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

No data available that match "cellular mitogen activated protein kinases"


No data available that match "cellular mitogen activated protein kinases"


  • The expression of MAPK target proteins was assessed by Western blotting. (karger.com)
  • Additionally, proinflammatory cytokines can activate several inflammatory transduction pathways, including mitogen activated protein kinase (MAPK). (karger.com)
  • 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)
  • 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)
  • Thus, depending on the cellular context, several distinct regions of the cytoplasmic domain of Mpl and signaling pathways may contribute to generate quantitative variations in MAPK activation. (asm.org)
  • This study reveals that DENSPM potently activates the mitogen-activated protein kinase (MAPK) pathways in melanoma cells and investigates the role of this response in determining cellular outcomes. (aacrjournals.org)
  • Recent studies have demonstrated that activation of the MAPK pathway ERK1/2 can activate the ets factor, Elk-1, which, in concert with serum response factor, participates in initiation of EGR-1 gene transcription (16) , thus placing EGR-1 downstream of MAPK activation. (aacrjournals.org)
  • All three MAPK pathways can be differentially activated, and their involvement in apoptosis is highly context- and model dependent. (aacrjournals.org)
  • A mitogen-activated protein kinase ( MAPK or MAP kinase ) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase ). (wikipedia.org)
  • MAPKs belong to the CMGC (CDK/MAPK/GSK3/CLK) kinase group. (wikipedia.org)
  • Because MAP2 kinases display very little activity on substrates other than their cognate MAPK, classical MAPK pathways form multi-tiered, but relatively linear pathways. (wikipedia.org)
  • In comparison to the three-tiered classical MAPK pathways, some atypical MAP kinases appear to have a more ancient, two-tiered system. (wikipedia.org)
  • To investigate whether activation of mitogen-activated protein kinase (MAPK) in damaged and/or undamaged primary afferents participates in neuropathic pain after partial nerve injury, we examined the phosphorylation of extracellular signal-regulated protein kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase (JNK) in the L4 and L5 dorsal root ganglion (DRG) in the L5 spinal nerve ligation (SNL) model. (jneurosci.org)
  • The MAPK family includes extracellular signal-regulated protein kinases (ERKs), p38 MAPK, and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK). (jneurosci.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)
  • 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)
  • Mitogen-activated protein kinase kinase (also known as MAP2K , MEK , MAPKK ) is a kinase enzyme which phosphorylates mitogen-activated protein kinase (MAPK). (wikipedia.org)
  • MEK is a member of the MAPK signaling cascade that is activated in melanoma. (wikipedia.org)
  • The MAPK family includes the subfamilies ERK, p38 MAPK and c-Jun N-terminal kinase (JNK). (biologists.org)
  • JNK ( Barr and Bogoyevitch, 2001 ) and p38 MAPK ( New and Han, 1998 ) are mainly activated by cellular stress. (biologists.org)
  • 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)
  • Upstream of the mammalian MAPKs, ERK1 and ERK2, is Raf (MAP3K) and MAPK/ERK kinase (MEK)1/2 (MAP2K). (biologists.org)
  • Kss1, a yeast mitogen-activated protein kinase (MAPK), in its unphosphorylated (unactivated) state binds directly to and represses Ste12, a transcription factor necessary for expression of genes whose promoters contain filamentous response elements (FREs) and genes whose promoters contain pheromone response elements (PREs). (pnas.org)
  • Numerous agonists activate mitogen-activated protein kinase (MAPK) cascades ( 1 ), which stimulate a relatively limited set of transcription factors ( 2 , 3 ) yet evoke diverse responses. (pnas.org)
  • In Drosophila melanogaster , the rolled MAPK functions downstream of several receptor-tyrosine kinases that specify different cell fates ( 4 , 5 ). (pnas.org)
  • Elements of this cascade include the MAPK kinase, Ste7, and its target MAPKs, Kss1 and Fus3 ( 9 , 10 ). (pnas.org)
  • clarification needed] The mammalian MAPK family of kinases includes three subfamilies: Extracellular signal-regulated kinases (ERKs) c-Jun N-terminal kinases (JNKs) p38 mitogen-activated protein kinases (p38s) Generally, ERKs are activated by growth factors and mitogens, whereas cellular stresses and inflammatory cytokines activate JNKs and p38s. (wikipedia.org)
  • The activation of arginase was preceded by a transient increase in intracellular cAMP, tyrosine kinase phosphorylation, and p38 mitogen-activated protein kinase (MAPK) activation. (jimmunol.org)
  • The induction of arginase was abolished by a protein kinase A (PKA) inhibitor, KT5720, and was down-regulated by tyrosine kinase inhibitors and a p38 MAPK inhibitor, SB203580. (jimmunol.org)
  • Furthermore, the induction of arginase was insensitive to the protein kinase C and p44/p42 MAPK kinase inhibitors. (jimmunol.org)
  • Together, these data demonstrate for the first time that IL-13 down-regulates NO production through arginase induction via cAMP/PKA, tyrosine kinase, and p38 MAPK signalings and underline the importance of arginase in the immunosuppressive activity of IL-13 in activated macrophages. (jimmunol.org)
  • The extracellular signal-regulated kinases (ERKs) comprise a particular branch of the mitogen-activated protein kinase cascades (MAPK) that transmits extracellular signals into the intracellular environment to trigger cellular growth responses. (mdpi.com)
  • Similar to other MAPK cascades, the MAPK-ERK pathway signals through three core kinases-Raf, MAPK/ERK kinase (MEK), and ERK-which drive the signaling mechanisms responsible for the induction of cellular responses from extracellular stimuli including differentiation, proliferation, and cellular survival. (mdpi.com)
  • Differential utilization of this pathway by multiple DNA viruses highlights the dynamic nature of the MAPK-ERK pathway within the cell and the importance of its function in regulating a wide variety of cellular fates that ultimately influence viral infection and, in some cases, result in tumorigenesis. (mdpi.com)
  • The mitogen-activated protein kinase (MAPK) superfamily consists of three main protein kinase families: the extracellular signal-regulated protein kinases (ERKs), the c-Jun N-terminal kinases (JNKs) and the p38 family of kinases. (biologists.com)
  • From these humble beginnings, studies of the mitogen-activated protein kinase(MAPK) superfamily have grown explosively and have fueled major advances in our understanding of the regulation of growth and development and the mechanisms by which cells respond to external stresses. (biologists.com)
  • It is now recognized that the MAPK superfamily is made up of three main and distinct signaling pathways: the extracellular signal-regulated protein kinases (ERKs), the c-Jun N-terminal kinases or stress-activated protein kinases (JNK/SAPK), and the p38 family of kinases( Fig. 1 ). (biologists.com)
  • The MAPK, a serine/threonine kinase,is activated by a MAPK kinase (MAPKK), which is a `dual-specific' kinase that phosphorylates at both Ser/Thr and Tyr sites, targeting a Thr-X-Tyr motif on the MAPK (where X is glutamate, proline or glycine for the ERK, JNK and p38 modules, respectively) ( Hoeflich and Woodgett, 2001 ). (biologists.com)
  • While using inhibitors to assess whether c-Jun N-terminal (JNK) kinases regulate hepatitis C virus (HCV) replication, we encountered unexpected off-target effects that led us to discover a role for a mitogen-activated protein kinase (MAPK)-related kinase, MAPK interacting serine/threonine kinase 1 (MKNK1), in viral entry. (yonsei.ac.kr)
  • Background: In the present study we tested the hypothesis that progression of streptozotocin (STZ)-induced diabetes (14-days to 28-days) would produce renal and vascular dysfunction that correlate with altered p38- mitogen-activated protein kinase (p38-MAPK) phosphorylation in kidneys and thoracic aorta. (ebscohost.com)
  • Besides the classic UPR pathway and genes related to calcium homeostasis, we report that two additional pathways, including the SLT2 mitogen-activated protein kinase (MAPK) pathway and the osmosensing MAPK pathway, were also required for survival during ER stress. (aacrjournals.org)
  • We further show that the SLT2 MAPK pathway was activated during ER stress, was responsible for increased resistance to ER stress, and functioned independently of the classic IRE1/HAC1 pathway. (aacrjournals.org)
  • A new independent 41 page research with title 'Mitogen Activated Protein Kinase Kinase Kinase 5 {Apoptosis Signal Regulating Kinase 1 or MAPK/ERK Kinase Kinase 5 or MAP3K5 or EC 2.7.11.25} - Pipeline Review, H2 2017' guarantees you will remain better informed than your competition. (medgadget.com)
  • Mitogen Activated Protein Kinase Kinase Kinase 5 (Apoptosis Signal Regulating Kinase 1 or MAPK/ERK Kinase Kinase 5 or MAP3K5 or EC 2.7.11.25) pipeline Target constitutes close to 11 molecules. (medgadget.com)
  • The latest report Mitogen Activated Protein Kinase Kinase Kinase 5 - Pipeline Review, H2 2017, outlays comprehensive information on the Mitogen Activated Protein Kinase Kinase Kinase 5 (Apoptosis Signal Regulating Kinase 1 or MAPK/ERK Kinase Kinase 5 or MAP3K5 or EC 2.7.11.25) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (medgadget.com)
  • Mitogen Activated Protein Kinase Kinase Kinase 5 (Apoptosis Signal Regulating Kinase 1 or MAPK/ERK Kinase Kinase 5 or MAP3K5 or EC 2.7.11.25) - Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) is a member of MAP kinase kinase kinase family encoded by MAP3K5 gene. (medgadget.com)
  • Furthermore, this report also reviews key players involved in Mitogen Activated Protein Kinase Kinase Kinase 5 (Apoptosis Signal Regulating Kinase 1 or MAPK/ERK Kinase Kinase 5 or MAP3K5 or EC 2.7.11.25) targeted therapeutics development with respective active and dormant or discontinued projects. (medgadget.com)
  • Despite the importance of mitogen-activated protein kinase (MAPK) signaling in eukaryotic biology, the mechanisms by which signaling yields phenotypic changes are poorly understood. (pnas.org)
  • Thus, the Kss1 MAPK cascade programs development by coordinately modulating a cell adhesion factor, a secreted host-destroying activity, and a specialized subunit of the Cdc28 cyclin-dependent kinase. (pnas.org)
  • Mitogen-activated protein kinase (MAPK) signal transduction cascades play crucial roles in both normal and abnormal eukaryotic development. (pnas.org)
  • However, until recently, it has been difficult to assess the entire ensemble of target genes activated by MAPK signaling. (pnas.org)
  • Mitochondrial contents, expression, and activation status of p38 mitogen-activated protein kinase (MAPK) and PPARγ coactivator 1α (PGC-1α) were compared between skeletal muscle samples from adiponectin gene knockout, adiponectin-reconstituted, and control mice. (diabetesjournals.org)
  • p38 is a member of the mitogen-activated protein kinase (MAPK) family and has been identified as a downstream molecule in the adiponectin-signaling pathway ( 15 , 18 , 19 ). (diabetesjournals.org)
  • Many major human oncogenes contribute to cancer in large part by activating the mitogenactivated protein kinases (MAPK) ERK1 and ERK2 (ERK). (mit.edu)
  • 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)
  • FK stimulated the phosphorylation of extracellular signal-activated kinases (ERK) 1/2 in a subpopulation of dopaminergic neurons, suggesting that the mitogen-activated protein kinase (MAPK) pathway was involved in the effects of cAMP-elevating agents. (aspetjournals.org)
  • Accordingly, inhibition of the upstream kinases of ERK 1/2 by 2′-amino-3′-methoxyflavone (PD98059) not only suppressed MAPK activation caused by FK but also abolished the survival promoting activity that this compound exerts on TH + neurons. (aspetjournals.org)
  • 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)
  • In recent years, it has become evident that MAPK signaling is regulated and fine-tuned by proteins that can bind to several MAPK signaling proteins simultaneously and, thereby, affect their function. (mdpi.com)
  • These so-called MAPK scaffolding proteins are, thus, important coordinators of the signaling response in cells. (mdpi.com)
  • In this review, we summarize the recent advances in the research on MAPK/extracellular signal-regulated kinase (ERK) pathway scaffolders. (mdpi.com)
  • The stress-activated protein kinase (SAPK) and mitogen-activated protein kinase (MAPK) subfamilies are crucial to environmental stress responses and responses to growth factors that cause transcriptional activation of genes required for cell proliferation, differentiation and programmed cell death. (eurekaselect.com)
  • The dual specificity kinases mitogen-activated protein kinase (MAPK) kinase (MKK)7 and MKK4 are the only molecules known to directly activate the stress kinases stress-activated protein kinases (SAPKs)/c-Jun N-terminal kinases (JNKs) in response to environmental or mitogenic stimuli. (pubmedcentralcanada.ca)
  • Loss of MKK7 did not affect activation of extracellular signal-regulated kinase (ERK)1/2 or p38 MAPK. (pubmedcentralcanada.ca)
  • Important members of the MAPK family are the extracellular signal-regulated kinases ERK1 and ERK2, ERK5, p38 MAPK, and the stress-activated protein kinases (SAPKs, also known as the c-Jun N-terminal kinases [JNKs]) 5 6 . (pubmedcentralcanada.ca)
  • Mitogen-activated protein kinases (MAPK) mediate cellular signal transduction during stress responses, as well as diverse growth and developmental processes in eukaryotes. (unboundmedicine.com)
  • Pathogen infection or treatments with conserved pathogen-associated molecular patterns (PAMPs) such as the bacterial flagellin-derived flg22 peptide are known to activate three Arabidopsis thaliana MAPK: MPK3, MPK4, and MPK6. (unboundmedicine.com)
  • Taken together, future investigations of MAPK roles in stress signaling should include MPK11 as a fourth PAMP-activated MAPK. (unboundmedicine.com)
  • Mitogen-activated protein kinase ( MAPK ) pathways are involved in several signal transduction processes in eukaryotes. (plantcell.org)
  • MPK6 physically interacts with and phosphorylates a basic helix-loop-helix transcription factor, MYC2, and is phosphorylated by a MAPK kinase, MKK3. (plantcell.org)
  • Any of a family of serine/threonine protein kinases belonging to the CMGC (CDK/MAPK/GSK3/CLK) kinase group, which are involved in cellular responses to various stimuli (e.g., mitogens, osmotic stress, heat shock and cytokines) and regulate cell growth, cycling, differentiation, mitosis and apoptosis. (thefreedictionary.com)
  • In Colo205 cells exposed to PEP005, a variety of signaling pathways were activated as shown by increased phosphorylation of PKCδ, Raf1, extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (MAPK), c-Jun NH 2 -terminal kinase, p38 MAPK, and PTEN. (aacrjournals.org)
  • Interestingly, PEP005 treatment also resulted in reduced expression of PKCα and reduced levels of phosphorylated active form of AKT/protein kinase B. These data suggest that PEP005-induced activation of PKCδ and reduced expression of PKCα resulted in apoptosis by mechanisms mediated by activation of Ras/Raf/MAPK and inhibition of the phosphatidylinositol 3-kinase/AKT signaling pathways. (aacrjournals.org)
  • As part of a signaling pathway known as the RAS/MAPK pathway, the RIT1 protein relays signals from outside the cell to the cell's nucleus. (medlineplus.gov)
  • The abnormally active protein alters normal RAS/MAPK signaling and leads to abnormal cell proliferation, which disrupts the development of organs and tissues throughout the body, resulting in the signs and symptoms of Noonan syndrome. (medlineplus.gov)
  • Bioinformatics analysis indicated that mitogen-activated protein kinase (MAPK) signaling was the major pathway in both levels of noise exposure. (cdc.gov)
  • Among the most active signal transduction pathways involved in the immune response are the mitogen-activated protein kinase (MAPK) pathways. (asm.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)
  • 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)
  • 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)
  • Both MAP2K1 /MEK1 and MAP2K2 /MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3 /ERK1 and MAPK1 /ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. (rcsb.org)
  • One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma ( PPARG ), a nuclear receptor that promotes differentiation and apoptosis. (rcsb.org)
  • The recruitment of Dok-R to the EGFR, which is mediated through its phosphotyrosine binding (PTB) domain, results in attenuation of mitogen-activated protein kinase (MAPK) activation. (elsevier.com)
  • 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)
  • MAPK/ERK are activated by diverse mechanisms. (novusbio.com)
  • 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)
  • An orally bioavailable inhibitor of mitogen-activated protein kinase kinase (MEK MAPK/ERK kinase) with potential antineoplastic activity. (cancer.gov)
  • Onset of apoptosis was preceded by an intense phosphorylation of the MAPKs, including extracellular signal-regulated kinase 1/2, c-Jun NH 2 -terminal kinase, and p38 in both SK-MEL-28 and MALME-3M cells. (aacrjournals.org)
  • The phosphorylation of proteins on the serine or threonine residues that immediately precede proline (pSer/Thr-Pro) is specifically catalyzed by the prolyl isomerase Pin1 and is a key signaling mechanism in cell proliferation and transformation. (aacrjournals.org)
  • Mitogen-activated protein (MAP) kinases are activated in response to a variety of stimuli through a protein kinase cascade that results in their phosphorylation on tyrosine and threonine residues. (asm.org)
  • Activates by phosphorylation the downstream MPK3 and MPK6. (uniprot.org)
  • This tandem activation loop phosphorylation (that was proposed to be either distributive or processive, dependent on cellular environment) is performed by members of the Ste7 protein kinase family, also known as MAP2 kinases . (wikipedia.org)
  • MAP2 kinases in turn, are also activated by phosphorylation, by a number of different upstream serine-threonine kinases ( MAP3 kinases ). (wikipedia.org)
  • 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)
  • Although phosphorylation of sodium channels has been shown to produce rapid modulation of sodium currents, these studies have been primarily focused on investigating the role of cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) (for review, see Cantrell and Catterall, 2001 ). (jneurosci.org)
  • 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)
  • The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. (nih.gov)
  • The conventional MAPKs constitute three consecutive phosphorylation events mediated by three Ser/Thr protein kinases. (mdpi.com)
  • Protein phosphorylation in particular plays a significant role in a wide range of cellular processes and is a very important posttranslational modification . (wikipedia.org)
  • Soluble extracts prepared from quiescent Swiss mouse 3T3 cells that had been briefly exposed to various mitogens exhibited a 2- to 3-fold elevation in phosphorylating activities toward ribosomal protein S6 and a synthetic peptide, Arg-Arg-Leu-Ser-Ser-Leu-Arg-Ala (RRLSSLRA), patterned after a phosphorylation site sequence from S6. (semanticscholar.org)
  • Using cell lines isolated from MCF+FIR populations, we found that the elevated NF-κB activity was correlated with enhanced clonogenic survival, and increased NF-κB subunit p65 levels were associated with a decrease in phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK in all radioresistant MCF+FIR cell lines. (aacrjournals.org)
  • However, major heterodimers of NF-κB p65 and p50, which are activated quickly following the phosphorylation and proteolysis of IκB ( 21 , 22 ), can function as pleiotropic gene regulators ( 23 ). (aacrjournals.org)
  • 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)
  • Inhibition of MAP kinase activity causes decreased MLCK function, MLC phosphorylation, and cell migration on extracellular matrix proteins. (rupress.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)
  • 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)
  • We are using high-throughput sequencing and biochemical experiments to determine whether these phosphorylation sites control the function of MLL proteins. (mit.edu)
  • Accumulation of denatured proteins during heat stress consumes HSP90 and releases HSF1 from the complex, which then undergoes phosphorylation, sumoylation, and trimerization prior to its nuclear import. (plantphysiol.org)
  • Once activated, SAPKs/JNKs regulate gene transcription via phosphorylation of transcription factors, including c-Jun, JunD, activating transcription factor (ATF)-2, nuclear factor of activated T cells (NFAT)4, or ELK-1 8 . (pubmedcentralcanada.ca)
  • According to the same study, apocynin inhibited the expression of iNOS and COX-2, reduced NF-a, and inhibited the phosphorylation of MAP kinases JNK, ERK and P38. (thefreedictionary.com)
  • In addition, phosphorylation of MAP kinases including JNK, ERK, and p38 induces innate immune response. (thefreedictionary.com)
  • Treatment of cells with sirtuin inhibitors, or siRNA knockdown of SIRT1 or SIRT2 proteins, increases MEK1 acetylation and subsequent phosphorylation of the extracellular signal-regulated kinase (ERK). (uncg.edu)
  • Searching for direct down-stream components, we previously isolated a novel transcription factor, which was activated upon phosphorylation by WIPK and designated as N. tabacum WIPK-interacting factor (NtWIF). (deepdyve.com)
  • 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)
  • A specific inhibitor of p38 MAP kinase, SB203580, abolished the stress-inducible in vivo phosphorylation of CHOP. (sciencemag.org)
  • Phosphorylation of intrinsically disordered regions of RNA-binding proteins contributes to the assembly of RNA granules. (asbmb.org)
  • and FILAMIN to GPCRs and may recognize different phosphorylation states of the receptors to determine the specificity of the cellular response to signaling. (bioportfolio.com)
  • These results show that phosphorylation of FHOD proteins by ERK1/2 is a critical switch for nuclear positioning and may play a role in the pathogenesis of cardiomyopathy caused by LMNA mutations. (bioportfolio.com)
  • 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)
  • 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)
  • p38 MAP kinase inhibition hence constitutes a promising therapeutic strategy for treatment of chronic inflammatory diseases, based upon its potential to inhibit key pathways driving the inflammatory and destructive processes in these debilitating diseases. (aspetjournals.org)
  • Signal transduction pathways serve as a molecular mechanism to accomplish this cellular response. (asm.org)
  • 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)
  • Mitogen-activated S6 kinase is stimulated via protein kinase C-dependent and independent pathways in Swiss 3T3 cells. (semanticscholar.org)
  • Recent studies have shown that some bacterial pathogens are able to activate mitogen-activated protein (MAP) kinase pathways in the host cell ( 13 , 23 , 32 , 33 ) to alter processes such as cell differentiation, growth, and death. (asm.org)
  • MAP kinase signaling pathways described thus far include the extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK) (also known as stress-activated protein kinases) and p38 MAP kinases. (asm.org)
  • For instance, NF-κB activates many genes involved in inflammation, cell transformation, and antiapoptotic responses ( 24 , 25 ), suggesting that both prosurvival and antisurvival pathways can be induced by NF-κB activation. (aacrjournals.org)
  • Taken together, ER stress-activated pathways are essential for the development and growth of solid tumors and inhibition of these pathways may lead to new anticancer therapies. (aacrjournals.org)
  • Thus, compared with 5-LO product synthesis induced by the Ca2+-mobilizing agent ionophore A23187, cell stress-induced 5-LO product formation involving 5-LO kinase pathways required ~10- to 100-fold higher concentrations of ZM230487 or L-739.010 for comparable 5-LO inhibition. (nih.gov)
  • We hypothesized that the addition of hyperoxia to large-V T ventilation would increase neutrophil infiltration by upregulation of the cytokine macrophage inflammatory protein-2 (MIP-2) and would increase apoptosis via the mitogen-activated protein kinase pathways. (biomedcentral.com)
  • Involvement of mitogen-activated protein kinase pathways in the nuclear responses and cytokine production induced by Salmonella typhimurium in cultured intestinal epithelial cells. (jimmunol.org)
  • Secretion of these proteins stimulates host cell signal transduction pathways that lead to a variety of cellular responses. (jimmunol.org)
  • Induction of these signaling pathways and the synthesis of IL-8 was strictly dependent on the function of the invasion-associated type III protein secretion system encoded by S. typhimurium. (jimmunol.org)
  • These results indicate that the inflammatory response induced by S. typhimurium may be due to the specific stimulation of MAP kinase signaling pathways leading to nuclear responses. (jimmunol.org)
  • In particular, whereas the MAP kinase and PKA pathways have been examined in several studies, no clear interaction has been yet been established between them for paclitaxel-induced apoptosis. (aacrjournals.org)
  • Paclitaxel (Taxol) activates a number of signal transduction pathways that lead to apoptosis.In contrast, paclitaxel also activates cell survival pathways, such as the Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway. (aacrjournals.org)
  • Additionally, paclitaxel activates signal transduction pathways leading to gene expression. (aacrjournals.org)
  • These molecules participate in several different intracellular signaling pathways that control a spectrum of cellular processes, including cell growth, differentiation, transformation, apoptosis, and stress responses 3 4 . (pubmedcentralcanada.ca)
  • Binding of OT to the cell surface transmembrane OTR activates the receptor which subsequently activates various intracellular signal pathways, this triggering the numerous effects of the hormone, including contraction (Figure 1 ). (hindawi.com)
  • Viruses repurpose host cellular synthetic and metabolic pathways to produce progeny. (springer.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)
  • 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)
  • Control of thrombopoietin-induced megakaryocytic differentiation by the mitogen-activated protein kinase pathway. (asm.org)
  • The predicted Mpk1 protein (Mpk1p) shares 48 to 50% sequence identity with Xenopus MAP kinase and with the yeast mating pheromone response pathway components, Fus3p and Kss1p. (asm.org)
  • Deletion of MPK1 resulted in a temperature-dependent cell lysis defect that was virtually indistinguishable from that resulting from deletion of BCK1, suggesting that the protein kinases encoded by these genes function in a common pathway. (asm.org)
  • Additional epistasis experiments, and the overall architectural similarity between the PKC1-mediated pathway and the pheromone response pathway, suggest that Pkc1p regulates a protein kinase cascade in which Bck1p activates a pair of protein kinases, designated Mkk1p and Mkk2p (for MAP kinase-kinase), which in turn activate Mpk1p. (asm.org)
  • Study in Chinese familial non-medullary thyroid carcinoma patients revealed that MAP2K5 variants A321T or M367 T can activate MAP2K5-ERK5 pathway, alter downstream gene expression, and subsequently induce thyroid epithelial cell malignant transformation. (nih.gov)
  • Signal transduction through the p38 mitogen-activated protein (MAP) kinase pathway is central to the transcriptional and translational control of cytokine and inflammatory mediator production. (aspetjournals.org)
  • 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)
  • EPEC-induced upregulation of egr-1 is mediated by the activation of the MEK/extracellular signal-regulated kinase signal transduction pathway and is dependent on the type III secretion system. (asm.org)
  • egr-1 is also induced during infection of mice by the A/E pathogen Citrobacter rodentium , suggesting that both Egr-1 and the activation of this mitogen-activated protein kinase signal transduction pathway may play a role in disease. (asm.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)
  • The endoplasmic reticulum (ER) maintains an oxidative environment that is optimized to promote the efficient folding of proteins destined for the secretory pathway. (aacrjournals.org)
  • Thus, we define a signaling pathway directly downstream of MAP kinase, influencing cell migration on the extracellular matrix. (rupress.org)
  • WRKY transcription factors and proteins encoded by the genes from the "PEN" pathway required for penetration resistance to filamentous pathogens). (nih.gov)
  • Inappropriate activation of one such pathway, the extracellular signal-regulated kinase cascade, promotes a significant fraction of human cancers. (pnas.org)
  • 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)
  • Activation of the MPK3 and MPK6 mitogen-activated protein kinase pathway led to the transcriptional activation of the HEAT SHOCK PROTEIN17.6A gene. (plantphysiol.org)
  • Activation and inhibition experiments demonstrated that protein kinase A and p38 participate sequentially upstream of the NHE1 in regulating the paclitaxel-induced apoptotic pathway. (aacrjournals.org)
  • This is the first demonstration of the role of the Hog1-mediated MAP kinase pathway in resistance to oxidative stress in pathogenic fungi, and it allows us to propose a molecular model for the oxidative stress response in C . albicans . (asm.org)
  • In Schizosaccharomyces pombe , two mechanisms seem to control the response to oxidative stress-the activation of the StyI/Spc1 mitogen-activated protein (MAP) kinase pathway and the function of the Yap1 homologue-although these phenomena seem to be interdependent. (asm.org)
  • It acts through its receptor, which belongs to the G-protein-coupled receptor superfamily, while Gq/phospholipase C (PLC)/inositol 1,4,5-triphosphate (InsP3) is the main pathway via which it exerts its action in the myometrium. (hindawi.com)
  • Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. (rcsb.org)
  • Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. (rcsb.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)
  • MEK 1 and 2, dual specificity threonine/tyrosine kinases often upregulated in various cancer cell types, play a key role in the activation of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth. (cancer.gov)
  • MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens , osmotic stress , heat shock and proinflammatory cytokines . (wikipedia.org)
  • The closest relatives of MAPKs are the cyclin-dependent kinases (CDKs). (wikipedia.org)
  • [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)
  • Mitogen-activated protein kinases (MAPKs) are expressed in neurons and are activated after injury, for example, after sciatic nerve transection and hypoxia. (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)
  • All mammalian cells possess multiple MAPKs involved in controlling cellular processes such as proliferation, differentiation, survival, apoptosis, gene regulation and motility [ 1 ]. (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)
  • It is well known from mammalian cells that anoxia has a major impact on the mitogen-activated protein kinases, MAPKs. (biologists.org)
  • Omi suppressed the activation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase 1 and 2 (ERK1/2) by cleaving the upstream kinase MEK1 (mitogen-activated or extracellular signal-regulated protein kinase kinase 1). (sciencemag.org)
  • To date, this cellular signal transduction network has received relatively little attention from comparative biochemists,despite the high probability that MAPKs have critical roles in the adaptive responses to thermal, osmotic and oxygen stresses. (biologists.com)
  • 1000-fold increase in specific activity so that, in effect, MAPKs are inactive unless phosphorylated by their respective upstream kinases ( Hoeflich and Woodgett,2001 ). (biologists.com)
  • 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) target a variety of protein substrates to regulate cellular signaling processes in eukaryotes. (nih.gov)
  • Here, we generated transgenic Arabidopsis thaliana plants with an inducible system to simulate in vivo activation of two stress-activated MAPKs, MPK3, and MPK6. (nih.gov)
  • Inhibitors have been employed in vitro to identify protein targets and mechanism of action of SAPKs/MAPKs. (eurekaselect.com)
  • The mitogen-activated protein kinases (MAPKs) are a family of serine/threonine kinases which transduce signals from the cell membrane to the nucleus in response to a wide range of stimuli 1 2 . (pubmedcentralcanada.ca)
  • Mitogen-activated kinases (MAPKs), consisting of three major categories of enzymes, ERK, p38, and JNK, couple cell-surface receptors to critical regulatory targets and gene transcription within cells. (arvojournals.org)
  • The three MAPKs each demonstrate a specific cellular distribution after ischemia, and are linked to apoptosis. (arvojournals.org)
  • Sano, Hiroshi 2007-10-06 00:00:00 Mitogen-activated protein kinases (MAPKs) constitute one of the most critical signaling components in plants. (deepdyve.com)
  • Mitogen-activated protein kinases (MAPKs) are highly conserved signalling proteins that regulate adaptation to various stresses. (biologists.org)
  • Complement anaphylatoxin C5a neuroprotects through mitogen-activated protein kinase-dependent inhibition of caspase 3. (semanticscholar.org)
  • In human monocyte and synovial fibroblast cell systems, PH-797804 blocks inflammation-induced production of cytokines and proinflammatory mediators, such as prostaglandin E 2 , at concentrations that parallel inhibition of cell-associated p38 MAP kinase. (aspetjournals.org)
  • Low-nanomolar biochemical enzyme inhibition potency correlated with p38 MAP kinase inhibition in human cells and in vivo studies. (aspetjournals.org)
  • In addition, a direct correspondence between p38 MAP kinase inhibition and anti-inflammatory activity was observed with PH-797804, thus providing confidence in dose projections for further human studies in chronic inflammatory disease. (aspetjournals.org)
  • Inhibition of extracellular signal-regulated protein kinase or c-Jun N-terminal protein kinase cascade, differentially activated by cisplatin, sensitizes human ovarian cancer cell line. (springer.com)
  • The direct pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) similarly enhances paclitaxel-induced tumor apoptosis in a dose-dependent manner. (aacrjournals.org)
  • Pharmacological inhibition of extracellular signal-regulated kinases (ERK) signaling blocks regeneration and wound healing in Nematostella. (biomedcentral.com)
  • heart , and inhibition of the ERK1/2 kinase activity ameliorates pathology, but the downstream effectors remain largely unknown. (bioportfolio.com)
  • Trametinib specifically binds to and inhibits MEK 1 and 2, resulting in an inhibition of growth factor-mediated cell signaling and cellular proliferation in various cancers. (cancer.gov)
  • The MAP/extracellular signal-regulated kinase-1 inhibitor PD 98059 reduced activation of all three kinases but failed to alter apoptosis in DENSPM-treated SK-MEL-28 cells. (aacrjournals.org)
  • Serine/Threonine Kinase receptors play a role in the regulation of cell proliferation, programmed cell death ( apoptosis ), cell differentiation, and embryonic development. (wikipedia.org)
  • respond to extracellular stimuli (mitogens) and regulate various cellular activities, such as gene expression, mitosis, differentiation, and cell survival/apoptosis. (wikipedia.org)
  • Each is proving to have major roles in the regulation of intracellular metabolism and gene expression and integral actions in many areas including growth and development, disease, apoptosis and cellular responses to external stresses. (biologists.com)
  • In MDA-MB-435 cells, paclitaxel treatment stimulated the activity of both protein kinase A and p38, and inhibited the activity of the Na + /H + exchanger isoform 1 (NHE1) with similar IC 50 concentrations as for its activation of apoptosis. (aacrjournals.org)
  • Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. (thefreedictionary.com)
  • These proteins play important roles in cell division, cell differentiation, and the self-destruction of cells (apoptosis). (medlineplus.gov)
  • Therefore activation of MAP/ERK can affect a broad array of cellular functions including proliferation, survival, apoptosis , motility, transcription , metabolism and differentiation. (novusbio.com)
  • Proteolytic activation of MST/Krs, STE20-related protein kinase, by caspase during apoptosis. (ebscohost.com)
  • 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 contrast, in the uninjured L4 DRG, the L5 SNL induced only p38 activation in tyrosine kinase A-expressing small- to medium-diameter neurons. (jneurosci.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)
  • Iavarone C, Acunzo M, Carlomagno F, Catania A, Melillo RM, Carlomagno SM, Santoro M, Chiariello M: Activation of the Erk8 mitogen-activated protein (MAP) kinase by RET/PTC3, a constitutively active form of the RET proto-oncogene. (drugbank.ca)
  • Interestingly, ERK2 was activated in response to reperfusion, suggesting an interface capable of ERK activation in the nuclear membrane. (biologists.org)
  • However, EPO-dependent mitogen-activated protein (MAP) kinase activation was observed in T-JJER and BF-ER cells but not in T-JER cells. (biomedsearch.com)
  • EPEC's secreted proteins induce signal transduction events within the host cell, including inositol phosphate fluxes and protein kinase C and phospholipase Cγ activation ( 2 , 10 , 16 ). (asm.org)
  • Activation of ataxia-telangiectasia mutated (ATM) protein, a sensor to radiation-induced DNA damage, was elevated with increased interaction with NF-κB subunits p65 and p50. (aacrjournals.org)
  • Mitogen-activated protein kinases [i.e., extracellular signal-regulated kinase (ERK), c-jun NH 2 -terminal kinase (JNK), and p38], which all are closely related with NF-κB activation, are also involved in the radiation response ( 26 - 28 ). (aacrjournals.org)
  • The addition of hyperoxia to high-V T ventilation augmented lung injury, as demonstrated by increased apoptotic cell death, neutrophil migration into the lung, MIP-2 production, MIP-2 mRNA expression, increased DNA binding activity of activator protein-1, increased microvascular permeability, and c-Jun NH 2 -terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) 1/2 activation. (biomedcentral.com)
  • 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)
  • suggesting that MAP kinase can lead to direct activation of the intracellular motility machinery independent of de novo gene transcription. (rupress.org)
  • In this report, we investigated the role that Ras/MAP kinase activation plays in regulating integrin-mediated cell migration. (rupress.org)
  • We also show that S. typhimurium infection of cultured intestinal epithelial cells results in the activation of the mitogen-activated protein (MAP) kinases ERK, JNK, and p38. (jimmunol.org)
  • These kinases are critical in normal physiological processes from development to memory, and their activation in cancer drives growth and metastatic invasion. (mit.edu)
  • Blockade of p38 mitogen-activated protein kinase activation inhibited HNE-induced phosphatidylserine exposure and increased TF activity. (ahajournals.org)
  • Conclusions- HNE increases TF coagulant activity in monocytic cells through a novel mechanism involving p38 mitogen-activated protein kinase activation that leads to enhanced phosphatidylserine exposure at the cell surface. (ahajournals.org)
  • Surprisingly, the archetypal cAMP-dependent protein kinase was apparently not responsible for ERK 1/2 activation. (aspetjournals.org)
  • A group of extracellular-signal regulated protein kinase (ERK) inhibitors has been constructed based almost exclusively on their ability to inhibit the ERK activation cascade. (eurekaselect.com)
  • Brozovic A, Osmak M. Activation of mitogen-activated protein kinases by cisplatin and their role in cisplatin-resistance. (springer.com)
  • Pae, "Reactive oxygen species in the activation of MAP kinases ," Methods in Enzymology, vol. (thefreedictionary.com)
  • We therefore investigated the effects of Hsp60 on the activation of the MAP kinases ERK1/2, JNK, and p38 and of the transcription factor NF[kappa]B which are preferentially activated by stress signals but are also essential for the coordination of adipocyte differentiation [44-46]. (thefreedictionary.com)
  • PEP005-induced activation of PKCδ was associated with its translocation from the cytosol to the nucleus and other cellular membranes. (aacrjournals.org)
  • The mutations lead to the production of an altered RIT1 protein that is either continuously turned on (active) or has prolonged activation, rather than promptly switching on and off in response to other cellular proteins. (medlineplus.gov)
  • 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)
  • Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. (rcsb.org)
  • by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2 - BRAF dimerization and BRAF activation (PubMed:29433126). (rcsb.org)
  • Differential activation of distinct mitogen-activated protein kinase signaling. (ebscohost.com)
  • In addition, myeloid p38 alpha limited acute inflammation via activation of anti-inflammatory gene expression dependent on mitogen- and stress-activated kinases. (sigmaaldrich.com)
  • At least 125 of the 500+ human protein kinases are serine/threonine kinases (STK). (wikipedia.org)
  • In enzymology , the term non-specific serine/threonine protein kinase describes a class of enzymes that belong to the family of transferases , specifically protein-serine/threonine kinases . (wikipedia.org)
  • While serine/threonine kinases all phosphorylate serine or threonine residues in their substrates, they select specific residues to phosphorylate on the basis of residues that flank the phosphoacceptor site, which together comprise the consensus sequence . (wikipedia.org)
  • CHOP thus serves as a link between a specific stress-activated protein kinase, p38, and cellular growth and differentiation. (sciencemag.org)
  • Furthermore, PD98059, a specific inhibitor of MEK1/2, and Juglone, a potent Pin1 inhibitor, markedly suppressed the expression of activator protein-2α and the HER-2 promoter activity induced by EGF or 12- O -tetradecanoylphorbol-13-acetate in MCF-7 cells. (aacrjournals.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)
  • PH-797804 is an ATP-competitive, readily reversible inhibitor of the α isoform of human p38 MAP kinase, exhibiting a K i = 5.8 nM. (aspetjournals.org)
  • Finally, IL-13 significantly inhibited NO production from LPS-activated macrophages, and this effect was reversed by an arginase inhibitor, l -norvaline. (jimmunol.org)
  • Our results suggest that, in addition to anti-proliferative properties, MEK1,2 inhibitors may be anti-angiogenic Tyrosine kinase inhibitor manufacture and possess restorative energy in the treatment of PHRP-positive tumours. (informationalwebs.com)
  • Hybridization to Affymetrix U95A GeneChips Spike regulates were added Tyrosine kinase inhibitor manufacture to 10?g of fragmented cRNA prior to overnight hybridization to human being U95A oligonucleotide arrays Tyrosine kinase inhibitor manufacture for 16?h at 42?C. Arrays were washed and stained with streptavidin/phycoerythrin, before scanning on an Affymetrix GeneChip scanner. (informationalwebs.com)
  • Global scaling of organic data utilizing Tyrosine kinase inhibitor manufacture a focus on strength of 500 created scale elements that ranged from 3.6 to 9.5. (informationalwebs.com)
  • The filtration system requirements stipulated that, and a minimal 2.5-fold change in mRNA abundance, at Tyrosine kinase inhibitor manufacture least among the probe pieces needed to be designated a value of 0.04, indicating that the transcript was present (beliefs. (informationalwebs.com)
  • Pretreatment of cells with the highly specific p38 MAP kinase inhibitor SB 203580 prevented S. typhimurium-induced IL-8 production. (jimmunol.org)
  • A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfiler TM service. (guidetopharmacology.org)
  • In A2780 cells, the kinase inhibitor also decreased the expression of copper transporter 1 (CTR1). (springer.com)
  • Here, we find that the combination of paclitaxel with a MEK inhibitor leads to a dramatic inactivation of the antiapoptotic Akt (protein kinase B) kinase. (aacrjournals.org)
  • We also report that Fasnall, a novel FASN inhibitor with anti-tumor activity [ 15 ] potently reduces HIV-1 production with minimal effects on cellular viability. (springer.com)
  • 3LHJ: Crystal Structure of p38a Mitogen-Activated Protein Kinase in Complex with a Pyrazolopyridinone Inhibitor. (rcsb.org)
  • In the search to understand these molecular processes, researchers uncovered an important new DAF-16 isoform - DAF-16d/f - that collaborates with other DAF-16 protein isoforms to regulate longevity. (thefreedictionary.com)
  • Sirtuins are class III deacetylases that regulate many essential processes, including cellular stress, genome stability, and metabolism. (uncg.edu)
  • An alternative would be to develop inhibitors that can target the accessory proteins that regulate MAP/ERK functions. (novusbio.com)
  • Non-visual system arrestins that negatively regulate G-PROTEIN-COUPLED RECEPTORS (GPCRs) and may also function independently of GPCR signaling. (bioportfolio.com)
  • 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)
  • 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 serine/threonine protein kinase ( EC 2.7.11.1 ) is a kinase enzyme that phosphorylates the OH group of serine or threonine (which have similar sidechains). (wikipedia.org)
  • These were formerly included in EC number "2.7.1.37", which was a general EC number for any enzyme that phosphorylates proteins while converting ATP to ADP (i.e. (wikipedia.org)
  • In the ERK MAP kinase cascade, activated Raf-1, a serine-threonine kinase, initiates the signaling cascade through MEK, which in turn phosphorylates a second serine-threonine kinase ERK. (aacrjournals.org)
  • ERK phosphorylates additional kinases and specific transcription factors important in cell proliferation and survival. (aacrjournals.org)
  • It plays an important role in the cascades of cellular responses evoked by changes in the environment. (medgadget.com)
  • Thank you for sharing this Molecular and Cellular Biology article. (asm.org)
  • Message Body (Your Name) thought you would be interested in this article in Molecular and Cellular Biology. (asm.org)
  • Molecular and cellular biology , 25 (9), 3831-3841. (elsevier.com)
  • 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)
  • While the catalytic domain of these kinases is highly conserved , the sequence variation that is observed in the kinome (the subset of genes in the genome that encode kinases) provides for recognition of distinct substrates. (wikipedia.org)
  • Of five housekeeping genes examined for make use of as an endogenous control, the ribosomal proteins S9 was driven to be minimal variable across period factors, and was selected. (informationalwebs.com)
  • The induced genes are involved in translocation, protein glycosylation, vesicular transport, cell wall biosynthesis, vacuolar protein targeting, and ER-associated degradation ( 10 ). (aacrjournals.org)
  • Además, hemos demostrado que respuestas asociadas a PTI, como el aumento en la concentración de calcio citoplásmico, la producción de especies reactivas de oxígeno, la fosforilación de MAP quinasas y la expresión de genes de defensa, no están afectadas en el mutante yda11. (upm.es)
  • These insights show how proteins can modulate the properties of fluids inside the cell, potentially influencing how genes are expressed. (asbmb.org)
  • We have shown that the same genes that heal puncture wounds are also activated after oral-aboral bisection, indicating a clear link with the initiation of regenerative healing. (biomedcentral.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)
  • The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. (nih.gov)
  • 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. (nih.gov)
  • 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)
  • This kinase was reported to interact with, phosphorylate and repress the activity of E47, which is a basic helix-loop-helix transcription factor known to be involved in the regulation of tissue-specific gene expression and cell differentiation. (mybiosource.com)
  • CHOP, a member of the C/EBP family of transcription factors, mediates effects of cellular stress on growth and differentiation. (sciencemag.org)
  • A yeast mitogen-activated protein kinase homolog (Mpk1p) mediates signalling by protein kinase C. (asm.org)
  • This kinase targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. (wikidoc.org)
  • Previously, we showed that hypoxia activates the UPR and mediates survival under these conditions. (aacrjournals.org)
  • The mitogen-activated protein kinase p38 mediates cellular responses to injurious stress and immune signaling. (sigmaaldrich.com)
  • The BCK1 gene is also predicted to encode a protein kinase which has been proposed to function downstream of the protein kinase C isozyme encoded by PKC1. (asm.org)
  • Involved in the innate immune MAP kinase signaling cascade (MEKK1, MKK4/MKK5 and MPK3/MPK6) downstream of bacterial flagellin receptor FLS2. (uniprot.org)
  • We propose a model by which MKNK1 acts to facilitate viral entry downstream of the epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK), both of which have been implicated in the entry process. (yonsei.ac.kr)
  • Thus the role of mammalian ERK1/2 kinases as regulators of cell proliferation is not a generic, but a highly specialized function. (wikipedia.org)
  • Schaeffer and Weber, 1999 ) respond to mitogens and survival signals and stimulate cell proliferation, growth and survival. (biologists.org)
  • These results indicate that Pin1 amplifies EGF signaling in breast cancer cells through its interaction with MEK1 and then enhances HER-2 expression, suggesting that Pin1 plays an important role in the overexpression of HER-2 through Pin1-MEK1-activator protein-2α signaling in breast cancer. (aacrjournals.org)
  • EPO-dependent long term proliferation of T-JER cells was conferred by expression of the constitutively activated form of MEK1. (biomedsearch.com)
  • Here, we demonstrate that acetylation of the mitogen-activated protein kinase kinase-1 (MEK1) stimulates its kinase activity, and that acetylated MEK1 is under the regulatory control of the sirtuin family members SIRT1 and SIRT2. (uncg.edu)
  • RAF1 then further activates the dual-specificity protein kinases MAP2K1 /MEK1 and MAP2K2 /MEK2. (rcsb.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)
  • The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. (nih.gov)
  • Nonreceptor tyrosine phosphatases in cellular signaling: regulation of mitogen-activated protein kinases. (readabstracts.com)
  • The structure, catalysis and regulation of the protein phosphatases and protein tyrosine phosphatases have been investigated. (readabstracts.com)
  • The regulation of the mitogen-activated protein kinase signaling by these phosphatases is discussed. (readabstracts.com)
  • In vivo regulation of protein-serine kinases by insulin in skeletal muscle of fructose-hypertensive rats. (semanticscholar.org)
  • These contribute in multiple ways to regulation of cellular metabolism and may have direct and indirect effects on virus replication. (yonsei.ac.kr)
  • 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)
  • Genetic regulation and cellular expression. (usda.gov)
  • This entry represents mitogen-activated protein kinase kinase kinase 7 (MAP3K7), which is a component of a protein kinase signal transduction cascade, acting as a mediator of TGF-beta signal transduction. (ebi.ac.uk)
  • Thus, the two substrates of this enzyme are ATP and a protein , whereas its two products are ADP and phosphoprotein . (wikipedia.org)
  • 1997). Another p38gamma substrates that do not require PDZ domain binding interactions are the mitochondrial protein Sab (Court et al. (atlasgeneticsoncology.org)
  • AS-ERK2 can be used to label its direct substrates with thiophosphate in an in vitro kinase reaction. (mit.edu)
  • High throughput identification of potential arabidopsis mitogen-activated protein kinases substrates. (mpg.de)
  • Proinflammatory cytokines have been reported to activate several transcription factors that are intimately linked to the expression of inflammatory and catabolic signals. (karger.com)
  • This kinase is activated by various environmental stresses and proinflammatory cytokines. (nih.gov)
  • In the case of infection, epithelial cells become activated to express and secrete proinflammatory and chemoattractant cytokines, including interleukin 8 (IL-8), GROα, GROβ, monocyte chemoattractant protein 1, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, or IL-1 (reviewed in reference 15 ). (asm.org)
  • SAPKs/JNKs are activated in response to a variety of cellular stresses such as changes in osmolarity or metabolism, DNA damage, heat shock, ischemia, shear stress, inflammatory cytokines such as TNF and IL-1, and ceramide 3 4 7 . (pubmedcentralcanada.ca)
  • Importantly, these inhibitors inhibited the neoplastic cell transformation induced by EGF in Pin1-overexpressing JB6 Cl41 cells, which showed enhanced cellular formation compared with the control cells. (aacrjournals.org)
  • Kinases are tempting therapeutic targets for drug development, but achieving sufficient specificity is often a challenge for chemical inhibitors. (yonsei.ac.kr)
  • Screening of a panel of inhibitors targeting kinases that may be modulated by off-target effects of AS601245 and SP600125 led us to identify MKNK1 as a host factor involved in HCV entry. (yonsei.ac.kr)
  • Nonredox-type 5-lipoxygenase (5-LO) inhibitors such as ZM230487 or L-739.010 potently suppress leukotriene biosynthesis at low cellular peroxide tone. (nih.gov)
  • C. J. Malemud, " Small Molecular Weight Inhibitors of Stress-Activated and Mitogen- Activated Protein Kinases", Mini-Reviews in Medicinal Chemistry (2006) 6: 689. (eurekaselect.com)
  • A screen of 72 inhibitors against 456 human kinases. (guidetopharmacology.org)
  • A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase Hotspot SM platform. (guidetopharmacology.org)
  • Generation of minimal protein identifiers of proteins from two-dimensional gels and recombinant proteins. (mpg.de)
  • Types include those acting directly as receptors ( Receptor protein serine/threonine kinase ) and Intracellular signaling peptides and proteins . (wikipedia.org)
  • Despite the requirement of FASN for nascent virion production, FASN activity was not required for intracellular Gag protein production, indicating that FASN dependent de novo fatty acid biosynthesis contributes to a late step of HIV-1 replication. (springer.com)
  • Moreover, the MAP kinase family members JNK, ERK, and p38 are also activated in response to a wide variety of extracellular stimuli. (aacrjournals.org)
  • Tras el reconocimiento de los PAMPs/DAMPs por receptores de membrana denominados PRRs (Pattern Recognition Receptors), como los receptores con dominio quinasa (RLKs) o los receptores sin dominio quinasa (RLPs), se activan respuestas moleculares, incluidas cascadas de MAP quinasas, que regulan la puesta en marcha de la inmunidad activada por PAMPs (PTI). (upm.es)
  • protein -coupled receptors (GPCRs), its application to the study of receptor homomers and heteromers have unveiled the diversity of complexes these GPCRs can form at the plasma membrane at a structural and functional level. (bioportfolio.com)
  • Super-Resolution Imaging of G Protein-Coupled Receptors Using Ground State Depletion Microscopy. (bioportfolio.com)
  • G protein-coupled receptors (GPCRs) comprise the largest family of integral membrane proteins, which are coupled to heterotrimeric G proteins to influence cell signaling. (bioportfolio.com)
  • G protein-coupled receptors (GPCRs) contain highly hydrophobic domains that are subject to aggregation when exposed to the crowded environment of the cytoplasm. (bioportfolio.com)
  • Since the consensus sequence residues of a target substrate only make contact with several key amino acids within the catalytic cleft of the kinase (usually through hydrophobic forces and ionic bonds ), a kinase is usually not specific to a single substrate, but instead can phosphorylate a whole "substrate family" which share common recognition sequences. (wikipedia.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)
  • In vitro studies demonstrated that ERK, p38 MAP kinase and Jun N-terminal kinase were all able to phosphorylate and activate this kinase, which suggested the role of this kinase as an integrative element of signaling in both mitogen and stress responses. (mybiosource.com)
  • Mitogen-activated protein kinase 9 is an enzyme that in humans is encoded by the MAPK9 gene . (wikidoc.org)
  • The systematic name of this enzyme class is ATP:protein phosphotransferase (non-specific) . (wikipedia.org)
  • A signaling enzyme, i.e., one that circulates extracellularly, influencing cells to begin protein manufacturing. (thefreedictionary.com)
  • MBS077469 is a ready-to-use microwell, strip-or-full plate ELISA (enzyme-linked immunosorbent assay) Kit for analyzing the presence of the Mitogen Activated Protein Kinase -Activa Protein Kinase 3 (MAPKAPK3) ELISA Kit target analytes in biological samples. (mybiosource.com)
  • In particular, compound 3f is highly potent in the enzyme and cell-based assays, selective in an Ambit kinase screen, and efficacious (ED(50) (rcsb.org)
  • Targeting Tyrosine Kinases in Acute Myeloid Leukemia: Why, Who and How? (mdpi.com)
  • X-ray structure of the ERK2 MAP kinase in its active form. (wikipedia.org)
  • 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)
  • This approach utilizes an ERK2 kinase with "gatekeeper" mutation that allows it to bind bulky ATP analogs (AS-ERK2). (mit.edu)
  • This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). (nih.gov)
  • We first confirmed, using activating transcription factor 3 and neuropeptide Y immunoreactivity, that virtually all L4 DRG neurons are spared from axotomy in this model. (jneurosci.org)
  • The transcription factor Egr-1 is an immediate-early-induced gene that is activated in most cell types in response to stress. (asm.org)
  • We study (1) transport proteins through which metals enter or leave cells, (2) signal transduction and transcriptional regulatory mechanisms that cells use to sense and respond to metals, and (3) proteins and cellular processes that are targeted by metals. (gu.se)
  • Similar to the RIT1 gene mutations that cause Noonan syndrome (described above), the mutations involved in these cancers likely result in a constitutively active protein. (medlineplus.gov)
  • 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)
  • Moreover, activated epithelial cells play an important role in the initiation of inflammatory and immune responses by transmitting signals to underlying cells of the reticuloendothelial system. (asm.org)
  • Although these NAD+-dependent deacetylases control adaptive cellular responses, identification of sirtuin-regulated signaling targets remain under-studied. (uncg.edu)
  • A typical example is wound-induced protein kinase (WIPK), which functions during pathogen responses in tobacco plants (Nicotiana tabacum). (deepdyve.com)
  • Over the last decade important advances have been made in our understanding of the molecular events underlying cellular responses to extracellular signals. (ebscohost.com)
  • Although much is known about the mechanism of action of Bacillus thuringiensis Cry toxins, the target tissue cellular responses to toxin activity is less understood. (biomedcentral.com)
  • The oxytocin receptor belongs to the rhodopsin-type class I G-protein-coupled receptor (GPCR) superfamily. (hindawi.com)
  • MAP kinases are also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. (mybiosource.com)
  • p38gamma (MAPK12) is a Serine/Threonine protein kinase of 367 amino acids with a predicted molecular mass of 42 kDa. (atlasgeneticsoncology.org)
  • The RIT1 gene mutations associated with Noonan syndrome change single protein building blocks (amino acids) in the RIT1 protein. (medlineplus.gov)
  • The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. (nih.gov)
  • Opposing Oncogenic Functions of p38 Mitogen-activated Protein Kinase Alpha and Beta in Human Pancreatic Cancer Cells. (nih.gov)
  • By reacting with DNA, proteins, and lipids, NO impairs normal cellular functions and thus exerts its cytotoxic effects ( 4 , 8 , 9 ). (jimmunol.org)
  • p38gamma (MAPK12) regulates many cellular functions by phosphorylating several proteins. (atlasgeneticsoncology.org)
  • This kinase functions as a mitogen-activated protein kinase (MAP kinase)- activated protein kinase. (mybiosource.com)
  • The kinase p38 alpha serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression. (sigmaaldrich.com)
  • Valosin containing protein (VCP), also named p97, is an essential hexameric AAA+ ATPase with diverse functions in the ubiquitin system. (bioportfolio.com)
  • One proposed function of trehalose is the stabilisation of proteins and membrane structures by formation of an organic glass, which 'freezes' the cell and its contents in time and space (reviewed in Crowe, 2002 ). (biologists.org)
  • Activated AMP-activated protein kinase and increased peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) have been suggested to mediate the regulatory effects of adiponectin on mitochondrial biogenesis and function ( 13 , 16 - 18 ). (diabetesjournals.org)
  • Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchymally derived signal that acts through the c- met receptor as a morphogen and mitogen for epithelial cells 1 and hepatocytes 2 and is implicated in both developmental and adult processes. (ahajournals.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)
  • Studies of the heterotrimeric G-proteins in N. crassa reveal a role in aerial hyphae formation and asexual sporulation ( K ays and B orkovich 2004 ) and additional roles in protoperithecium function ( K im and B orkovich 2004 ). (genetics.org)
  • TNF-α, IL-1β, and IL-6 are macrophage- and fibroblast-derived proteins that induce expression of inflammatory mediators such as COX-2, inducible nitric-oxide synthase, adhesion molecules, and metalloproteinases, resulting in synovial inflammation and associated cartilage and bone destruction. (aspetjournals.org)
  • p38 kinase along with ERK and JNK are key MAP kinase signaling enzymes that cells use to adapt to inflammatory and stressful conditions. (aspetjournals.org)
  • These proteins have an effect on cellular replication and cellular death in inflammatory, ischemic, and malignant diseases. (thefreedictionary.com)
  • They affect cellular replication and death in inflammatory, ischemic, and malignant diseases. (thefreedictionary.com)
  • HSFA4A interacts with mitogen-activated protein kinases MPK3 and MPK6 in yeast and plant cells. (plantphysiol.org)
  • These enzymes transfer phosphates to the oxygen atom of a serine or threonine sidechain in proteins . (wikipedia.org)
  • RNA granules are spots in the cell in which RNA molecules and RNA-binding proteins aggregate to carry out RNA modifications that affect gene expression. (asbmb.org)
  • Some nematodes can survive almost complete desiccation by entering an ametabolic state called anhydrobiosis requiring the accumulation of protective molecules such as trehalose and LEA proteins. (biologists.org)
  • In immunohistochemical analyses or using expression of fluorescence-tagged proteins, treatment with sorafenib and vorinostat together (sorafenib + vorinostat) promoted colocalization of CD95 with caspase 8 and CD95 association with the endoplasmic reticulum markers calnexin, ATG5, and Grp78/BiP. (aspetjournals.org)
  • Understanding the molecular signaling network associated with the IR-induced adaptive response will provide essential information on specific gene/protein targets to resensitize radioresistant tumor cells. (aacrjournals.org)
  • In a variety of human tumors, investigators have reported elevated expression of UPR targets, such as Grp78 (also called binding protein or BiP) and Grp94 ( 11 ). (aacrjournals.org)
  • ERK controls cellular phenotypes by phosphorylating over two hundred known substrate proteins, however new ERK targets are reported frequently. (mit.edu)
  • Targets of the selective autophagic machinery include organelles, protein aggregates, and even invading microorganisms. (hindawi.com)
  • Since host therapeutic targets evolve more slowly than viral therapeutic targets, antiviral therapy targeting host proteins would likely impose a high barrier to drug resistance. (springer.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)
  • Here, we show that MKK3-MPK6 is activated by blue light in a MYC2-dependent manner. (plantcell.org)
  • Esta Tesis describe la caracterización funcional de la MAP quinasa quinasa quinasa (MAP3K) YODA (YDA), que actúa como un regulador clave de la PTI en Arabidopsis. (upm.es)
  • Nuestros datos indican que esta función es independiente de las respuestas inmunes mediadas por los receptores previamente caracterizados FLS2 y CERK1, que reconocen los PAMPs flg22 y quitina, respectivamente, y que están implicados en la resistencia de Arabidopsis frente a bacterias y hongos. (upm.es)
  • La expresión constitutiva de la proteína CA-YDA en plantas de Arabidopsis no provoca un aumento de las respuestas PTI, lo que sugiere la existencia de mecanismos de resistencia adicionales regulados por YDA que son diferentes de los regulados por FLS2 y CERK1. (upm.es)
  • EPEC attaches to intestinal epithelial cells by the interaction of an outer membrane protein, intimin, and a type III secreted protein that is translocated into the host cell membrane, Tir. (asm.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)
  • Here we report the isolation of a Saccharomyces cerevisiae gene encoding a functional analog of mammalian MAP kinases, designated MPK1 (for MAP kinase). (asm.org)
  • It is well known from various mammalian cells that anoxia has a major impact on the mitogen-activated protein kinase ERK, but a possible similar effect in fish cells has not been investigated. (biologists.org)
  • The mitochondrion is an organelle in mammalian cells that converts nutritional metabolites into adenosine triphosphate for cellular energy supply. (diabetesjournals.org)
  • The alfalfa ( Medicago sativa ) TDY1 gene encodes a mitogen-activated protein kinase homolog. (usda.gov)