff, Michel R. The Comprehensive Sourcebook of Bacterial Protein Toxins. Academic Press ... "Impact of the Yersinia pseudotuberculosis-derived mitogen (YPM) on the murine immune system". Adv. Exp. Med. Biol. 529: 133-5. ...
Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase, in Proc. Natl. Acad. Sci. U.S.A., ... Iijima S, Teraoka H, Date T, Tsukada K, DNA-activated protein kinase in Raji Burkitt's lymphoma cells. Phosphorylation of c-Myc ... Rob M Ewing, Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, et al., Large-scale mapping of human protein-protein interactions ... Gazin C, Rigolet M, Briand JP, et al., Immunochemical detection of proteins related to the human c-myc exon 1, in EMBO J., vol ...
... and Mitogen-activated protein kinases (MAPK).[28] Messages are translated on the rough endoplasmic reticulum (rough ER) and ... CaMKII activates the Ras proteins, which go on to activate p42/44 MAPK, which drives AMPAR insertion directly into the ... which in turn activates protein phosphatases PP1 and calcineurin. However, AMPAR endocytosis has also been activated by voltage ... "Calcium/calmodulin-dependent protein kinase II phosphorylation drives synapse-associated protein 97 into spines". J. Biol. Chem ...
... cell division is necessary for permanent neurotensin cell sensitization and leads to chronic mitogen-activated protein kinase ... Neurotenzinski receptor tip 1 je protein koji je kod ljudi kodiran NTSR1 genom.[1][2] ... 1999). "TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction.". J. Biol. Chem. ... aktivnost neurotenzinskog receptora, G-protein spregnutog. Celularna komponenta. • endoplazmatični retikulum. • Goldži aparat. ...
"Role of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinase kinase in adenosine A2B receptor ... Adenozinski A2B receptor (ADORA2B) je G-protein spregnuti adenozinski receptor. Ovaj protein je kodiran humanim ADORA2B genom.[ ... signalni put G-protein spregnutog receptora. • aktivnost adenilat ciklaze. • JNK kaskada. • izlučivanje. ... aktivnost A2B adenouinskog receptora, G-protein spregnutog. • receptorska aktivnost. Celularna komponenta. • integralno sa ...
positive regulation of protein kinase activity. • ERBB2 signaling pathway. • regulation of cell motility. • epidermal growth ... positive regulation of epidermal growth factor-activated receptor activity. • تمايز خلوي. • positive regulation of cytokine ... "Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin.". ... positive regulation of protein kinase B signaling. • توصيل الإشارة. • negative regulation of epidermal growth factor receptor ...
Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... phospholipase C-activating G-protein coupled receptor signaling pathway. • retina development in camera-type eye. • Ras protein ... protein complex binding. • signal transducer activity. • protein binding. • GTPase activity. • GTPase binding. • G-protein ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ...
... a hyaluronan-binding protein that regulates ras signaling, correlates with overexpression of mitogen-activated protein kinase ... It forms links with several protein kinases associated with cell locomotion, for example, extracellular signal-regulated ... MAP kinase (MAPK), pp60(c-src), and the downstream targets of Rho kinase (ROK).[22] RHAMM can also cooperate with CD44 to ... protein kinase (ERK), p125fak, and pp60c-src.[32][33][34] During fetal development, the migration path through which neural ...
... mitogen-activated-protein kinase-activating protein kinase) has a preference for Ser40, but also phosphorylates Ser19 about ... "Phosphorylation and activation of human tyrosine hydroxylase in vitro by mitogen-activated protein (MAP) kinase and MAP-kinase- ... that are phosphorylated by a variety of protein kinases.[12][25] Ser40 is phosphorylated by the cAMP-dependent protein kinase.[ ... protein binding. • amino acid binding. • monooxygenase activity. • protein domain specific binding. Cellular component. • ...
"Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated protein kinase/heat shock protein 27 pathway ... 2003). "The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic ... aktivnost G-protein spregnutog receptora. { • lipidno vezivanje. Celularna komponenta. • ćelijska membrana. • integralno sa ... Receptor slobodnih masnih kiselina 2 (FFA2) je G protein spregnuti receptor kodiran FFAR2 genom.[1] ...
... mitogen-activated protein kinase, MAPK)訊息的梯瀑效應(cascade)的活化、粒線體活性氧(reactive oxygen species, ROS)的產生、C型磷脂酶(phospholipase C, PLC)及 ... Regulation of Na+-K+-ATPase by cAMP-dependent protein kinase anchored on membrane via its anchoring protein Kinji Kurihara, ... 3.6.5.1: 异三聚体G蛋白(英语:Heterotrimeric G protein). *Gαs ... 蛋白質交互作用對鈉鉀幫浦媒介的訊息傳遞
mitogen-activated protein kinase kinase kinase binding. • protein binding. • thioesterase binding. • protein kinase binding. • ... Activated Cdc42 activates by conformational changes[4] p21-activated kinases PAK1 and PAK2, which in turn initiate actin ... "The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily ... Joberty G, Petersen C, Gao L, Macara IG (August 2000). "The cell-polarity protein Par6 links Par3 and atypical protein kinase C ...
... (also known as MAP2K, MEK, MAPKK) is a kinase enzyme which phosphorylates mitogen- ... Mitogen-Activated+Protein+Kinase+Kinases at the US National Library of Medicine Medical Subject Headings (MeSH) ... Retrieved from "https://en.wikipedia.org/w/index.php?title=Mitogen-activated_protein_kinase_kinase&oldid=921615706" ... The activators of p38 (MKK3 and MKK6), JNK (MKK4 and MKK7), and ERK (MEK1 and MEK2) define independent MAP kinase signal ...
General protein information Go to the top of the page Help Preferred Names. mitogen-activated protein kinase 3. Names. MAP ... mRNA and Protein(s) * NM_001040056.3 → NP_001035145.1 mitogen-activated protein kinase 3 isoform 2 ... mitogen-activated protein kinases (MAPK), and nuclear factor (NF)-kappaB. PubMed env HIV-1 gp120 activates c-Jun N-terminal ... mitogen-activated protein kinase 3provided by HGNC. Primary source. HGNC:HGNC:6877 See related. Ensembl:ENSG00000102882 MIM: ...
mitogen-activated protein kinase 8 interacting protein 3provided by HGNC. Primary source. HGNC:HGNC:6884 See related. Ensembl: ... MAPK8IP3 mitogen-activated protein kinase 8 interacting protein 3 [ Homo sapiens (human) ] Gene ID: 23162, updated on 12-Aug- ... MAPK8IP3 mitogen-activated protein kinase 8 interacting protein 3 [Homo sapiens] MAPK8IP3 mitogen-activated protein kinase 8 ... JNK/SAPK-associated protein-1. JNK/stress-activated protein kinase-associated protein 1. homolog of Drosophila Sunday driver 2 ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... White boxes represent UTRs (untranslated regions). Orange: protein coding regions. The black lines connecting boxes represent ...
MAP3K3, mitogen-activated protein kinase kinase kinase 3. Orthology source: HomoloGene, HGNC ... J:31860 Blank JL, et al., Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3. Regulation of ... sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase. J Biol Chem. 1996 Mar 8;271(10 ... protein coding gene. Chr11:106084613-106156653 (+). 129S1/SvImJ MGP_129S1SvImJ_G0019293. protein coding gene. Chr11:109362561- ...
wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary ... knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound ...
Protein-Serine-Threonine Kinases [D08.811.913.696.620.682.700]. *Mitogen-Activated Protein Kinases [D08.811.913.696.620.682. ... Proline-Directed Protein Kinases [D08.811.913.696.620.682.700.646]. *Mitogen-Activated Protein Kinases [D08.811.913.696.620.682 ... Extracellular Signal-Regulated MAP Kinases [D12.644.360.450.169]. *Mitogen-Activated Protein Kinase 3 [D12.644.360.450.169.750] ... Extracellular Signal-Regulated MAP Kinases [D12.776.476.450.169]. *Mitogen-Activated Protein Kinase 3 [D12.776.476.450.169.750] ...
c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1, D17Wsu15e, Jip3, JNK-interacting protein ... MAPK8IP3, mitogen-activated protein kinase 8 interacting protein 3. Orthology source: HomoloGene, HGNC ... JUN/SAPK-associated protein 1, mKIAA1066, sunday driver 2, Syd2 ... IPR019143 JNK/Rab-associated protein-1, N-terminal. IPR011047 ... IPR032486 JNK-interacting protein, leucine zipper II. ... MAPK8IP3, mitogen-activated protein kinase 8 interacting ...
... mitogen-activated protein kinase kinase kinase 3), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol. ... MAPK cascade activation of MAPKK activity blood vessel development protein kinase activity MAP kinase kinase kinase activity ... MAPK cascade activation of MAPKK activity blood vessel development protein kinase activity MAP kinase kinase kinase activity ... SCOP (Structural Classification of Proteins). 2C60 2JRH 2O2V 2PPH 4Y5O 4YL6 CATH (Classification of proteins structures). 2C60 ...
... protein kinase binding, protein serine/threonine kinase activity, activation of MAPK activity, activation of protein kinase ... View protein in PROSITE. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 ... View protein in PROSITE. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 ... Mitogen activated protein kinase kinase 3, isoform CRA_bImported. ,p>Information which has been imported from another database ...
... dual specificity mitogen-activated protein kinase kinase 3), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol ... X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA LOC100996792 (dual specificity mitogen-activated protein kinase ... LOC100996792 100996792 dual specificity mitogen-activated protein kinase kinase 3. Aliases. GeneCards (Weizmann). LOC100996792 ...
Compare 36 different MAPK1/3 ELISA Kits & buy the right one directly at antibodies-online.com! ... Mitogen-Activated Protein Kinase Kinase 1 ELISA Kits * Mitogen-Activated Protein Kinase Kinase 1 Interacting Protein 1 ELISA ... Mitogen-Activated Protein Kinase Associated Protein 1 ELISA Kits * Mitogen-Activated Protein Kinase Binding Protein 1 ELISA ... Mitogen-Activated Protein Kinase Kinase Kinase 1 ELISA Kits * Mitogen-Activated Protein Kinase Kinase Kinase 5 ELISA Kits ...
Targeting of Mitogen-Activated Protein Kinases and Phosphatidylinositol 3 Kinase Inhibits Hepatocyte Growth Factor/Scatter ... Targeting of Mitogen-Activated Protein Kinases and Phosphatidylinositol 3 Kinase Inhibits Hepatocyte Growth Factor/Scatter ... Targeting of Mitogen-Activated Protein Kinases and Phosphatidylinositol 3 Kinase Inhibits Hepatocyte Growth Factor/Scatter ... Targeting of Mitogen-Activated Protein Kinases and Phosphatidylinositol 3 Kinase Inhibits Hepatocyte Growth Factor/Scatter ...
... phosphoinositide 3-kinase (PI3K) pathways in the absence of GHS-R1a. Download Prime PubMed App to iPhone, iPad, or Android ... Ghrelin and unacylated ghrelin stimulate human osteoblast growth via mitogen-activated protein kinase (MAPK)/ ... TY - JOUR T1 - Ghrelin and unacylated ghrelin stimulate human osteoblast growth via mitogen-activated protein kinase (MAPK)/ ... Ghrelin and unacylated ghrelin stimulate human osteoblast growth via mitogen-activated protein kinase (MAPK)/phosphoinositide 3 ...
Protein phosphatase 2A acts as a mitogen-activated protein kinase kinase kinase 3 (MEKK3) phosphatase to inhibit ... Using a functional genomic approach, we have identified a protein serine/threonine phosphatase, protein phosphatase 2A (PP2A), ... Furthermore, knockdown of PP2Ac expression enhances LPA-induced MEKK3-mediated IkappaB kinase beta (IKKbeta) phosphorylation ... the precise mechanism for the termination of MEKK3 kinase activity is not fully understood. ...
Effects of protein kinase C modulation by PEP005, a novel ingenol angelate, on mitogen-activated protein kinase and ... Effects of protein kinase C modulation by PEP005, a novel ingenol angelate, on mitogen-activated protein kinase and ... Effects of protein kinase C modulation by PEP005, a novel ingenol angelate, on mitogen-activated protein kinase and ... Effects of protein kinase C modulation by PEP005, a novel ingenol angelate, on mitogen-activated protein kinase and ...
... p38 Mitogen-activated protein kinase mediates cell death and p21-activated kinase mediates cell survival during ... Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for activation of p38α and p38δ MAPK isoforms by TGF-β1 in ... We identify mitogen-activated protein kinase (MAPK) kinase 3 (MKK3) as a key activator of p38 MAPK in glioma; MKK3 activation ... For the first time, we report mitogen-activated protein kinase (MAPK) kinase 3 (MKK3) to be up-regulated with glioma invasion ...
... kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways reduces melanoma ... Akt and Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (Erk) pathways by the use of ... Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer 2004;4:937 ... Antibodies used were: anti-phospho-p44/42 mitogen-activated protein kinase (Thr202/Tyr204, 1:1,000), anti-phospho-Akt (Ser473, ...
... kinase/Akt and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase blocks 1984-1 invasion in vitro. A ... kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways inhibited the growth ... Kinase/Akt and Raf/Mitogen-Activated Protein Kinase Kinase/Extracellular Signal-Regulated Kinase Pathways Reduces Melanoma ... kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways reduces vascular ...
Protein Kinase B/Mitogen-Activated Protein Kinase Signaling after Growth Arrest-Specific Protein 6/Mer Receptor Tyrosine Kinase ... Protein Kinase B/Mitogen-Activated Protein Kinase Signaling after Growth Arrest-Specific Protein 6/Mer Receptor Tyrosine Kinase ... The RhoA/protein kinase B (Akt)/mitogen-activated protein (MAP) kinases, including p38 MAP kinase, extracellular signal- ... In this study, the RhoA/protein kinase B (Akt)/mitogen-activated protein (MAP) kinases axis in RAW 264.7 cells was identified ...
... apoptosis in human leukemia cells by inhibitors of the mitogen-activated protein kinase kinase/mitogen-activated protein kinase ... c-Jun NH2-terminal kinase; MAP, mitogen-activated protein; MEK, MAP kinase kinase; ERK, extracellular signal-regulated kinase; ... paclitaxel also activates cell survival pathways, such as the Raf-mitogen-activated protein kinase kinase (MEK)-extracellular ... induced cell death by mitogen-activated protein kinase kinase inhibition in human cancer cell lines. Mol. Pharmacol., 60: 290- ...
MAP Kinase Kinase 1 * Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors * Mitogen-Activated Protein Kinase ... Activation of fatty acid synthesis during neoplastic transformation: role of mitogen-activated protein kinase and ... acting in major part through the mitogen-activated protein (MAP) kinase and phosphatidylinositol (PI) 3-kinase signaling ... Mitogen-Activated Protein Kinases / antagonists & inhibitors * Mitogen-Activated Protein Kinases / physiology* * ...
... a mitogen-activated protein kinase kinase kinase is induced simultaneously with genes for a mitogen-activated protein kinase ... Mitogen-activated protein kinase (MPK) cascades are three-tiered signaling kinase modules that can be found in all eukaryotes ( ... Zhang, S., and Klessig, D.F. (1998). The tobacco wounding-activated mitogen-activated protein kinase is encoded by SIPK. Proc. ... priming is associated with accumulation of mRNA and inactive proteins of mitogen-activated protein kinases (MPKs), MPK3 and ...
Kinase/Mitogen-Activated Protein Kinase Pathways in Artery-Vein Specification. Brothers and Sisters: Molecular Insights into ... inhibition of mitogen/extracellular signal-activated protein kinase kinase (MEK), an upstream activator of ERK, results in loss ... and the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathways, plays a central ... Takahashi T, Ueno H, Shibuya M. VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for ...
... protein kinase C, and Ras activation and p38 mitogen-activated protein kinase (MAPK) phosphorylation through PI3K and Akt ... protein kinase C (PKC), and mitogen-activated protein kinases (MAPKs) coupled with the activation of the microbicidal mechanism ... Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J. Biol. Chem. 273:18623-18632. ... Leishmania donovani promastigotes evade the activation of mitogen-activated protein kinases p38, c-Jun N-terminal kinase, and ...
MKK3 and MKK6 both phosphorylate and activate p38 MAP kinase at its activation site, Thr-Gly-Tyr, but do not phosphorylate or ... MKK3 and MKK6 are two closely related dual-specificity protein kinases that activate p38 MAP kinase (1-5). ... MAP2K3; mitogen-activated protein kinase kinase 3; PRKMK3; dual specificity mitogen-activated protein kinase kinase 3; dual ... specificity mitogen activated protein kinase kinase 3; MAP kinase kinase 3; MAPK/ERK kinase 3; MAPKK3; MEK3; MKK3; MEK 3; MAPKK ...
... and regulate the activity of numerous protein kinases of the JNK signaling pathway, and thus function as a scaffold protein in ... Studies of the similar gene in mouse suggested that this protein may interact with, ... The protein encoded by this gene shares similarity with the product of Drosophila syd gene, required for the functional ... JNK/stress-activated protein kinase-associated protein 1; mitogen-activated protein kinase 8-interacting protein 3; SYD2. ...
We found that treatment of cultures with the mitogen-activated protein kinase (MAPK) pathway inhibitor PD98059 prevented hrC5a- ... MAPK pathways, whose activation by hrC5a is inhibited by PD98059 and C177, include the extracellular signal-regulated kinase ( ... Based on this evidence, we further explored possible signaling pathways involved in hrC5a inhibition of caspase 3 activation ... C5a prevented nuclear DNA fragmentation coincidental to inhibition of the pro-apoptotic caspase 3 activity mediated by ...
... including transforming growth factor-beta activated kinase-1 (TAK1) and its interacting protein, protein phosphatase 2C beta ( ... and protein phosphatase 2C beta (PPM1B), and these interactions were also TNF-alpha-inducible in different cell types. Further ... Given the multifunctional nature of 14-3-3 family proteins and the recent finding of their presence in the TNF-alpha/NF-kappaB ... For the first time, we found that TNF-alpha stimulation enhances the interactions between 14-3-3 epsilon and some key ...
Clinical validation of coexisting activating mutations within EGFR, mitogen-activated protein kinase, and phosphatidylinositol ... Clinical validation of coexisting activating mutations within EGFR, mitogen-activated protein kinase, and phosphatidylinositol ... Clinical validation of coexisting activating mutations within EGFR, mitogen-activated protein kinase, and phosphatidylinositol ... Clinical validation of coexisting activating mutations within EGFR, mitogen-activated protein kinase, and phosphatidylinositol ...
Activa Protein Kinase 3 ELISA Kit-NP_001230855.1 (MBS077469) product datasheet at MyBioSource, ELISA Kits ... This kinase functions as a mitogen-activated protein kinase (MAP kinase)- activated protein kinase. MAP kinases are also known ... Protein type: Protein kinase, CAMK; EC 2.7.11.1; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); CAMK group; MAPKAPK ... MAPKAPK3 elisa kit :: Pigeon Mitogen Activated Protein Kinase -Activa Protein Kinase 3 ELISA Kit. ...
  • 8 Ras has emerged as a convergent molecular switch that integrates and propagates extracellular signals to downstream cascades, the best characterized of which are the phosphatidylinositol-3-kinase (PI3K) and the mitogen-activated protein kinase (MAPK) pathways. (ahajournals.org)
  • In Colo205 cells exposed to PEP005, a variety of signaling pathways were activated as shown by increased phosphorylation of PKCδ, Raf1, extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (MAPK), c-Jun NH 2 -terminal kinase, p38 MAPK, and PTEN. (aacrjournals.org)
  • Interestingly, PEP005 treatment also resulted in reduced expression of PKCα and reduced levels of phosphorylated active form of AKT/protein kinase B. These data suggest that PEP005-induced activation of PKCδ and reduced expression of PKCα resulted in apoptosis by mechanisms mediated by activation of Ras/Raf/MAPK and inhibition of the phosphatidylinositol 3-kinase/AKT signaling pathways. (aacrjournals.org)
  • For the first time, we report mitogen-activated protein kinase (MAPK) kinase 3 (MKK3) to be up-regulated with glioma invasion in vitro and in vivo . (aacrjournals.org)
  • Recently, a chemical genetic approach has revealed evidence that artery-vein specification is governed by cross talk between phosphoinositide 3-kinase and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in artery-vein specification. (ahajournals.org)
  • In addition, we discuss relatively novel chemical genetic studies of zebrafish vascular development that have provided evidence that a crosstalk between 2 ubiquitous signaling pathways, the phosphoinositide 3-kinase (PI3K) and the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathways, plays a central antagonistic role in artery-vein specification during vasculogenesis. (ahajournals.org)
  • Herein, we show that SAG induces extracellular signal-regulated kinase 1 (ERK-1) and ERK-2 phosphorylation through phosphoinositide 3-kinase (PI3K), protein kinase C, and Ras activation and p38 mitogen-activated protein kinase (MAPK) phosphorylation through PI3K and Akt activation. (asm.org)
  • ERK-1 and ERK-2 activation results in an increase in the production of reactive oxygen species (ROS) 3 to 6 h after SAG treatment, while p38 MAPK activation and subsequent tumor necrosis factor alpha release result in the production of nitric oxide (NO) 24 h after SAG treatment. (asm.org)
  • It phosphorylates and thus activates MAPK14/p38-MAPK. (genecards.org)
  • The mitogen-activated protein kinase (MAPK) cascade plays a pivotal role in diverse signaling pathways related to plant development and stress responses. (springer.com)
  • Cargnello M, Roux P (2011) Activation and function of the MAPKs and their substrates, the MAPK activated protein kinases. (springer.com)
  • The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:12189133). (genecards.org)
  • Mitogen-activated protein kinase (MAPK) phosphatase-3 (MKP-3) and its substrates (extracellular signal-regulated kinase [ERK] and p38) play an important role in pathophysiological mechanisms of acute postoperative and chronic neuropathic pain in the spinal cord. (dartmouth.edu)
  • To explore the function of Caspase-3 and p38 MAPK in MMT-induced apoptosis in PC-3M cells . (bvsalud.org)
  • The effect on cells viability and Caspase-3 activity of SB203580, a specific inhibitor of p38 MAPK , were also examined. (bvsalud.org)
  • Caspase-3 and p38 MAPK are involved in MMT-induced PC-3M cells apoptosis . (bvsalud.org)
  • Immunohistochemical analyses revealed that phosphorylated (p)-protooncogenic protein kinase 1, p-ribosomal protein S6 kinase, p-ERK1/2, and p-P38 MAPK proteins were present at low levels in a majority of endometrial cells but were most abundant in the nuclei of endometrial luminal epithelium and conceptus trophectoderm of pregnant ewes. (elsevier.com)
  • IGF-II also elicited a rapid increase in p-ERK1/2 and p-P38 MAPK proteins that was maximal at 15 or 30 min posttreatment. (elsevier.com)
  • Three major MAPK families have been identified: the extracellular signal-regulated kinases (ERKs), the c-Jun amino-terminal protein kinases (JNKs) and the p38 kinases. (springer.com)
  • More than 60% of melanomas have the BRAF V600E mutation, which activates the mitogen-activated protein kinase (MAPK) pathway [ 1 ]. (mdpi.com)
  • Signal-induced proliferation, differentiation, or stress responses of cells depend on mitogen-activated protein kinase (MAPK) cascades, the core modules of which consist of members of three successively acting kinase families (MAPK kinase kinase [MAP3K], MAPK kinase, and MAPK). (asm.org)
  • Mitogen-activated protein kinase (MAPK) cascades are protein kinase signal transduction pathways that have been remarkably conserved in evolution. (asm.org)
  • also called MEKK), a MAPK kinase (MAP2K), and a MAPK. (asm.org)
  • In line with the notion that the ERK MAPK is a primary target of Ras and Raf signaling, ERK has been demonstrated to be essential in triggering proliferation in response to growth factors ( 33 ) and appears to be critical for proliferation in response to heterotrimeric G proteins ( 30 , 46 ). (asm.org)
  • METHODS: We studied how two structurally distinct forms of type I collagen, monomer versus polymerized fibrils, affect cell proliferation, mitogen-activated protein kinase (MAPK) activation, and expression of G1-phase regulatory proteins in cultured rat mesangial cells (MCs). (biomedsearch.com)
  • Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 (MAPKK 6) or MAPK/ERK kinase 6 is an enzyme that in humans is encoded by the MAP2K6 gene , on chromosome 17 . (wikipedia.org)
  • A mitogen-activated protein kinase ( MAPK or MAP kinase ) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase ). (wikipedia.org)
  • MAPKs belong to the CMGC (CDK/MAPK/GSK3/CLK) kinase group. (wikipedia.org)
  • Because MAP2 kinases display very little activity on substrates other than their cognate MAPK, classical MAPK pathways form multi-tiered, but relatively linear pathways. (wikipedia.org)
  • In comparison to the three-tiered classical MAPK pathways, some atypical MAP kinases appear to have a more ancient, two-tiered system. (wikipedia.org)
  • PI3K activation was found to support phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). (aspetjournals.org)
  • Moreover, p38 MAPK activation and insulin activation of NETs were found to be sensitive to external Ca 2+ depletion, blockade of voltage-sensitive Ca 2+ channels, and inhibition of protein phosphatase 2A. (aspetjournals.org)
  • Effects of tyrosine kinase and PI3K inhibitors on basal NET uptake appear to arise from a loss of cell surface NET protein, whereas the p38 MAPK-dependent enhancement of NE transport occurs without a detectable enhancement of surface NET. (aspetjournals.org)
  • Arsenite has also been shown to induce activation of mitogen-activated protein kinase (MAPK) 3 ( 2 ) family member proteins, some of which may play a key role in apoptosis induction in leukemia cells ( 10 ). (jimmunol.org)
  • Furthermore, the expression of MAPK phosphatase 3 (MKP3) mRNA was evaluated and the effect of MKP3 overexpression was assessed. (jimmunol.org)
  • Cyclic mechanical stretch decreases cell migration by inhibiting phosphatidylinositol 3-kinase- and focal adhesion kinase-mediated JNK1 activation. (nih.gov)
  • In this study, we evaluated the effect of blocking the two Ras downstream pathways phosphatidylinositol-3-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase on melanoma development and regression in the TPRas mouse model. (aacrjournals.org)
  • In conclusion, this study strongly supports the role of the phosphatidylinositol-3-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways in the development and maintenance of Ras-dependent melanomas and supports the notion that specific inhibition of these effectors may represent a very promising avenue for the treatment and prevention of the disease. (aacrjournals.org)
  • Topical treatment with inhibitors of the phosphatidylinositol 3′-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways inhibited the growth of TPras transgenic melanomas in severe combined immunodeficient mice, blocked invasive behavior, and reduced angiogenesis. (aacrjournals.org)
  • The inhibitor Ly294002, which is specific for phosphatidylinositol 3′-kinase, effectively reduced melanoma cell growth both in vitro and in vivo . (aacrjournals.org)
  • The direct pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) similarly enhances paclitaxel-induced tumor apoptosis in a dose-dependent manner. (aacrjournals.org)
  • We now show that, in contrast to nutritional regulation of lipogenesis in liver or adipose tissue, changes in fatty acid metabolism during in vitro transformation of the human mammary epithelial cell line MCF-10a are driven by increases in epidermal growth factor signaling, acting in major part through the mitogen-activated protein (MAP) kinase and phosphatidylinositol (PI) 3-kinase signaling cascades. (nih.gov)
  • To validate coexisting mutations within epidermal growth factor receptor (EGFR), mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways. (elsevier.com)
  • Exposure of cells to insulin inhibited the activation of MEKK1 by GSK3β, and this inhibitory effect of insulin was abolished by the phosphatidylinositol 3-kinase inhibitor wortmannin. (elsevier.com)
  • The present study used organotypic corticostriatal slices taken from postnatal day 2 rat pups to investigate the protective effect of lithium and the role of the phosphatidylinositol-3 kinase (PI-3K)/Akt and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways in PCP-induced cell death. (utmb.edu)
  • We hypothesized that Gas6 is a survival factor for oligodendrocytes and receptor activation signals downstream to the phosphatidylinositol 3 (PI3)-kinase/Akt pathway to increase cell survival in the absence of cell proliferation. (jneurosci.org)
  • We identified distinct phosphatidylinositol 3-OH kinase (PI3K)-linked pathways supporting basal and insulin-triggered NE transport in the human noradrenergic neuroblastoma, SK-N-SH. (aspetjournals.org)
  • To dissect which of these pathways may be responsible for the observed antagonism, known EGFR-regulated downstream signaling pathways including RAS, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase (p44/p42), and protein kinase C were inactivated with both pharmacological inhibitors and transient transfection experiments with dominant-negative and constitutively active constructs in the presence of exogenous EGF stimulation. (aacrjournals.org)
  • Signaling pathways that activate an epithelial growth program in macrophages are still poorly defined. (aspetjournals.org)
  • Paclitaxel (Taxol) activates a number of signal transduction pathways that lead to apoptosis.In contrast, paclitaxel also activates cell survival pathways, such as the Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway. (aacrjournals.org)
  • Additionally, paclitaxel activates signal transduction pathways leading to gene expression. (aacrjournals.org)
  • Moreover, SAG has been found to inhibit selective protein tyrosine phosphatases (Src homology 2 domain-containing tyrosine phosphatase 1 [SHP1] and SHP2) in vitro and augment cytokine signaling and responses in hematopoietic cell lines ( 46 ), suggesting the role of phosphatases and possibly other signal transduction pathways in SAG-induced control of Leishmania infection. (asm.org)
  • Ellinger-Ziegelbauer H, Brown K, Kelly K, Siebenlist U: Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative. (drugbank.com)
  • c) OA-induced activation of PKC-beta enhances oxidative stress, which activates signaling pathways responsible for the increased VEGF synthesis/secretion. (mdpi.com)
  • Lithium prevented PCP-induced inhibition of the two pathways and activation of GSK-3β. (utmb.edu)
  • These data strongly suggest that the protective effect of lithium against PCP-induced neuroapoptosis is mediated through independent stimulation of the PI-3K/Akt and ERK pathways and suppression of GSK-3β activity. (utmb.edu)
  • Collectively, these results support the hypothesis that IGF-II coordinately activates multiple cell signaling pathways critical to survival, growth, and differentiation of the ovine conceptus during early pregnancy. (elsevier.com)
  • During chronic inflammation, a variety of intracellular signaling pathways are activated, comprising of cell surface receptors, tyrosine kinases, and transcription factors, leading to overexpression of proinflammatory genes involved in the development of chronic diseases [ 2 ]. (hindawi.com)
  • The SAPK and p38 pathways are primarily activated by proinflammatory cytokines, such as tumor necrosis factor alpha and interleukin-1, and various stress signals, such as UV treatment or osmotic stress (reviewed in references 9 and 18 ). (asm.org)
  • These pathways can effectively convey stimuli from the cell membrane (where many MAP3Ks are activated) to the nucleus (where only MAPKs may enter) or to many other subcellular targets. (wikipedia.org)
  • On the other hand, radiation was found to inhibit BCNU-induced apoptosis through EGFR-mediated activation of both PI3-K and mitogen-activated protein kinase (p44/p42) pathways, also via RAS. (aacrjournals.org)
  • Thus, prostate cancer tumor growth after castration or treatment with hormone receptor antagonists may be mediated by AR mutation or its ligand-independent activation by upstream tyrosine kinase pathways. (aacrjournals.org)
  • N-syndecan (syndecan-3) is a transmembrane proteoglycan that is abundantly expressed in the major axonal pathways and in the migratory routes of the developing brain. (rupress.org)
  • Regulatory roles of conserved phosphorylation sites in the activation T-loop of the MAP kinase ERK1. (nih.gov)
  • We report that glucose (10 mM) induces an increase in cytosolic calcium concentration that leads to cAMP-induced protein kinase A (PKA) activation, promoting nuclear translocation of activated ERK1/2. (nih.gov)
  • Pretreatment with the A 3 agonists upregulated phosphorylated ERK1/2 levels but did not modify phosphorylated JNK and p38 levels. (springer.com)
  • In contrast to the stress-responsive MAPKs, ERK1 and -2 are largely activated by mitogenic or differentiation-inducing stimuli. (asm.org)
  • Quantitative sandwich enzyme immunoassay (EIA) systems, that can distinguish between active-form subtypes of mitogen-activated protein kinases (p44 and p42 MAP kinase, also called ERK1 and ERK2), were developed employing subtype-specific antibodies as a solid phase and an antibody specific for the phosphorylated region of MAP kinases as the detector. (biomedsearch.com)
  • Both ERK1 and ERK2 were activated immediately after stimulation, and the activity reached a maximum at 5-10 min. (biomedsearch.com)
  • The first mitogen-activated protein kinase to be discovered was ERK1 ( MAPK3 ) in mammals. (wikipedia.org)
  • Thus the role of mammalian ERK1/2 kinases as regulators of cell proliferation is not a generic, but a highly specialized function. (wikipedia.org)
  • In the case of classical MAP kinases, the activation loop contains a characteristic TxY (threonine-x-tyrosine) motif (TEY in mammalian ERK1 and ERK2 , TDY in ERK5 , TPY in JNKs , TGY in p38 kinases ) that needs to be phosphorylated on both the threonine and the tyrosine residues in order to lock the kinase domain in a catalytically competent conformation. (wikipedia.org)
  • This revealed a time-dependent transient phosphorylation of both ERK1/2 and p90(RSK) by intracellular acidosis (intracellular pH approximately 6.6), with maximum activation occurring at 3 min and a return to basal levels by 20 min. (curehunter.com)
  • The proliferative effects of ghrelin and UAG were suppressed by inhibitors of extracellular-signal-regulated kinase (ERK) and phosphoinositide-3 kinase, and both peptides rapidly induced ERK phosphorylation. (unboundmedicine.com)
  • Furthermore, knockdown of PP2Ac expression enhances LPA-induced MEKK3-mediated IkappaB kinase beta (IKKbeta) phosphorylation and NF-kappaB activation. (sigmaaldrich.com)
  • Crizotinib demonstrated concentration-dependent inhibition of ALK, ROS1, and c-Met phosphorylation in cell-based assays using tumor cell lines and demonstrated antitumor activity in mice bearing tumor xenografts that expressed echinoderm microtubule-associated protein-like 4 (EML4)- or nucleophosmin (NPM)-ALK fusion proteins or c-Met. (drugcentral.org)
  • Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. (genecards.org)
  • The phosphorylation of MAP kinase is thought to be a prerequisite for translocation. (portlandpress.com)
  • Unexpectedly, tyrosine phosphorylation of MAP kinase is unchanged in the nuclear fraction during ischaemia, indicating that unphosphorylated MAP kinase translocates from the cytosol to the nucleus. (portlandpress.com)
  • During reperfusion (0-30 min), after ischaemia for 20 min, tyrosine phosphorylation of MAP kinase in the nuclear fraction is increased with a peak at 10 min of reperfusion. (portlandpress.com)
  • The activation is confirmed by MAP kinase activity with similar kinetics to the tyrosine phosphorylation. (portlandpress.com)
  • These findings demonstrate that nuclear MAP kinase is activated by tyrosine phosphorylation during reperfusion, probably by MEK-2. (portlandpress.com)
  • This tandem activation loop phosphorylation (that was proposed to be either distributive or processive, dependent on cellular environment) is performed by members of the Ste7 protein kinase family, also known as MAP2 kinases . (wikipedia.org)
  • MAP2 kinases in turn, are also activated by phosphorylation, by a number of different upstream serine-threonine kinases ( MAP3 kinases ). (wikipedia.org)
  • RCF3 interacts with the phosphatases C-TERMINAL DOMAIN PHOSPHATASE-LIKE1 and 2 (CPL1 and CPL2), ultimately affecting the phosphorylation of one of the main DICER-LIKE1 (DCL1) accessory proteins, HYPONASTIC LEAVES1 (HYL1), with a concomitant effect on miRNA production. (pnas.org)
  • These interactions are essential to regulate the phosphorylation status, and thus the activity, of the double-stranded RNA binding protein and DICER-LIKE1 (DCL1) cofactor HYPONASTIC LEAVES1 (HYL1). (pnas.org)
  • In addition, glucose starvation not only signals to shut down mTOR, but also results in the transient phosphorylation of the p53 protein. (pnas.org)
  • Lipidomic analysis indicated that G6PD inhibition and knockdown decreased 20-HETE levels in pulmonary arteries as well as 20-HETE-induced 1 ) mitochondrial superoxide production, 2 ) activation of mitogen-activated protein kinase 1 and 3, 3 ) phosphorylation of ETS domain-containing protein Elk-1 that activate transcription of tumor necrosis factor-α gene ( Tnfa ), and 4 ) expression of tumor necrosis factor-α (TNF-α). (physiology.org)
  • In the PI3K-Akt cascade, PI3K phosphorylates lipids to form second messengers PI (3 ,4 ,5) P 3 and PI (3 ,4) P 2 in response to extracellular stimuli. (aacrjournals.org)
  • In addition, increased PI3K (phosphoinositide 3-kinase) pathway activity has been demonstrated, through the loss of activity of the tumor suppressor gene, PTEN [ 2 ]. (mdpi.com)
  • Basal and insulin-modulated NET activities were reduced by the tyrosine kinase inhibitor genistein and the PI3K inhibitors wortmannin and LY-294002, but not by the PKC inhibitor staurosporine. (aspetjournals.org)
  • TOR (target of rapamycin) is an evolutionarily conserved serine-threonine protein kinase that belongs to the PIKK [phosphoinositide 3-kinase (PI3K)-related kinase) family, and it plays an important role in regulating cell growth and proliferation ( 1 ). (pnas.org)
  • In mammals, mTOR (mammalian TOR) is regulated by a kinase cascade consisting of PI3K, PI3K-dependent kinase 1, and AKT and by regulators of this cascade, including PTEN and tuberous sclerosis (TSC) 1 and TSC2 ( Fig. 1 ). (pnas.org)
  • Mouse Anti Human Mitogen-Activated Protein Kinase 3 MAPK3 antibody storage GENTAUR recommends for long therm storage to freeze at -24 C. For short time storage up to 30 days we suggest fridge storage at 1 to 10 C. Prevent multiple freeze taw cycles of Mouse Anti Human Mitogen-Activated Protein Kinase 3 MAPK3. (antibody-antibodies.com)
  • Mouse Anti Human Mitogen-Activated Protein Kinase 3 MAPK3 Human samples 80 % of the research is conducted on human samples. (antibody-antibodies.com)
  • GENTAUR suppliers human normal cells, cell lines, RNA extracts and lots of antibodies and ELISA kits to Human proteins as well as Mouse Anti Human Mitogen-Activated Protein Kinase 3 MAPK3. (antibody-antibodies.com)
  • PD98059 (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-1), a MEK inhibitor, was from Tocris. (ahajournals.org)
  • Both Ly294002 and U0126, a mitogen-activated protein kinase kinase 1/2 inhibitor, reduced invasion, which correlated with reduction of the metalloproteinase matrix metalloproteinase 2. (aacrjournals.org)
  • Inhibition of Mer with small interfering RNA (siRNA) or the RhoA/Rho kinase pathway by RhoA siRNA or Rho kinase pharmacologic inhibitor suppressed Gas6-induced HGF mRNA and protein expression in macrophages and blocked epithelial cell proliferation and wound closure induced by the conditioned medium. (aspetjournals.org)
  • Here, we find that the combination of paclitaxel with a MEK inhibitor leads to a dramatic inactivation of the antiapoptotic Akt (protein kinase B) kinase. (aacrjournals.org)
  • A benzamide and indazole derivative that acts as a TYROSINE KINASE inhibitor of the VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR. (drugcentral.org)
  • Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), ROS1 (c-ros), and Recepteur d'Origine Nantais (RON). (drugcentral.org)
  • A quinazoline derivative and ANTINEOPLASTIC AGENT that functions as a PROTEIN KINASE INHIBITOR for EGFR associated tyrosine kinase. (drugcentral.org)
  • Neratinib is a kinase inhibitor that irreversibly binds to Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4. (drugcentral.org)
  • Administration of PD98059 (MEK inhibitor, N=8, vehicle N=9) reduced p-ERK-1/2 expression in the incised tissue and blocked hypersensitivity in MKP-3 KO mice (N=6). (dartmouth.edu)
  • The influence on cells viability of Z-DEVD-FMK, a Caspase-3 -specific peptide inhibitor, was also examined. (bvsalud.org)
  • The Kinase Selectivity Profiling Systems provide a convenient 8-tube strip format that is optimized for fast and simple kinase inhibitor profiling. (promega.com)
  • The effect of Ang II was abolished by the AT1R antagonist candesartan and the mitogen-activated protein kinase inhibitor UO126, whereas the Ang type 2 receptor antagonist PD-123319 and NO synthase inhibitor N G -nitro- l -arginine methyl ester had no effect. (ahajournals.org)
  • Incubation with 5% FCS reduced expression of the cdk-inhibitor protein p27Kip1 on monomer but not on polymerized type I collagen. (biomedsearch.com)
  • PI3-kinase inhibitors blocked the anti-apoptotic effect of rhGas6, whereas a MEK/ERK inhibitor had no effect. (jneurosci.org)
  • Upon inhibition of EGFR with the EGFR tyrosine kinase inhibitor, AG1478, it was found that this cross-resistance between sequential administration of radiation and BCNU was abrogated. (aacrjournals.org)
  • Because mutations in the androgen receptor (AR) and activation of HER2 and Akt may account, in part, for prostate cancer progression after castration or treatment with antiandrogens, we sought to determine whether an inhibitor of Hsp90 function could degrade these Hsp90 client proteins and inhibit the growth of prostate cancer xenografts with an acceptable therapeutic index. (aacrjournals.org)
  • Using a functional genomic approach, we have identified a protein serine/threonine phosphatase, protein phosphatase 2A (PP2A), as a MEKK3 phosphatase. (sigmaaldrich.com)
  • In the ERK MAP kinase cascade, activated Raf-1, a serine-threonine kinase, initiates the signaling cascade through MEK, which in turn phosphorylates a second serine-threonine kinase ERK. (aacrjournals.org)
  • Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. (drugbank.com)
  • In vitro biochemical or cellular assays have shown that midostaurin or its major human active metabolites CGP62221 and CGP52421 inhibit the activity of wild type FLT3, FLT3 mutant kinases (ITD and TKD), KIT (wild type and D816V mutant), PDGFR-alfa/beta, VEGFR2, as well as members of the serine/threonine kinase PKC (protein kinase C) family. (drugcentral.org)
  • The proapoptotic factor glycogen synthase kinase (GSK)-3β was also dephosphorylated at serine 9 and thus activated. (utmb.edu)
  • This gene encodes a serine/threonine protein kinase that forms a component of protein kinase-mediated signal transduction cascades. (wikipedia.org)
  • Glycogen synthase kinase 3β (GSK3β) is implicated in many biological events, including embryonic development, cell differentiation, apoptosis, and insulin response. (elsevier.com)
  • Although activation of A 3 adenosine receptors attenuates reperfusion lung injury and associated apoptosis, the signaling pathway that mediates this protection remains unclear. (springer.com)
  • 0.01) attenuated indices of injury and apoptosis, including the percentage of injured alveoli, wet/dry weight ratio, myeloperoxidase activity, TUNEL ( in situ TdT-mediated dUTP nick end labeling)-positive cells, and caspase 3 activity and expression. (springer.com)
  • By identifying microRNAs implicated in Endoplasmic Reticulum stress-induced cardiomyocyte apoptosis, it is envisaged that protein targets involved in same can be identified through specifically selected microRNAs. (freepatentsonline.com)
  • 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 . (wikipedia.org)
  • Intracellular genotoxic stresses, including DNA damage, hypoxia, and oncogene activation, activate p53, which in turn initiates cellular tumor suppression programs such as apoptosis or cell cycle arrest ( 14 ). (pnas.org)
  • Observations with TPras melanoma cells that express dominant negative Δp85 or kinase-inactive Raf 301 supported the specificity of the phenomena observed with the chemical inhibitors. (aacrjournals.org)
  • Inhibitors of MAP and PI 3-kinases downregulated SREBP-1 levels and decreased transcription from the FAS promoter, reducing FAS expression and fatty acid synthesis in transformed MCF-10a cells and in MCF-7 and HCT116 carcinoma cells. (nih.gov)
  • A screen of 72 inhibitors against 456 human kinases. (guidetopharmacology.org)
  • 2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. (guidetopharmacology.org)
  • Benesova L, Minarik M, Jancarikova D, Belsanova B, Pesek M (2010) Multiplicity of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors. (nature.com)
  • Experiments based on a panel of pharmacological inhibitors or activators suggested that the cAMP action on TRPC6 was not mediated by PKA, PKG, or EPAC (exchange protein activated by cAMP). (core.ac.uk)
  • The Kinase Enzyme Systems allow you to easily screen and profile kinase inhibitors. (promega.com)
  • The protein encoded by this gene is a member of the MAP kinase family. (nih.gov)
  • The protein encoded by this gene shares similarity with the product of Drosophila syd gene, required for the functional interaction of kinesin I with axonal cargo. (nih.gov)
  • Studies of the similar gene in mouse suggested that this protein may interact with, and regulate the activity of numerous protein kinases of the JNK signaling pathway, and thus function as a scaffold protein in neuronal cells. (nih.gov)
  • This gene encodes a member of the mitogen-activated protein (MAP) kinase family. (antibodies-online.com)
  • These TPRas mice express the human activated Ha-Ras gene under the mouse tyrosinase promoter, which restricts the expression of the molecule mainly in melanocytes. (aacrjournals.org)
  • This kinase was reported to interact with, phosphorylate and repress the activity of E47, which is a basic helix-loop-helix transcription factor known to be involved in the regulation of tissue-specific gene expression and cell differentiation. (mybiosource.com)
  • Translocations can affect the ALK gene resulting in the expression of oncogenic fusion proteins. (drugcentral.org)
  • The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. (genecards.org)
  • MAP2K3 (Mitogen-Activated Protein Kinase Kinase 3) is a Protein Coding gene. (genecards.org)
  • Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity . (genecards.org)
  • Mitogen-activated protein kinase kinase kinase 6 is a protein that in humans is encoded by the MAP3K6 gene. (wikipedia.org)
  • In humans the sole known ligand for the Axl/Rse/Mer kinases is growth arrest-specific gene 6 (Gas6), which in the CNS is secreted by neurons and endothelial cells. (jneurosci.org)
  • Here, we describe REGULATOR OF CBF GENE EXPRESSION 3 (RCF3) as a tissue-specific regulator of miRNA biogenesis in plants. (pnas.org)
  • We have identified the Arabidopsis thaliana K homology (KH) domain protein REGULATOR OF CBF GENE EXPRESSION 3 (RCF3) as a cofactor affecting miRNA biogenesis in specific plant tissues. (pnas.org)
  • The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. (novusbio.com)
  • This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11, as well as G-beta gamma subunits. (wikipedia.org)
  • Gene expression profiles of ovarian cancer cells treated with ACFP were generated by cDNA microarray, and the expression of apoptotic-specific genes, such as bcl -xl, bax , akt , caspase -3, CDC 25C and cyclin B1, was assessed by real time PCR and western blot analysis. (biomedcentral.com)
  • Gene expression profiling highlighted that ACFP treatment in ovarian cancer cells repressed the expression of bcl- xl, akt , CDC 25C and cyclin B1 and promoted the expression of bax and caspase -3 in a time- and dose-dependent manner. (biomedcentral.com)
  • C-jun-amino-terminal kinase-interacting protein 3 is an enzyme that in humans is encoded by the MAPK8IP3 gene. (wikipedia.org)
  • Complement anaphylatoxin C5a neuroprotects through mitogen-activated protein kinase-dependent inhibition of caspase 3. (semanticscholar.org)
  • The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. (genecards.org)
  • Peripheral phosphorylated ERK-1/2 (p-ERK-1/2) inhibition was performed in MKP-3 KO mice. (dartmouth.edu)
  • Finally, specific GSK-3β inhibition did not prevent PCP-induced dephosphorylation of Akt and ERK. (utmb.edu)
  • To verify our finding, we provide evidence that the protein expression of Parkinson protein 7, including new protein synthesis, is sensitive to mTORC1 inhibition. (mcponline.org)
  • Moreover, inhibition of G6PD increased protein kinase G1α activity, which, at least partially, mitigated superoxide production and Elk-1 and TNF-α expression. (physiology.org)
  • In summary, our findings indicate that 20-HETE elicited mitochondrial superoxide production and promoted secretory phenotype of vascular smooth muscle cells by activating MAPK1-Elk-1, all of which are blocked by inhibition of G6PD. (physiology.org)
  • NICD interacts with RBPJk and together they activate downstream target genes, including HES (Hairy and Enhancer of Split) and HEY (HES-related with YRPW motif) family transcription factors, ultimately leading to inhibition of osteoblast differentiation, seemingly at a stage before OSX activation. (wikipathways.org)
  • JNK/stress-activated protein kinase associated protein 1 is required for early development of telencephalic commissures in embryonic brains. (creativebiomart.net)
  • GSK3β has now been shown to induce activation of the mitogen-activated protein kinase kinase kinase MEKK1 and thereby to promote signaling by the stress-activated protein kinase pathway. (elsevier.com)
  • Stress-activated protein kinases are one subclass of MAP kinases. (novusbio.com)
  • Protein phosphatase 2A acts as a mitogen-activated protein kinase kinase kinase 3 (MEKK3) phosphatase to inhibit lysophosphatidic acid-induced IkappaB kinase beta/nuclear factor-kappaB activation. (sigmaaldrich.com)
  • Mitogen-Activated Protein Kinase Phosphatase-3 (MKP-3) in the Surgical" by Sladjana Skopelja-Gardner, Madhurima Saha et al. (dartmouth.edu)
  • and Romero-Sandoval, E Alfonso, "Mitogen-Activated Protein Kinase Phosphatase-3 (MKP-3) in the Surgical Wound is Necessary for the Resolution of Postoperative Pain in Mice" (2017). (dartmouth.edu)
  • There is high degree of consensus that in AD kinase and/or phosphatase activities are deregulated, resulting in hyperphosphorylation of TAU. (hindawi.com)
  • In a first step, DCL1, aided by cofactors including the C2H2-zinc finger protein SERRATE (SE), the nuclear cap-binding complex (CBC), the double-stranded RNA-binding protein HYPONASTIC LEAVES1 (HYL1), and the HYL1 phosphatase C-TERMINAL DOMAIN PHOSPHATASE-LIKE1 (CPL1), removes the two single-stranded RNA tails of the pri-miRNAs to form a largely double-stranded miRNA precursor (premiRNA) ( 2 ⇓ ⇓ - 5 ). (pnas.org)
  • Belongs to the protein-tyrosine phosphatase family. (abcam.com)
  • Contains 1 tyrosine-protein phosphatase domain. (abcam.com)
  • Here, we review the role of transcriptional regulators of lipid metabolism including liver X receptors α/β, peroxisome proliferator-activated receptor γ, estrogen receptors α/β (ERα/β), and sterol regulatory element-binding proteins in T-cells. (frontiersin.org)
  • These receptors lie at the interface between lipid metabolism and immune cell function and are endogenously activated by lipids and/or hormones. (frontiersin.org)
  • Recent studies suggest that G protein-coupled receptors linked to protein kinase C (PKC) down-regulate cell surface NET protein levels and diminish NE uptake capacity. (aspetjournals.org)
  • During b-catenin-dependent WNT signaling, b-catenin is stabilized following binding of WNT to its receptors Frizzled (FZD) and lipoprotein receptor-related protein 5 (LRP5) or LRP6, leading to the transcription of b-catenin target genes and ultimately stimulating progression from the RUNX2+ stage to the RUNX2+OSX+ stage, and from RUNX2+OSX+ cells to mature osteoblasts. (wikipathways.org)
  • FGFs function by binding to cell surface Tyr kinase FGF receptors (FGFR1-FGFR4 in humans and mice), leading to the activation of multiple signaling modules. (wikipathways.org)
  • These peptides are the products of sequential processing of APP (amyloid precursor protein) by BACE1 and γ -secretase [ 3 ]. (hindawi.com)
  • The crystallization of proteins in complex with linear motif-containing peptides is often challenging because the energy gained upon crystal packing between symmetry mates in the crystal may be on a par with the binding energy of the protein-peptide complex. (iucr.org)
  • The moderate binding affinity of LM-containing peptides can hinder successful crystallization of the desired protein-peptide complex. (iucr.org)
  • Because linear motif-containing peptides are often unstructured alone and the energy gained upon crystal packing between symmetry mates may be on a par with the binding energy of the complex, the bona fide peptide-binding protein surface may mediate crystal packing rather than physiological LM binding. (iucr.org)
  • 3 ] reported that the anti-cancer bioactive peptide (ACBP), purified from goat spleens that were immunized with human gastric cancer extracts, significantly inhibited gastric cancer cell growth in vitro and gastric tumor growth in vivo, indicating that therapeutic peptides may represent a powerful anti-cancer tool. (biomedcentral.com)
  • ERK phosphorylates additional kinases and specific transcription factors important in cell proliferation and survival. (aacrjournals.org)
  • The formation of ALK fusion proteins results in activation and dysregulation of the gene's expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins. (drugcentral.org)
  • It is demonstrated here that the MEKK3 kinase inhibits cell proliferation, a biologic response not commonly associated with members of the MAP3K family of kinases. (asm.org)
  • X-ray structure of the ERK2 MAP kinase in its active form. (wikipedia.org)
  • Furthermore, for extracellular signal-regulated kinase 2 (ERK2) the protein-peptide docking surface is comprised of a small hydrophobic surface patch that is often engaged in the crystal packing of apo ERK2 crystals. (iucr.org)
  • Here, a rational surface-engineering approach is presented that involves mutating protein surface residues that are distant from the peptide-binding ERK2 docking groove to alanines. (iucr.org)
  • Unfortunately, ERK2 readily crystallized in the apo form and we only managed to grow protein-peptide cocrystals with the docking peptide from MNK1 (pepMNK1), which is an ERK2 substrate. (iucr.org)
  • Analysis of crystal-packing contacts subsequently revealed that the protein-peptide binding surface of ERK2 WT was blocked by a symmetry-related kinase molecule in all apo crystals, while ERK2-pepMNK1 crystals could `luckily' form because this peptide mediated a different type of crystal packing. (iucr.org)
  • pleiotrophin), N-syndecan mediates cortactin-Src kinase-dependent neurite outgrowth. (rupress.org)
  • The protein encoded by MAPK1/3 is a member of the MAP kinase family. (antibodies-online.com)
  • SFTPA1 rapidly activated mitogen-activated protein kinase 1/3 (MAPK1/3) in myometrial cells. (bioone.org)
  • Bacterial lipopolysaccharide (LPS), an agent known to trigger uterine contractions and preterm birth, also activated MAPK1/3. (bioone.org)
  • The addition of rough-type LPS to SFTPA1 blocked the interaction of SFTPA1 with its binding sites and the activation of MAPK1/3 and PTGS2 by SFTPA1. (bioone.org)
  • The protein kinase MEKK3 (MAP3K3) is essential for embryonic angiogenesis in mice and interacts physically with CCM2, but how this interaction is mediated and its relevance to cerebral vasculature are unknown. (rcsb.org)
  • Midostaurin is a small molecule that inhibits multiple receptor tyrosine kinases. (drugcentral.org)
  • An indole and pyrrole derivative that inhibits VEGFR-2 and PDGFR BETA RECEPTOR TYROSINE KINASES. (drugcentral.org)
  • Microarray analysis revealed that transcripts for the Axl and Mer receptor tyrosine kinases are expressed at high levels in O4 + -immunopanned oligodendrocytes isolated from second trimester human fetal spinal cord. (jneurosci.org)
  • Common genetic alterations in human melanomas include loss of the tumor suppressor locus CDKN2a , known as a melanoma susceptibility locus ( 3 ), and acquisition of activating mutations or hyperactivation of the Ras pathway. (aacrjournals.org)
  • EGFR mutations did not coexist with BRAF mutations, neither kinase-activated nor kinase-impaired mutations. (elsevier.com)
  • Mutational profiling of DNA reisolated from subareas with the same or different histomorphology, using an alternative assay, confirmed that coexisting mutations might present within the same (whole or subclonal) population or different populations and clarified that the so-called coexisting activating KRAS and BRAF mutations originally reported in a specimen were indeed present in separate lung nodules submitted in the same block. (elsevier.com)
  • Gefitinib reversibly inhibits the kinase activity of wild-type and certain activating mutations of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor, thereby inhibiting further downstream signalling and blocking EGFR-dependent proliferation. (drugcentral.org)
  • Violacein induces p44/42 mitogen-activated protein kinase-mediated solid tumor cell death and inhibits tumor cell migration. (nih.gov)
  • In breast cancer, the MKK3/6 pathway, activated through H-Ras, induces the invasive phenotype. (aacrjournals.org)
  • Ischaemia (0-40 min) induces the translocation of MAP kinase from the cytosol fraction to the nuclear fraction. (portlandpress.com)
  • The Tat protein of HIV-1 induces tumor necrosis factor-alpha production. (wikipedia.org)
  • The RhoA/protein kinase B (Akt)/mitogen-activated protein (MAP) kinases, including p38 MAP kinase, extracellular signal-regulated protein kinase, and Jun NH 2 -terminal kinase axis in RAW 264.7 cells, was identified as Gas6/Mer downstream signaling pathway for the upregulation of HGF mRNA and protein. (aspetjournals.org)
  • Thus Gas6 sustains human fetal oligodendrocyte viability by receptor activation and downstream signaling via the PI3-kinase/Akt pathway. (jneurosci.org)
  • These results suggest that a membrane raft integrity-dependent cell surface event is a prerequisite for NaAsO 2 -induced protein tyrosine kinase/c-Jun amino-terminal kinase activation, superoxide production, and downstream caspase activation. (jimmunol.org)
  • The encoded protein is a p38 MAP kinase and is activated by proinflammatory cytokines and cellular stress. (antibodies-online.com)
  • Is activated by cytokines and environmental stress in vivo. (genecards.org)
  • This protein phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. (wikipedia.org)
  • MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens , osmotic stress , heat shock and proinflammatory cytokines . (wikipedia.org)
  • 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. (curehunter.com)
  • 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. (curehunter.com)
  • MAPKK 6 is a member of the dual specificity protein kinase family, which functions as a mitogen-activated protein (MAP) kinase kinase. (wikipedia.org)
  • This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. (nih.gov)
  • Ahlfors R, Macioszek V, Rudd J, Brosche M, Schlichting R, Scheel D, Kangasjarvi J (2004) Stress hormone-independent activation and nuclear translocation of mitogen-activated protein kinases in Arabidopsis thaliana during ozone exposure. (springer.com)
  • Here, we investigate the translocation and activation of MAP kinase during ischaemia and reperfusion in perfused rat heart. (portlandpress.com)
  • 3 In addition to mediating tumor-stromal interaction in a paracrine loop, 4 HGF/SF can induce vascular endothelial growth factor (VEGF) 5 and promote angiogenesis. (ahajournals.org)
  • It is thought that the invasive behavior of glioblastoma multiforme cells that are left behind after debulking surgery is one of the most important causes for poor clinical outcome, enabling tumor cells to actively egress from the main mass and invade into the surrounding normal brain where they are out of reach of surgical resection, radiation, and chemotherapy ( 3 ). (aacrjournals.org)
  • The operational fluctuation between invasion and proliferation as a working hypothesis in malignant glioma pathobiology is supported by the finding that tumor recurrence often occurs within 3 cm of the resection cavity, substantiating the dispersing glioma cells as the source of recurrent tumors ( 5 ). (aacrjournals.org)
  • These results confirm an important role for SREBP-1 in neoplastic lipogenesis, and provide a likely basis for the linkage of upregulated fatty acid metabolism with neoplastic transformation and with tumor virulence, since MAP and PI 3-kinase signaling contributes to both. (nih.gov)
  • The MEKK3-mediated block of proliferation also reverses Ras-induced cellular transformation, suggesting possible tumor-suppressing functions for this kinase. (asm.org)
  • Oxidative stress, as a result of peroxisome proliferation, and DNA damage have been described in the human prostate adenocarcinoma cell line LNCaP [ 12 , 13 ] and the mouse Leydig tumor cell line MA-10 [ 14 ] exposed to high concentrations of DEHP (3 mM). (biomedcentral.com)
  • The tumor suppressor p53 is a major checkpoint protein in mammalian cells ( 12 , 13 ). (pnas.org)
  • 1 - 3 Studies have shown significant superinduction of proinflammatory agents like interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS) during the osteoarthritic process. (dovepress.com)
  • The bar plot below shows the proportion of tumor samples that have any kind of altering mutation(s) in the given protein. (phosphosite.org)
  • Adipose tissue produces various adipocytokines/chemokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1, that induce inflammation. (diabetesjournals.org)
  • MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. (antibodies-online.com)
  • The findings of this study suggest that MKP-3 is pivotal for normal resolution of acute postoperative allodynia, through the regulation of peripheral p-ERK-1/2. (dartmouth.edu)
  • The encoded kinase participates in the regulation of vascular endothelial growth factor (VEGF) expression. (wikipedia.org)
  • In this review, we will focus on the role of cellular lipid metabolism in the regulation of plasma membrane (PM) lipid composition and the importance of this to T-cell function-a mechanism which has only just begun to be explored ( 2 , 3 ). (frontiersin.org)
  • Lipids and proteins are both essential PM constituents, but while PM proteins have been widely studied, there is a gap in our knowledge about the fundamental role and regulation of lipid PM components ( 4 ). (frontiersin.org)
  • Together, these results suggest an involvement of the MEKK3 kinase in negative regulation of cell cycle progression, and they provide the first insights into biologic activities of this kinase. (asm.org)
  • The pathway maps illustrate protein interactions and regulation to provide a comprehensive picture of signaling and disease processes. (bio-rad.com)
  • However, the precise mechanism for the termination of MEKK3 kinase activity is not fully understood. (sigmaaldrich.com)
  • Objective To evaluate the clinical significance of expression of mitogen-activated protein kinase /extracellular signal-regulated kinase kinase kinase 3 (MEKK3) in the early-stage cervical cancer . (bvsalud.org)
  • A conditionally activated form of MEKK3 stably expressed in fibroblasts arrests these cells in early G 1 . (asm.org)
  • MEKK3 critically blocks mitogen-driven expression of cyclin D1, a cyclin which is essential for progression of fibroblasts through G 1 . (asm.org)
  • Genetic data from transgenic mouse models (18 , 19 , 20) have demonstrated that expression of activated Ras is essential for the genesis and maintenance of melanomas. (aacrjournals.org)
  • H-ras transformation of MCF-10a cells resulted in upregulation of MAP kinase and PI 3-kinase signals, upregulation of sterol regulatory element binding protein 1 (SREBP-1) transcription factor levels, and upregulation of FAS expression and FA synthesis. (nih.gov)
  • This kinase can be activated by insulin, and is necessary for the expression of glu. (genecards.org)
  • This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. (genecards.org)
  • Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. (genecards.org)
  • In WT mice, peripheral p-p38 and p-ERK-1/2 expression increased (5- and 3-fold, respectively) on postoperative days 1 and 5, and returned to basal levels 7-12 days after surgery (N=3 per group). (dartmouth.edu)
  • Peripheral p-p38 levels in MKP-3 KO mice followed a similar expression pattern as WT mice. (dartmouth.edu)
  • the purpose of this study was therefore to determine whether A 3 adenosine receptor stimulation with reperfusion modulates expression of the different mitogen-activated protein kinases. (springer.com)
  • Because mTORC1 is at the core of translation, we have investigated mTORC1 function in global and regional protein expression. (mcponline.org)
  • To determine the role of mTORC1 activation in protein expression, we have used an unbiased, large-scale proteomic approach. (mcponline.org)
  • We have also found that curtailing the activity of mTORC1 bidirectionally alters the expression of proteins associated with epilepsy, Alzheimer's disease, and autism spectrum disorder-neurological disorders that exhibit elevated mTORC1 activity. (mcponline.org)
  • Our work offers a comprehensive view of mTORC1 and its role in regulating regional protein expression in normal and diseased states. (mcponline.org)
  • Furthermore, ERK is able to activate or is required for cyclin D1 expression in various cell lines, with D-type cyclins playing an essential role in G 1 progression ( 1 , 19 , 55 ). (asm.org)
  • Protein expression of cyclins D1 and E was markedly down-regulated in MCs plated on polymerized type I collagen for eight hours in 5% FCS, as compared with MCs on monomer type I collagen. (biomedsearch.com)
  • In vitro , we have observed an actual antagonistic effect between sequential administration of radiation and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) chemotherapy in three primary human glioblastoma cell lines (referred as the GBME3-5 cell lines), which also happen to demonstrate strong expression of the epidermal growth factor receptor (EGFR). (aacrjournals.org)
  • The effect of 17-AAG on the expression of Hsp90 regulated signaling proteins in prostate cancer cells and xenografts was determined. (aacrjournals.org)
  • 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. (nih.gov)
  • Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. (novusbio.com)
  • In mononuclear trophectoderm cells isolated from d-15 conceptuses, IGF-II increased the abundance of p-pyruvate dehydrogenase kinase 1, p-protooncogenic protein kinase 1, p-glycogen synthase kinase 3B, p-FK506 binding protein 12-rapamycin associated protein 1, and p-ribosomal protein S6 kinase protein within 15 min, and the increase was maintained for 90 min. (elsevier.com)
  • The decrease in Akt is not reflected at the protein or mRNA level but rather attributed to kinase inactivation. (aacrjournals.org)
  • Here, we show that during development of chemically induced resistance in Arabidopsis thaliana , priming is associated with accumulation of mRNA and inactive proteins of mitogen-activated protein kinases (MPKs), MPK3 and MPK6. (plantcell.org)
  • Testosterone administration in hypogonadal patients also restored mRNA and nuclear extract protein levels from MNC to that in eugonadal patients. (bireme.br)
  • Owing to the possibility of mismatching between antigens from another resource and antibodies used in this supplier's kits (e.g., antibody targets conformational epitope rather than linear epitope), some native or recombinant proteins from other manufacturers may not be recognized by this supplier's products. (antikoerper-online.de)
  • The p70S6 kinase and eIF4E binding protein 1 (4EBP1) are key regulators of translation, and they are among the most well characterized targets of mTOR ( 5 , 6 ). (pnas.org)
  • By increasing dopamine in the striatum, addictive drugs alter the balance of dopamine and glutamate signals converging onto striatal medium-sized spiny neurons (MSNs) and activate intracellular events involved in long-term behavioral alterations. (isharonline.org)
  • Tangles comprise intracellular assemblies of hyperphosphorylated TAU, a protein which as monomer-among other functions-binds to and stabilizes microtubules [ 4 , 5 ]. (hindawi.com)
  • however, the stimulation by Ang II has been traditionally attributed to the activation of protein kinase C and/or the decrease in the intracellular cAMP level. (ahajournals.org)
  • In addition, nutrients and energy metabolism can regulate mTOR activity through changing the conformation of the mTOR complex ( 3 ) or through altering intracellular AMP levels, which signal to mTOR by means of AMP-activated kinase (AMPK) and the TSC1/TSC2 complex (ref. 4 and Fig. 1 ). (pnas.org)
  • Potentially as the initial cell surface event for intracellular signaling, NaAsO 2 induced aggregation of GPI-anchored protein Thy-1 and superoxide production. (jimmunol.org)
  • 14-3-3 epsilon dynamically interacts with key components of mitogen-activated protein kinase signal module for selective modulation of the TNF-alpha-induced time course-dependent NF-kappaB activity. (semanticscholar.org)
  • After incubation of PC-3M cells with 1 mmol/L MMT, the activity of Caspase-3 was examined. (bvsalud.org)
  • Furthermore, blocking either PI-3K/Akt or MEK/ERK pathway abolished the protective effect of lithium, whereas inhibiting GSK-3β activity mimicked the protective effect of lithium. (utmb.edu)
  • Moreover, excessive mTORC1 activation during diseased states represses basal and activity-induced protein synthesis. (mcponline.org)
  • We provide evidence that a brief repression of mTORC1 activity in vivo by rapamycin has little effect globally, yet leads to a significant remodeling of synaptic proteins, in particular those proteins that reside in the postsynaptic density. (mcponline.org)
  • Moreover, polymerized type I collagen markedly reduced cyclin E-associated kinase activity in the presence of 5% FCS. (biomedsearch.com)
  • The pharmacodynamics of target protein degradation was associated with the toxicology and antitumor activity of the drug. (aacrjournals.org)
  • Iron response protein (IRP) binding activity is a useful indirect measurement of changes in Fe status, as reductions in cell Fe levels lead to increases in IRP binding. (nih.gov)
  • They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. (drugbank.com)
  • This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. (genecards.org)
  • Coexisting BRAF p.V600E mutation was observed in 3 of 4 AKT1 p.E17K-mutated lung cancers. (elsevier.com)
  • Moreover, the mechanisms by which p53 regulates mTOR involves AMP kinase activation and requires the tuberous sclerosis (TSC) 1/TSC2 complex, both of which respond to energy deprivation in cells. (pnas.org)
  • Lithium pretreatment dose-dependently reduced PCP-induced caspase-3 activation and DNA fragmentation in layers II to IV of the cortex. (utmb.edu)
  • We demonstrated that NaAsO 2 -induced caspase activation is dependent on curcumin-sensitive c-Jun amino-terminal kinase and barely dependent on SB203580-sensitive p38 kinase or PD98059-sensitive extracellular signal-regulated kinase. (jimmunol.org)
  • This study aimed to understand the role of MKP-3 and its target MAPKs at the site of surgical incision in nociceptive behavior. (dartmouth.edu)
  • The closest relatives of MAPKs are the cyclin-dependent kinases (CDKs). (wikipedia.org)
  • [3] It is yet unclear if the atypical MAPKs form a single group as opposed to the classical ones. (wikipedia.org)
  • [4] In contrast to the classical MAP kinases, these atypical MAPKs require only a single residue in their activation loops to be phosphorylated. (wikipedia.org)
  • Linear motifs (LMs) are simple protein-protein interaction tools which are generally less than 20 amino acids in length. (iucr.org)
  • Substrates of the encoded protein include the transcription factor ATF2 and the microtubule dynamics regulator stathmin. (antibodies-online.com)
  • We used the MIN6 beta cell line and isolated rat islets to clarify the signaling mechanism(s) used by glucose to activate cAMP-responsive element binding protein (CREB), a transcription factor crucial for beta cell biology, and to evaluate the possible downregulation of this mechanism mediated by long-term hyperglycemia. (nih.gov)
  • Component of a protein kinase signal transduction cascade. (nih.gov)
  • Wild-type (WT) and MKP-3 knockout (KO) mice underwent unilateral plantar hind paw incision. (dartmouth.edu)
  • Peripheral p-ERK-1/2 levels in MKP-3 KO mice remained elevated 12 days after surgery (2.5-fold, N=3 per group). (dartmouth.edu)
  • TNF-α, interleukin-6, and monocyte chemoattractant protein-1 [MCP-1]) compared with HFD-fed control mice. (diabetesjournals.org)
  • β cyclodextrin, which sequestrates cholesterol from the membrane rafts, inhibited NaAsO 2 -induced activation of protein tyrosine kinases and MAP family kinases, degradation of PARP, and production of superoxide. (jimmunol.org)
  • These inflammatory proteins cause insulin resistance by modulating insulin signaling and lipid metabolism ( 1 , 4 ). (diabetesjournals.org)
  • Also, other proteins which involved in the same pathway with mapk8ip3 were listed below. (creativebiomart.net)
  • Some of the functions are cooperated with other proteins, some of the functions could acted by mapk8ip3 itself. (creativebiomart.net)
  • We selected most functions mapk8ip3 had, and list some proteins which have the same functions with mapk8ip3. (creativebiomart.net)
  • mapk8ip3 has direct interactions with proteins and molecules. (creativebiomart.net)
  • We selected proteins and molecules interacted with mapk8ip3 here. (creativebiomart.net)
  • High-resolution crystal structure of human Mapkap kinase 3 in complex with a high affinity ligand. (expasy.org)
  • 8. A method according to claim 5 further comprising the step of assessing evolutionary conservation of the 3′ untranslated region of mRNAs from said target genes and selecting those genes having evolutionary conserved target sites in the 3′ untranslated region of their corresponding mRNAs. (freepatentsonline.com)
  • Detects a band of approximately 60 kDa in an E-coli fusion protein sample (predicted molecular weight: 42 kDa). (abcam.com)