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 family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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.
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 group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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)
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.
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 superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
A 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.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Agents that inhibit PROTEIN KINASES.
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.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
A 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.
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.
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.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
A 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 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.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to CYTOKINES.
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.
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.
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 group of phenyl benzopyrans named for having structures like FLAVONES.
Four carbon unsaturated hydrocarbons containing two double bonds.
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.
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.
Compounds with three fused rings that appear like a naphthalene fused to piperidone or like a benz(de)isoquinoline-1,3-dione (not to be confused with BENZYLISOQUINOLINES which have a methyl separating the naphthyl from the benzyl rings). Members are CYTOTOXINS.
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 180-kDa MAP kinase kinase kinase with specificity for MAP KINASE KINASE 4 and MAP KINASE KINASE 6.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
A 150-kDa MAP kinase kinase kinase that may play a role in the induction of APOPTOSIS. It has specificity for MAP KINASE KINASE 3; MAP KINASE KINASE 4; and MAP KINASE KINASE 6.
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 phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
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 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 70-kDa MAPK kinase kinase with specificity for MAP KINASE KINASE 5.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
A family of 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.
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 ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.
The rate dynamics in chemical or physical systems.
A 70-kDa MAP kinase kinase kinase with specificity for MAP KINASE KINASE 5. It is activated during the cellular response to GROWTH FACTORS, oxidative stress, and hyperosmotic conditions.
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 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.
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.
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.
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.
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.
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.
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.
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 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.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
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.
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.
Proteins prepared by recombinant DNA technology.
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.
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.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A cell line derived from cultured tumor cells.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
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 class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
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)
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
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.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A 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 group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
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.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
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 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.
Elements of limited time intervals, contributing to particular results or situations.
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.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
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.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.
A group of 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)
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.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A 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
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
A family of 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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
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.
A mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 7.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
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.
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.
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).
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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 family of closely-related serine-threonine kinases that were originally identified as the cellular homologs of the retrovirus-derived V-RAF KINASES. They are MAP kinase kinase kinases that play important roles in SIGNAL TRANSDUCTION.
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)
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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.
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.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.
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.
A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A 38-kDa mitogen-activated protein kinase found expressed at high levels in LUNG; KIDNEY; TESTIS; PANCREAS; and SMALL INTESTINE. It may play a role in regulating functions such as CELL DIFFERENTIATION and APOPTOSIS of EPITHELIAL CELLS.
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.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
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.
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)
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).
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
A 38-kDa mitogen-activated protein kinase found primarily in SKELETAL MUSCLE.
The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.
Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.
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.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
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 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 serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.
A 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.
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.
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.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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 family of non-receptor, PROLINE-rich protein-tyrosine kinases.
The phosphoric acid ester of serine.
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
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.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
A 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.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A 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 lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A 110-kDa extracellular signal-regulated MAP kinase that is activated in response to cellular stress and by GROWTH FACTOR RECEPTORS-mediated pathways.
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 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.
Cellular DNA-binding proteins encoded by the c-jun genes (GENES, JUN). They are involved in growth-related transcriptional control. There appear to be three distinct functions: dimerization (with c-fos), DNA-binding, and transcriptional activation. Oncogenic transformation can take place by constitutive expression of c-jun.
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.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
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).
Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC 3.6.1.47.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
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 protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.
Proteins isolated from the roots of the pokeweed, Phytolacca americana, that agglutinate some erythrocytes, stimulate mitosis and antibody synthesis in lymphocytes, and induce activation of plasma cells.
A 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).
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.
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.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
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.
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.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
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.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Compounds with a BENZENE fused to IMIDAZOLES.
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 subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

All-trans-retinoic acid inhibits Jun N-terminal kinase by increasing dual-specificity phosphatase activity. (1/3608)

Jun N-terminal kinases (JNKs) are serine-threonine kinases that play a critical role in the regulation of cell growth and differentiation. We previously observed that JNK activity is suppressed by all-trans-retinoic acid (t-RA), a ligand for retinoic acid nuclear receptors (RARs), in normal human bronchial epithelial cells, which are growth inhibited by t-RA. In this study, we investigated the mechanism by which t-RA inhibits JNK and the possibility that this signaling event is blocked in non-small cell lung cancer (NSCLC) cells. Virtually all NSCLC cell lines are resistant to the growth-inhibitory effects of t-RA, and a subset of them have a transcriptional defect specific to retinoid nuclear receptors. We found that in NSCLC cells expressing functional retinoid receptors, serum-induced JNK phosphorylation and activity were inhibited by t-RA in a bimodal pattern, transiently within 30 min and in a sustained fashion beginning at 12 h. Retinoid receptor transcriptional activation was required for the late, but not the early, suppression of JNK activity. t-RA inhibited serum-induced JNK activity by blocking mitogen-activated protein (MAP) kinase kinase 4-induced signaling events. This effect of t-RA was phosphatase dependent and involved an increase in the expression of the dual-specificity MAP kinase phosphatase 1 (MKP-1). t-RA did not activate MKP-1 expression or inhibit JNK activity in a NSCLC cell line with retinoid receptors that are refractory to ligand-induced transcriptional activation. These findings provide the first evidence that t-RA suppresses JNK activity by inhibiting JNK phosphorylation. Retinoid receptor transcriptional activation was necessary for the sustained inhibition of JNK activity by t-RA, and this signaling event was disrupted in NSCLC cells with retinoid receptors that are refractory to ligand-induced transcriptional activation.  (+info)

Vitamin E succinate (VES) induces Fas sensitivity in human breast cancer cells: role for Mr 43,000 Fas in VES-triggered apoptosis. (2/3608)

Fas (CD95/APO-1) is an important mediator of apoptosis. We show that Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 human breast cancer cells become responsive to anti-Fas (CD95) agonistic antibody-triggered apoptosis after pretreatment or cotreatment with vitamin E succinate (VES; RRR-alpha-tocopheryl succinate). In contrast, no enhancement of anti-Fas agonistic antibody-triggered apoptosis was observed following VES pretreatment or cotreatment with Fas-sensitive primary cultures of human mammary epithelial cells, immortalized MCF-10A cells, or T47D human breast cancer cells. Although VES is itself a potent apoptotic triggering agent, the 6-h pretreatment procedure for Fas sensitization did not initiate VES-mediated apoptosis. The combination of VES plus anti-Fas in pretreatment protocols was synergistic, inducing 2.8-, 3.0-, and 6.3-fold enhanced apoptosis in Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 cells, respectively. Likewise, cotreatment of Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 cells with VES plus anti-Fas enhanced apoptosis 1.9-, 2.0-, and 2.6-fold, respectively. Functional knockout of Fas-mediated signaling with either Fas-neutralizing antibody (MCF-7-, MDA-MB-231-, and MDA-MB-435-treated cells) or Fas antisense oligomers (MDA-MB-435-treated cells only), reduced VES-triggered apoptosis by approximately 50%. Analyses of whole cell extracts from Fas-sensitive cells revealed high constitutive expression of Mr 43,000 Fas, whereas Fas-resistant cells expressed low levels that were confined to the cytosolic fraction. VES treatment of the Fas-resistant cells caused a depletion of cytosolic Mr 43,000 Fas with a concomitant increase in Mr 43,000 membrane Fas. These data show that VES can convert Fas-resistant human breast cancer cells to a Fas-sensitive phenotype, perhaps by translocation of cytosolic Mr 43,000 Fas to the membrane and show that VES-mediated apoptosis involves Mr 43,000 Fas signaling.  (+info)

Raf-1 is activated by the p38 mitogen-activated protein kinase inhibitor, SB203580. (3/3608)

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

Nuclear localization of mitogen-activated protein kinase kinase 1 (MKK1) is promoted by serum stimulation and G2-M progression. Requirement for phosphorylation at the activation lip and signaling downstream of MKK. (4/3608)

Stimulation of mammalian cells results in subcellular relocalization of Ras pathway enzymes, in which extracellular signal-regulated protein kinases rapidly translocate to nuclei. In this study, we define conditions for nuclear localization of mitogen-activated protein kinase kinase 1 (MKK1) by examining effects of perturbing the nuclear export signal (NES), the regulatory phosphorylation sites Ser218 and Ser222, and a regulatory domain at the N terminus. After disrupting the NES (Delta32-37), nuclear uptake of MKK was enhanced when quiescent cells were activated with serum-phorbol 12-myristate 13-acetate or BXB-Raf-1 cotransfection. Uptake was enhanced by mutation of Ser218 and Ser222 to Glu and Asp, respectively, and blocked by mutation of these residues to Ala, although mutation of Lys97 to Met, which renders MKK catalytically inactive, did not interfere with uptake. Therefore, nuclear uptake of MKK requires incorporation of phosphate or negatively charged residues at the activation lip but not enzyme activity. On the other hand, uptake of an active MKK mutant with disrupted NES (Delta32-51) was elevated in quiescent as well as stimulated cells, and pretreatment of cells with the MKK inhibitor 1,4-diamino-2, 3-dicyano-1,4-bis[2-aminophenylthio]butadiene blocked nuclear uptake. Thus, signaling downstream of MKK is also necessary for translocation. Finally, wild type MKK containing an intact NES translocates to nuclei during mitosis before envelope breakdown. Comparison of mutants with Ser to Glu and Asp or Ala substitutions indicates that Ser phosphorylation is also required for mitotic nuclear uptake of MKK.  (+info)

Expression of c-Myc in response to colony-stimulating factor-1 requires mitogen-activated protein kinase kinase-1. (5/3608)

The mitogen-inducible gene c-myc is a key regulator of cell proliferation and transformation. Yet, the signaling pathway(s) that regulate its expression have remained largely unresolved. Using the mitogen-activated protein kinase kinase (MEK1/2) inhibitor PD98059 and dominant negative forms of Ras (N17) and ERK1 (K71R), we found that activation of Ras and extracellular signal-regulated kinase (ERK) is necessary for colony-stimulating factor-1 (CSF-1)-mediated c-Myc expression and DNA synthetic (S) phase entry. Quiescent NIH-3T3 cells expressing a partially defective CSF-1 receptor, CSF-1R (Y809F), exhibited impaired ERK1 activation and c-Myc expression and failed to enter the S phase of the cell division cycle in response to CSF-1 stimulation. Ectopic expression of a constitutively active form of MEK1 in cells expressing CSF-1R (Y809F) rescued c-Myc expression and S phase entry, but only in the presence of CSF-1-induced cooperating signals. Therefore, MEK1 participates in an obligate signaling pathway linking CSF-1R to c-Myc expression, but other signals from CSF-1R must cooperate with the MEK/ERK pathway to induce c-Myc expression and S phase entry in response to CSF-1 stimulation.  (+info)

Mitogen-activated protein kinase cascade and transcription factors: the opposite role of MKK3/6-p38K and MKK1-MAPK. (6/3608)

Recent studies have revealed that mitogen-activated protein kinase (MAPK) consists of at least three subfamilies, namely classical MAPK (also known as ERK), stress-activated protein kinase/c-Jun N-terminal kinase (JNK) and p38 kinase. TGF-beta-activating kinase (TAK)-1 is a novel MAPKKK which is reported to stimulate p38K and/or the JNK pathway. To elucidate the functional roles of the TAK1 pathway, we transfected its constitutive active form (TAK1dN) and negative form (TAK1K63W) into LLC-PK1 cells. TAKdN inhibited [3H]thymidine uptake and reduced the percentages of S and G2/M phases. TAK1K63W ameliorated the inhibitory effects of TGF-beta on [3H]thymidine uptake and increased the percentages of S and G2/M phases. Western blot analysis demonstrates that the level of cyclin D1 protein was regulated negatively by overexpression of TAK1dN. Moreover, overexpression of TAK1dN inhibited cyclin D1 promoter activity. In contrast, constitutive active MKK1, the classical p42/44 MAPK activator, increased cyclin D1 promoter activity and level of protein. Overexpression of the active form of MKK1 increased [3H]thymidine uptake, while the inactive form decreased the uptake. In conclusion, cyclin D1 promoter activity and cell cycle progression are regulated negatively by the TAK1 pathway and positively by the classical MAPK pathway.  (+info)

Activation of c-fos promoter by Gbetagamma-mediated signaling: involvement of Rho and c-Jun N-terminal kinase. (7/3608)

Several extracellular stimuli mediated by G protein-coupled receptors activate c-fos promoter. Recently, we and other groups have demonstrated that signals from G protein-coupled receptors stimulate mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. The activation of these three MAPKs is mediated in part by the G protein betagamma subunit (Gbetagamma). In this study, we characterized the signals from Gbetagamma to c-fos promoter using transient transfection of c-fos luciferase into human embryonal kidney 293 cells. Activation of m2 muscarinic acetylcholine receptor and overexpression of Gbetagamma, but not constitutively active Galphai2, stimulated c-fos promoter activity. The c-fos promoter activation by m2 receptor and Gbetagamma was inhibited by beta-adrenergic receptor kinase C-terminal peptide (betaARKct), which functions as a Gbetagamma antagonist. MEK1 inhibitor PD98059 and kinase-deficient mutant of JNK kinase, but not p38 MAPK inhibitor SB203580, attenuated the m2 receptor- and Gbetagamma-induced c-fos promoter activation. Activated mutants of Ras and Rho stimulated the c-fos promoter activity, and the dominant negative mutants of Ras and Rho inhibited the c-fos promoter activation by m2 receptor and Gbetagamma. Moreover, c-fos promoter activation by m2 receptor, Gbetagamma, and active Rho, but not active Ras, was inhibited by botulinum C3 toxin. These data indicated that both Ras- and Rho-dependent signaling pathways are essential for c-fos promoter activation mediated by Gbetagamma.  (+info)

Cot protooncoprotein activates the dual specificity kinases MEK-1 and SEK-1 and induces differentiation of PC12 cells. (8/3608)

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)

LOC100996792 (dual specificity mitogen-activated protein kinase kinase 3), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity).
GDC-0623, also known as G-868, is an orally active, selective MEK inhibitor with potential antineoplastic activity. MEK inhibitor GDC-0623 specifically inhibits mitogen-activated protein kinase kinase (MEK or MAP/ERK kinase), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers.
This trial aims to evaluate the efficacy of fulvestrant +/- selumetinib [AZD6244] in patients with advanced stage breast cancer progressing after aromatase
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Background Multi-drug proneness and level of resistance to metastasize are main clinical complications in cancers treatment. on cell migration and in cell protein-protein association Neurog1 had been researched by wound-healing and closeness ligation assays, respectively. Outcomes We present right here, that N11 treatment network 336113-53-2 marketing leads to i) significant caspase-mediated apoptotic cell loss of […]. Read More ». ...
SEK1 / MKK4 (phospho Ser80) antibody (mitogen-activated protein kinase kinase 4) for ICC/IF, IHC-P, WB. Anti-SEK1 / MKK4 (phospho Ser80) pAb (GTX55115) is tested in Human samples. 100% Ab-Assurance.
MEK1/2 (phospho Ser217) antibody (mitogen-activated protein kinase kinase 1) for IHC, WB. Anti-MEK1/2 (phospho Ser217) pAb (GTX52336) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
TABLE-US-00001 TABLE 1 Oligo Accession Gene ID Number Number number Gene Name Symbol APOB-10167- 12138 NM_000384 Apolipoprotein B (including Ag(x) antigen) APOB 20-12138 APOB-10167- 12139 NM_000384 Apolipoprotein B (including Ag(x) antigen) APOB 20-12139 MAP4K4-2931- 12266 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 13-12266 (MAP4K4), transcript variant 1 MAP4K4-2931- 12293 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 16-12293 (MAP4K4), transcript variant 1 MAP4K4-2931- 12383 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 16-12383 (MAP4K4), transcript variant 1 MAP4K4-2931- 12384 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 16-12384 (MAP4K4), transcript variant 1 MAP4K4-2931- 12385 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 16-12385 (MAP4K4), transcript variant 1 MAP4K4-2931- 12386 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 ...
BioAssay record AID 758814 submitted by ChEMBL: Inhibition of PAK1 in human OVCAR3 cells assessed as MEK phosphorylation by TR-FRET assay.
These reference sequences exist independently of genome builds. Explain. These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above. ...
The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. [provided by RefSeq, Mar 2012 ...
May be involved in an oxidative stress-mediated signaling cascade that phosphorylates downstream MAP kinases MPK3 and MPK6. May suppress auxin signaling that promotes cell cycle. Functionally redundant to ANP2 and ANP3 in the positive regulation of cytokinesis.
View mouse Map3k15 ChrX:159988433-160123351 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Cell microarrays are a promising tool for performing large-scale functional genomic screening in mammalian cells at reasonable cost, but owing to technical limitations they have been restricted for use with a narrow range of cell lines and short-term assays. Here, we describe MicroSCALE (Microarrays of Spatially Confined Adhesive Lentiviral Features), a cell microarray-based platform that enables application of this technology to a wide range of cell types and longer-term assays. We used MicroSCALE to uncover kinases that when overexpressed partially desensitized B-RAFV600E-mutant melanoma cells to inhibitors of the mitogen-activated protein kinase kinase kinase (MAPKKK) RAF, the MAPKKs MEK1 and 2 (MEK1/2, mitogen-activated protein kinase kinase 1 and 2), mTOR (mammalian target of rapamycin), or PI3K (phosphatidylinositol 3-kinase). These screens indicated that cells treated with inhibitors acting through common mechanisms were affected by a similar profile of overexpressed proteins. In ...
The worlds first wiki where authorship really matters. Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts.
The worlds first wiki where authorship really matters. Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts.
Transforming growth factor-β (TGF-β) signals through its receptor, composed of the type I and type II subunits (TβRI and TβRII), to stimulate a pathway involving Smads, as well as Smad-independent signaling. Sorrentino et al. found that in cells transfected with TAK1 [TGF-β-associated kinase 1, a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family that is upstream of p38 and ubiquitin], TGF-β1 stimulated the ubiquitylation of TAK1, as well as the phosphorylation of TAK1, which is an indication of activation. When a mutant form of ubiquitin that could not form Lys63-linked chains was transfected into the cells, TAK1 ubiquitylation and phosphorylation, recruitment of TAB2 (TAK-associated binding protein 2), and activation of p38 was diminished. Pharmacological inhibition of TβRI kinase activity failed to block TGF-β-stimulated TAK1 and p38 activation but did block Smad activation, suggesting that activation of the p38 MAPK pathway was independent of the kinase ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
The kinase pathway comprising RAS, RAF, mitogen-activated protein kinase kinase (MEK) and extracellular signal regulated kinase (ERK) is activated in most human tumours, often through gain-of-function mutations of RAS and RAF family members. Using small-molecule inhibitors of MEK and an integrated g …
Homo sapiens mitogen-activated protein kinase kinase kinase 7 (MAP3K7), transcript variant A, mRNA. (H00006885-R01V) - Products - Abnova
Homo sapiens mitogen-activated protein kinase kinase kinase 4 (MAP3K4), transcript variant 1, mRNA. (H00004216-R06) - Products - Abnova
Gene target information for MAP3K20 - mitogen-activated protein kinase kinase kinase 20 (human). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
Certest tarjoaa laajan valikoiman kvalitatiivisia immunokromatografisia testejä mahasuolikanavan sairauksien sekä hengitystieinfektioiden diagnoosin…
TY - JOUR. T1 - Mitogen-activated protein kinase (MAP kinase), MAP kinase kinase and c-Mos stimulate glucose transport in Xenopus oocytes. AU - Merrall, N. W.. AU - Plevin, R. J.. AU - Stokoe, D.. AU - Cohen, P.. AU - Nebreda, A. R.. AU - Gould, G. W.. PY - 1993/10/15. Y1 - 1993/10/15. N2 - Mitogens and growth factors acutely stimulate glucose transport in all cells to supply energy for their growth and division, but little is known about the signalling mechanism by which these agonists promote sugar uptake. Here we show that the transport of deoxyglucose and 3-O-methylglucose into Xenopus laevis oocytes is stimulated about 2.5-fold when mitogen-activated protein kinase (MAP kinase) is microinjected into these oocytes. We also demonstrate that microinjection of the proto-oncogene product c-Mos (an activator of MAP kinase kinase, which activates MAP kinase in Xenopus oocytes), and purified MAP kinase kinase produce similar increases in deoxyglucose transport. Since the activation of MAP kinase is ...
The mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1) mediates activin B signals required for eyelid epithelium morphogenesis during mouse fetal development. The present study investigates the role of MEKK1 in epithelial wound healing, another activin-regulated biological process. In a skin wound model, injury markedly stimulates MEKK1 expression and activity, which are in turn required for the expression of genes involved in extracellular matrix (ECM) homeostasis. MEKK1 ablation or down-regulation by interfering RNA significantly delays skin wound closure and impairs activation of Jun NH2-terminal kinases, induction of plasminogen activator inhibitor (PAI)-1, and restoration of cell-cell junctions of the wounded epidermis. Conversely, expression of wild-type MEKK1 accelerates reepithelialization of full-thickness skin and corneal debridement wounds by mechanisms involving epithelial cell migration, a cell function that is partially abolished by neutralizing antibodies for PAI-1 and
This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008 ...
The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase has been shown to activate MAPK8/JNK and MKK4/SEK1, and this kinase itself can be phoshorylated, and thus activated by JNK kinases. This kinase functions preferentially on the JNK signaling pathway, and is reported to be involved in nerve growth factor (NGF) induced neuronal apoptosis. [provided by RefSeq, Jul 2008 ...
Catalytic domain of the Protein Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6. Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 4 (MAPKKKK4 or MAP4K4) and MAPKKKK6 (or MAP4K6) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K4/MAP4K6 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4Ks (or MAPKKKKs) are involved in MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). Each MAPK cascade is activated ...
Thank you for sharing this Drug Metabolism & Disposition article.. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.. ...
MAP3K5 Full-Length MS Protein Standard (NP_005914), Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine, was produced in human 293 cells (HEK293) with fully chemically defined cell culture medium to obtain incorporation efficiency at Creative-Proteomics. Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress
The mitogen-activated protein kinase (MAPK) pathway is intimately implicated in the molecular pathogenesis of non-small-cell lung cancer (NSCLC). Aberrant MAPK signaling resulting from the upstream activating mutations converges on mitogen-activated protein kinase kinase 1/2 (MEK1/2), making MEK inhibition an attractive strategy for the treatment of NSCLC. Several MEK inhibitors have demonstrated anticancer activity in patients with NSCLC. Areas covered: In this article, we discuss the biological rationale for the use of MEK inhibitors and summarize the clinical experience with MEK1/2 inhibitors for the treatment of NSCLC, from initial phase I studies to phase II/III studies, both as monotherapy or in combination with other anticancer agents ...
Exhibits JUN kinase kinase kinase activity. Involved in positive regulation of nervous system development and protein phosphorylation. Predicted to localize to the membrane. Is expressed in diencephalon lateral wall mantle layer; dorsal grey horn; late tubule; midbrain mantle layer; and ureter. Orthologous to human MAP3K13 (mitogen-activated protein kinase kinase kinase 13 ...
Next-day shipping cDNA ORF clones derived from MAP4K2 mitogen-activated protein kinase kinase kinase kinase 2 available at GenScript, starting from $99.00.
The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli. Source: KEGG http://www.genome.jp/dbget-bin/www_bget?pathway:map04010 ...
The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli ...
The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli ...
MAPK forms the backbone of four primary signal transduction cascades leading to the phosphorylation and activation of extracellular signal-regulated kinases 1 and 2 (ERK1--2), JNK, p38 and ERK5. MAPK kinases 1 and 2, commonly known at MEK1--2, are referred to as MEK. Because of their importance in cell proliferation and signaling, MAPK pathways are being targeted for new drugs for oncology, inflammation and other conditions. Several inhibitors of MEK1--2 (MAPK kinases 1 and 2) are nearing, or are currently in, clinical trials for oncology ...
The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli ...
The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli ...
ASK1, 0.1 ml. Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK).
Phosphorylation of mitogen-activated protein kinases (MAPKs) on specific tyrosine and threonine sites by MAP kinase kinases (MAPKKs) is thought to be the sole activation mechanism. Here, we report an unexpected activation mechanism for p38α MAPK that does not involve the prototypic kinase cascade. Rather it depends on interaction of p38α with TAB1 [transforming growth factor-β-activated protein kinase 1 (TAK1)-binding protein 1] leading to autophosphorylation and activation of p38α. We detected formation of a TRAF6-TAB1-p38α complex and showed stimulus-specific TAB1-dependent and TAB1-independent p38α activation. These findings suggest that alternative activation pathways contribute to the biological responses of p38α to various stimuli. ...
[ChEMBL Target Description] ID:CHEMBL4948, Name:Dual specificity mitogen-activated protein kinase kinase 5, Description:, Synonyms:
MAP2K2 - MAP2K2 Mutant (G132V), Myc-DDK-tagged ORF clone of Homo sapiens mitogen-activated protein kinase kinase 2 (MAP2K2) as transfection-ready DNA available for purchase from OriGene - Your Gene Company.
MAP2K5 - MAP2K5 (GFP-tagged) - Human mitogen-activated protein kinase kinase 5 (MAP2K5), transcript variant 2 available for purchase from OriGene - Your Gene Company.
SUZHOU, China, July 30, 2018 /PRNewswire/ -- CStone Pharmaceuticals (CStone) today announced that its IND application for CS3006, a small-molecule inhibitor of mitogen-activated protein kinase (MEK), has been approved by the China National Drug Administration (CNDA) for clinical trials, just 3 months after the CNDA...
Nik a protein kinase of the STE group of kinases. Binds to TRAF2 and stimulates NF-kappaB activity. It shares sequence similarity with several other MAPKK kinases. It participates in an NF-kappaB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor (TNF/NGF) family and to the interleukin-1 type-I receptor. Note: This description may include information from UniProtKB ...
A szérumok, kezelések és a boosterek igazi turbóerőt jelentenek a bőrápolásban, olyan pluszt adnak a bőrápolásodhoz, amivel elképesztő látványos változásokat érhetsz el. Legyen szó ráncokról, pigmentfoltokról vagy vízhiányról, itt a megoldás! A delux és mini kiszerelések ideálisak utazáshoz, vagy akár egy tartósabb teszthez is, a termékek ugyanis cirka 3-4 hétig elegendőek ...
MEK1小鼠单克隆抗体[32G3](ab70833)可与小鼠, 大鼠, 人样本反应并经WB, ELISA实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
MEK3兔多克隆抗体(ab5428)可与小鼠, 人样本反应并经WB, ELISA, IHC实验严格验证,被4篇文献引用并得到1个独立的用户反馈。所有产品均提供质保服务,中国75%以上现货。
Pontus Jäntti Sulkapallokoulu, Ristihaantie 2, Espoo (2020) - Pontus Jäntti Sulkapallokoulu järjestää valmennusta sekä lapsille et
Tyrosine kinase growth factor receptors activate mitogen-activated protein kinases which then translocate into the nucleus ... Mitogen-activated protein kinase 4 is an enzyme that in humans is encoded by the MAPK4 gene. Mitogen-activated protein kinase 4 ... "Genomic loci of human mitogen-activated protein kinases". Oncogene. 9 (2): 647-9. PMID 8290275. "Entrez Gene: MAPK4 mitogen- ... Robinson MJ, Cobb MH (April 1997). "Mitogen-activated protein kinase pathways". Current Opinion in Cell Biology. 9 (2): 180-6. ...
"Fluid shear stress activation of focal adhesion kinase. Linking to mitogen-activated protein kinases". J. Biol. Chem. 272 (48 ... Corbalan-Garcia S, Yang SS, Degenhardt KR, Bar-Sagi D (1996). "Identification of the mitogen-activated protein kinase ... "Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation ... nucleotide exchange protein Sos and a 75-kDa protein that is a substrate for T cell antigen receptor-activated tyrosine kinases ...
... calmodulin-modulated myosin light chain kinase; RAF/MEK/Mitogen-activated protein kinases; PKC/Ca2+/Calcineurin/Nuclear factor ... to activate the Rho family of GTPases signaling proteins and Gi-Gβγ G proteins to activateRaf/MEK/mitogen-activated kinase ... regulation of proliferation by activation of the epidermal growth factor receptor and mitogen-activated protein kinase ... phospholipase C/IP3/cell Ca2+ mobilization/diacylglycerol/protein kinase Cs; ...
"Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6". The ... "Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 (MAPKK 6) or MAPK/ERK kinase 6 is ... protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • protein ...
... is also known as MEK1 (see Mitogen-activated protein kinase kinase). MEK1 is a meiotic chromosome-axis-associated kinase ... This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon activation by a wide ... protein tyrosine kinase activity. • nucleotide binding. • MAP kinase kinase activity. • protein kinase activity. • protein ... "Entrez Gene: MAP2K1 mitogen-activated protein kinase kinase 1".. *^ a b Goldfarb T, Lichten M (2010). "Frequent and efficient ...
Jensen LE, Whitehead AS (2003). "Pellino2 activates the mitogen activated protein kinase pathway". FEBS Lett. 545 (2-3): 199- ... Butler MP, Hanly JA, Moynagh PN (2007). "Kinase-active interleukin-1 receptor-associated kinases promote polyubiquitination and ... Protein pellino homolog 1 is a protein that in humans is encoded by the PELI1 gene. GRCh38: Ensembl release 89: ENSG00000197329 ... direct evidence for PELLINO proteins being ubiquitin-protein isopeptide ligases". J. Biol. Chem. 282 (41): 29729-29737. doi: ...
The protein encoded by this gene is a member of the MAP (mitogen-activated protein) kinase family. MAP kinases are also known ... including cyclin-dependent kinase 2 (CDK2), mitogen-activated protein kinase 12 (MAPK12), and lactotransferrin (LTF), among ... Mitogen-activated protein kinase 15, also known as MAPK15, ERK7, or ERK8, is an enzyme that in humans is encoded by the MAPK15 ... "Entrez Gene: MAPK15 mitogen-activated protein kinase 15". Chia J, Tham KM, Gill DJ, Bard-Chapeau EA, Bard FA (2014). "ERK8 is a ...
"Identification of substrates and regulators of the mitogen-activated protein kinase ERK5 using chimeric protein kinases". J. ... This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the ... Mitogen-activated protein kinase 7 also known as MAP kinase 7 is an enzyme that in humans is encoded by the MAPK7 gene. MAPK7 ... "Characterization of the mitogen-activated protein kinase phosphorylation sites on the connexin-43 gap junction protein". J. ...
"Regulation of lymphoid enhancer factor 1/T-cell factor by mitogen-activated protein kinase-related Nemo-like kinase-dependent ... Coulombe P, Meloche S (August 2007). "Atypical mitogen-activated protein kinases: structure, regulation and functions". Biochim ... 2003). "The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta- ... This enzyme is a member of the Mitogen-activated protein kinase (MAPK) family, although not explicitly designated as such (it ...
Mitogen-activated protein kinase (MAPK) networks are the pathways and signaling of MAPK, which is a protein kinase that ... Unfortunately, only eight out of the twenty mitogen-activated protein kinases have been studied. The most commonly studied ... Mitogen-activated protein kinase (MAPK) networks can be found in eukaryotic cells. MAPK pathways in plants are known to ... "Mitogen-Activated Protein (MAP) Kinase Pathways: Regulation and Physiological Functions1". Endocrine Reviews. 22 (2): 153-183. ...
Navas TA, Baldwin DT, Stewart TA (1999). "RIP2 is a Raf1-activated mitogen-activated protein kinase kinase". J. Biol. Chem. 274 ... This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded ... 1999). "Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-kappaB". J. Biol. Chem. 274 (19 ... McCarthy JV, Ni J, Dixit VM (1998). "RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase". J. Biol. Chem. 273 ( ...
Furthermore, the receptor stimulates the mitogen-activated protein kinase pathways. It is ubiquitously and constitutively ... Dalemar LR, Ivy Jong YJ, Wilhelm B, Baenziger NL (1996). "Protein kinases A and C rapidly modulate expression of human lung ... Bradykinin receptor B2 is a G-protein coupled receptor for bradykinin, encoded by the BDKRB2 gene in humans. The B2 receptor is ... Alternate start codons result in two isoforms of the protein. Bradykinin receptor GRCh38: Ensembl release 89: ENSG00000168398 ...
... a novel mitogen-activated protein kinase with distinct properties". J. Biol. Chem. 272 (31): 19509-17. doi:10.1074/jbc.272.31. ... Kamakura S, Moriguchi T, Nishida E (1999). "Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. ... mitogen-activated protein kinase". J. Biol. Chem. 272 (7): 4219-24. doi:10.1074/jbc.272.7.4219. PMID 9020136. Janknecht R, ... The protein encoded by this gene is phosphorylated by the kinases, MAPK1 and MAPK8. Several transcript variants have been ...
"Mechanical Regulation of Mitogen-activated Protein Kinase Signaling in Articular Cartilage". Journal of Biological Chemistry. ... In addition, kinases (e.g., focal adhesion kinase, FAK) and adapter proteins (e.g., paxillin, Pax, talin, Tal and Shc) are ... Protein domains, connected by intrinsically disordered flexible linker domains, induce long-range allostery via protein domain ... When an integrin receptor binds to its ECM ligand and is activated, additional integrins cluster around the activated site. ...
"Protein tyrosine phosphatase epsilon inhibits signaling by mitogen-activated protein kinases". Mol. Cancer Res. 1 (7): 541-50. ... Roskoski R (2005). "Src kinase regulation by phosphorylation and dephosphorylation". Biochem. Biophys. Res. Commun. 331 (1): 1- ... The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling ... "Entrez Gene: PTPRE protein tyrosine phosphatase, receptor type, E". Peretz A, Gil-Henn H, Sobko A, Shinder V, Attali B, Elson A ...
The protein encoded by this gene is a scaffolding protein that brings together mitogen-activated protein kinases and their ... C-jun-amino-terminal kinase-interacting protein 4 is a scaffold protein that in humans is encoded by the SPAG9 gene. ... Extracellular signals are transduced into cells through mitogen-activated protein kinases. The structural organization of these ... Ichijo H (Nov 1999). "From receptors to stress-activated MAP kinases". Oncogene. 18 (45): 6087-93. doi:10.1038/sj.onc.1203129. ...
Yang SH, Galanis A, Sharrocks AD (June 1999). "Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors ... with a mitogen-activated protein kinase, ERK5/BMK1". Nucleic Acids Res. 26 (20): 4771-7. doi:10.1093/nar/26.20.4771. PMC 147902 ... Yang SH, Galanis A, Sharrocks AD (1999). "Targeting of p38 Mitogen-Activated Protein Kinases to MEF2 Transcription Factors". ... "Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins". Nucleic Acids Res. 29 (3): 732-42. doi: ...
de 1997). «Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase». Proc. Natl. Acad. Sci. ... de 1999). «Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors». Mol. Cell. Biol. (UNITED STATES) ... Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase ... de 2000). «Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase». J ...
"Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase". The Journal of Biological ... Regulation of stathmin is cell cycle dependent and controlled by the cell's protein kinases in response to specific cell ... Identification of four sites phosphorylated in intact cells and in vitro by cyclic AMP-dependent protein kinase and p34cdc2". ... Maucuer A, Camonis JH, Sobel A (April 1995). "Stathmin interaction with a putative kinase and coiled-coil-forming protein ...
1997). „Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S ... 1997). „Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. ENGLAND. 16 (8): 1909- ... 2003). „The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 ... 2001). „A novel 14-kilodalton protein interacts with the mitogen-activated protein kinase scaffold mp1 on a late endosomal/ ...
... 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 ...
"Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... Xu S, Cobb MH (1998). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". J. Biol. Chem. ... 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. ...
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 ...
... mitogen-activated-protein kinase-activating protein kinase) has a preference for Ser40, but also phosphorylates Ser19 about ... kinase and MAP-kinase-activated kinases 1 and 2". European Journal of Biochemistry / FEBS. 217 (2): 715-22. doi:10.1111/j.1432- ... that are phosphorylated by a variety of protein kinases.[12][25] Ser40 is phosphorylated by the cAMP-dependent protein kinase.[ ... Tyrosine hydroxylase is activated by phosphorylation dependent binding to 14-3-3 proteins.[34] Since the 14-3-3 proteins also ...
LF acts as a Zn2+-dependent endoprotease that snips off the N-terminus of mitogen-activated protein kinase kinases (MAPKK). ... the tripartite protein toxin, called anthrax toxin. Anthrax toxin is a mixture of three protein components: (i) protective ... the synergistic effect of these three proteins leads to cellular death through a cascade of events that allow the proteins to ... Ratcheting up protein translocation with anthrax toxin. Prot Sci. 2012, 21(5):606-24. Abrami, L.; Liu, S.; Cosson, P.; Leppla, ...
... induced gene expression in articular chondrocytes is associated with activation of mitogen-activated protein kinases and NF- ... Expression of IL-17 in human memory CD45RO+ T lymphocytes and its regulation by protein kinase A pathway.". Cytokine. 11 (4): ... Rouvier E, Luciani MF, Mattei MG, Denizot F, Golstein P (1993). „CTLA-8, cloned from an activated T cell, bearing AU-rich ... Laan M, Palmberg L, Larsson K, Lindén A (2002). „Free, soluble interleukin-17 protein during severe inflammation in human ...
A second pathway contributing to cell survival occurs through activation of the mitogen-activated protein kinase (MAPK) kinase ... "Tropomyosin-Receptor-Kinases Signaling in the Nervous System". Maedica. 8 (1): 43-48. PMC 3749761. PMID 24023598 ... The active Ras protein phosphorylates several proteins, along with the serine/threonine kinase, Raf.[7] Raf in turn activates ... positive regulation of Ras protein signal transduction. • transmembrane receptor protein tyrosine kinase signaling pathway. • ...
... 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 ... protein kinase (ERK), p125fak, and pp60c-src.[19][20][21] During fetal development, the migration path through which neural ... The introduction of protein-based cross-links,[53] the introduction of free-radical scavenging molecules such as sorbitol,[54] ...
MAP kinase kinase kinase (MAP3K or MKKK). *MAP kinase kinase kinases *MAP3K1 ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... is performed by members of the Ste7 protein kinase family, also known as MAP2 kinases. MAP2 kinases in turn, are also activated ...
MAP Kinase Kinase Kinase 1*. *Mammals. *Mitogen-Activated Protein Kinase Kinases*. *Protein-Serine-Threonine Kinases/metabolism ... Mitogen-activated protein kinase pathways.. Robinson MJ1, Cobb MH.. Author information. 1. University of Texas Southwestern ... Nearly all cell surface receptors utilize one or more of the mitogen-activated protein kinase cascades in their repertoire of ... MAP Kinase Kinase 1. *MAP2K1 protein, human. *Mitogen-Activated Protein Kinase Kinases ...
... surface and in the cytoplasm of innate immune cells activates members of each of the major mitogen-activated protein kinase ( ... Mitogen-activated protein kinases in innate immunity.. Arthur JS1, Ley SC. ... Mitogen-Activated Protein Kinases/antagonists & inhibitors. *Mitogen-Activated Protein Kinases/immunology*. *Toll-Like ... MAPK) subfamilies--the extracellular signal-regulated kinase (ERK), p38 and Jun N-terminal kinase (JNK) subfamilies. In ...
These effects were proportional to the extent of MAP kinase inhibition and reversed by coexpression of the wild-type p44mapk. ... The mitogen-activated protein kinases (MAP kinases) p42mapk and p44mapk are serine/threonine kinases rapidly activated in cells ... Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation. G Pagès, P Lenormand, G ... Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation ...
... mitogen-activated protein kinase 12), Authors: Maria Isabel Cerezo-Guisado, Ana Cuenda. Published in: Atlas Genet Cytogenet ... SAP kinase-3, a new member of the family of mammalian stress-activated protein kinases.. ... Kinase-like_dom_sf MAP_kinase_CS MAPK_p38 Prot_kinase_dom Protein_kinase_ATP_BS ... MAPK cascade magnesium ion binding protein serine/threonine kinase activity protein serine/threonine kinase activity MAP kinase ...
... virus type 1 and its coat protein gp120 induce apoptosis and activate JNK and ERK mitogen-activated protein kinases in human ... a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... "The JIP group of mitogen-activated protein kinase scaffold proteins". Molecular and Cellular Biology. 19 (10): 7245-54. doi: ...
... protein kinase C, or other mitogen-activated protein kinases including MEK, ERK, or JNK (Gallagher et al., 1997; Young et al., ... Human serotonin transporter variants display altered sensitivity to protein kinase G and p38-mitogen-activated protein kinase. ... 1998) Extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases regulate inducible nitric ... 1997) Pyridinyl imidazole inhibitors of p38 mitogen-activated protein kinase bind in the ATP site. J Biol Chem 272:12116-12121. ...
Mitogen-activated protein (MAP) kinases are important mediators involved in the intracellular network of interacting proteins ... Induction of mitogen-activated protein kinase phosphatase 1 by the stress-activated protein kinase signaling pathway but not by ... Mitogen-activated protein (MAP) kinase is regulated by the MAP kinase phosphatase (MKP-1) in vascular smooth muscle cells. J ... Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase). EMBO J. 1991;10: ...
However, intramolecular interactions consistent with an inactive protein kinase fold were not formed. MD with p38α showed that ... The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ... The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ... Comparative Molecular Dynamics Simulations of Mitogen-Activated Protein Kinase-Activated Protein Kinase 5 Inger Lindin 1, ...
... by proinflammatory stimuli selectively initiates intracellular signal transduction via sequential phosphorylation of kinases. ... Selective activation and functional significance of p38α mitogen-activated protein kinase in lipopolysaccharide-stimulated ... Selective activation and functional significance of p38α mitogen-activated protein kinase in lipopolysaccharide-stimulated ... stimulation of human neutrophils is known to result in activation of p38 mitogen-activated protein kinase (MAPk); however, the ...
Mitogen-Activated Protein Kinase 3 [D08.811.913.696.620.682.700.567.342.750]. *Proline-Directed Protein Kinases [D08.811. ... "Mitogen-Activated Protein Kinase 3" by people in Harvard Catalyst Profiles by year, and whether "Mitogen-Activated Protein ... Protein-Serine-Threonine Kinases [D08.811.913.696.620.682.700]. *Mitogen-Activated Protein Kinases [D08.811.913.696.620.682. ... Mitogen-Activated Protein Kinase 3*Mitogen-Activated Protein Kinase 3. *Mitogen Activated Protein Kinase 3 ...
MKK2 is one of the upstream activator kinases of ERK2 that binds its MAPK substrate with a linear docking motif (Garai et al., ... Protein-peptide complex crystallization: a case study on the ERK2 mitogen-activated protein kinase. ... Mitogen-activated protein kinase (MAPK)-binding linear motifs bind to the MAPK docking groove and represent a functionally well ... motif from a downstream MAP kinase-activated protein kinase (MAPKAP) that is a known ERK2 substrate (RSK1; Garai et al., 2012. ...
Specifically, members of the mitogen-activated protein (MAP) kinase family of serine-threonine kinases may contribute to the ... Widmann C, Gibson S, Jarpe MB, Johnson GL: Mitogen-activated protein kinase: conservation of a three-kinase module from yeast ... To test the potential for members of the mitogen-activated protein (MAP) kinase family to contribute to type 2 diabetes, we ... Enhanced Basal Activation of Mitogen-Activated Protein Kinases in Adipocytes From Type 2 Diabetes. Potential Role of p38 in the ...
... target a variety of protein substrates to regulate cellular signaling processes in eukaryotes. In plants, the number of ... Mitogen-activated protein kinases (MAPKs) target a variety of protein substrates to regulate cellular signaling processes in ... Sustained mitogen-activated protein kinase activation reprograms defense metabolism and phosphoprotein profile in Arabidopsis ... WRKY transcription factors and proteins encoded by the genes from the "PEN" pathway required for penetration resistance to ...
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. ... Mitogen-Activated Protein Kinases: 952*JNK Mitogen-Activated Protein Kinases: 1056*Mitogen-Activated Protein Kinase 8: 68 ... Mitogen-Activated Protein Kinases: 952*JNK Mitogen-Activated Protein Kinases: 1056*Mitogen-Activated Protein Kinase 8: 68 ...
Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases. ... Dual specificity mitogen-activated protein kinase kinase 1, ERK activator kinase 1, MAP kinase kinase 1, MAPK/ERK kinase 1, ... ... Enhanced activation of mitogen-activated protein kinase and myosin light chain kinase by the Pro33 polymorphism of integrin ... Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector. Orth, K., Palmer, L.E., Bao, Z.Q ...
However, intramolecular interactions consistent with an inactive protein kinase fold were not formed. MD with p38α showed that ... The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ... The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ... Mitogen-activated protein kinase kinase kinases 1-4 (MEKK1-4), the dual leucine zipper kinase (DLK), the mixed lineage kinase ( ...
A family of serine/threonine protein kinases, known as the mitogen-activated protein (MAP) kinases, is involved in ... Di Pietro, A., F. I. Garcia-Maceira, E. Meglecz and M. I. G. Roncero, 2001 A mitogen-activated protein kinase of the vascular ... Pandey, A., M. G. Roca, N. D. Read and N. L. Glass, 2004 Role of a mitogen-activated protein kinases pathway during conidial ... Madhani, H. D., T. Galitski, E. S. Lander and G. R. Fink, 1999 Effectors of a developmental mitogen-activated protein kinase ...
We characterize the role of p38 mitogen-activated protein kinase/mitogen activated protein kinase kinase-3 and c-Jun-NH2- ... C57/BL6 wild-type mice and mice genetically deleted for mitogen-activated protein kinase kinase-3 (mkk-3−/−) or c-Jun-NH2- ... Mitogen-Activated Protein Kinases Regulate Susceptibility to Ventilator-Induced Lung Injury. Author: Dolinay, Tamás; Kaminski, ... Mitogen-Activated Protein Kinases Regulate Susceptibility to Ventilator-Induced Lung Injury. DSpace/Manakin Repository. * DASH ...
MAP kinase) is a 42 kd serine/threonine protein kinase whose enzymatic activity requires phosphorylation of both tyrosyl and ... and may be characteristic of a family of protein kinases regulating cell cycle transitions. ... Mitogen-activated protein kinase (MAP kinase) is a 42 kd serine/threonine protein kinase whose enzymatic activity requires ... Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase) EMBO J. 1991 Apr; ...
Three related kinases use distinct structural features to discriminate between linear docking motifs in potential binding ... Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove ... Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove ... Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove ...
MAP kinase) family of protein serine/threonine kinases. Ion-exchange chromatography yielded a peak of MAP kinase activity ... Multiple hemopoietic growth factors stimulate activation of mitogen-activated protein kinase family members.. M J Welham, V ... Multiple hemopoietic growth factors stimulate activation of mitogen-activated protein kinase family members. ... Multiple hemopoietic growth factors stimulate activation of mitogen-activated protein kinase family members. ...
... activated by an upstream activator, the mitogen-activated protein kinase kinase MAPKK (MEK), by Western blot analysis, sequence ... 1992) Mitogen-activated protein (MAP) kinase transforms tau protein into an Alzheimer-like state. EMBO J 11:2131-2138. ... Mitogen-Activated Protein Kinases (Erk1,2) Phosphorylate Lys-Ser-Pro (KSP) Repeats in Neurofilament Proteins NF-H and NF-M. ... 1995) PD 98059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J ...
1994 Receptor protein-tyrosine kinases and their signal transduction pathways. Annu. Rev. Cell Biol. 10: 251-337. ... 1994 MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. Curr. Opin. Genet. Dev. 4: 82-89. ... A Genetic Screen for Novel Components of the Ras/Mitogen-Activated Protein Kinase Signaling Pathway That Interact With the yan ... A Genetic Screen for Novel Components of the Ras/Mitogen-Activated Protein Kinase Signaling Pathway That Interact With the yan ...
p38 Mitogen-Activated Protein Kinases Medicine & Life Sciences 79% * Carbon Monoxide Medicine & Life Sciences 78% ... CO inhibited smooth muscle cell proliferation by activating p38 mitogen-activated protein kinase (MAPK) and p21Waf1/ciP1. ... CO inhibited smooth muscle cell proliferation by activating p38 mitogen-activated protein kinase (MAPK) and p21Waf1/ciP1. ... CO inhibited smooth muscle cell proliferation by activating p38 mitogen-activated protein kinase (MAPK) and p21Waf1/ciP1. ...
JNK Mitogen-Activated Protein Kinases * Mitogen-Activated Protein Kinase 1 * Mitogen-Activated Protein Kinases ... the p42 mitogen-activated protein kinase and c-Jun amino-terminal kinase pathways in Xenopus oocytes, have been shown to ... JNK Mitogen-Activated Protein Kinases * Mating Factor * Mitogen-Activated Protein Kinase 1 / metabolism* ...
The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions ... Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs ... For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in ... Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. ...
Phospholipase C-β 2 interacts with mitogen-activated protein kinase kinase 3. Barr, A.J., Marjoram, R.J., Xu, J. and Snyderman ... CD148 enhances platelet responsiveness to collagen by maintaining a pool of active Src family kinases. Journal of Thrombosis ... Phospholipase C-β 2 interacts with mitogen-activated protein kinase kinase 3. Biochemical and Biophysical Research ... Protein-Protein Interactions. Barr, A.J. and Overduin, M. 2019. JoVE Methods Collection Highlights: Protein-Protein ...
It shows genes and PPIs with information about pathways, protein-protein interactions (PPIs), Gene Ontology (GO) annotations ... a web resource for human protein-protein interactions. ... mitogen-activated protein kinase 3. Image. Gene Ontology ... TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation ... Protein-Protein Interactions. 3 interactors: COMMD8 MAPK3 PTPN3 161 interactors: ADRBK1 AKR1C1 AMOT ARRB1 ATP1A1 BAZ1B BCL2 ...
p38 Mitogen-Activated Protein Kinases 40% * Nitric Oxide 31% * Ro 31-8220 30% ... Protein Kinase Inhibitors 20% * Protein-Tyrosine Kinases 17% * Protein C Inhibitor 11% ...
MAP Kinase Signaling System Medicine & Life Sciences 79% * mitogen-activated protein kinase Agriculture & Biology 78% ... consistent with the roles of these kinases in promoting osteoclast survival. Adenoviral delivery of TIEG1 (AdTIEG1) to TIEG1-/- ... consistent with the roles of these kinases in promoting osteoclast survival. Adenoviral delivery of TIEG1 (AdTIEG1) to TIEG1 ... consistent with the roles of these kinases in promoting osteoclast survival. Adenoviral delivery of TIEG1 (AdTIEG1) to TIEG1 ...
This is regulated by the stress activated mitogen-activated protein kinases SAPK/JNK and p38. ... The Atf1 transcription factor is a target for the Sty1 stress-activated MAP kinase pathway in fission yeast. ... The Atf1 transcription factor is a target for the Sty1 stress-activated MAP kinase pathway in fission yeast. ...
Activation of mitogen-activated protein kinase pathways by cyclic GMP and cyclic GMP-dependent protein kinase in contractile ... Connections to Cyclic GMP-Dependent Protein Kinases are shown below. Double-click or tap a node for more information. ... Adenosine receptor, protein kinase G, and p38 mitogen-activated protein kinase-dependent up-regulation of serotonin ... Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein kinase. ...
Further, it has been demonstrated that various other receptor kinases such as PI3K and mitogen-activated protein kinases also ... Role of a mitogen-activated protein kinase pathway in the induction of phase II detoxifying enzymes by chemicals. J Biol Chem ... 4-Hydroxynonenal induces rat gamma-glutamyl transpeptidase through mitogen-activated protein kinase-mediated electrophile ... Protein kinases are the most attractive group of drug targets after G-protein-coupled receptors and can be found downstream or ...
... , Qiong Mu, Likun Wang, ... Thrombin induces NO release from cultured rat microglia via protein kinase C, mitogen-activated protein kinase, and NF-kappa B ... Ohnishi M, Katsuki H, Izumi Y, et al. Mitogen-activated protein kinases support survival of activated microglia that mediate ... Ma XL, Kumar S, Gao F, et al.Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves ...
Here we describe results that show that although MAP kinase can hyperphosphorylate tau in vitro, activation of MAP kinase in ... The findings imply that GSK-3 beta may be a stronger candidate than MAP kinase for inducing tau hyperphosphorylation in vivo. ... A proportion of the microtubule-associated protein, tau, is in an elevated state of phosphorylation in foetal and adult brain ... transformed fibroblasts does not result in hyperphosphorylation of transfected tau, whereas glycogen synthase kinase-3 beta ( ...
Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor. ... primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase ... P12931: Proto-oncogene tyrosine-protein kinase Src. Protein function Non-receptor protein tyrosine kinase which is activated ... receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling ...
Stress-activated map kinase-interacting protein 1; SIN1; SAPK-interacting protein 1; mSIN1; Mitogen-activated protein kinase 2- ... Kinases. [+] 2 Kinases. +. Interacting Target Name. Ribosomal protein S6 kinase beta-1 (S6K1). Clinical trial Target. ... Serine/threonine-protein kinase mTOR (mTOR). Synonyms. Target of rapamycin; TOR kinase; Rapamycin target protein 1; Rapamycin ... STK14A; Serine/threonine-protein kinase 14A; S6K-beta-1; S6K; Ribosomal protein S6 kinase I; P70S6K1; p70-S6K 1; P70-S6K; p70 ...
eFFECTORs STRI product candidates target the eIF4F complex and its activating kinase, mitogen-activated protein kinase 1/2 ( ... including receptor tyrosine kinases (RTKs), KRAS, Cyclin D, CDK4/6 and MYC. In vivo studies have shown potent tumor regression ... Furthermore, by targeting a human protein required for viral replication, known as a host protein, zotatifin is expected to be ... converge to activate the translation of select mRNA into proteins that are frequent culprits in key disease-driving processes. ...
... and Mitogen-Activated Protein Kinase/Extracellular Signal Regulated Kinase signaling). Data from Genotype-Tissue Expression ... Extracellular Signal-Regulated MAP Kinases Medicine & Life Sciences 64% * Glycated Hemoglobin A Medicine & Life Sciences 62% ... and Mitogen-Activated Protein Kinase/Extracellular Signal Regulated Kinase signaling). Data from Genotype-Tissue Expression ... and Mitogen-Activated Protein Kinase/Extracellular Signal Regulated Kinase signaling). Data from Genotype-Tissue Expression ...
... mitogen-activated protein kinases (MAPKs), and glycogen synthase kinase 3 beta (GSK-3). Furthermore, the pathways are mediated ...
... cell is chosen from a cluster of similar myoblasts that are specified by activation of the Ras/mitogen-activated protein kinase ... Checkpoint Control Kinases *Chloride Cotransporter *Corticotropin-Releasing Factor Receptors *Corticotropin-Releasing Factor, ... B) pupa harvested for 50 h at 18 C accompanied by 4 h at 29 C. At 18 C, the GAL80 proteins is normally useful and represses ... To check on if the GAL80ts proteins was useful in the pupal mesoderm specifically, pupae had been grown up for 50 h at 18 C ...
... of cytoplasmic or of cell STMN1 membrane-bound regulatory protein such as for example mitogen-activated proteins kinases, ... phosphatidylinositol 3-OH kinase (PI3K), ion stations, and G-protein-coupled receptors. Genomic ramifications of oestrogen are ... and activate at adverse potentials. Currents via Kv4.3 stations impact the resting membrane potentials and excitability of ... and up-regulation of huge conductance Ca2+-activated K+ stations (Jamali 2003), ATP-sensitive K+ stations (Ranki 2002), small ...
In part 1, N-Alb-P excretion , 4.3 mg was associated with increase of blood pressure, excretion of total protein, hypoxanthine ... especially non-albumin protein (NAlb-P), is due to the presence of stones or reflects alteration of oxidative metabolism. To ... In IRCU it is uncertain whether variation of urinary protein, ... p38 and C-Jun N-terminal kinase, and mitogen-activated protein ... oxygen species-mediated pancreatic beta-cell death is regulated by interactions between stress-activated protein kinases, ...
... p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kappa B (NF-B) in DLD-1, HT-29, LoVo and Colo-205 cells. As a ... Open up in another window Open up in another window Shape 1 Aftereffect of mitogen triggered proteins kinase kinase (MEK) ... C) Quantification of phosphorylated protein expression, normalized corresponding protein, respectively. The results showed the ... and Bcl-2-like protein 1 (Bcl-xL) and enhanced expression of the pro-apoptotic factors Bcl-2 associated X protein (Bax) and Bcl ...
... patients with myasthenia gravis and modulates inflammatory Cytokines production by targeting mitogen-activated protein kinase 1 ... We found that several miRNAs in MTB 1 are able to target the activities of the MAPK family of serine-threonine protein kinases ... miR-93 also directly modulates the activity of the protein serine-threonine kinase, LATS2 to control tumor angiogenesis and ... Wu N, Sulpice E, Obeid P, Benzina S, Kermarrec F, Combe S, Gidrol X: The miR-17 family links p63 protein to MAPK signaling to ...
Sentence from paper : In addition, growing evidence has shown that MITF is activated by the mitogen-activated protein kinase ( ... MAPK) signaling pathways, including extracellular signal-regulated kinases (ERK), c-jun N-terminal kinases (JNK) and p38 MAPK ... Activating: Stimulation of Pathway A up-regulates a gene or activates a protein that is representative of Pathway B. ... The name of database that the value in "Molecule A Identifier" comes from, e.g., "UniProt" if the molecule is a protein. ...
... in part by the recent discovery that Raf kinases the Ras effectors that transmission down the mitogen-activated protein kinase ... concept that Ras protein may work as oligomers was initially described. Posted on April 8, 2017. by Michele Pena ... concept that Ras protein may work as oligomers was initially described almost three decades ago when Santos et al. More ... The effect is an appealing one provided the latest knowledge of the need for dimerization in the legislation of Raf kinases. ...
Aberrant activation of the mitogen-activated protein kinase pathway frequently drives tumor growth, and the ERK1/2 kinases are ... drive tumor growth through aberrant activation of the mitogen activated protein kinase (MAPK) signaling pathway. Acute myeloid ... ASTX029 Extracellular Signal-Related Protein Kinases (ERK 1/2) Inhibitor (Solid Tumors) ... 2021 AACR: Immune modulation by the dual-mechanism ERK inhibitor, ASTX029, in MAPK-activated tumor models. 15 April 2021. /in ...
... phosphatidylinositol 3-kinase, Akt and mitogen-activated protein kinase. J Neurochem 2003; 87: 182-194. ... involvement of mitogen-activated protein kinases. Biochim Biophys Acta. 2002; 1589: 15-30. ... phosphatidylinositol 3-kinase, Akt and mitogen-activated protein kinaseJ Neurochem, 2003, vol. 87, 182-194 [0072] ... 0017] The glycogen synthase kinase-3β (GSK-3β) is a serine-threonine protein kinase. GSK-3β itself is regulated and inhibited ...
... phosphatidylinositol-3 kinase and the mitogen-activated protein kinases, leading to the transcription of several genes. Cell ... phosphatidylinositol-3 kinase and the mitogen-activated protein kinases, leading to the transcription of several genes. Cell ... phosphatidylinositol-3 kinase and the mitogen-activated protein kinases, leading to the transcription of several genes. Cell ... phosphatidylinositol-3 kinase and the mitogen-activated protein kinases, leading to the transcription of several genes. Cell ...
... role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by ... role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by ... Calmodulin-Dependent Protein Kinase II Signaling Circulation (2015) doi: 10.1161/circulationaha.114.010686 ... P Raynal Signal strength dictates phosphoinositide 3-kinase contribution to Ras/extracellular signal-regulated kinase 1 and 2 ...
... role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by ... role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by ... Calmodulin-Dependent Protein Kinase II Signaling Circulation (2015) doi: 10.1161/circulationaha.114.010686 ... P Raynal Signal strength dictates phosphoinositide 3-kinase contribution to Ras/extracellular signal-regulated kinase 1 and 2 ...
... phosphoinositide 3 kinase Akt and also the Ras mitogen activated pro tein kinase pathways, is often activated by the kinase ... Contrary to other receptor tyrosine kinases, most functions of your insulin receptor call for accessory molecules known as ... Ligand binding to your a subunits activates the intrinsic kinase. Posted on April 25, 2014. by topo5813 ... Ligand binding to your a subunits activates the intrinsic kinase activity located while in the b subunits and subsequently ...
  • 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)
  • MAPKs belong to the CMGC (CDK/MAPK/GSK3/CLK) kinase group. (wikipedia.org)
  • The closest relatives of MAPKs are the cyclin-dependent kinases (CDKs). (wikipedia.org)
  • These pathways can effectively convey stimuli from the cell membrane (where many MAP3Ks are activated) to the nucleus (where only MAPKs may enter) or to many other subcellular targets. (wikipedia.org)
  • [4] In contrast to the classical MAP kinases, these atypical MAPKs require only a single residue in their activation loops to be phosphorylated. (wikipedia.org)
  • Treatment of cells with a variety of growth factors triggers a phosphorylation cascade that leads to activation of mitogen-activated protein kinases (MAPKs, also called extracellular signal-regulated kinases, or ERKs). (pnas.org)
  • MAPKs belong to an evolutionarily conserved and ubiquitous signal transduction superfamily of Ser/Thr protein kinases that regulate multiple cellular processes including apoptosis, growth, differentiation and responses to environmental stimuli. (plos.org)
  • The MAPK superfamily includes three primary signaling cascades: the extracellular signal regulated kinases (ERK1/2), the c-Jun NH 2 -terminal kinases (JNK) and the p38 MAPKs. (plos.org)
  • Evidence from exercise studies in nondiabetics suggests that the extracellular-signal-regulated kinases (Erk1/2), p38, and c-JUN NH2-terminal kinase (Jnk) mitogen-activated protein kinases (MAPKs) are important regulators of muscle adaptation. (hindawi.com)
  • Differences between alveolar macrophages and cell lines in activation of mitogen-activated protein kinases (MAPKs) stimulated by lipo-polyscccharide (LPS). (cdc.gov)
  • Stimulation of primary macrophages and cell lines by LPS has been shown to activate MAPKs. (cdc.gov)
  • To determine if differences in MAPK activation may explain the difference in response to lung surfactant between primary macrophages and the cell lines, we compared the activation of MAPKs, p38, extracelluar-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK/SAPK), in rat alveolar macrophages and three macrophage cell lines, RAW 264.7, J-774, and NR8383. (cdc.gov)
  • p38gamma (MAPK12), also known as Stress-activated protein kinase 3 (SAPK3) belongs to the p38 subfamily of MAPKs. (atlasgeneticsoncology.org)
  • 2008). All p38 MAPKs are strongly activated in vivo by environmental stresses and inflammatory cytokines, and less by serum and growth factors. (atlasgeneticsoncology.org)
  • A feature that makes p38gamma unique among the p38 MAPKs is its short C-terminal sequence -KETXL, an amino acid sequence ideal for binding PDZ domains in proteins. (atlasgeneticsoncology.org)
  • Mitogen-activated protein kinases (MAPKs) are expressed in neurons and are activated after injury, for example, after sciatic nerve transection and hypoxia. (jneurosci.org)
  • However, despite the coexpression of mitogen-activated protein kinases (MAPKs) and voltage-gated sodium channels in neurons, phosphorylation and modulation of these channels by MAP kinases have not been investigated. (jneurosci.org)
  • Mammalian mitogen-activated protein kinases (MAPKs) are cytoplasmic protein-Ser/Thr kinases that participate in signal transduction by catalysing the transfer of the γ-phosphoryl group from ATP to a hydroxyl group of the protein substrate. (mdpi.com)
  • The conventional MAPKs constitute three consecutive phosphorylation events mediated by three Ser/Thr protein kinases. (mdpi.com)
  • Conventional MAPKs include the extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 MAPKs (p38 α, β, γ, and δ), c-Jun terminal kinases 1-3 (JNK1-3) and the ERK5 [ 1 ]. (mdpi.com)
  • Mitogen-activated protein kinases (MAPKs) play a pivotal role in the mitogenic signal transduction pathway and are essential components of the MAPK cascade, which includes MEK (also known as MAP kinase kinase), Raf-1, and Ras. (aacrjournals.org)
  • Constitutive activation of MAPKs in tumor tissue, as determined by the appearance of phosphorylated forms, was found in 12 cases (48%), and this activation was confirmed by a direct in vitro kinase assay of immunoprecipitate using myelin basic protein as the substrate. (aacrjournals.org)
  • Cargnello M, Roux P (2011) Activation and function of the MAPKs and their substrates, the MAPK activated protein kinases. (springer.com)
  • In this context, the p38 mitogen-activated protein kinases (MAPKs), a family of stress-activated MAPKs, 2 3 have been examined as the candidate kinases during preconditioning. (ahajournals.org)
  • The data are compatible with the hypothesis that p38 MAPKs may mediate the protective signaling pathways or function as protective kinases during the late phase of pharmacological preconditioning. (ahajournals.org)
  • If activation of p38 MAPKs is a necessary signaling event for the protection to manifest on day 2, then inhibition of this kinase will lead to the abrogation of late preconditioning. (ahajournals.org)
  • It is well known from mammalian cells that anoxia has a major impact on the mitogen-activated protein kinases, MAPKs. (biologists.org)
  • Upstream of the mammalian MAPKs, ERK1 and ERK2, is Raf (MAP3K) and MAPK/ERK kinase (MEK)1/2 (MAP2K). (biologists.org)
  • MAPKs are serine -threonine protein kinases that are activated by diverse stimuli (e.g., growth factors , stress stimuli, cytokines , ultraviolet irradiation , heat shock, and osmotic shock) via protein kinase cascades . (emf-portal.org)
  • MAPKs are subdivided in extracellular signal-regulated kinases ( ERKs ), c-Jun N-terminal kinases ( JNKs ), and p38 mitogen activated protein kinases . (emf-portal.org)
  • Mitogen-activated protein kinases (MAPKs) are evolutionary conserved enzymes which play a key role in signal transduction mediated by cytokines, growth factors, neurotransmitters and various types of environmental stresses. (semanticscholar.org)
  • These MAPKs are activated by dual phosphorylation on tyrosine and threonine residues through a conserved cascade of upstream kinases, termed MAPK kinases (MKK) and MAPK kinase kinases (MKKK). (asm.org)
  • Because FGF signaling is mediated largely by the mitogen-activated protein kinase (MAPK) pathway ( 26 , 27 ), these studies suggest that MAPK may play a critical role in the specification of neural fate and anteroposterior pattern. (pnas.org)
  • The mitogen-activated protein kinase (MAPK) pathway is the canonical signaling pathway for many receptor tyrosine kinases, such as the Epidermal Growth Factor Receptor. (mdpi.com)
  • Downstream of the receptors, this pathway involves the activation of a kinase cascade that culminates in a transcriptional response and affects processes, such as cell migration and adhesion. (mdpi.com)
  • In this review, we summarize the recent advances in the research on MAPK/extracellular signal-regulated kinase (ERK) pathway scaffolders. (mdpi.com)
  • These data suggest the induction of MKP-1, not only after stimulation of the cell growth-promoting ERK pathway but also in response to activation of stress-responsive MAP kinase signaling cascades. (ahajournals.org)
  • However, inhibition of the p38 pathway prevented the insulin-stimulated decrease in GLUT4 protein levels. (diabetesjournals.org)
  • We investigated the MAPk kinase (MKK) that activates p38 MAPk in response to LPS, the p38 MAPk isoforms that are activated as part of this pathway, and the functional responses affected by p38 MAPk activation. (jci.org)
  • These findings support a pathway by which LPS stimulation of neutrophils results in activation of MKK3, which in turn activates p38α MAPk, ultimately regulating adhesion, NF-κB activation, enhanced gene expression of TNF-α, and regulation of TNF-α synthesis. (jci.org)
  • Thus, we define a signaling pathway directly downstream of MAP kinase, influencing cell migration on the extracellular matrix. (rupress.org)
  • To better understand the role of MAP kinase signaling in Neurospora crassa , and to identify downstream target genes of the pathway, we isolated, cloned, and disrupted the FUS3 homolog mak-2 . (genetics.org)
  • Ste12p is a transcription factor target of Fus3p that activates genes of the mating pathway in yeast, and we also characterized the N. crassa STE12 homolog pp-1 . (genetics.org)
  • The role of the MAP kinase pathway in both sexual and asexual development as well as secondary metabolism is consistent with the dual regulation of the mating process and pathogencity observed in fungal pathogens. (genetics.org)
  • MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. (reportbuyer.com)
  • Both MEK and ERK are critical components of the RAS-regulated RAF-MEK-ERK pathway, which is often activated in different types of cancers. (reportbuyer.com)
  • The receptor tyrosine kinase (RTK) signaling pathway is used reiteratively during the development of all multicellular organisms. (genetics.org)
  • AZD6244 ( ARRY-142886 ) is an investigational anticancer drug that is designed to block a critical component (MEK (methyl ethyl ketone)) of a pathway (MAP (mitogen-activated protein) kinase pathway) that causes some lung cancer cells to grow. (clinicaltrials.gov)
  • The MAP kinase pathway could be overactive in a proportion of lung cancers, including some which also have another mutation in a protein known as KRAS (Kirsten rat sarcoma viral oncogene homolog). (clinicaltrials.gov)
  • Integrins and growth factors are capable of activating the ras/MAP kinase pathway in vitro, yet how these signals influence endothelial cells during angiogenesis is unknown. (rupress.org)
  • One of the best studied signalling routes is the mitogen activated protein (MAP) kinase signal transduction pathway which plays a crucial role in many aspects of immune mediated inflammatory responses. (ebscohost.com)
  • Here, our current understanding of the MAP kinase pathway is reviewed, as well as recent advances in the design of novel agents that are able to modulate the activity of these signalling cascades. (ebscohost.com)
  • Cites a study published in the October 2001 issue of the journal 'Nature Neuroscience,' on how neurotrophins use the extracellular signal-related protein kinase 5 pathway to mediate a retrograde survival response. (ebscohost.com)
  • Cell signal transduction through the mitogen-activated protein kinase pathway. (ebscohost.com)
  • Presents a series of articles about cell signal transduction through mitogen-activated protein (MAP) kinase pathway. (ebscohost.com)
  • Presents a conserved tyrosine kinase-activated signal transduction pathway that comprises the plasma membrane-bound protein Ras and the protein kinases Raf, MAP-kinase and MAP kinase. (ebscohost.com)
  • Most interestingly, deletion of HOG1 resulted in a drastic increase in the mean survival time of systemically infected mice, supporting a role for this MAP kinase pathway in virulence of pathogenic fungi. (asm.org)
  • Our results suggest that MAP kinase activation is, at least in part, an important component for mitotic signal from the EPOR, and CTLL-2 cells probably lack signaling molecule(s) in JAK2 and the Ras-MAP kinase pathway. (biomedsearch.com)
  • The Ras/mitogen-activated protein kinase (MAPK) signaling pathway has long been identified as a convergence point for numerous (normal and pathologic) signaling inputs, rendering it an appealing target for therapeutic intervention ( 4 ). (aacrjournals.org)
  • Recent highlights of Chinese herbs in treatment of allergic disease: Acting via mitogen-activated protein kinase signal pathway. (semanticscholar.org)
  • Furthermore, macrophages isolated from MKP-1-null mice showed dramatic defects in their spreading/migration and impairment in extracellular signal-regulated kinase, but not c-Jun N-terminal kinase and p38, pathway activation. (scialert.net)
  • ATP has been shown to activate the phospholipase C/diacylglycerol/protein kinase C (PKC) pathway. (eurekamag.com)
  • The present study was designed to examine the effect of ATP on activation of the mitogen-activated protein kinase (MAPK) signaling pathway and its physiological role in human granulosa-luteal cells. (eurekamag.com)
  • Control of thrombopoietin-induced megakaryocytic differentiation by the mitogen-activated protein kinase pathway. (asm.org)
  • We show here that TPO-induced differentiation in UT7 cells is tightly dependent on a strong, long-lasting activation of the mitogen-activated protein kinase (MAPK) pathway. (asm.org)
  • In breast cancer, the MKK3/6 pathway, activated through H-Ras, induces the invasive phenotype. (aacrjournals.org)
  • Another approach to therapeutically target an overactive Ras pathway is to block critical signal transduction cascades that are initiated by activated Ras. (aspetjournals.org)
  • Three major families of the MAPK pathway exist in mammalian species: c-Jun NH 2 -terminal kinases (JNK), the extracellular signal-regulated protein kinase (ERK), and the p38 mitogen-activated protein kinase (p38). (asm.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)
  • Mitogen-activated protein kinase pathways. (nih.gov)
  • however, the endogenous signals activating these pathways are unknown ( 25 ). (pnas.org)
  • The activators of p38 (MKK3 and MKK6), JNK (MKK4 and MKK7), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways. (wikipedia.org)
  • Moreover, it was recently revealed that the p38alpha is also activated via alternative pathways, which are MKK independent. (rcsb.org)
  • We demonstrate that mitogen-activated protein kinase pathways mediate inflammatory lung injury during ventilator-induced lung injury. (plos.org)
  • Recent research has focused on intracellular signaling pathways involved in the development of VILI, among which include the mitogen-activated protein kinase (MAPK) pathways, key regulators of inflammation [7] - [9] . (plos.org)
  • Therefore, recently cloned dual-specificity protein tyrosine phosphatases (PTPases), which exhibit dual-catalytic activity toward phosphotyrosine and phosphothreonine in substrate proteins, may play a pivotal role in the regulation of MAP kinase-signaling pathways. (ahajournals.org)
  • 15 16 Furthermore, the kinetics of gene expression and the cellular localization are consistent with a role for MKP-1 in the compensatory inactivation of stimulated MAP kinase-signaling pathways. (ahajournals.org)
  • The mitogen-activated protein kinase (MAPK) cascade plays a pivotal role in diverse signaling pathways related to plant development and stress responses. (springer.com)
  • Protein kinase C (PKC) isoforms are serine/threonine kinases involved in signal transduction pathways that govern a wide range of physiological processes including differentiation, proliferation, gene expression, brain function, membrane transport and the organization of cytoskeletal and. (ebscohost.com)
  • Histidine protein kinases and response regulators form the basis of phosphotransfer signal transduction pathways. (ebscohost.com)
  • In Saccharomyces cerevisiae , a model eukaryotic cell system, some of these pathways involve members of the MAP kinase family (from mitogen-activated protein kinase), a set of enzymes performing essential functions in cell physiology first discovered in mammalian cells but later shown to be also present in lower eukaryotes ( 3 , 12 ). (asm.org)
  • 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)
  • Additionally, proinflammatory cytokines can activate several inflammatory transduction pathways, including mitogen activated protein kinase (MAPK). (karger.com)
  • MAPK pathways are generally thought of as three-kinase modules, consisting of a MAP kinase kinase kinase (MAP3K) upstream of a MAPK kinase kinase (MAP2K), which in turn activates the MAP kinase ( Kyriakis and Avruch, 2001 ). (biologists.org)
  • Because it is anticipated that several small MAP kinase inhibiting molecules will be evaluated for efficacy in inflammatory diseases, here we review current knowledge of the MAP kinase signalling pathways as well as potential inhibitory drugs. (bmj.com)
  • The mitogen-activated protein (MAP) kinase cascades are key signal transduction pathways involved in the cellular production of cytokines. (asm.org)
  • The dual-specific phosphatase 1 (DUSP 1), mitogen-activated protein kinase phosphatase-1 (MKP-1), has been shown to be an important negative regulator of the inflammatory response by regulating the p38 and Jun N-terminal protein kinase (JNK) MAP kinase pathways to influence pro- and anti-inflammatory cytokine production. (asm.org)
  • Among the most active signal transduction pathways involved in the immune response are the mitogen-activated protein kinase (MAPK) pathways. (asm.org)
  • The kinase-mediated phosphorylation involved in the MAPK pathways is balanced by the presence of a dephosphorylating system comprised of phosphatases to create a dichotomous regulatory process ( 17 ). (asm.org)
  • The i.t injection of extracellular signal-regulated kinase (ERK) inhibitor blocked morphine-induced analgesia, without interfering with the morphine-induced hyperalgesia. (frontiersin.org)
  • Koselugo (selumetinib) is inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2). (reportbuyer.com)
  • Randomized Phase II Study of AZD6244 (Mitogen-activated Protein Kinase Inhibitor) MEK-Inhibitor With Erlotinib in KRAS Wild Type Advanced Non-Small Cell Lung Cancer (NSCLC) and a Randomized Phase II Study of AZD6244 With Erlotinib in Mutant KRAS Adva. (clinicaltrials.gov)
  • The increased p38 MAPK activity was completely abolished when the infarct-sparing effect of CCPA was abrogated by either the protein kinase C (PKC) inhibitor chelerythrine or the tyrosine kinase inhibitor lavendustin A. This is a very provocative study, and it is also the first to demonstrate activation of the p38 MAPK 24 hours after preconditioning. (ahajournals.org)
  • To analyze the ERK3A-Myc and ERK3B-Myc proteins, which were unstable due to proteasome- dependent degradation, animal caps (N=25, each sample) were dissected at stage 9, cultured with 10 μM MG132 (a proteasome inhibitor) until stage 12, and then lysed with 50 μl of lysis buffer. (xenbase.org)
  • Treatment of the cells with suramin (a P2 purinoceptor antagonist), neomycin (a phospholipase C inhibitor), staurosporin (a PKC inhibitor), or PD98059 (an MAPK/ERK kinase inhibitor) significantly attenuated the ATP-induced activation of MAPK. (eurekamag.com)
  • Using the specific MAP kinase kinase inhibitor-PD 098059, we show that activation of MAPK is necessary for the Fc gamma R-dependent induction of c-fos and tumor necrosis factor alpha mRNA expression in monocytes and NK cells. (rupress.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)
  • In general, MAP kinases are activated by phosphorylation on tyrosine and threonine residues and inactivated by dephosphorylation. (ahajournals.org)
  • Therefore, MAP kinase phosphatase-1 (MKP-1), a dual-specificity protein tyrosine phosphatase that exhibits catalytic activity toward both regulatory sites on MAP kinases, is suggested to be responsible for the downregulation of extracellular signal-regulated kinase (ERK), stress-activated protein kinase (SAPK), and p38 MAP kinase. (ahajournals.org)
  • A common feature for activation of all MAP kinase isoforms is the requirement for phosphorylation of both a threonine and a neighboring tyrosine regulatory site by a specific upstream protein kinase for activation. (ahajournals.org)
  • 3 MEK, the specific activator of ERK, is a dual-specificity protein kinase that phosphorylates both threonine and tyrosine regulatory sites in ERK. (ahajournals.org)
  • Thus, highly specific protein kinase cascades lead to dual phosphorylation of tyrosine and threonine residues on these MAP kinases, inducing their full activation. (ahajournals.org)
  • Stimulation of hemopoietic cells with IL-3, IL-4, IL-5, granulocyte-macrophage-CSF and Steel factor-(SLF) induced tyrosine phosphorylation of a number of protein substrates. (jimmunol.org)
  • Two of these proteins, designated p42 and p44, were tyrosine phosphorylated rapidly in response to treatment with IL-3, IL-5, granulocyte-macrophage-CSF and SLF, but not IL-4. (jimmunol.org)
  • Immunoblotting of column fractions with antiphosphotyrosine antibodies showed coelution of the peak of MAP kinase enzyme activity with the p42 and p44 tyrosine phosphorylated species, and with two proteins of 42 and 44 kDa which were immunoreactive with anti-MAP kinase antibodies. (jimmunol.org)
  • Extracellular Signal-Regulated Kinases (ERK) also known as the Mitogen-activated Protein Kinase (MAPK), MAPK/ERK proteins are a family of protein-serine/threonine kinases that are activated via the phosphorylation of tyrosine . (novusbio.com)
  • Cross-linking the receptors for the Fc domain of IgG (Fc gamma R) on leukocytes induces activation of protein tyrosine kinases. (rupress.org)
  • Nearly all cell surface receptors utilize one or more of the mitogen-activated protein kinase cascades in their repertoire of signal transduction mechanisms. (nih.gov)
  • Abstract -Mitogen-activated protein (MAP) kinase cascades are major signaling systems by which cells transduce extracellular cues into intracellular responses. (ahajournals.org)
  • Furthermore, serine/threonine kinases are often involved with the regulation of gene expression by serving as intermediates in signal transduction cascades that link extracellular and intracellular stimuli to the nucleus ( 13 ). (diabetesjournals.org)
  • MAPK forms the backbone of four primary signal transduction cascades leading to the phosphorylation and activation of extracellular signal-regulated kinases 1 and 2 (ERK1--2), JNK, p38 and ERK5. (reportbuyer.com)
  • Accordingly, we next examined downstream IL-6 signaling via the STAT3, STAT1, and Ras-dependent mitogen-activated protein kinase (MAPK) cascades. (jimmunol.org)
  • They are the final components of the cascades , activated by phosphorylation by mitogen-activated protein kinase kinases (MAPKKs) which in turn are activated by mitogen-activated protein kinase kinase kinases (MAPKKKs). (emf-portal.org)
  • A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. (umassmed.edu)
  • These results demonstrate that members of the MAP kinase family are involved in common signal transduction events elicited by IL-3, IL-5, granulocyte-macrophage-CSF and Steel factor, but not those involving IL-4. (jimmunol.org)
  • Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING. (curehunter.com)
  • The use of synthetic peptide substrates confirmed SLF and IL-5 activate isoforms of MAP kinases. (jimmunol.org)
  • We will not only review the well-known members of the family, such as kinase suppressor of Ras (KSR), but also put a special focus on the function of the recently identified or less studied scaffolders, such as fibroblast growth factor receptor substrate 2, flotillin-1 and mitogen-activated protein kinase organizer 1. (mdpi.com)
  • The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ERK3 and ERK4. (mdpi.com)
  • We show here that MAP kinase activation is required for haptotaxis cell migration on a collagen substrate based on its ability to directly phosphorylate MLCK leading to the phosphorylation of MLC. (rupress.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)
  • ERK controls cellular phenotypes by phosphorylating over two hundred known substrate proteins, however new ERK targets are reported frequently. (mit.edu)
  • 5 6 Furthermore, ischemic preconditioning activates MAPKAPK2, the downstream signaling substrate of p38 MAPK, 5 6 demonstrating that activation of the p38 MAPK signaling cascade, not just one element of the MAPK module, is part of the signaling events involved in preconditioning. (ahajournals.org)
  • 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. (wikidoc.org)
  • Although the role of MAPK in signal transduction and in injury-induced regulation of gene expression is well established, the ability of these kinases to phosphorylate and modulate voltage-gated sodium channels has not been reported. (jneurosci.org)
  • In this study, we investigated the association of MAP kinase p38 with Na v 1.6 in brain tissue and examined the regulation by MAP kinase p38 of the Na v 1.6 sodium current. (jneurosci.org)
  • However, little is known about the kinetics and regulation of MAP kinase activity in vivo, where the more complex extracellular matrix environment in a tissue may influence both the level and duration of this activity. (rupress.org)
  • Demonstrates the effect of either the down-regulation of beta6 expression or loss of the binding site on beta6 for extracellular signal-related kinase 2 on matrix metalloproteinase-9 (MMP-9) secretion. (ebscohost.com)
  • Role of mitogen-activated protein kinase in the regulation of. (ebscohost.com)
  • 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)
  • Mitogen-activated protein kinases (MAPK) mediate cellular signal transduction during stress responses, as well as diverse growth and developmental processes in eukaryotes. (apsnet.org)
  • MAP2 kinases in turn, are also activated by phosphorylation, by a number of different upstream serine-threonine kinases ( MAP3 kinases ). (wikipedia.org)
  • In addition, PD 098059, an antagonist of MEK (MAP kinase/ERK kinase), the upstream kinase of ERK, significantly reduced the PDGF-induced activation of ERK and potently inhibited the expression of MKP-1 after stimulation with PDGF, thereby demonstrating the induction of MKP-1 in response to activation of the ERK signaling cascade. (ahajournals.org)
  • In the classical setting, MAPK/ERK is activated by many upstream growth factors/cytokine receptors in response to radiation, hypoxia, physical forces, TNF , RANKL , and toll-like receptors (1). (novusbio.com)
  • Evidence is provided that MAP kinase (ERK1 and ERK2) influences the cells' motility machinery by phosphorylating and, thereby, enhancing myosin light chain kinase (MLCK) activity leading to phosphorylation of myosin light chains (MLC). (rupress.org)
  • Integrin-mediated cellular adhesion to the extracellular matrix leads to intracellular signaling, including activation of focal adhesion kinase with subsequent activation of downstream effector molecules including mitogen-activated protein (MAP) 1 kinases ERK1 and ERK2 (Q. (rupress.org)
  • Rabbit polyclonal antibodies to MAP kinase (ERK1 and ERK2), MEK1, and RAF-1 were purchased from Santa Cruz Biotechnology (Santa Cruz, CA). Anti-myosin IIB antibodies were kindly provided by Dr. Robert Adelstein (Molecular Cardiology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD). Anti-MLCK antibodies have been previously described (de Lanerolle et al. (rupress.org)
  • Many major human oncogenes contribute to cancer in large part by activating the mitogenactivated protein kinases (MAPK) ERK1 and ERK2 (ERK). (mit.edu)
  • Mitogen-activated protein kinase kinase (also known as MAP2K , MEK , MAPKK ) is a kinase enzyme which phosphorylates mitogen-activated protein kinase (MAPK). (wikipedia.org)
  • To determine whether MAP kinases were involved in the downregulation of IRS-1 and GLUT4 protein levels, selective inhibitors were used to inhibit these MAP kinases in 3T3-L1 adipocytes treated chronically with insulin. (diabetesjournals.org)
  • Since the identification of the p38 mitogen-activated protein kinase (MAPK) as a key signal-transducing molecule in the expression of the proinflammatory cytokine tumor necrosis factor (TNF) more than 10 years ago, huge efforts have been made to develop inhibitors of p38 MAPK with the intent to modulate unwanted TNF activity in diseases such as autoimmune diseases or sepsis. (nih.gov)
  • Mitogen Activated Protein Kinase Kinase 2 inhibitors - Pipeline Insight, 2021," report provides comprehensive insights about 10+ companies and 10+ pipeline drugs in Mitogen Activated Protein Kinase Kinase 2 inhibitors pipeline landscape. (reportbuyer.com)
  • Several inhibitors of MEK1--2 (MAPK kinases 1 and 2) are nearing, or are currently in, clinical trials for oncology. (reportbuyer.com)
  • MEK inhibitors have shown objective responses when used as monotherapy, particularly in tumors with known BRAF-activating mutations. (reportbuyer.com)
  • The companies and academics are working to assess challenges and seek opportunities that could influence Mitogen Activated Protein Kinase Kinase 2 inhibitors R&D. The therapies under development are focused on novel approaches for Mitogen Activated Protein Kinase Kinase 2 inhibitors. (reportbuyer.com)
  • This segment of the Mitogen Activated Protein Kinase Kinase 2 inhibitors report encloses its detailed analysis of various drugs in different stages of clinical development, including phase III, II, I, preclinical and Discovery. (reportbuyer.com)
  • 10+ key companies which are developing the Mitogen Activated Protein Kinase Kinase 2 inhibitors. (reportbuyer.com)
  • The companies which have their Mitogen Activated Protein Kinase Kinase 2 inhibitors drug candidates in the most advanced stage, i.e. phase III include, Astrazeneca. (reportbuyer.com)
  • Mitogen Activated Protein Kinase Kinase 2 inhibitors pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. (reportbuyer.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)
  • An alternative would be to develop inhibitors that can target the accessory proteins that regulate MAP/ERK functions. (novusbio.com)
  • In the present in vivo study, we have investigated whether inhibitors of the Na + /Mg 2+ exchanger quinidine and imipramine influence the development of hypertension and whether this is associated with modulation of mitogen-activated protein (MAP) kinase activation in arteries and kidneys of hypertensive rats. (portlandpress.com)
  • This has led to current initiation of clinical trials in inflammatory disease states evaluating small molecule inhibitors of MAP kinase proteins and encouraging results have been obtained. (bmj.com)
  • Thus, MAP kinase kinase (MEK) inhibitors may be a rational approach to NF1 therapy. (aspetjournals.org)
  • The farnesyltransferase inhibitors were developed from biochemical experiments on H-Ras proteins, and it is likely that K-Ras (and perhaps also N-Ras) proteins can be alternatively modified by geranylgeranylation when farnesyltransferase activity is blocked ( Adjei, 2001 ). (aspetjournals.org)
  • Neurospora crassa is a well-characterized model organism ideally suited to examining the role of MAP kinase function in mating behavior and development. (genetics.org)
  • JNK ( Barr and Bogoyevitch, 2001 ) and p38 MAPK ( New and Han, 1998 ) are mainly activated by cellular stress. (biologists.org)
  • MEK is a member of the MAPK signaling cascade that is activated in melanoma. (wikipedia.org)
  • The general hypothesis is that the preconditioning stimulus will induce the activation of a cascade of stress-responsive kinases, which in turn transduce the stress signal into the generation of a protective protein or activation of a protective kinase. (ahajournals.org)
  • IL-6 triggers cell growth via the Ras-dependent mitogen-activated protein kinase cascade. (jimmunol.org)
  • Growing evidence suggests that the Ras/mitogen-activated protein kinase (MAPK) signaling cascade represents a pivotal molecular circuitry participating directly or indirectly in prostate cancer evolution. (aacrjournals.org)
  • We show in this study that sodium channels and p38 MAP kinase colocalize in rat brain tissue and that activated p38α phosphorylates L1 of Na v 1.6, specifically at serine 553 (S553), in vitro . (jneurosci.org)
  • 4 Phosphorylated and activated ERK migrates to the nucleus, where it phosphorylates several transcription factors. (ahajournals.org)
  • Both signals converge at the Pbs2p level, which in turn phosphorylates and activates Hog1p, which mediates the intracellular accumulation of osmolytes such as glycerol ( 4 ). (asm.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)
  • p38gamma (MAPK12) is a Serine/Threonine protein kinase of 367 amino acids with a predicted molecular mass of 42 kDa. (atlasgeneticsoncology.org)
  • Linear motifs (LMs) are simple protein-protein interaction tools which are generally less than 20 amino acids in length. (iucr.org)
  • Mitogen-activated protein kinases (MAPK) are a family of evolutionarily conserved molecules that transduce extracellular stimuli into intracellular responses, by changing transcription as well as inducing posttranslational modifications of target proteins. (frontiersin.org)
  • This kinase targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. (wikidoc.org)
  • Phosphorylation provides a fast posttranslational modification of proteins that has been shown to regulate the acute response of cells to a variety of stimuli. (jneurosci.org)
  • Extracellular stimuli such as platelet-derived growth factor (PDGF), 12-O-tetradecanoylphorbol 13-acetate (TPA), and angiotensin II, which activated ERK but not SAPK/p38 MAP kinase, induced a transient induction of MKP-1 mRNA and its intracellular protein. (ahajournals.org)
  • 1 2 Binding of extracellular stimuli to their cell membrane receptors induces a sequence of protein kinase reaction, leading to phosphorylation and activation of MEK (MAP kinase/ERK kinase). (ahajournals.org)
  • Activation of leukocytes by proinflammatory stimuli selectively initiates intracellular signal transduction via sequential phosphorylation of kinases. (jci.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)
  • 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)
  • This approach utilizes an ERK2 kinase with "gatekeeper" mutation that allows it to bind bulky ATP analogs (AS-ERK2). (mit.edu)
  • AS-ERK2 can be used to label its direct substrates with thiophosphate in an in vitro kinase reaction. (mit.edu)
  • In the whole rat heart, ERK2 is inactivated in response to ischemia, followed by translocation of the inactive kinase to the nuclear compartment ( Mizukami and Yoshida, 1997 ). (biologists.org)
  • Interestingly, ERK2 was activated in response to reperfusion, suggesting an interface capable of ERK activation in the nuclear membrane. (biologists.org)
  • In contrast to ERK, more recently described MAP kinases such as stress-activated protein kinase (SAPK), also referred to as c-Jun N-terminal kinase (JNK), and p38 MAP kinase are suggested to inhibit cellular proliferation and to induce apoptosis. (ahajournals.org)
  • Proteolytic activation of MST/Krs, STE20-related protein kinase, by caspase during apoptosis. (ebscohost.com)
  • PD 098059 [2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one] selectively inhibited the MAPK-activating enzyme, MAPK/ERK kinase (MEK), without significant inhibitory activity of MAPK itself. (pnas.org)
  • Mitogen-activated protein kinase 9 is an enzyme that in humans is encoded by the MAPK9 gene . (wikidoc.org)
  • Because MAPK has been shown to down-regulate Smad1, MAPK may disrupt bone morphogenetic protein 4 (BMP-4) signaling during neural specification. (pnas.org)
  • These states are regulated by the balance between the intrinsic GTPase activity of the proteins: their interactions with inhibitory proteins and with activating proteins that regulate the exchange of GDP for GTP. (aacrjournals.org)
  • We show that inhibition of MEK1/2 (a MAPK kinase) leads to increased metachromatic staining of MC granules, indicative of increased proteoglycan content. (frontiersin.org)
  • Indeed, MEK1/2 inhibition caused a profound increase in the expression of the gene coding for the serglycin core protein and of genes coding for various enzymes involved in the biosynthesis/sulfation of the GAGs attached to the serglycin core protein. (frontiersin.org)
  • MAPK kinases 1 and 2, commonly known at MEK1--2, are referred to as MEK. (reportbuyer.com)
  • EPO-dependent long term proliferation of T-JER cells was conferred by expression of the constitutively activated form of MEK1. (biomedsearch.com)
  • Not unexpectedly, insulin resistance in cells and animals is associated with increased serine kinase activity toward IRS-1 ( 12 ). (diabetesjournals.org)
  • The MAPK12 gene encodes a 367 amino-acid protein of about 42 kDa. (atlasgeneticsoncology.org)
  • The protein encoded by this gene is a member of the MAP kinase family. (wikidoc.org)
  • This gene and MAPK8 are also known as c-Jun N-terminal kinases. (wikidoc.org)
  • suggesting that MAP kinase can lead to direct activation of the intracellular motility machinery independent of de novo gene transcription. (rupress.org)
  • The relevance of the mitogen-activated protein (MAP) kinase Hog1p in Candida albicans was addressed through the characterization of C. albicans strains without a functional HOG1 gene. (asm.org)
  • Here, using gene knockout and knockdown techniques along with gene profiling, we show that extracellular signal-regulated kinase 3 (ERK3), a poorly characterized atypical mitogen-activated protein kinase (MAPK), regulates the epithelial architecture in vertebrates. (xenbase.org)
  • The NF1 tumor-suppressor gene encodes neurofibromin, which includes a GTPase-activating domain for Ras inactivation. (aspetjournals.org)
  • The activation of the terminal kinases results in the nuclear translocation and promoter binding of transcription factors resulting in the gene expression of numerous mediators involved in the inflammatory response ( 12 ). (asm.org)
  • A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. (curehunter.com)
  • Proinflammatory cytokines have been reported to activate several transcription factors that are intimately linked to the expression of inflammatory and catabolic signals. (karger.com)
  • 2005). These proteins are scaffold proteins usually targeted to the plasma membrane cytoskeleton at specialised sites such as the neuromuscular junction and gap junctions through protein-protein interactions. (atlasgeneticsoncology.org)
  • We also isolated mutations in five previously uncharacterized genes, one of which, split ends , we have characterized molecularly and have shown to encode a member of the RRM family of RNA-binding proteins. (genetics.org)
  • Zou J, Wang R, Li R, Kong Y, Wang J, Ning X, Zhang L, Wang S, Hu X, Bao Z. The genome-wide identification of mitogen-activated protein kinase kinase (MKK) genes in Yesso scallop Patinopecten yessoensis and their expression responses to bacteria challenges. (umassmed.edu)
  • Fc gamma R-dependent mitogen-activated protein kinase activation in leukocytes: a common signal transduction event necessary for expression of TNF-alpha and early activation genes. (rupress.org)
  • Once activated, MAP kinases phosphorylate a variety of proteins and relay signals downstream, often ending in activation of transcriptional factors ( Cano and Mahadevan, 1995 ). (jneurosci.org)
  • Thus the role of mammalian ERK1/2 kinases as regulators of cell proliferation is not a generic, but a highly specialized function. (wikipedia.org)
  • Extracellular signal-regulated kinase (ERK) remains the best characterized mammalian MAP kinase. (ahajournals.org)
  • The MAPK family includes p38MAPK, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), which have been reported to be activated in the synovium of RA patients [ 8 , 9 ]. (karger.com)
  • Phosphorylation of vascular and renal extracellular-signal-regulated protein kinase 1/2 (ERK1/2), p38MAP kinase and c-Jun N-terminal kinase (JNK) were assessed using phospho-specific antibodies. (portlandpress.com)
  • These findings demonstrate that chronic deficiency of MKP-1 leads to decreased atherosclerosis via mechanisms involving impaired macrophage migration and defective extracellular signal-regulated kinase signaling. (scialert.net)
  • Western blot analysis, using a monoclonal antibody that detected the phosphorylated forms of extracellular signal-regulated kinase-1 and -2 (p42(mapk) and p44 (mapk), respectively), demonstrated that ATP activated MAPK in a dose- and time-dependent manner. (eurekamag.com)
  • These NF1 cells also demonstrated increased constitutive activity of the extracellular signal-regulated kinases 1 and 2 (ERK1,2) mitogen-activated protein (MAP) kinases compared with a sporadic malignant schwannoma cell line that maintains neurofibromin expression (STS-26T). (aspetjournals.org)
  • Isolated bone marrow-derived macrophages (BMDMs) from MKP-2 −/− mice showed increased phosphorylation of the extracellular signal-regulated kinase (ERK), decreased phosphorylation of JNK and p38, and increased induction of MKP-1 following LPS stimulation. (asm.org)
  • Although MKK3, MKK4, and MKK6 all activated p38 MAPk in experimental models, only MKK3 was found to activate recombinant p38 MAPk in LPS-treated neutrophils. (jci.org)
  • Prior UO results in reduced postischemic phosphorylation of c-Jun N-terminal stress-activated protein kinase 1/2 (JNK1/2), p38, mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), and MKK3/6. (curehunter.com)
  • 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)
  • In summary, type 2 diabetes is associated with an increased basal activation of the MAP kinase family. (diabetesjournals.org)
  • C57/BL6 wild-type mice and mice genetically deleted for mitogen-activated protein kinase kinase-3 ( mkk-3 −/− ) or c-Jun-NH 2 -terminal kinase-1 ( jnk1 −/− ) were ventilated, and lung injury parameters were assessed. (plos.org)
  • Inhibition of MAP kinase activity causes decreased MLCK function, MLC phosphorylation, and cell migration on extracellular matrix proteins. (rupress.org)
  • Inhibition of MAP kinase kinase (MEK) during this sustained αvβ3-dependent ERK signal blocked the formation of new blood vessels while not influencing preexisting blood vessels on the CAM. (rupress.org)
  • Our data demonstrate that Ang II induces severe hypertension in Sprague-Dawley rats and this is associated with increased phosphorylation of vascular and renal MAP kinases. (portlandpress.com)
  • Our results indicate that occupancy of Fc gamma RI and Fc gamma RII on the monocytic cell line THP-I and on polymorphonuclear leukocytes (PMN) induces, transiently and with fast kinetics, MAPK phosphorylation, as indicated by decreased electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and increased amounts of the proteins in antiphosphotyrosine antibody immunoprecipitates. (rupress.org)
  • 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)
  • Serine and threonine kinases may contribute to insulin resistance and the development of type 2 diabetes. (diabetesjournals.org)
  • Serine and threonine kinases are believed to play an important role in the onset of insulin resistance by regulating IRS-1 and GLUT4 protein levels through both pre- and posttranslational mechanisms ( 6 , 10 ). (diabetesjournals.org)
  • Thus serine/threonine kinases have the potential to contribute to the diminished GLUT4 mRNA levels in insulin-resistant adipose tissue. (diabetesjournals.org)
  • Specifically, members of the mitogen-activated protein (MAP) kinase family of serine-threonine kinases may contribute to the development of insulin resistance. (diabetesjournals.org)
  • A family of serine/threonine protein kinases, known as the mitogen-activated protein (MAP) kinases, is involved in extracellular signal perception during growth and differentiation processes in eukaryotic organisms. (genetics.org)
  • We demonstrate that these common substrates are members of the mitogen-activated protein kinase (MAP kinase) family of protein serine/threonine kinases. (jimmunol.org)
  • SAPK3/p38gamma binds to a variety of these proteins, such as alpha1-syntrophin, SAP90/PSD95 and SAP97/hDlg , and under stress conditions is able to phosphorylate them and modulate their activity (Hasegawa et al. (atlasgeneticsoncology.org)
  • 1997). Another p38gamma substrates that do not require PDZ domain binding interactions are the mitochondrial protein Sab (Court et al. (atlasgeneticsoncology.org)
  • Activation of substrates of p38 MAPK and cell cycle regulatory proteins were evaluated by western blotting. (arvojournals.org)
  • In contrast, expression of mutationally active MAP kinase kinase causes activation of MAP kinase leading to phosphorylation of MLCK and MLC and enhanced cell migration. (rupress.org)
  • 10 Recently, MAP kinase phosphatase-1 (MKP-1), a mammalian VH-1-like dual-specificity PTPase, has been isolated. (ahajournals.org)
  • To test the hypothesis that mitogen-activated protein kinase phosphatase (MKP)-1 is actively involved in atherogenesis. (scialert.net)
  • mice lacking G-protein-coupled receptor kinase 3 also failed to increase p-p38-IR after KOR activation in vivo , failed to show swim stress-induced immobility, or develop conditioned place aversion to U50488. (jneurosci.org)
  • Mitogen-activated protein (MAP) kinases are important mediators involved in the intracellular network of interacting proteins that transduce extracellular cues to intracellular responses. (ahajournals.org)
  • To examine the role of G(s) protein, the intracellular cAMP level was determined after treatment with ATP or hCG. (eurekamag.com)
  • Sites of activation were visualized using phosphoselective antibodies against activated κ receptors (KOR-P) and against phospho-p38 MAPK. (jneurosci.org)
  • Antibodies and purified kinases. (jneurosci.org)
  • Novus Biologicals offers a great selection of tools for your MAP/ERK research needs, including highly specific antibodies, RNAi and protein controls. (novusbio.com)
  • Furthermore, anisomycin, a potent stimulus of SAPK and p38 MAP kinase, also induced MKP-1 mRNA expression. (ahajournals.org)
  • 8 9 Interestingly, the mechanism involved in the activation of SAPK and p38 MAP kinase is similar to that involved in the activation of ERK. (ahajournals.org)
  • MKP-1 (the human homologue is called CL100 [97% identity]) was demonstrated to dephosphorylate and inactivate not only ERK 11 12 13 14 but also SAPK and p38 MAP kinase. (ahajournals.org)
  • JNK kinases (also known as SAPK kinases) are a subfamily. (umassmed.edu)
  • Previously, we have shown that ectopic expression of a constitutively active protein (yan ACT ) inhibits the differentiation of multiple cell types. (genetics.org)
  • When gain-of-function mutations occur in Ras /Raf, a commonly observed phenomenon in many types of cancers , MAP/ERK proteins become constitutively activated. (novusbio.com)
  • and (iv) TPO-induced megakaryocytic differentiation in UT7-mpl delta3 cells was partially restored by expression of a constitutively activated mutant of MEK. (asm.org)
  • Since both growth factor receptors and integrins activate MAP kinase in vitro, we examined the role of MAP kinase and the requirement for integrin ligation during angiogenesis in vivo. (rupress.org)
  • However, intramolecular interactions consistent with an inactive protein kinase fold were not formed. (mdpi.com)
  • Here, we show that repeated swim stress caused activation of both κ-opioid receptor (KOR) and p38 mitogen-activated protein kinase (MAPK) coexpressed in GABAergic neurons in the nucleus accumbens, cortex, and hippocampus. (jneurosci.org)
  • The Ras subfamily of small GTP-binding proteins direct signal transduction between the membrane and the nucleus. (aacrjournals.org)