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.
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 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 superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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.
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 mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
A 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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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 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.
Amino acid sequences found in transported proteins that selectively guide the distribution of the proteins to specific cellular compartments.
Agents that inhibit PROTEIN KINASES.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A 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.
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 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.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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.
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A group of phenyl benzopyrans named for having structures like FLAVONES.
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 sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A family of 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 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.
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.
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.
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.
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.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
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.
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.
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.
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).
Proteins prepared by recombinant DNA technology.
The rate dynamics in chemical or physical systems.
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.
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.
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 class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
Four carbon unsaturated hydrocarbons containing two double bonds.
A 110-kDa extracellular signal-regulated MAP kinase that is activated in response to cellular stress and by GROWTH FACTOR RECEPTORS-mediated pathways.
A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.
A 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 fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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 ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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)
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
A 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.
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.
A mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 7.
Elements of limited time intervals, contributing to particular results or situations.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A cell line derived from cultured tumor cells.
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.
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.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC
A 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.
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.
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.
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.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to CYTOKINES.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
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)
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.
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.
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
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A 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.
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 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 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.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
A 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 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.
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.
A dual specificity phosphatase subtype that plays a role in intracellular signal transduction by inactivating MITOGEN-ACTIVATED PROTEIN KINASES. It has specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES and JNK MITOGEN-ACTIVATED PROTEIN KINASES.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
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.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
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 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.
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.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A 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 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).
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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 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.
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 multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.
Cellular DNA-binding proteins encoded by the c-jun genes (GENES, JUN). They are involved in growth-related transcriptional control. There appear to be three distinct functions: dimerization (with c-fos), DNA-binding, and transcriptional activation. Oncogenic transformation can take place by constitutive expression of c-jun.
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.
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.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
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.
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.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
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.
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.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
A 150-kDa MAP kinase kinase kinase that may play a role in the induction of APOPTOSIS. It has specificity for MAP KINASE KINASE 3; MAP KINASE KINASE 4; and MAP KINASE KINASE 6.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
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 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.
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.
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 species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.
Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.
Proteins that are coded by immediate-early genes, in the absence of de novo protein synthesis. The term was originally used exclusively for viral regulatory proteins that were synthesized just after viral integration into the host cell. It is also used to describe cellular proteins which are synthesized immediately after the resting cell is stimulated by extracellular signals.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Proteins found in any species of fungus.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
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.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
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.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
A 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.
Proteins found in any species of bacterium.
Representations, normally to scale and on a flat medium, of a selection of material or abstract features on the surface of the earth, the heavens, or celestial bodies.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Adherence of cells to surfaces or to other cells.
A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
Gated transport mechanisms by which proteins or RNA are moved across the NUCLEAR MEMBRANE.
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.
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.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
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).
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.

Effect of inhibition of cholesterol synthetic pathway on the activation of Ras and MAP kinase in mesangial cells. (1/5946)

Intermediary metabolites of cholesterol synthetic pathway are involved in cell proliferation. Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, blocks mevalonate synthesis, and has been shown to inhibit mesangial cell proliferation associated with diverse glomerular diseases. Since inhibition of farnesylation and plasma membrane anchorage of the Ras proteins is one suggested mechanism by which lovastatin prevents cellular proliferation, we investigated the effect of lovastatin and key mevalonate metabolites on the activation of mitogen-activated protein kinase (MAP kinase) and Ras in murine glomerular mesangial cells. The preincubation of mesangial cells with lovastatin inhibited the activation of MAP kinase stimulated by either FBS, PDGF, or EGF. Mevalonic acid and farnesyl-pyrophosphate, but not cholesterol or LDL, significantly prevented lovastatin-induced inhibition of agonist-stimulated MAP kinase. Lovastatin inhibited agonist-induced activation of Ras, and mevalonic acid and farnesylpyrophosphate antagonized this effect. Parallel to the MAP kinase and Ras data, lovastatin suppressed cell growth stimulated by serum, and mevalonic acid and farnesylpyrophosphate prevented lovastatin-mediated inhibition of cellular growth. These results suggest that lovastatin, by inhibiting the synthesis of farnesol, a key isoprenoid metabolite of mevalonate, modulates Ras-mediated cell signaling events associated with mesangial cell proliferation.  (+info)

Age-dependent decline in mitogenic stimulation of hepatocytes. Reduced association between Shc and the epidermal growth factor receptor is coupled to decreased activation of Raf and extracellular signal-regulated kinases. (2/5946)

The proliferative potential of the liver has been well documented to decline with age. However, the molecular mechanism of this phenomenon is not well understood. Cellular proliferation is the result of growth factor-receptor binding and activation of cellular signaling pathways to regulate specific gene transcription. To determine the mechanism of the age-related difference in proliferation, we evaluated extracellular signal-regulated kinase-mitogen-activated protein kinase activation and events upstream in the signaling pathway in epidermal growth factor (EGF)-stimulated hepatocytes isolated from young and old rats. We confirm the age-associated decrease in extracellular signal-regulated kinase-mitogen-activated protein kinase activation in response to EGF that has been previously reported. We also find that the activity of the upstream kinase, Raf kinase, is decreased in hepatocytes from old compared with young rats. An early age-related difference in the EGF-stimulated pathway is shown to be the decreased ability of the adapter protein, Shc, to associate with the EGF receptor through the Shc phosphotyrosine binding domain. To address the mechanism of decreased Shc/EGF receptor interaction, we examined the phosphorylation of the EGF receptor at tyrosine 1173, a site recognized by the Shc phosphotyrosine binding domain. Tyrosine 1173 of the EGF receptor is underphosphorylated in the hepatocytes from old animals compared with young in a Western blot analysis using a phosphospecific antibody that recognizes phosphotyrosine 1173 of the EGF receptor. These data suggest that a molecular mechanism underlying the age-associated decrease in hepatocyte proliferation involves an age-dependent regulation of site-specific tyrosine residue phosphorylation on the EGF receptor.  (+info)

Genetic analysis of rolled, which encodes a Drosophila mitogen-activated protein kinase. (3/5946)

Genetic and molecular characterization of the dominant suppressors of D-raf(C110) on the second chromosome identified two gain-of-function alleles of rolled (rl), which encodes a mitogen-activated protein (MAP) kinase in Drosophila. One of the alleles, rl(Su23), was found to bear the same molecular lesion as rl(Sem), which has been reported to be dominant female sterile. However, rl(Su23) and the current stock of rl(Sem) showed only a weak dominant female sterility. Detailed analyses of the rl mutations demonstrated moderate dominant activities of these alleles in the Torso (Tor) signaling pathway, which explains the weak dominant female sterility observed in this study. The dominant rl mutations failed to suppress the terminal class maternal-effect mutations, suggesting that activation of Rl is essential, but not sufficient, for Tor signaling. Involvement of rl in cell proliferation was also demonstrated by clonal analysis. Branching and integration of signals in the MAP kinase cascade is discussed.  (+info)

Ciliary neurotrophic factor and stress stimuli activate the Jak-STAT pathway in retinal neurons and glia. (4/5946)

Ciliary neurotrophic factor (CNTF) is pleiotrophic for central, peripheral, and sensory neurons. In the mature retina, CNTF treatment enhances survival of retinal ganglion and photoreceptor cells exposed to otherwise lethal perturbation. To understand its mechanism of action in vivo, the adult rat retina was used as a model to investigate CNTF-mediated activation of Janus kinase/signal transducer and activator of transcription (Jak-STAT) and ras-mitogen activated protein kinase (ras-MAPK). Intravitreal injection of Axokine, an analog of CNTF, phosphorylates STAT3 and MAPK and produces delayed upregulation of total STAT3 and STAT1 protein in rat retina. Activated STAT3 is predominantly localized in nuclei of retinal Muller (glial) cells, ganglion cells, and astrocytes, but not in photoreceptors. Although CNTF alpha-receptor (CNTFRalpha) mRNA and protein are localized predominantly if not exclusively in retinal neurons, coincident CNTF-mediated STAT3 signaling was observed in both glia and neurons. CNTF-induced activation of Jak-STAT signaling prompted us to investigate STAT3 phosphorylation after a variety of stress-mediated, conditioning stimuli. We show that STAT3 is activated in the retina after exposure to subtoxic bright light, mechanical trauma, and systemic administration of the alpha(2)-adrenergic agonist xylazine, all of which have been shown previously to condition photoreceptors to resist light-induced degeneration. These results demonstrate that CNTF directly stimulates Jak-STAT and ras-MAPK cascades in vivo and strongly suggest that STAT3 signaling is an underlying component of neural responsiveness to stress stimuli. The observation that CNTF activates STAT3 in ganglion cells, but not in photoreceptors, suggests that Jak-STAT signaling influences neuronal survival via both direct and indirect modes of action.  (+info)

EGF receptor/Rolled MAP kinase signalling protects cells against activated Armadillo in the Drosophila eye. (5/5946)

beta-catenin/Armadillo are transcriptional co-activators that mediate Wnt signalling in normal development. Activated forms of beta-catenin are oncogenic. We have constructed mutant forms of Drosophila Armadillo which correspond to common human oncogenic mutations, and find them to activate Armadillo constitutively. When expressed in the Drosophila eye, these eventually induce apoptosis in all cell types. Intriguingly, cells in the eye are resistant to the effects of activated Armadillo for a long period prior to the onset of cell death at the mid-pupal stage. This latency is conferred by EGF receptor (EGFR)/MAP kinase signalling, which prevents activated Armadillo from inducing apoptosis; when EGFR signalling naturally ceases, the cells rapidly die. Nemo, the Drosophila homologue of NLK in mice and LIT-1 in Caenorhabditis elegans, does not antagonize activated Armadillo, suggesting that the Nemo-like MAP kinases may not generally interact with Armadillo/beta-catenin. Thus, our results show that activated Armadillo is subject to a specific negative control by EGFR/Rolled MAP kinase signalling.  (+info)

ERK7 is an autoactivated member of the MAPK family. (6/5946)

Extracellular signal-regulated kinase 7 (ERK7) shares significant sequence homology with other members of the ERK family of signal transduction proteins, including the signature TEY activation motif. However, ERK7 has several distinguishing characteristics. Unlike other ERKs, ERK7 has been shown to have significant constitutive activity in serum-starved cells, which is not increased further by extracellular stimuli that typically activate other members of the mitogen-activated protein kinase (MAPK) family. On the other hand, ERK7's activation state and kinase activity appear to be regulated by its ability to utilize ATP and the presence of its extended C-terminal region. In this study, we investigated the mechanism of ERK7 activation. The results suggest that 1) MAPK kinase (MEK) inhibitors do not suppress ERK7 kinase activity; 2) intramolecular autophosphorylation is sufficient for activation of ERK7 in the absence of an upstream MEK; and 3) multiple regions of the C-terminal domain of ERK7 regulate its kinase activity. Taken together, these results indicate that autophosphorylation is sufficient for ERK7 activation and that the C-terminal domain regulates its kinase activity through multiple interactions.  (+info)

Drosophila Fos mediates ERK and JNK signals via distinct phosphorylation sites. (7/5946)

During Drosophila development Fos acts downstream from the JNK pathway. Here we show that it can also mediate ERK signaling in wing vein formation and photoreceptor differentiation. Drosophila JNK and ERK phosphorylate D-Fos with overlapping, but distinct, patterns. Analysis of flies expressing phosphorylation site point mutants of D-Fos revealed that the transcription factor responds differentially to JNK and ERK signals. Mutations in the phosphorylation sites for JNK interfere specifically with the biological effects of JNK activation, whereas mutations in ERK phosphorylation sites affect responses to the EGF receptor-Ras-ERK pathway. These results indicate that the distinction between ERK and JNK signals can be made at the level of D-Fos, and that different pathway-specific phosphorylated forms of the protein can elicit different responses.  (+info)

A circadian output in Drosophila mediated by neurofibromatosis-1 and Ras/MAPK. (8/5946)

Output from the circadian clock controls rhythmic behavior through poorly understood mechanisms. In Drosophila, null mutations of the neurofibromatosis-1 (Nf1) gene produce abnormalities of circadian rhythms in locomotor activity. Mutant flies show normal oscillations of the clock genes period (per) and timeless (tim) and of their corresponding proteins, but altered oscillations and levels of a clock-controlled reporter. Mitogen-activated protein kinase (MAPK) activity is increased in Nf1 mutants, and the circadian phenotype is rescued by loss-of-function mutations in the Ras/MAPK pathway. Thus, Nf1 signals through Ras/MAPK in Drosophila. Immunohistochemical staining revealed a circadian oscillation of phospho-MAPK in the vicinity of nerve terminals containing pigment-dispersing factor (PDF), a secreted output from clock cells, suggesting a coupling of PDF to Ras/MAPK signaling.  (+info)

FIG. 1. LPS stimulation induces a p105-free pool of TPL-2 which activates MEK. BMDMs (BALB/c) were stimulated with LPS for the indicated times. (A) TPL-2 was immunoprecipitated from cell lysates with anti-TPL-2 antibody, and its MEK kinase activity was determined by coupled MEK/ERK kinase assay. Labeled MBP substrate was visualized by autoradiography after SDS-PAGE, and the levels of immunoprecipitated TPL-2 were determined by Western blotting. Lysates were also subjected to Western blotting with an anti-phospho-(S217/S221)-MEK-1/2 antibody (phospho-MEK) to determine activation of endogenous MEK by LPS. (B) TPL-2 was immunoprecipitated from cell lysates. Beads were incubated with 0.5 U of PP2A, 0.5 U of PP2A plus the phosphatase inhibitors NaF and okadaic acid (PP2A + Inhibitors), or control buffer. Immunoprecipitated TPL-2 was revealed by Western blotting. (C) Cell lysates and anti-p105 immunoprecipitates were subjected to Western blotting. (D) Total cell lysates (lysates) and p105 cleared ...
Maudsley S., Pierce K.L., Zamah A.M., Miller W.E., Ahn S., Daaka Y., Lefkowitz R.J., Luttrell L.M.. Many G protein-coupled receptors (GPCRs) activate MAP kinases by stimulating tyrosine kinase signaling cascades. In some systems, GPCRs stimulate tyrosine phosphorylation by inducing the transactivation of a receptor tyrosine kinase (RTK). The mechanisms underlying GPCR-induced RTK transactivation have not been clearly defined. Here we report that GPCR activation mimics growth factor-mediated stimulation of the epidermal growth factor receptor (EGFR) with respect to many facets of RTK function. beta(2)-Adrenergic receptor (beta(2)AR) stimulation of COS-7 cells induces EGFR dimerization, tyrosine autophosphorylation, and EGFR internalization. Coincident with EGFR transactivation, isoproterenol exposure induces the formation of a multireceptor complex containing both the beta(2)AR and the transactivated EGFR. beta(2)AR-mediated EGFR phosphorylation and subsequent beta(2)AR stimulation of ...
The MAPK/ERK pathway is a central signaling pathway for many cellular processes, including proliferation, differentiation, and survival. With physiologic signaling, the transcriptional response is coupled to MAPK pathway activation, which is intricately regulated and depends on both the type and duration of upstream stimulus. Negative-feedback regulators of the MAPK pathway, such as the ERK phosphatase DUSP6, are strongly induced to limit the intensity and duration of ERK pathway activation and maintain MAPK signaling homeostasis (11). In cancer, tumors harboring constitutive MAPK/ERK activation express high levels of negative-feedback regulators that are often used as a surrogate biomarker for MAPK/ERK pathway signaling strength, and their rapid decline upon MAPK pathway inhibition indicates therapeutic efficacy, but is also exploited by cancer cells for early adaptation, development of persistent disease, and eventual emergence of resistant disease (11, 39).. The development of potent ...
S. Xie*, B. Schurink, F. Wolbers, R. Luttge*, and G. Hassink. Nanoscaffolds stiffness affects primary cortical cell network formation. J. Vac. Sci. Technol. B. 2014, 32(6), 06FD03.. S. Xie*, R. Luttge*. Imprint lithography provides topographical nanocues to guide cell growth in primary cortical cell culture. Microelectron. Eng. 2014, 124, 30-36.. Xie, S. J.; Lu, Y. X.; Zhang, S. C.; Wang, L.D.; Zhang X.R.*. Electro-optical gas sensor based on a planar light-emitting electrochemical cell microarray, Small. 2010, 6(17), 1897-1899.. Xiaoyan Wang, Kenichi Harimoto,Sijia Xie, Hao Cheng, Jing Liu, and Zhao Wang*. Matrix Protein Biglycan Induces Osteoblast Differentiation through Extracellular Signal-Regulated Kinase and Smad Pathways. Biol. Pharm. Bull. 2010, 33(11) 1891-1897. ...
p38 Mitogen-Activated Protein Kinases;Tumor Necrosis Factor-alpha;Extracellular Signal-Regulated MAP Kinases;Interferon-gamma;Nitric Oxide;Microglia;Astrocytes;RNA, Messenger;Reverse Transcriptase Polymerase Chain Reaction;MAP Kinase Signaling ...
p38 Mitogen-Activated Protein Kinases;Tumor Necrosis Factor-alpha;Extracellular Signal-Regulated MAP Kinases;Interferon-gamma;Nitric Oxide;Microglia;Astrocytes;RNA, Messenger;Reverse Transcriptase Polymerase Chain Reaction;MAP Kinase Signaling ...
However, the results presented in Fig. 7E, and the observation that Tpl2 overexpression increases ERK1/2 activity (32), suggest that Tpl2 expression could be rate-limiting for the activation of ERK pathway ...
The extracellular-signal-regulated kinase (ERK) pathway is one of the major signaling cassettes of the mitogen activated protein kinase (MAPK) signaling ..
FIG. 3. ERK MAP kinase signaling enhances PEA3 sumoylation. (A to F) In vivo sumoylation of wild-type PEA3 or the indicated mutant forms of PEA3 in transfected 293 cells was probed as described for Fig. 1C. (A) PMA and/or MG132 was added 6 h before harvesting, as indicated. Ubc9 and His-tagged SUMO-2 were cotransfected with PEA3. SUMO-conjugated PEA3 was detected by immunoblotting (IB) with anti-PEA3 antibodies (left panel) and total precipitated SUMO conjugates were detected by anti-SUMO-2 antibodies (right panel). (B) The levels of input PEA3 protein in panel A were normalized and the amounts of precipitated samples run on the gel were normalized, due to PMA affecting overall PEA3 levels. This enabled comparisons to be made based on equal amounts of PEA3 protein. (C) Cells were cotransfected with Ubc9, His-tagged SUMO-2, and the indicated PEA3 derivatives and sumoylation was detected following 6 h of treatment with PMA. (D) PEA3 was contransfected with His-tagged SUMO-2 and dnUbc9, and cells ...
TY - JOUR. T1 - Lithium protection of phencyclidine-induced neurotoxicity in developing brain. T2 - The role of phosphatidylinositol-3 kinase/Akt and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathways. AU - Xia, Yan. AU - Wang, Cheng Z.. AU - Liu, Jie. AU - Anastasio, Noelle. AU - Johnson, Kenneth M.. PY - 2008/9. Y1 - 2008/9. N2 - Phencyclidine (PCP) and other N-methyl-D-aspartate (NMDA) receptor antagonists have been shown to be neurotoxic to developing brains and to result in schizophrenia-like behaviors later in development. Prevention of both effects by antischizophrenic drugs suggests the validity of PCP neurodevelopmental toxicity as a heuristic model of schizophrenia. Lithium is used for the treatment of bipolar and schizoaffective disorders and has recently been shown to have neuroprotective properties. The present study used organotypic corticostriatal slices taken from postnatal day 2 rat pups to investigate the protective effect of ...
In the present study, we established a novel function for LX acting on a previously unappreciated cell target, namely, human T cells. Both 15-epi-LXA4 and LXB4 inhibited TNF-α secretion from PBMC stimulated by anti-CD3 Abs. We also found that stable analogs of 15-epi-LXA4 and LXB4, namely, ATLa1, ATLa2, and 5-(R/S)-methyl-LXB4, each share this activity and inhibit TNF-α secretion to a similar extent as their corresponding origins, implying that these analogs could be used for improved in vivo treatment of T cell-mediated inflammation. Most results obtained to date indicate that TNF-α, which is produced by T cells upon stimulation by Ags, is also critical for the establishment of chronic inflammatory disorders such as arthritis, inflammatory bowel disease, and others (20, 37), and therefore serves as a primary target for therapeutic intervention (21, 38). Of interest, TNF-α also plays a role in the resolution phase of inflammation (18, 39), rendering the regulation of its bioavailability an ...
Although classic genetic analyses, such as those described above, have revealed much about the molecular pathways involved in artery-vein specification, such approaches have limitations when it comes to examining signaling pathways that function at multiple stages in development. With a typical nonconditional mutation, the primary role for a gene at later stages of development is often difficult to distinguish from indirect consequences of disrupting the gene at an earlier stage. The Hedgehog pathway, for example, plays a critical role in vasculogenesis, but is also involved in development of numerous other structures at various developmental time points.34 Moreover, classic genetic approaches can be hampered by genetic redundancy.35 A powerful alternative approach, chemical genetic analysis, can overcome the challenges posed by repeated utilization of a signaling pathway during development and by genetic redundancy. Recently, Hedgehog signaling inhibitor cyclopamine was instrumental in ...
ATM and the catalytic subunit of DNA-dependent protein kinase activate NF-kappaB through a common MEK/extracellular signal-regulated kinase/p90(rsk) signaling pathway in response to distinct forms of DNA damage. Mol Cell Biol. 2004 Mar; 24(5):1823-35 ...
The RAS/ERK pathway has been intensely studied for about three decades, not least because of its role in human pathologies. ERK activation is observed in the majority of human cancers; in about one-third of them, it is driven by mutational activation of pathway components. The pathway is arguably one of the best targets for molecule-based pharmacological intervention, and several small-molecule inhibitors are in clinical use. Genetically engineered mouse models have greatly contributed to our understanding of signaling pathways in development, tissue homeostasis, and disease. In the specific case of the RAS/ERK pathway, they have revealed unique biological roles of structurally and functionally similar proteins, new kinase-independent effectors, and unsuspected relationships with other cascades. This short review summarizes the contribution of mouse models to our current understanding of the pathway. ...
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as MAPK1, extracellular signal-regulated kinase 2, PRKM1, PRKM2, ERT1, p41-ERK1, p41-MAPK, p42-MAPK, MAP kinase 1, MAP kinase 2, MAPK1, MAPK2, p38, p40, and p41.. ...
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as MAPK1, extracellular signal-regulated kinase 2, PRKM1, PRKM2, ERT1, p41-ERK1, p41-MAPK, p42-MAPK, MAP kinase 1, MAP kinase 2, MAPK1, MAPK2, p38, p40, and p41.. ...
Abl interactor 1 also known as Abelson interactor 1 (Abi-1) is a protein that in humans is encoded by the ABI1 gene. Abl interactor 1 has been found to form a complex with EPS8 and SOS1, and is thought to be involved in the transduction of signals from Ras to Rac. In addition, the encoded protein may play a role in the regulation of EGF-induced Erk pathway activation as well as cytoskeletal reorganization and EGFR signaling. Several transcript variants encoding multiple isoforms have been found for this gene. Abi1 is adaptor protein. It interacts with c-Abl and WAVE2 which is an actin polymerization regulator. It is known that Abi1 enhances the phosphorylation of WAVE2 by c-Abl. The phosphorylation of c-Abl promotes actin polymerization. Furthermore, Abi1 is a component of the WAVE complex. Some research has shown that knockdown of Abi1 by siRNA promoted degradation of WAVE complex proteins.[citation needed] ABI1 has been shown to interact with ENAH, NCKAP1, EPS8, and SOS1. GRCh38: Ensembl ...
Multiple signaling proteins are activated in pancreatic duct cell carcinogenesis including those associated with the ERK, PKB/AKT, mTOR and STAT3 pathways. The ERK pathway activation appears also increased in duct epithelia adjacent to carcinoma, suggesting tumor micro-environmental effects.
Many stimuli mediate activation and nuclear translocation of ERK (extracellular-signal-regulated kinase) by phosphorylation on the TEY (Thr-Glu-Tyr) motif. This is necessary to initiate transcriptional programmes controlling cellular responses, but the mechanisms that govern ERK nuclear targeting are unclear. Single-cell imaging approaches have done much to increase our understanding of input-output relationships in the ERK cascade, but few studies have addressed how the range of ERK phosphorylation responses observed in cell populations influences subcellular localization. Using automated microscopy to explore ERK regulation in single adherent cells, we find that nuclear localization responses increase in proportion to stimulus level, but not the level of TEY phosphorylation. This phosphorylation-unattributable nuclear localization response occurs in the presence of tyrosine phosphatase and protein synthesis inhibitors. It is also seen with a catalytically inactive ERK2-GFP (green fluorescent ...
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Figure 2: Examples of the probability distribution (a, b, and c) and trace plots (d, e, and f) of reaction rates 2 (which indicates the simultaneous recruitment of Shc and Grb2-SOS complex from the cytosol to the cell membrane by the recruitment of EGFR (a and d)), 16 (which shows the activation of MEK proteins by active Raf (b and e)), and 38 (which refers to the dissociation of active ERK and RSK complex (c and f)) of Model 2 under ...
The Alpha SureFire® Ultra™ HV Multiplex p-ERK 1/2 + Total ERK assay kit is used to measure both the phosphorylation (Thr202/Tyr204) and total levels of endogenous
Fujishita Teruaki , Kajino-Sakamoto Rie , Kojima Yasushi , Taketo Makoto Mark , Aoki Masahiro Extracellular signal-regulated kinase is an MAPK that is most closely associated with cell proliferation, and the MEK/ERK signaling pathway is implicated in various human cancers. Although epidermal g … Cancer Science 106(6), 692-699, 2015-06 IR Ichushi Web ...
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Influence of caffeine and hyaluronic acid on collagen biosynthesis in human skin fibroblasts Magdalena Donejko,1 Andrzej Przylipiak,1 Edyta Rysiak,2 Katarzyna Gluszuk,2 Arkadiusz Surazynski2 1Department of Esthetic Medicine, 2Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Bialystok, Bialystok, Poland Aim: The aim of this study was to evaluate the effect of caffeine on collagen biosynthesis in human skin fibroblasts and the influence of hyaluronic acid (HA) on this process. Materials and methods: Collagen, [3H]-thymidine incorporation, and prolidase activity were measured in confluent human skin fibroblast cultures that had been treated with 1, 2, and 5 mM caffeine and with caffeine and 500 µg/mL HA. Western immunoblot analysis was performed to evaluate expression of ß1-integrin receptor, insulin-like growth factor receptor phospho-Akt protein and mitogen-activated protein kinase (phospho-extracellular signal-regulated kinase). Results: Caffeine inhibited collagen
TY - JOUR. T1 - Epidermal Growth Factor-Activated Extracellular Signal-Regulated Kinase Suppresses Growth Hormone Expression and Stimulates Proliferation in MtT/E Cells. AU - Nogami, H.. AU - Soya, H.. AU - Hiraoka, Y.. AU - Aiso, Sadakazu. AU - Hisano, S.. PY - 2012/2/1. Y1 - 2012/2/1. N2 - The mechanism for the inhibition of growth hormone (GH) expression by the epidermal growth factor (EGF) was examined in two clonal cell lines, MtT/E and MtT/S. The former has a negligible basal level of GH, whereas the latter has a high basal GH. The treatment of MtT/E cells with retinoic acid resulted in a significant increase in GH mRNA and subsequently GH. This stimulatory response to retinoic acid was strongly suppressed by EGF. This suppression was associated with an increase in the phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk1/2). The MEK [mitogen-activated protein kinase (MAPK) kinases that activate ERK1 and ERK2] inhibitor, PD98059, clearly inhibited the phosphorylation of ...
Antisera. Primary murine monoclonal antibodies included mouse anti-human Hsp90α/β SPA-830 (Stressgen, Victoria, British Columbia, Canada) and D01, a mouse anti-p53 mouse monoclonal antibody recognizing wild-type and mutant p53 (Santa Cruz Biotechnology, Santa Cruz, CA). The primary rabbit polyclonal antisera included antibodies to human ER-α (sc-7207; Santa Cruz Biotechnology), Akt (9272; Cell Signaling Technology, Beverly, MA), phosphorylated Akt (pAkt) recognizing phosphorylated Ser473 (9271; Cell Signaling Technology), Akt phosphosubstrate antibody recognizing the motif (R/K)X(R/K)XX(pT/pS) (9611; Cell Signaling Technology), extracellular signal-regulated kinase (9102; Cell Signaling Technology), phosphorylated extracellular signal-regulated kinase antibody recognizing phosphorylated Thr202 and Thr204 (9101; Cell Signaling Technology), Hsp90α (SPS771; Stressgen), Rb (554136; Becton Dickinson, San Jose, CA), phosphorylated Rb (pRb; 9308; Cell Signaling Technology), CDK2 (sc-163; Santa Cruz ...
Söderström T.S., Poukkula M., Holmström T.H., et al. Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in activated T cells abrogates TRAIL-induced apoptosis upstream of the mitochondrial amplification loop and caspase-8. (англ.) // J. Immunol. (англ.)русск. : journal. - 2002. - Vol. 169, no. 6. - P. 2851-2860. - PMID 12218097. ...
Inhibition of the Raf/MEK/ERK pathway is sufficient to partially restore CD24 mRNA but not protein expression in RasV12 cells. (A-C) RasV12 cells were treated
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Although extracellular signal-regulated kinase (ERK) ? has been shown for its necessity for a variety of the Raf/MEK/ERK pathway signaling its sufficiency in mediating the pathway signaling has not been firmly established. promote ERK autophosphorylation is sufficient to induce growth arrest and differentiation whereas ERK2-I84A and ERK2-R65S/D319N are not as effective. When compared to the […]. ...
Aronov A.M., Baker C., Bemis G.W., Cao J., Chen G., Ford P.J., Germann U.A., Green J., Hale M.R., Jacobs M., Janetka J.W., Maltais F., Martinez-Botella G., Namchuk M.N., Straub J., Tang Q., Xie X.. The Ras/Raf/MEK/ERK signal transduction is a key oncogenic pathway implicated in a variety of human cancers. We have identified a novel series of pyrazolylpyrroles as inhibitors of ERK. Aided by the discovery of two distinct binding modes for the pyrazolylpyrrole scaffold, structure-guided optimization culminated in the discovery of 6p, a potent and selective inhibitor of ERK.. J. Med. Chem. 50:1280-1287(2007) [PubMed] [Europe PMC] ...
Diabetic patients are prone to developing Alzheimers disease (AD), in which microglia play a critical role. However, the direct effect of high glucose (HG) on microglia and the role of extracellular-signal-regulated kinase 5 (ERK5) signaling in this interaction have not been examined before. Here, these questions were addressed in microglia cultured in HG versus normal glucose (NG) conditions. Initially, HG induced microglial differentiation into the M2a phenotype with concomitant ERK5 activation. However, longer exposure to HG further induced differentiation of microglia into the M2b-like phenotype, followed by the M1-like subtype, concomitant with a gradual loss of ERK5 activation. BIX021895, a specific inhibitor of ERK5 activation, prevented M2a- differentiation of microglia, but induced earlier M2b-like polarization followed by M1-like polarization. Transfection of microglia with a sustained activated form of MEK5 (MEK5DD) prolonged the duration of the M2a phenotype, and prevented later
Tumors with mutant BRAF or mutant KRAS are dependent on ERK signaling and are sensitive to inhibitors of the pathway. Selective RAF, MEK and ERK inhibitor have...
The expression of CD47 on the cancer cell surface transmits "dont eat me" signalling that not only inhibits phagocytosis of cancer cells by phagocytes but also impairs anti-cancer T cell responses.
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REFERENCES. 1. Porter PMD. Westernizing Womens Risks? Breast cancer in lower-income countries. N Engl J Med. 2008;358(3):213-6. [ Links ] 2. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):359-86. [ Links ] 3. Cheng SY. Thyroid hormone receptor mutations and disease: Beyond thyroid hormone resistance. Trends Endocrinol Metab. 2005;16(4):176-82. [ Links ] 4. Williams GR. Neurodevelopmental and neurophysiological actions of thyroid hormone. J Neuroendocrinol. 2008;20(6):784-94. [ Links ] 5. Moeller LC, Broecker-Preuss M. Transcriptional regulation by nonclassical action of thyroid hormone. Thyroid Res. 2011;4(Suppl 1):S6. [ Links ] 6. Bergh JJ, Lin H-Y, Lansing L, Mohamed SN, Davis FB, Mousa S, et al. Integrin AVB3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction ...
Three-tiered kinase modules, such as the Raf-MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase)-ERK (extracellular signal-regulated kinase) mitogen-activated protein kinase pathway, are widespread in biology, suggesting that this structure conveys evolutionarily advantageous properties. We show that the three-tiered kinase amplifier module combined with negative feedback recapitulates the design principles of a negative feedback amplifier (NFA), which is used in electronic circuits to confer robustness, output stabilization, and linearization of nonlinear signal amplification. We used mathematical modeling and experimental validation to demonstrate that the ERK pathway has properties of an NFA that (i) converts intrinsic switch-like activation kinetics into graded linear responses, (ii) conveys robustness to changes in rates of reactions within the NFA module, and (iii) stabilizes outputs in response to drug-induced perturbations of the amplifier. These properties ...
The HER-2 oncogene, a member of the erythroblastosis oncogene B (ERBB)-like oncogene family, has been shown to be amplified in many types of cancer, including breast cancer. However, the molecular mechanism of HER-2 overexpression is not completely understood. 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. Here, we found that Pin1 interacts with mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) protein kinase 1, resulting in the induction of HER-2 expression. Pin1−/− mouse embryonic fibroblasts exhibited a decrease in epidermal growth factor (EGF)-induced MEK1/2 phosphorylation compared with Pin1+/+ mouse embryonic fibroblast. In addition, a knockdown of Pin1 resulted in the inhibition of MEK1/2 phosphorylation induced by EGF in MCF-7 cells. Furthermore, PD98059, ...
ERKs (Extracellular-signal-regulated kinases) are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells. Many different stimuli, including growth factors, cytokines, virus infection, ligands for heterotrimeric G protein-coupled receptors, transforming agents, and carcinogens, activate the ERK pathway. In the MAPK/ERK pathway, Ras activates c-Raf, followed by mitogen-activated protein kinase kinase (abbreviated as MKK, MEK, or MAP2K) and then MAPK1/2 (below). Ras is typically activated by growth hormones through receptor tyrosine kinases and GRB2/SOS, but may also receive other signals. ERKs are known to activate many transcription factors, such as ELK1, and some downstream protein kinases. Disruption of the ERK pathway is common in cancers, especially Ras, c-Raf and receptors such as HER2.
Several studies have shown that ERK in the ACC is activated and contributes to the affective aspect in the inflammatory and phantom pain.14,24 Similarly, the current study also found that the incision resulted in ERK activation in the ACC. However, the incision-evoked ERK activation is biphasic and different from those in inflammatory pain or neuropathic pain. The activation pattern of p-ERK in formalin-induced inflammatory pain is still not fully determined. In a recent study by Wei and Zhuo, p-ERK in the ACC was observed to be transiently up-regulated in the formalin test.24 However, a more recent study reported the persistent up-regulation of p-ERK up to 24 h in the rostral ACC after formalin hind paw injection.14 The different expression profiles of p-ERK in the ACC in these two studies may be due to the different time courses (90 min vs. 24 h) and subregions of ACC. Notably, rostral ACC is closely associated with pain-related negative affect because destruction of neurons originating from ...
Growth factors and mitogens use the Ras/Raf/MEK/ERK signaling cascade to transmit signals from their receptors to regulate gene expression and prevent apoptosis. Some components of these pathways are mutated or aberrantly expressed in human cancer (e.g., Ras, B-Raf). Mutations also occur at genes en …
Recently, we demonstrated that interaction of multimeric HIV-1 envelope gp120 with the CD4 receptor induces T cell activation, resulting both in NF-κB nuclear translocation and AP-1 activation. Furthermore, analysis of biochemical events generated upon HIV-CD4 interaction was found to activate several cellular kinases, including p56lck, Raf-1, and ERK-2, suggesting a possible involvement of a Raf-1-dependent ERK signaling pathway in this process. The purpose of this study was to investigate the role of MEK and ERK in the signal-transduction pathway(s) leading to AP-1 and NF-κB activation following engagement of CD4 with HIV-1. We demonstrate in this study that both MEK-1 and ERK-1 are dowstream cellular intermediates in this CD4 receptor-dependent activation cascade that are required for efficient activation of the two DNA-binding proteins.. Although the signaling pathway that leads to AP-1 activation following engagement of CD4 with HIV-1 was not known, it is well established that AP-1 ...
Primary antibodies used were rabbit or guinea pig anti-DGKζ (K. Kim et al., 2009), mouse anti-PKCα (BD Biosciences), mouse (Sigma), rabbit (Sigma), or guinea pig (Synaptic Systems) anti-calbindin, mouse anti-metabotropic glutamate receptor 1 (mGluR1, BD Biosciences), mouse anti-FLAG (M2, Sigma), rabbit anti-synapsin 1/2 (Synaptic Systems), mouse anti-β-actin (Santa Cruz Biotechnology), rabbit anti-mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/Erk, Cell Signaling Technology), rabbit anti-phosphorylated MAPK (Cell Signaling Technology), rabbit anti-GluA2 (Millipore), rabbit anti-PICK1 (Abcam), and rabbit anti-PSD-93/chapsyn-110 (1634) (M.H. Kim et al., 2009) antibodies. Secondary antibodies used were HRP-conjugated anti-mouse or anti-rabbit IgG (GE Healthcare), HRP-conjugated anti-guinea pig IgG (Jackson ImmunoResearch Laboratories), AlexaFluor-647-conjugated anti-mouse IgG (Jackson ImmunoResearch Laboratories), AlexaFluor-647-conjugated anti-rabbit IgG ...
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each group). Ultrastructure features in normal group ((a) ×4000, (b) ×8000, (c) ×10000), model group ((d) ×4000, (e) ×8000, (f) ×8000), PC6 group ((g) ×6000, (h) ×8000, (i) ×8000), and LI4 group ((j) ×5000, (k) ×8000, (l) ×8000). Cardiocyte and micrangium ((a, d, g, j), ×4000~6000), myofibril, I band, and Z-line ((b, e, h, k), ×8000), intercalated disc ((c,f,i, l), ×8000~10000). Some changes of the ultrastructure: mitochondria swelling ((d, e), cell apoptosis (j), endothelial cell interstitial hyperplasia (d), muscle plasma nets expansion (e), out-sync contraction of contraction band ((e, j), and intercalated disc deformation ((f, i, l). With reference to normal group, compared EA group with model group, EA significantly reduced cardiac muscular tissue damage ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Importantly, this work underscores the significance of ERK-dependent signaling in TAA development in MFS. ERK-dependent signaling has been demonstrated previously to contribute to aortic dilation in MFS (18, 20). ANG stimulates ERK1/2 activation via the AT1aR and both Gq proteins as well as βarr2. ERK activated via these different transducers is both spatially and temporally distinct (3) with unique functional outcomes (22, 34). Whereas βarr2-dependent ERK activation appears to lead to TGF-β-independent, proaneurysmal signaling, ANG-stimulated activation of TGF-β signaling has been reported previously to involve Gq proteins (35). Interestingly, G protein- and βarr2-dependent ERK1/2 activation has been shown to require EGFR transactivation in VSMC (21), suggesting the EGFR could serve as a mediator of AT1aR-mediated pathogenic signaling in MFS. This hypothesis is supported by our preliminary work demonstrating a reduction in aortic dilation in FbnC1039G/+ mice treated with the EGFR inhibitor ...
Oncotarget | Thomas B. Davis, Mingli Yang, Heiman Wang, Changgong Lee, Timothy J. Yeatman, W. Jack Pledger
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应激及应激相关情绪疾病普遍伴随前额叶依赖的认知灵活性损害且可被多种抗抑郁治疗所改善。日益增加的临床和实验性研究还表明,前额叶功能异常导致固着性认知和情感偏误,可能构成了抑郁症和焦虑症的一个重要的病因学因素。迄今为止,对应激诱导前额叶认知灵活性缺损的细胞分子机理所知甚少。细胞外信号调节蛋白激酶(Extracellular signal-regulated kinase, ERK)广泛参与应激反应、情绪和认知功能调节。本研究旨在探讨前额叶ERK信号蛋白在慢性应激诱导的认知灵活性和情绪行为改变中的作用。首先,研究建立了拟人类威斯康辛卡片分类测试的啮齿类动物认知灵活性检测模型--注意定势转移任务(Attentional Set-shifting Task, ...
This collection of references is based on Cardioprotection induced by Na1/K1-ATPase activation involves extracellular signal-regulated kinase 1/2 and phosphoinositide 3-kinase/Akt pathway: Chronic heart failure (CHF) is a common, costly, disabling, and deadly condition in which a problem with the st ... ...
This collection of references is based on Cardioprotection induced by Na1/K1-ATPase activation involves extracellular signal-regulated kinase 1/2 and phosphoinositide 3-kinase/Akt pathway: Chronic heart failure (CHF) is a common, costly, disabling, and deadly condition in which a problem with the st ... ...
KO validated. Cited in 1 publication. View Human/Mouse Phospho-ERK1 (ERK1 T202/Y204, ERK2 T185/Y187) Antibody (MAB18251) validated in Human and Mouse.
MAP kinases) are activated. (Also known as extracellular signal-regulated kinases - ERKs or MAP/ERK kinase (MEK)). As a result ... The active RAS can in turn activate RAF, a Ser/Thr kinase. In the next step mitogen-activated protein kinases ( ... "Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in ... Extracellular loops of the FPR responsible for N-for-Met-Leu-Phe (Nfor-MLF) binding are shown in red. Formyl peptide receptor ( ...
Beta arrestin has been shown to form complexes with MAP kinase, leading to activation of Extracellular signal-regulated kinases ... D2 receptor signaling may mediate protein kinase B, arrestin beta 2, and GSK-3 activity, and inhibition of these proteins ... Neve, KA; Seamans, JK; Trantham-Davidson, H (August 2004). "Dopamine receptor signaling". Journal of receptor and signal ... Altered striatal dopamine signaling ↓DRD2, ↑DRD3. ↑DRD1, ↓DRD2, ↑DRD3. ↑DRD1, ↓DRD2, ↑DRD3. ↑DRD2. ↑DRD2. [36] ...
MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for ... the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase ... Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 (MAPKK 6) or MAPK/ERK kinase 6 is ... "p38alpha isoform Mxi2 binds to extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase and regulates its ...
MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for ... protein in the c-Jun NH2-terminal kinase signaling pathways suppresses the extracellular signal-regulated kinase signaling ... "p38α Isoform Mxi2 Binds to Extracellular Signal-Regulated Kinase 1 and 2 Mitogen-Activated Protein Kinase and Regulates Its ... This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon activation by a wide ...
MAP kinase)- activated protein kinase. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), act as an ... MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase". J Biol Chem. 271 (14): 8488-92. doi:10.1074/ ... MAP) kinase-activated protein kinase, is targeted by three MAP kinase pathways". Mol. Cell. Biol. 16 (12): 6687-97. doi:10.1128 ... p38 MAP kinase and Jun N-terminal kinase were all able to phosphorylate and activate this kinase, which suggested the role of ...
... extracellular signal-regulated protein kinase 1 (ERK1), ERK2, and p38 MAP kinase phosphorylation. Although GnRH is located in ... Kisspeptin-GPR54 signaling has an important role in initiating secretion of gonadotropin-releasing hormone (GnRH) at puberty, ... Disrupting GPR54 signaling can cause hypogonadotrophic hypogonadism in rodents and humans. The Kiss1 gene is located on ... This event is thought to involve kisspeptin/GPR54 signaling, which leads to the eventual activation of GnRH neurons. Several ...
The Extracellular Signal-Regulated Kinases MAP Kinase Resource . Extracellular+Signal-Regulated+MAP+Kinases at the US National ... "MAP kinase-kinase", thus qualifying as a "MAP kinase kinase kinase". The MAP kinase-kinase, which activates ERK, was named " ... extracellular signal-regulated kinases (ERKs) or classical MAP kinases are widely expressed protein kinase intracellular ... Mitogen-activated protein kinase 1 (MAPK1) is also known as extracellular signal-regulated kinase 2 (ERK2). Two similar protein ...
... mitogen-activated protein kinases MeSH D12.644.360.450.169 - extracellular signal-regulated map kinases MeSH D12.644.360.450. ... map kinase kinase kinase 1 MeSH D12.644.360.400.200 - map kinase kinase kinase 2 MeSH D12.644.360.400.300 - map kinase kinase ... map kinase kinase 1 MeSH D12.644.360.440.200 - map kinase kinase 2 MeSH D12.644.360.440.300 - map kinase kinase 3 MeSH D12.644. ... map kinase kinase 4 MeSH D12.644.360.440.500 - map kinase kinase 5 MeSH D12.644.360.440.600 - map kinase kinase 6 MeSH D12.644. ...
MAP kinase) family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that ... Kim DW, Cochran BH (February 2000). "Extracellular signal-regulated kinase binds to TFII-I and regulates its activation of the ... regulates extracellular signal-regulated kinase docking and RSK activity". Mol. Cell. Biol. 23 (14): 4796-804. doi:10.1128/mcb. ... the kinases that phosphorylate and activate the extracellular signal-regulated kinases". J. Biol. Chem. 268 (32): 23933-9. PMID ...
MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical ... "p38alpha isoform Mxi2 binds to extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase and regulates its ... "Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in ... regulates extracellular signal-regulated kinase docking and RSK activity". Mol. Cell. Biol. 23 (14): 4796-804. doi:10.1128/mcb. ...
... kinase family. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), and are involved in signaling ... "Extracellular signal-regulated kinase 8 (ERK8) controls estrogen-related receptor α (ERRα) cellular localization and inhibits ... MAP) kinase by RET/PTC3, a constitutively active form of the RET proto-oncogene" (PDF). The Journal of Biological Chemistry. ... and is likely activated by an SRC-dependent signaling pathway. SRC is a non-receptor tyrosine kinase (and proto-oncogene) that ...
... mitogen-activated protein kinases MeSH D08.811.913.696.620.682.700.567.342 - extracellular signal-regulated map kinases MeSH ... map kinase kinase kinase 1 MeSH D08.811.913.696.620.682.700.559.200 - map kinase kinase kinase 2 MeSH D08.811.913.696.620.682. ... map kinase kinase kinase 3 MeSH D08.811.913.696.620.682.700.559.400 - map kinase kinase kinase 4 MeSH D08.811.913.696.620.682. ... extracellular signal-regulated map kinases MeSH D08.811.913.696.620.682.700.646.750.249.500 - mitogen-activated protein kinase ...
... kinase activities of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase", leading to macrophage ... YopJ, which shares an operon with YpkA, "...interferes with the mitogen-activated protein (MAP) ... enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2 ... Secretion is regulated in this fashion so that proteins are not expelled into the extracellular matrix and elicit an immune ...
... regulate the activation of the extracellular signal-regulated kinases ERK1 and ERK2 by association through a kinase interaction ... The way that HePTP effectively inhibits the MAPK signaling is by interacting with the MAP kinases Erk1, Erk2, and p38 through a ... 2002), "Crosstalk between cAMP and MAP kinase signaling in the regulation of cell proliferation", Trends in Cell Biology, 12 (6 ... 1999), "Inhibition of T cell signaling by MAP kinase-targeted hematopoietic tyrosine phosphatase (HePTP)", J. Biol. Chem., 274 ...
"Direct suppression of TCR-mediated activation of extracellular signal-regulated kinase by leukocyte protein tyrosine ... The noncatalytic N-terminus of this PTP can interact with MAP kinases and suppress the MAP kinase activities. This PTP was ... Saxena M, Williams S, Taskén K, Mustelin T (September 1999). "Crosstalk between cAMP-dependent kinase and MAP kinase through a ... Saxena M, Williams S, Taskén K, Mustelin T (1999). "Crosstalk between cAMP-dependent kinase and MAP kinase through a protein ...
Another chemical in the brain that Aβ regulates is JNK; this chemical halts the extracellular signal-regulated kinases (ERK) ... Aβ was found manipulating the level of nicotine in the brain along with the MAP kinase, another signaling receptor, to cause ... This can eventually disrupt or even kill neurons, which are cells that transmit and process signals in the brain and other ... "Nicotinic Acetylcholine Receptor Signalling: Roles in Alzheimer's Disease and Amyloid Neuroprotection". Pharmacological Reviews ...
Hebert, A. E.; Dash, P. K. (2002). "Extracellular signal-regulated kinase activity in the entorhinal cortex is necessary for ... street names forming a straight line on the map, but omitting intermediate streets Map Random - streets on map presented in ... Memory consolidation in the entorhinal cortex is achieved through extracellular signal-regulated kinase activity. The medial ... Researchers added two more maps and made them smaller. It should be noted, though, that the second map set in this trial was ...
... and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase ... MAP kinase MAP kinase kinase MAP kinase kinase kinase kinase List of unusual biological names Morrison, Deborah K. (2012-11-01 ... These MAP kinases include the extracellular regulated kinases (ERKs), the c-Jun N-terminal Kinases (JNKs), and the p38 MAP ... is a serine/threonine-specific protein kinase which acts upon MAP kinase kinase. Subsequently, MAP kinase kinase activates MAP ...
Extracellular signal-regulated kinases (ERKs) c-Jun N-terminal kinases (JNKs) p38 mitogen-activated protein kinases (p38s) ... Signal transduction MAP kinase kinase MAP kinase kinase kinase MAP kinase kinase kinase kinase MAPK1 (ERK2) MAPK3 (ERK1) MAPK7 ... Similarly, both dual-specificity MAP kinase phosphatases and MAP-specific tyrosine phosphatases bind to MAP kinases through the ... Nemo-like kinase: atypical MAPK) ERK1/2 kinases ERK1/2 pathway JNK kinases p38 MAP kinases ASK1 (MAP3K5) Pearson G, Robinson F ...
... including extracellular signal-regulated kinases (ERKs), PLK1, and CDK1 itself. Upon reaching some threshold level of ... MAPs). The subcellular localization of cdc25 also shifts from the cytosol to the nucleus during prophase. This is accomplished ... DNA damage is detected by the kinases ATM and ATR, which activate Chk1, an inhibitory kinase of Cdc25. Chk1 inhibits Cdc25 ... Though much is known about the genetic network which regulates G2 phase and subsequent entry into mitosis, there is still much ...
"Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein". Mol ... "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/ ... "Protein kinase C mu is negatively regulated by 14-3-3 signal transduction proteins". J. Biol. Chem. 274 (14): 9258-64. doi: ... "Protein kinase C mu is negatively regulated by 14-3-3 signal transduction proteins". J. Biol. Chem. 274 (14): 9258-64. doi: ...
February 2006). "Identification of extracellular signal-regulated kinase 3 as a new interaction partner of cyclin D3". ... December 2000). "Arabidopsis map kinase 4 negatively regulates systemic acquired resistance". Cell. 103 (7): 1111-20. doi: ... Mitogen-activated protein kinase 4 is a member of the mitogen-activated protein kinase family. Tyrosine kinase growth factor ... Gonzalez FA, Raden DL, Rigby MR, Davis RJ (June 1992). "Heterogeneous expression of four MAP kinase isoforms in human tissues ...
Mandl M, Slack DN, Keyse SM (Mar 2005). "Specific inactivation and nuclear anchoring of extracellular signal-regulated kinase 2 ... They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are ... Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases ... a dual specificity MAP kinase protein phosphatase". Proteins. 66 (1): 253-8. doi:10.1002/prot.21224. PMID 17078075. S2CID ...
"Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein". Mol ... "Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP". Nature. 401 (6749): 173-7. doi:10.1038/43686. PMID ... "Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein". Mol ... "Raf kinase inhibitor protein interacts with NF-kappaB-inducing kinase and TAK1 and inhibits NF-kappaB activation". Mol. Cell. ...
... neuronal differentiation via activation of B-Raf-extracellular signal-regulated kinase and p38 mitogen-activated protein kinase ... "High-throughput mapping of a dynamic signaling network in mammalian cells". Science. 307 (5715): 1621-5. Bibcode:2005Sci... ...
"Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and ... They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are ... Groom LA, Sneddon AA, Alessi DR, Dowd S, Keyse SM (July 1996). "Differential regulation of the MAP, SAP and RK/p38 kinases by ... phosphatase MKP-3 and its ability to anchor MAP kinase in the cytoplasm are mediated by a conserved nuclear export signal". The ...
... though chloroplasts can also give out signals regulating gene expression in the nucleus, called retrograde signaling.[34] ... It can be regulated through phosphorylation, but by a different protein kinase than the one that phosphorylates Toc34.[41] Its ... Chloroplast DNA Interactive gene map of chloroplast DNA from Nicotiana tabacum. Segments with labels on the inside reside on ... just like if you were headed for the extracellular space. In those cases, chloroplast-targeted proteins do initially travel ...
... was also found to be regulated by N1IC, which suggest a mechanism of ABCC1 regulated by presenilin 1 and notch signaling.[29] ... positive regulation of MAP kinase activity. • positive regulation of catalytic activity. • mitochondrial transport. • post- ... Presenilin possesses a 9 transmembrane domain topology, with an extracellular C-terminus and a cytosolic N-terminus.[7][8] ... Wnt signaling pathway[edit]. Wnt signaling pathway has been shown to be involved in several critical steps in embryogenesis and ...
calcium-mediated signaling using extracellular calcium source. • transmembrane transport. • calcium ion transport. • regulation ... The activity of CaV1.2 channels is tightly regulated by the Ca2+ signals they produce. An increase in intracellular Ca2+ ... Interactive pathway map[edit]. Click on genes, proteins and metabolites below to link to respective Wikipedia articles. [§ 1] ... "A potential site of functional modulation by protein kinase A in the cardiac Ca2+ channel alpha 1C subunit". FEBS Letters. 384 ...
... and two kinases of the JNK MAP kinase pathway (MLK2 and MKK7). He then determined that CNK1 acts together with these four ... In 2010, Hall analysed a number of Rho signalling pathways, which regulate the formation of apical junctions in human bronchial ... is implicated in the regulation of the actin organisation in presence of extracellular growth factors. Immunofluorescence and ... This led to the conclusion that CNK1 couples specific Rho exchange factors to the JNK MAP kinase pathway, providing specificity ...
Mitogen-activated protein kinase (EC *Extracellular signal-regulated *MAPK1. *MAPK3 ... Demetrick DJ, Zhang H, Beach DH (1994). "Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes". Cytogenet ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... Dephospho-(reductase kinase) kinase (EC *AMP-activated protein kinase α *PRKAA1 ...
"TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway". Genes Dev. 25 (19): 2069-78. doi: ... extracellular region. • plasma membrane. • membrane raft. • extracellular space. Biological process. • regulation of protein ... TNF phosphorylates insulin receptor serine residues, blocking signal transduction.. *On metabolism and food intake: regulates ... tumor necrosis factor-mediated signaling pathway. • positive regulation of I-kappaB kinase/NF-kappaB signaling. • necroptotic ...
T cell receptor signaling pathway. • T cell activation. • regulation of catalytic activity. • Rho protein signal transduction. ... protein kinase binding. • small GTPase binding. • Rac GTPase binding. Cellular component. • cytoplasm. • cell-cell junction. • ... extracellular exosome. • cytoskeleton. • cytosol. • actin filament. • phagocytic vesicle. Biological process. • defense ... The presence of a number of different motifs suggests they are regulated by a number of different stimuli, and interact with ...
The PrP-activated signal transduction pathway is associated with axon and dendritic outgrowth with a series of kinases.[25][46] ... extracellular exosome. • cell nucleus. • extrinsic component of membrane. • cytosol. • postsynaptic density. • inclusion body. ... A possible role in regulating neuronal excitability". Neurosci. Lett. 103 (2): 139-44. doi:10.1016/0304-3940(89)90565-X. PMID ... Liao YC, Lebo RV, Clawson GA, Smuckler EA (July 1986). "Human prion protein cDNA: molecular cloning, chromosomal mapping, and ...
Early signaling steps implicate the following kinases and phosphatases after TCR triggering: *Lck - a Src family kinase ... The specific and efficient signaling via TCR might be regulated by dynamic oligomerization into TCR microclusters on the ... Orthologues of the 4 loci have been mapped in various species.[3][4] Each locus can produce a variety of polypeptides with ... Crystal structure of human CD8 molecule Only a fragment of extracellular portion of human CD8α is shown. Co-receptor CD8 bind ...
extracellular space. • cytoplasm. • cytosol. Biological process. • stress-activated protein kinase signaling cascade. • ... "Tonicity-responsive enhancer binding protein regulates the expression of aldose reductase and protein kinase C δ in a mouse ... There are a few putative pseudogenes for this gene, and one of them has been confirmed and mapped to chromosome 3.[6] ... Graham A, Heath P, Morten JE, Markham AF (March 1991). "The human aldose reductase gene maps to chromosome region 7q35". Human ...
Fyn and Lyn kinase. It also activates phosphatidylinositol 3-kinase (PI3K) and AKT signaling pathway and induce expression of ... MAP (mitogen-activated protein kinase) kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine ... extracellular region. • extracellular space. • cytoplasm. • cytosol. • nuclear speck. Biological process. • negative regulation ... IL-15 regulates the activation and proliferation of T and natural killer (NK) cells. Survival signals that maintain memory T ...
cellular response to extracellular stimulus. • signal transduction by p53 class mediator. • intrinsic apoptotic signaling ... cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine kinase activity. • ... p21 is negatively regulated by ubiquitin ligases both over the course of the cell cycle and in response to DNA damage. ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038/ ...
These events promote many signaling cascades (such as the MAP kinase pathway) that generate responses like chemotaxis, ... The first two extracellular loops of chemokine receptors each has a conserved cysteine residue that allow formation of a ... Neutrophils: are regulated primarily by CXC chemokines. An example CXCL8 (IL-8) is chemoattractant for neutrophils and also ... Signal transductionEdit. Chemokine receptors associate with G-proteins to transmit cell signals following ligand binding. ...
... enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2 ... YopJ, que comparte un operón con YpkA, "...interfire coas actividades de quinase MAP (proteína activada por mitóxeno) da JNK (c ... Galyov EE, Håkansson S, Forsberg A, Wolf-Watz H (1993). "A secreted protein kinase of Yersinia pseudotuberculosis is an ... p38, and c-Jun NH2-terminal kinase. Correlation with its inhibitory effect on tumor necrosis factor-alpha production". J. Biol ...
2002). "Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signal-regulated kinase pathway". J. Biol. ... 1995). "Mapping of the gene for hormone sensitive lipase (LIPE) to chromosome 19q13.1→q13.2". Cytogenet. Cell Genet. 69 (3-4): ... protein kinase binding. • serine hydrolase activity. Cellular component. • cytoplasm. • membrane. • lipid droplet. • plasma ... Also, it may be activated by a cAMP-dependent protein kinase (PKA). This pathway is significantly less effective than the first ...
Also, the ABCA4 maps to a region of chromosome 1p21 that contains the gene for Stargardt's disease. This gene is found to be ... They are known to be involved in ion transport, toxin secretion, and signal transduction. Of the nine MRP proteins, four of ... Many of the drugs that are transported out by ABCB1 are small, nonpolar drugs that diffuse across the extracellular medium into ... Matte A, Tari LW, Delbaere LT (Apr 1998). "How do kinases transfer phosphoryl groups?". Structure. 6 (4): 413-9. doi:10.1016/ ...
... "p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha- ... extracellular matrix organization. • response to drug. • cellular response to indole-3-methanol. • extracellular matrix ... Huntsman DG, Caldas C (Mar 1999). "Assignment1 of the E-cadherin gene (CDH1) to chromosome 16q22.1 by radiation hybrid mapping ... enhances Wnt signaling and is over-expressed in hepatocellular carcinoma". Hepatology. 38 (1): 178-86. doi:10.1053/jhep. ...
The biosynthetic pathways are regulated by riboswitches.[20] If there is sufficient thiamine present in the cell then the ... all extracellular fluid. Unlike the highly phosphorylated forms of thiamine, ThMP and free thiamine are capable of crossing ... by a thiamine-phosphate kinase (ThMP + ATP → ThDP + ADP, EC In most bacteria and in eukaryotes, ThMP is hydrolyzed ... "Food Fortification Global Mapping Study" (PDF). European Commission. pp. 121-128.. CS1 maint: multiple names: authors list ( ...
This gene uses alternative polyadenylation signals.[5][6] Interactive pathway map[edit]. Click on genes, proteins and ... Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... extracellular vesicle. • cell body. • membrane. • photoreceptor inner segment. • myelin. • plasma membrane. • photoreceptor ... 1b9y: STRUCTURAL ANALYSIS OF PHOSDUCIN AND ITS PHOSPHORYLATION-REGULATED INTERACTION WITH TRANSDUCIN BETA-GAMMA ...
It forms links with several protein kinases associated with cell locomotion, for example, extracellular signal-regulated ... MAP kinase (MAPK), pp60(c-src), and the downstream targets of Rho kinase (ROK).[22] RHAMM can also cooperate with CD44 to ... a hyaluronan-binding protein that regulates ras signaling, correlates with overexpression of mitogen-activated protein kinase ... a b c d Wayne D. Comper, Extracellular Matrix Volume 2 Molecular Components and Interactions, 1996, Harwood Academic Publishers ...
positive regulation of MAP kinase activity. • epidermal growth factor receptor signaling pathway. • regulation of protein ... extracellular region. • lysosomal membrane. • extracellular exosome. • platelet alpha granule lumen. • extracellular. • ... Salivary EGF, which seems to be regulated by dietary inorganic iodine, also plays an important physiological role in the ... positive regulation of protein kinase B signaling. • negative regulation of Notch signaling pathway. • regulation of JAK-STAT ...
positive regulation of protein kinase B signaling. • negative regulation of MDA-5 signaling pathway. • regulation of ... 2000). "Protein kinase C [micro] is regulated by the multifunctional chaperon protein p32". J. Biol. Chem. 275 (32): 24601-7. ... C1QBP/p32 is an endogenous substrate for MAP kinase and is translocated to the nucleus upon mitogenic stimulation". Biochem. ... extracellular region. • cell surface. • mitochondrial matrix. • nucleolus. • cytoplasm. • membrane. • mitochondrion. • cell ...
"Oxidative Stress-Induced Caspases are Regulated in Human Myeloid HL-60 Cells by Calcium Signal". Current Signal Transduction ... "Connection Map for Fas Signaling Pathway". Science's STKE. 2007 (380): tr1. doi:10.1126/stke.3802007tr1. S2CID 84909531.. ... Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ... Released viral particles and proteins present in extracellular fluid are able to induce apoptosis in nearby "bystander" T ...
... extracellular regulated kinases 1&2),[30] and increases the enzyme activity to a lesser extent than for Ser40 phosphorylation.[ ... MAP) kinase and MAP-kinase-activated kinases 1 and 2". European Journal of Biochemistry / FEBS. 217 (2): 715-22. doi:10.1111/j. ... See also: Receptor/signaling modulators • Adrenergics • Dopaminergics • Melatonergics • Serotonergics • Monoamine reuptake ... that are phosphorylated by a variety of protein kinases.[12][25] Ser40 is phosphorylated by the cAMP-dependent protein kinase.[ ...
Kacimi, R., Gerdes, A. (2003) Alterations in G protein and MAP kinase signaling pathways during cardiac remodeling in ... Reversible ubiquitination regulates the Smad/TGF-beta signalling pathway. Biochem. Soc. Trans. 34: 761-763 ... deposition of extracellular matrix, wall thickening, and ventricular remodeling in a manner that promotes dysfunction.[10] ... One of the main signaling receptors involved in this pathway is the TGF-β1 co-receptor (complex of type I and type II receptors ...
"The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily ... Human Cdc42 is a small GTPase of the Rho family, which regulates signaling pathways that control diverse cellular functions ... extracellular exosome. • filopodium. • plasma membrane. • spindle. • apical part of cell. • secretory granule. • neuronal cell ... mitogen-activated protein kinase kinase kinase binding. • protein binding. • thioesterase binding. • protein kinase binding. • ...
"Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion". Genes ... 1 Reverse signaling in growth cone survival *1.1 Formation of the retinotopic map ... Reverse signaling in growth cone survival[edit]. "Reverse" signaling is one unique property of ephrin ligands that allows for ... a ligand of the Eph-related kinases is developmentally regulated in the brain". Cytokine. 9 (8): 540-9. doi:10.1006/cyto. ...
... p38alpha isoform Mxi2 binds to extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase and regulates its ... 2001). „Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions". ... 2004). „Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in ... 1999). „Extracellular signal-regulated kinase (ERK) interacts with signal transducer and activator of transcription (STAT) 5a ...
MAP Kinase 1 or MAPK 1 or Extracellular Signal Regulated Kinase 2 or ERK-2 or Protein Tyrosine Kinase ERK2 or EC - ... Global Markets Directs, Mitogen Activated Protein Kinase 1 (MAP... ... 46 Pages Report] Check for Discount on Mitogen Activated Protein Kinase 1 ( ... Mitogen Activated Protein Kinase 1 (MAP Kinase 1 or MAPK 1 or Extracellular Signal Regulated Kinase 2 or ERK-2 or Protein ...
ERT1 or MAP Kinase Isoform p42 or Extracellular Signal Regulated Kinase 2 or Mitogen ... ERT1 or MAP Kinase Isoform p42 or Extracellular Signal Regulated Kinase 2 or Mitogen Activated Protein Kinase 2 or MAPK1 or EC ... ERT1 or MAP Kinase Isoform p42 or Extracellular Signal Regulated Kinase 2 or Mitogen Activated Protein Kinase 2 or MAPK1 or EC ... Mitogen Activated Protein Kinase 1 (ERT1 or MAP Kinase Isoform p42 or Extracellular Signal Regulated Kinase 2 or Mitogen ...
Insulin-stimulated MAP2 kinase,MAP kinase 1,MAP kinase 3,MAP kinase isoform p44,MAPK 1,MAPK 3,Mapk3,Microtubule-associated ... Extracellular signal-regulated kinase 1,Insulin-stimulated MAP2 kinase,MAP kinase 1,MAP kinase 3,MAP kinase isoform p44,MAPK 1, ... Extracellular signal-regulated kinase 1,Insulin-stimulated MAP2 kinase,MAP kinase 1,MAP kinase 3,MAP kinase isoform p44,MAPK 1, ... Extracellular signal-regulated kinase 1,Insulin-stimulated MAP2 kinase,MAP kinase 1,MAP kinase 3,MAP kinase isoform p44,MAPK 1, ...
As a control, we examined the effects of the MAP or extracellular-signal-regulated kinase (MEK) antagonist PD098059 (35) on ... mitogen-activated protein kinase;. VLCMR,. very low Ca2+, Mg2+ Ringer;. MKP-1,. MAP kinase phosphatase-1;. ΔP-MKP-1,. ... Transforming growth factor-β-family signaling pathways have been shown to regulate the MAPK signaling cascade in both positive ... Because FGF signaling is mediated largely by the mitogen-activated protein kinase (MAPK) pathway (26, 27), these studies ...
Extracellular Signal-Regulated MAP Kinases/genetics*. *Extracellular Signal-Regulated MAP Kinases/metabolism ... The downstream targets of the pathway are members of the extracellular regulated kinases (Erk1/2) family, suggesting that this ... The receptor-tyrosine kinase (RTK)/Ras/Raf pathway is an essential cascade for mediating growth factor signaling. It is ... Autophosphorylation of purified Erk2(R65S), Erk2(T188A), and Erk2(T188D) was tested by incubating the proteins in a kinase ...
... representing one of the few examples of tandem mutations in a signaling cascade. As a … ... Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors* * Genes, ras * Humans * Lung Neoplasms / drug therapy* ... The role of mitogen-activated ERK-kinase inhibitors in lung cancer therapy Clin Lung Cancer. 2005 Nov;7(3):221-3. doi: 10.3816/ ... The most promising approach to date appears to be the inhibition of mitogen-activated ERK kinase or MEK. In this review, the ...
Extracellular Signal-Regulated MAP Kinases / metabolism* * Heparin-binding EGF-like Growth Factor ... adrenoreceptor agonists cause extracellular signal-regulated kinase (ERK) phosphorylation. Present work examines the signaling ... heparin-binding-EGF neutralization or phosphatidylinositol 3-kinase (PI3-kinase) inhibitors. Conditioned medium from UK14304- ... EGF receptor transactivation and PI3-kinase mediate stimulation of ERK by alpha(2A)-adrenoreceptor in intestinal epithelial ...
MAP) kinase family, the extracellular signal-regulated kinases (ERKs). ... 1991) ERKs, extracellular signal-regulated MAP-2 kinases. Curr Opin Cell Biol 3:1025-1032. ... Growth factors induce nuclear translocation of MAP kinases (p42mapk and p44mapk) but not of their activator MAP kinase kinase ( ... 1994) Ras/MAP kinase-dependent and -independent signaling pathways target distinct ternary complex factors. Genes Dev 8:1803- ...
EC Kinase C; EC Kinase C-alpha; EC Signal-Regulated MAP Kinases; EC ... Extracellular Signal-Regulated MAP Kinases / metabolism. Humans. Phosphatidylinositol 3-Kinases / metabolism. Pressure / ... Protein-Tyrosine Kinases / antagonists & inhibitors, metabolism*. Signal Transduction / physiology. Time Factors. p38 Mitogen- ... CONCLUSIONS: Extracellular pressure stimulates cell proliferation and activates several signals. However, the mitogenic effect ...
Gene: [22q112/PRKM1] protein kinase, mitogen-activated 1; MAP kinase 1 (p40, p41); extracellular signal-regulated kinase 2 (p42 ... They are part of complex protein kinase cascades. MAPKs are activated by dual-specificity MAPK kinases (MAPKKs; see GEM:05^/ ... 1] Mitogen-activated protein kinases (PRKMs, or MAPKs) are serine-threonine protein kinases that are activated in response to a ...
Mitogen-activated protein (MAP) kinases (or extracellular signal regulated kinases; Erks) and stress-activated protein (SAP) ... kinases mediate cellular responses to a wide variety of signals. In the Erk MAP kinase pathway, activation of MAP kinases takes ... The p38 SAP kinase substrate MAP-kinase-activated protein kinase-2 (MAPKAP kinase-2) contains a putative nuclear localisation ... This translocation to the nucleus is essential to MAP kinase signalling because it enables the kinase to phosphorylate ...
MAP kinase 1,MAP kinase 3,MAP kinase isoform p44,MAPK 1,MAPK 3,Mapk3,Microtubule-associated protein 2 kinase \ U1357r for more ... Extracellular signal-regulated kinase 1,Insulin-stimulated MAP2 kinase, ... Extracellular signal-regulated kinase 1,Insulin-stimulated MAP2 kinase,MAP kinase 1,MAP kinase 3,MAP kinase isoform p44,MAPK 1, ... Extracellular signal-regulated kinase 1,Insulin-stimulated MAP2 kinase,MAP kinase 1,MAP kinase 3,MAP kinase isoform p44,MAPK 1, ...
MAP kinase; ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal protein kinase; MBP, myelin basic protein; GST, ... extracellular signal-regulated kinase (ERK) kinase-dependent MAP kinase activation needed to elicit HL-60 cell differentiation ... Marshal C. J. Specificity of receptor tyrosine kinase signaling: transient vs. sustained extracellular signal-regulated kinase ... Role of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Cascade in Gonadotropin-releasing Hormone- ...
... extracellular signal-regulated kinase; MAP, mitogen-activated protein; PtdIns, phosphatidylinositol; PTEN, phosphatase and ... indicating that PTEN influences TLR4 signaling upstream of the MAP kinases ERK and p38. TLR4-induced activation of MAP kinases ... Previous reports have indicated that during TLR4 signaling, Akt serves to down-regulate MAP kinase activation and the ... B, LPS signals through TLR4 to activate MAP kinases through the MyD88/IL-1R-associated kinase/TRAF6 complex. Further downstream ...
The extracellular signal regulated kinase (ERK) cascade is an important signaling pathway that underl ... Extracellular Signal-Regulated MAP Kinases / metabolism*. Neuronal Plasticity / physiology. Neurons / physiology. Signal ... The extracellular signal regulated kinase (ERK) cascade is an important signaling pathway that underlies synaptic plasticity, ... Dysregulation of ERK signaling in the striatum by repeated drug exposure contributes to the development of addictive behavior. ...
Extracellular signal-regulated kinase (ERK) remains the best characterized mammalian MAP kinase.1 2 Binding of extracellular ... A diverse array of extracellular signals utilize MAP kinase signaling cascades to initiate a variety of cell signaling outcomes ... Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation ... kinase phosphatase 1 by the stress-activated protein kinase signaling pathway but not by extracellular signal-regulated kinase ...
Extracellular Signal-Regulated MAP Kinases. 1. 2012. 702. 0.030. Why? Cytokines. 2. 2017. 6907. 0.030. Why? ...
Extracellular Signal-Regulated MAP Kinases). ... promoted extracellular signal-regulated kinase (ERK) signaling ... MAP Quinases Reguladas por Sinal Extracelular/metabolismo. Glucos deos/uso terap utico. C lulas Ciliadas Auditivas/efeitos dos ... PURPOSE: microRNAs (miRNAs) are non-coding RNAs composed of 20 to 22 nucleotides that regulate development and differentiation ... Mechanistic studies revealed that PF could decrease cellular ROS levels, suppress the activation of ERK signaling and, ...
Extracellular Signal-Regulated MAP Kinases); EC (Ptprb protein, mouse); EC (Receptor-Like Protein Tyrosine ... Therefore, PTPRB regulates branching morphogenesis in the mammary epithelium by modulating the response of the FGFR signalling ... Our results thus identify a novel signaling mechanism by which STIM1-induced Ca signaling activates Pyk2 to inhibit the ... Focal Adhesion Kinase 2); EC (src-Family Kinases); EC (Receptor-Like Protein Tyrosine Phosphatases, Class 3 ...
Extracellular Signal-Regulated MAP Kinases). ... cell death via suppression of glucose-regulated protein 78.. [ ... MAP Quinases Reguladas por Sinal Extracelular/metabolismo. Seres Humanos. Hipertermia Induzida. Neoplasias Hep ticas ... Gene Ontology and functional analysis showed the upregulation of extracellular matrix deposition genes, such as collagen type I ... cell growth inhibition and apoptosis induction effects of 10M were related to DNA damage and activation of the p53 signaling ...
... mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; MAP, mean arterial blood pressure; HR, heart rate ... ACT-058362 also inhibits U-II-induced calcium mobilization and mitogen-activated protein kinase phosphorylation. The binding ...
Extracellular Signal-Regulated MAP Kinases [D12.644.360.450.169]. *Mitogen-Activated Protein Kinase 3 [D12.644.360.450.169.750] ... Extracellular Signal-Regulated MAP Kinases [D12.776.476.450.169]. *Mitogen-Activated Protein Kinase 3 [D12.776.476.450.169.750] ... Extracellular Signal-Regulated MAP Kinases [D08.811.913.696.620.682.700.567.342]. *Mitogen-Activated Protein Kinase 3 [D08.811. ... Extracellular Signal-Regulated MAP Kinases [D08.811.913.696.620.682.700.646.750.249]. *Mitogen-Activated Protein Kinase 3 [ ...
... to the membrane activating kinase (MAPK). Finally, the MAP kinases activate the extracellular signal-regulated kinase (ERK-1/-2 ... The insulin/IGF-1 signaling cascade does not only regulate the PI3K pathway but also the MAP kinase (MAPK, mitogen-activated ... insulin and IGF-1 activate the MAP kinase (MAPK, mitogen-activated protein kinase) signaling cascade (Figure 1) [36, 46, 47]. ... casein kinase 1; DYRK, dual specificity tyrosine-phosphorylation-regulated kinase; JNK, c-Jun N-terminal kinase; IKK, IκB- ...
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the ... Extracellular Signal-Regulated MAP Kinases (Extracellular Signal Regulated Kinases) 6. STAT5 Transcription Factor ... kinase-1-dependent MEK-extracellular signal-regulated protein kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2 (JNK1/2) ... signal transducer and activator of transcription 5, extracellular signal-regulated kinases, MMP-9 and pan-janus kinase/stress- ...
Extracellular Signal-Regulated MAP Kinases/metabolism*; Female; Inflammasomes/metabolism*; Kupffer Cells/metabolism*; Kupffer ... MAP Kinase Signaling System/drug effects*; Mice; Phagocytosis/drug effects*; Trichloroethylene/pharmacology; Trichloroethylene/ ... DCAC exposure led to induction of phos-ERK and phos-AKT signaling. These findings suggest that DCAC induces apoptosis and ...
Extracellular Signal-Regulated MAP Kinases/biosynthesis*; Homeostasis; Immunocompetence/physiology; Ions/adverse effects; Iron- ... Phosphorylated extracellular signal-regulated kinase (ERK) 1 and 2 levels were also measured since activated ERKs are involved ... Mitogen-Activated Protein Kinase 3/biosynthesis; Nitric Oxide Synthase Type II/biosynthesis*; Phosphorylation; Rats; Signal ... in signaling pathways that lead to increased iNOS expression. The results indicate that V and Al, and to a lesser extent Mn, ...
Ebner, H.; Fiechtner, B.; Pelster, B.; Krumschnabel, G. (2006): Extracellular signal regulated MAP-kinase signalling in ... Ebner, HL.; Fiechtner, B.; Pelster, B.; Krumschnabel, G. (2005): Activation of extracellular signalling related kinases in ... Effect of osmotic shock on activation of MAP kinases in trout hepatocytes.. 1st Annual Meeting of the Center for Molecular ... The bidirectional interaction between the hypoxic signaling pathway and the circadian clock.. In: CHRONOBIOLOGY INTERNATIONAL ...
Beta arrestin has been shown to form complexes with MAP kinase, leading to activation of Extracellular signal-regulated kinases ... D2 receptor signaling may mediate protein kinase B, arrestin beta 2, and GSK-3 activity, and inhibition of these proteins ... Neve, KA; Seamans, JK; Trantham-Davidson, H (August 2004). "Dopamine receptor signaling". Journal of receptor and signal ... Altered striatal dopamine signaling ↓DRD2, ↑DRD3. ↑DRD1, ↓DRD2, ↑DRD3. ↑DRD1, ↓DRD2, ↑DRD3. ↑DRD2. ↑DRD2. [36] ...
MAP, mitogen-activated protein; ERK, extracellular signal-regulated kinase.. Method for Visualizing and Accessing the Relative ... I. two-dimensional mapping of human erythrocyte lysate proteins. Blood 53, 1121- 1132. ... Bergquist, J., Palmblad, M., Wetterhall, M., Hakansson, P., and Markides, K. E. (2002) Peptide mapping of proteins in human ... Blood plasma contains numerous secreted or shed low abundance proteins that are critical for signaling cascades and regulatory ...
... mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; MEK, MAP kinase. ... 2019). MicroRNA-135a-3p regulates angiogenesis and tissue repair by targeting p38 signaling in endothelial cells. FASEB J. 33, ... Faigle, R., and Song, H. (2013). Signaling mechanisms regulating adult neural stem cells and neurogenesis. Biochim. Biophys. ... is regulated by Notch-mediated signaling and other transcription factors such as Wnt and the Sonic Hedgehog signaling pathway ( ...
  • citation needed] In the MAPK/ERK pathway, Ras activates c-Raf, followed by mitogen-activated protein kinase kinase (abbreviated as MKK, MEK, or MAP2K) and then MAPK1/2 (below). (
  • Activation of the ERK1/2 pathway by aberrant RAS/RAF signalling, DNA damage, and oxidative stress leads to cellular senescence. (
  • Activation of the fibroblast growth factor (FGF) receptor-signaling pathway can also initiate neural development and the establishment of posterior neural identity. (
  • Because FGF signaling is mediated largely by the mitogen-activated protein kinase (MAPK) pathway ( 26 , 27 ), these studies suggest that MAPK may play a critical role in the specification of neural fate and anteroposterior pattern. (
  • Present work examines the signaling pathway triggering ERK activation and investigates the consequence of alpha(2A)-adrenoreceptor stimulation on cell migration. (
  • In conclusion, alpha(2A)-adrenoreceptor activates ERK and Akt in intestinal cells by a common pathway which depends on PI3-kinase activation and results from EGF receptor transactivation, via an autocrine/paracrine pathway implying MMP activation and heparin-binding-EGF shedding. (
  • The receptor-tyrosine kinase (RTK)/Ras/Raf pathway is an essential cascade for mediating growth factor signaling. (
  • The downstream targets of the pathway are members of the extracellular regulated kinases (Erk1/2) family, suggesting that this family is a mediator of the oncogenic capability of the cascade. (
  • There are at least two distinct pathways by which glutamate signals through the SRE: an SRF-dependent pathway that can operate in the absence of Elk and an Elk-dependent pathway. (
  • Activation of the Elk-dependent pathway of transcription seems to require phosphorylation of Elk-1 by extracellular signal-regulated kinases (ERKs), providing evidence for a physiological function of ERKs in glutamate signaling in neurons. (
  • In the Erk MAP kinase pathway, activation of MAP kinases takes place in the cytoplasm and the activated enzyme moves to the nucleus. (
  • In the p38 SAP kinase pathway, MAPKAP kinase-2 serves both as an effector of p38 by phosphorylating substrates and as a determinant of cellular localisation of p38. (
  • These data suggest the induction of MKP-1, not only after stimulation of the cell growth-promoting ERK pathway but also in response to activation of stress-responsive MAP kinase signaling cascades. (
  • The extracellular signal regulated kinase (ERK) cascade is an important signaling pathway that underlies synaptic plasticity, cellular excitability, learning and arousal. (
  • We demonstrated that neomycin exposure induced severe hearing loss and HC damage, which was mediated by activated mitochondrial apoptosis pathway, promoted extracellular signal-regulated kinase (ERK) signaling as well as enhanced reactive oxygen species (ROS) generation in HCs. (
  • Mechanistic studies revealed that PF could decrease cellular ROS levels, suppress the activation of ERK signaling and, subsequently, mitigate the imbalance of mitochondrial apoptotic pathway, thus protecting HCs from neomycin-induced apoptosis. (
  • Further study revealed that the potent activity in the cell growth inhibition and apoptosis induction effects of 10M were related to DNA damage and activation of the p53 signaling pathway. (
  • Pelster, B. (2013): Linking oxygen to time: The bidirectional interaction between the hypoxic signaling pathway and the circadian clock. (
  • MDA-MB-231 and MDA-MB-468 ERalpha-/EGFR+ cell lines were assessed for localization of Jab1 and levels of downstream genes by immunofluorescence and nuclear protein extract assay following treatment with epidermal growth factor (EGF) and extracellular signal-regulated kinase (ERK) pathway inhibitor. (
  • MAPK pathway is often mutated in cancer thus the efficient inhibition of ERK function may be the key to overcome previously described resistance to upstream kinases inhibitors. (
  • Our data highlight the important role of activation of the RAS-RAF-mitogen-activated protein/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase-mitogen-activated protein kinase pathway in the initiation and progression of serrated neoplasms. (
  • Somatic mutations of the RAS genes, leading to activation of this signaling pathway and malignant transformation, are common in human cancers. (
  • These results suggest that TGF-β1-induced CTGF mRNA expression is mediated through the JNK-dependent pathway, whereas p38 MAP kinase and ERK pathways minimally contribute. (
  • Marked activation of the JNK pathway through SEK1 and apoptosis signal-regulating kinase 1 (ASK1), an upstream kinase of SEK1, was demonstrated by the transient transfection of cDNA for wild-type SEK1 or ASK1 together with JNK into COS-7 cells. (
  • All these data suggest that the selective JNK activation by HNE is critical for the apoptosis of PC12 cells and that the HNE-mediated apoptosis is likely to be mediated through the activation of the ASK1-SEK1-JNK pathway without activation of extracellular signal-regulated kinase or p38 MAP kinase. (
  • Furthermore, estrogen can have non-genomic effects inducing the phosphorylation of components of various signaling pathways (e.g., the MAPK pathway) or calcium regulation (reviewed in reference Levin, 2005 ). (
  • Mutations in the mitogen-activated protein kinase (MAPK) signaling pathway involving the genes RET , BRAF , NTRK , and RAS have been reported in independent cohorts in up to 70% of patients with PTC ( 10-15 ). (
  • Regulated AP-1 transcriptional activity, a target of the JNK signal transduction pathway, was also selectively blocked in MKK4 (−/−) cells. (
  • These data establish that MKK4 is a JNK activator in vivo and demonstrate that MKK4 is an essential component of the JNK signal transduction pathway. (
  • Furthermore, dominant-negative MKK4 acts as a specific inhibitor of the JNK signal transduction pathway ( 19 - 22 ). (
  • These data indicate a central role for the MAP kinase kinase MKK4 in the JNK signal transduction pathway ( 1 ). (
  • We have a long-standing interest in the genetic pathway that connects insulin to FOXO transcription factors, a central pathway to regulate lifespan from worms to humans. (
  • The enzyme serves as a key factor in the signal transduction pathway of MAP kinase, therefore it takes part in the cell development (transcription regulation, proliferation, differentiation etc. (
  • However, whether the ERRα pathway plays a fundamental role in regulating myogenesis has not been investigated. (
  • The RhoA/protein kinase B (Akt)/mitogen-activated protein (MAP) kinases, including p38 MAP kinase, extracellular signal-regulated protein kinase, and Jun NH 2 -terminal kinase axis in RAW 264.7 cells, was identified as Gas6/Mer downstream signaling pathway for the upregulation of HGF mRNA and protein. (
  • Inhibition of Mer with small interfering RNA (siRNA) or the RhoA/Rho kinase pathway by RhoA siRNA or Rho kinase pharmacologic inhibitor suppressed Gas6-induced HGF mRNA and protein expression in macrophages and blocked epithelial cell proliferation and wound closure induced by the conditioned medium. (
  • Our data provide evidence that macrophages can be reprogrammed by Gas6 to promote epithelial proliferation and wound repair via HGF, which is induced by the Mer/RhoA/Akt/MAP kinase pathway. (
  • Here we show that Stab2 functions in a signal transduction pathway regulating arterial-venous differentiation during zebrafish embryogenesis. (
  • These results argue that Stab2 is involved in a novel signaling pathway that plays an important role in regulating Erk phosphorylation and establishing arterial-venous identity. (
  • We have identified a novel pathway of ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK) signaling that results in nuclear factor κB (NF-κB) activation and chemoresistance in response to DNA damage. (
  • Collectively, our findings suggest that distinct members of the phosphatidylinositol kinase family activate a common prosurvival MAPK/IKK/NF-κB pathway that opposes the apoptotic response following DNA damage. (
  • As a consequence of phosphorylation, the IκB-α protein is rapidly ubiquitinated on lysine residues 21 and 22 and degraded through the proteasome pathway, thereby allowing for migration of NF-κB to the nucleus, where it regulates the expression of a variety of genes involved in cell survival ( 6 , 52 ). (
  • As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. (
  • Whereas protection by B. megaterium was linked to impaired egg laying, corresponding to a known trade-off between fecundity and resistance, the mechanism underlying protection conferred by P. mendocina depended on weak induction of immune genes regulated by the p38 MAPK pathway. (
  • This kinase is an important proximal component of the MAP kinase pathway involved in transmitting the signals from growth factors, neurotransmitters, and hormones at the cell surface to the transcriptional events in the nucleus. (
  • By mediating the tPA response in macrophages, the NMDA-R provides a pathway by which the fibrinolysis system may regulate innate immunity. (
  • The RAS-RAF-MEK (MAP-ERK kinase)-ERK (extracellular signal-regulated kinase) pathway plays a central role in driving proliferation, survival, and metastasis signals in tumor cells, and the prevalence of oncogenic mutations in RAS and BRAF and upstream nodes makes this pathway the focus of significant oncology drug development efforts. (
  • The RAS-RAF-MEK (MAP-ERK kinase)-ERK (extracellular signal-regulated kinase) pathway controls cell growth, differentiation, survival, and migration in normal tissues. (
  • The scope of physiologic responses to RAF-MEK-ERK pathway activation is partly dictated by the magnitude and the duration of the signal. (
  • Sturm and colleagues suggest that the pathway architecture enables high signaling rates and amplification, with the negative loops providing rich dynamic properties such as oscillations and switch-like properties similar to a negative feedback amplifier ( 10 ). (
  • Negative feedback occurs at multiple levels and the transcriptional output of the pathway includes the dual-specificity phosphatase (DUSP) family of ERK phosphatases as well as the SPRY proteins that are negative regulators of RAS signaling. (
  • These qualities dictate the response to stimuli and this model provides a basis for understanding signaling in the context of normal physiologic processes, as well as in cancer in which the pathway is often dysregulated through oncogenic mutations such as BRAF V600E , which is expressed in approximately 50% of human melanomas, 35% to 60% of thyroid tumors, and a lower proportion of ovarian, colorectal, and lung carcinomas ( 11 ). (
  • These results provide evidence that the neurotrophic effects of PACAP-38 on human SH-SY5Y neuroblastoma cells are mediated by the PAC1 receptor through a cAMP-dependent but PKA-independent mechanism, and furthermore suggest that this involves Epac-dependent activation of ERK as well as activation of the p38 MAP kinase signaling pathway. (
  • These results suggest that ERKs are involved in the signal trans-duction pathway through which ZP stimulation works during the process of fertilization. (
  • The mitogen-activated protein kinase (MAP kinase) pathway participates in a number of reactions of the cell when responding to various external stimuli. (
  • Thomson Reuters provided interactive pathway maps for 260 canonical pathways. (
  • The pathway maps illustrate protein interactions and regulation to provide a comprehensive picture of signaling and disease processes. (
  • CD40-resistant lines expressed pre-B-cell markers, including RAG and VPREB, whereas CD40-sensitive cells resembled mature B cells and expressed higher levels of transcripts encoding several members of the CD40 signaling pathway, including LCK and VAV. (
  • We were interested in investigating further the role of the FGF signalling pathway in the specification of scleraxis positive somite progenitors. (
  • Although p90 ribosomal S6 kinase (RSK) is known as an important downstream effector of the ribosomal protein S6 kinase/extracellular signal-regulated kinase (Ras/ERK) pathway, its endogenous role, and precise molecular function remain unclear. (
  • Collectively, these studies reveal a novel regulatory mechanism of the Ras/ERK pathway by RSK, which negatively regulates ERK activity by acting as a cytoplasmic anchor in Drosophila (Kim, 2006). (
  • Although these targets seem to appropriately explain the roles of RSK as a downstream effector of the Ras/ERK signaling pathway, there has been insufficient evidence to consider them as the actual downstream targets of RSK in vivo . (
  • The report provides comprehensive information on the Mitogen Activated Protein Kinase 1 (MAP Kinase 1 or MAPK 1 or Extracellular Signal Regulated Kinase 2 or ERK-2 or Protein Tyrosine Kinase ERK2 or EC, targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (
  • Additionally, the report provides an overview of key players involved in Mitogen Activated Protein Kinase 1 (MAP Kinase 1 or MAPK 1 or Extracellular Signal Regulated Kinase 2 or ERK-2 or Protein Tyrosine Kinase ERK2 or EC targeted therapeutics development and features dormant and discontinued projects. (
  • citation needed] The term, "extracellular signal-regulated kinases", is sometimes used as a synonym for mitogen-activated protein kinase (MAPK), but has more recently been adopted for a specific subset of the mammalian MAPK family. (
  • The MAP kinase-kinase, which activates ERK, was named "MAPK/ERK kinase" (MEK). (
  • Receptor-linked tyrosine kinases, Ras, Raf, MEK, and MAPK could be fitted into a signaling cascade linking an extracellular signal to MAPK activation. (
  • We have investigated the activity and function of mitogen-activated protein kinase (MAPK) during neural specification in Xenopus . (
  • Because MAPK has been shown to down-regulate Smad1, MAPK may disrupt bone morphogenetic protein 4 (BMP-4) signaling during neural specification. (
  • In this paper, we show that overexpression of a MAPK antagonist prevents neural specification in response to endogenous signals. (
  • Prior UO results in reduced postischemic phosphorylation of c-Jun N-terminal stress-activated protein kinase 1/2 (JNK1/2), p38, mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), and MKK3/6. (
  • APRTPGGRR is the most efficient substrate for phosphorylation reaction by ERK and is phosphorylated by kinases on threonine 97 and can also be phosphorylated by MAPK p38. (
  • Selumetinib is an inhibitor of the MAPK kinases, MEK-1/2 downstream of RAF, and would therefore be an attractive therapeutic candidate to investigate in IRPTC. (
  • Furthermore, ODN MT01 activated Runx2 phosphorylation via ERK1/2 mitogen-activated protein kinase (MAPK) and p38 MAPK. (
  • Repeated morphine exposure (10-20 microm) for 6 days increased the number of neurons expressing phosphorylated (p) mitogen-activated protein (MAP) kinases, including the extracellular signal-regulated kinase (pERK), c-jun N-terminal kinase (pJNK) and P38 (pP38 MAPK). (
  • Both ATM and DNA-PK promote sequential activation of the mitogen-activated protein kinase (MAPK)/p90 rsk signaling cascade in a p53-independent fashion. (
  • Erk2 is also known as microtubule-associated protein-2 kinase MAP kinase 2, p42-MAPK, or EGF receptor T669 (ERT1). (
  • Some protein kinases operate in more than one mitogen-activated protein-kinase (MAPK) cascade. (
  • The role of p38 mitogen-activated protein kinase (MAPK) in ischaemic preconditioning remains controversial. (
  • p38 Mitogen-activated protein kinase (p38 MAPK) is activated by short episodes of ischaemia-reperfusion as well as by sustained ischemia followed by reperfusion. (
  • Here, we demonstrate that myotomally derived FGFs act through the MAPK signal transduction cascade and in particular, ERK1/2 to activate scleraxis expression in a population of mesenchymal progenitor cells in the dorsal sclerotome. (
  • 1 2 Binding of extracellular stimuli to their cell membrane receptors induces a sequence of protein kinase reaction, leading to phosphorylation and activation of MEK (MAP kinase/ERK kinase). (
  • Since these oligopeptides were produced by bacteria or synthetic analogs of such products, it was suggested that the N-formyl oligopeptides are important chemotatic factors and their receptors are important chemotactic factor receptors that act respectively as signaling and signal-recognizing elements to initiate inflammation responses in order to defend against bacterial invasion. (
  • Estrogens signal through two nuclear receptors: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). (
  • The estrogen-related receptors (ERRs) regulate energy substrate uptake, mitochondrial respiration, and biogenesis and may target structural gene programs in striated muscle. (
  • Numerous reports have stated that activation of supersensitive D1 receptors in the DA-depleted striatum leads to the phosphorylation of ERK1/2, which belongs to a class of mitogen-activated protein kinases (MAPKs) and is implicated in transcriptional and translational efficiency [5,9,10]. (
  • Tissue-type plasminogen activator (tPA) is the major intravascular activator of fibrinolysis and a ligand for receptors involved in cell signaling. (
  • Signals from cell surface receptors are transmitted through RAS-GTP to the RAF-MEK-ERK kinase cascade to intracellular substrates in the cytoplasm and nucleus. (
  • The motility of microglial cells is regulated by intracellular signals through various signaling cascades including receptors and kinases. (
  • Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the β-adrenergic receptor kinase I, which specifically blocks signaling mediated by the βγ subunits of G proteins, blocked the GnRHa-induced ERK activation. (
  • Mitogen-activated protein (MAP) kinases are important mediators involved in the intracellular network of interacting proteins that transduce extracellular cues to intracellular responses. (
  • Therefore, recently cloned dual-specificity protein tyrosine phosphatases (PTPases), which exhibit dual-catalytic activity toward phosphotyrosine and phosphothreonine in substrate proteins, may play a pivotal role in the regulation of MAP kinase-signaling pathways. (
  • The phosphorylated ITAMs serve as docking sites for Src homology 2 domain-containing cytosolic proteins, including the tyrosine kinase Syk, the Ras adapter Shc, and the p85 subunit of phosphatidylinositol (PtdIns) 3-kinase. (
  • The close phylogenetic relation of signaling in chemotaxis and olfaction was recently proved by detection formyl peptide receptor like proteins as a distinct family of vomeronasal organ chemosensors in mice. (
  • Additionally we are shipping MAPKAP Kinase 3 Antibodies (67) and MAPKAP Kinase 3 Proteins (16) and many more products for this protein. (
  • Osteoblasts are derived from mesenchymal stem cells, and can differentiate into mature and functional osteoblasts that produce extracellular matrix proteins and regulators of matrix mineralization [ 1 ]. (
  • Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP [( PUBMED:1898771 )] in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. (
  • 11 LRP1 functions in endocytosis and cell signaling in response to diverse ligands, including proteinases and intracellular proteins released in tissue injury. (
  • Accurate multiple alignments of 86 domains that occur in signaling proteins have been constructed and used to provide a Web-based tool (SMART: simple modular architecture research tool) that allows rapid identification and annotation of signaling domain sequences. (
  • The majority of signaling proteins are multidomain in character with a considerable variety of domain combinations known. (
  • Mutations in ras and B-raf genes have been described in lung cancer, representing one of the few examples of tandem mutations in a signaling cascade. (
  • In the preconditioned heart, genes for MAPKAP kinase 3 were up-regulated. (
  • Research has shown that Ginnalin A can demonstrate an anti-metastatic effect by regulating the expression of important genes in metastasis on cancer cell lines. (
  • Recent genomic studies employing transcript expression profiling and chromatin immunoprecipitation (ChIP) in heart showed that ERRα and ERRγ regulate genes involved at all steps of oxidative energy metabolism from substrate uptake through mitochondrial ATP synthesis and export ( 12 ). (
  • However, Runx2 can regulate the expression of osteoblast-specific genes including ALP, type I collagen and osteocalcin. (
  • The pairwise comparison analysis demonstrated four significantly up-regulated ( COBRA1, ITGB4 , STAU2 , and HMGN3 ) genes and one down-regulated ( ANK3 ) gene. (
  • This functional genomic analysis demonstrates the reported interaction between ethanol and ethanol-regulated genes. (
  • Moreover, it confirms the relationship between ethanol-regulated genes and various signaling pathways associated with ethanol-induced apoptosis. (
  • We previously reported the effect of ethanol at low concentration (namely 1 mM) on induction of different signaling pathways initiated through protein kinases phosphorylation with subsequent expression of transcription factors (AP1, Elk1, Stat1, SRF and NFκB) and expression of apoptotic genes (Fas receptor, Fas ligand, FADD and caspase 8) [ 19 ]. (
  • These kinases are encoded by distinct genes and together form a family of kinases whose activation is dependent upon dual phosphorylation on specific threonine and tyrosine residues. (
  • application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signaling domains, approximately 350 greater than previously annotated. (
  • To examine the role of ERK cascade in the antiproliferative effect of GnRHa, PD98059, an inhibitor of mitogen-activated protein/ERK kinase, was used. (
  • These results provide evidence that GnRHa stimulation of ERK activity may be mediated by Gβγ protein, not by PMA-sensitive protein kinase C nor extracellular Ca 2+ in the Caov-3 human ovarian cancer cell line, suggesting that this cascade may play an important role in the antiproliferative effect of GnRHa. (
  • In addition, PD 098059, an antagonist of MEK (MAP kinase/ERK kinase), the upstream kinase of ERK, significantly reduced the PDGF-induced activation of ERK and potently inhibited the expression of MKP-1 after stimulation with PDGF, thereby demonstrating the induction of MKP-1 in response to activation of the ERK signaling cascade. (
  • Macrophage FcγR clustering by immune complexes initiates a signaling cascade that results in phagocytosis of the immune complex ( 1 ). (
  • The extracellular signal-regulated kinase (ERK) is a component of the mitogen-activated protein (MAP) cascade. (
  • This phosphorylation is mediated by a protein kinase cascade that is composed of a MAP kinase kinase kinase that phosphorylates and activates one or more MAP kinase kinases that, in turn, phosphorylates and activates each MAP kinase. (
  • The TLR agonists, flagellin (FLG) and lipopolysaccharide (LPS) stimulate functional activation and cytokine gene expression via the extracellular signal regulated kinase 1/2 (ERK 1/2) MAP kinase cascade. (
  • It is not clear whether this classic Ras cascade plays a role in TLR signaling in avian cells. (
  • This protein enhances the activation of MAPK2, and thus is thought to function as an adaptor to enhance the efficiency of the MAP kinase cascade. (
  • CONCLUSIONS: Extracellular pressure stimulates cell proliferation and activates several signals. (
  • FcγR clustering in macrophages activates signaling events that result in phagocytosis. (
  • MAP2K1 is located upstream to the MAP kinases and activates them by multiple intra and extracellular signals. (
  • In molecular biology, extracellular signal-regulated kinases (ERKs) or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells. (
  • ERKs are known to activate many transcription factors, such as ELK1, and some downstream protein kinases. (
  • Phosphorylation of ERKs leads to the activation of their kinase activity. (
  • Erks) and stress-activated protein (SAP) kinases mediate cellular responses to a wide variety of signals. (
  • MAP kinases are also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. (
  • In mammalian cells, the best characterized sub-group of the MAP Kinase family are the Extracellular Signal Regulated Kinases (ERKs). (
  • Analysis of cDNAs encoding MAP Kinase suggest that numerous other ERKs may exist. (
  • Extracellular signal-regulated kinases(ERKs), belonging to the family of mitogen-activated protein kinases (MAPKs), are cytoplasmic and nuclear serine/threonine kinases involved in the signal transduction of several extracellular effectors. (
  • MAP kinases, also known as extracellular signal-regulated kinases ( ERKs ), are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. (
  • Ras is typically activated by growth hormones through receptor tyrosine kinases and GRB2/SOS, but may also receive other signals. (
  • They were found during a search for protein kinases that are rapidly phosphorylated after activation of cell surface tyrosine kinases such as the epidermal growth factor receptor. (
  • In amphibian embryos, several lines of evidence indicate that neural fate is repressed by bone morphogenetic protein 4 (BMP-4) and anterior neural specification occurs via a reduction in signaling through the BMP-4 receptor ( 2 , 3 ). (
  • Disruption of BMP-4 signaling via prolonged dissociation ( 4 - 7 ) or overexpression of a dominant-negative activin receptor ( 8 , 9 ) or a dominant-negative BMP-4 ( 10 ) leads to neural specification in isolated ectoderm. (
  • Disruption of FGF signaling via overexpression of a dominant-negative FGF receptor (XFD) has produced inconsistent results, e.g., although XFD overexpression in ectoderm can inhibit neural induction by noggin or endogenous signals ( 23 ), uniform expression in germ-line transgenic embryos disrupts posterior regionalization ( 24 ), although neural specification is not affected ( 25 ). (
  • Both effects are strongly attenuated by inhibition or desensitization of epidermal growth factor (EGF) receptor, matrix metalloproteinase (MMP) blockade, heparin-binding-EGF neutralization or phosphatidylinositol 3-kinase (PI3-kinase) inhibitors. (
  • Conditioned medium from UK14304-treated CaCo2-3B stimulates ERK in parental CaCo2 by a mechanism sensitive to EGF receptor and PI3-kinase inhibitors. (
  • Analyzing the molecular events leading to PTEN influence on LPS/Toll-like receptor 4 (TLR4) signaling, we found that LPS-induced activation of mitogen-activated protein kinases is suppressed in PTEN −/− cells. (
  • 4 Upon receptor clustering by immune complexes, the tyrosines in the ITAM are phosphorylated by the membrane-associated Src family tyrosine kinases ( 8 ). (
  • ERK is activated in the striatum by coordinated dopamine and glutamate receptor signaling, where it underlies corticostriatal synaptic plasticity and influences striatal cell excitability. (
  • Tie2 is a tyrosine kinase receptor located predominantly on vascular endothelial cells that plays a central role in vascular stability. (
  • Interestingly, studies in rodents suggest that reduced insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) signaling decrease AD pathology, that is, β -amyloid toxicity. (
  • Formyl peptide receptor (FPR) signaling pathways. (
  • Abnormal dopamine receptor signaling and dopaminergic nerve function is implicated in several neuropsychiatric disorders. (
  • Sustained D1 receptor activity is kept in check by Cyclin-dependent kinase 5 . (
  • Dopamine receptor activation of Ca 2+ /calmodulin-dependent protein kinase II can be cAMP dependent or independent. (
  • Since epidermal growth factor receptor (EGFR), like S100A7, is often expressed in estrogen receptor-alpha-negative (ERalpha-) breast cancer, we set out to investigate the role of Jab1 in mediating EGFR signaling, another facet of the ERalpha- phenotype. (
  • The involvement of supersensitive D1 receptor stimulation and ERK1/2 signaling in the striatum and SN was further supported by more recent studies. (
  • Growth arrest-specific protein 6 (Gas6)/Mer receptor tyrosine kinase (Mer) signaling modulates cytokine secretion and helps to regulate the immune response and apoptotic cell clearance. (
  • Rost, M.S., Sumanas, S. (2014) Hyaluronic acid receptor Stabilin-2 regulates Erk phosphorylation and arterial--venous differentiation in zebrafish. (
  • The IKKs bind NF-κB-inducing kinase (NIK) ( 25 , 33 ), a member of the mitogen-activated protein (MAP) kinase kinase kinase family that interacts with TNF receptor-associated factor 2 ( 20 ), linking IκB degradation and NF-κB activation to the TNF receptor complex. (
  • Our research focuses on receptor signal transduction in the brain, in embryonic development and in neurodegenerative diseases. (
  • The tPA signaling response was distinguished from the signature of signaling events elicited by proinflammatory LRP1 ligands, such as receptor-associated protein (RAP), which included sustained IκBα phosphorylation and activation of all 3 MAP kinases (ERK1/2, c-Jun kinase, and p38 MAP kinase). (
  • In addition to LRP1, we demonstrate that the N -methyl-D-aspartic acid receptor (NMDA-R) is expressed by macrophages and essential for anti-inflammatory cell signaling and regulation of cytokine expression by tPA. (
  • The NMDA-R and Toll-like receptor-4 were not required for proinflammatory RAP signaling. (
  • CT-1 has hypertrophic and cardioprotective properties and acts through LIF receptor β/glycoprotein 130 (gp130)-coupled signaling pathways. (
  • The LIF receptor binds CT-1, and then gp130 associates with the ligand-receptor complex and transduces the proximal signal. (
  • The α6β4 integrin-a laminin-5 receptor-mediates assembly of hemidesmosomes and recruitment of Shc and phosphoinositide 3-kinase through the unique cytoplasmic extension of β4. (
  • Saelzler MP, Spackman CC, Liu Y, Martinez LC, Harris JP, Abe MK: ERK8 down-regulates transactivation of the glucocorticoid receptor through Hic-5. (
  • In mammalian cells, a second parasite factor, malaria pigment or hemozoin (Hz), signals NOS induction through ERK- and nuclear factor kappa B-dependent pathways and has been demonstrated to be a novel proinflammatory ligand for Toll-like receptor 9. (
  • cAMP mediated protein kinase A activity also results in the phosphorylation of DARPP-32 , an inhibitor of protein phosphatase 1 . (
  • Interestingly, the i.t. administration of PD98059, an ERK upstream kinase (MEK) inhibitor, completely blocked the formalin-induced inflammatory nociceptive responses. (
  • Pretreatment of PC12 cells with SB203580, a specific inhibitor of p38 MAP kinase, had no effect on HNE-induced apoptosis. (
  • PACAP-induced differentiation was prevented by the adenylyl cyclase inhibitor, 2',5'-dideoxyadenosine (DDA), but not the protein kinase A (PKA) inhibitor, H89, or by siRNA-mediated knock-down of the PKA catalytic subunit. (
  • PACAP-induced neuritogenesis was blocked by the MEK1 inhibitor PD98059 and partially by the p38 MAP kinase inhibitor SB203580. (
  • The mitogen-activated protein-kinase inhibitor PD098059 was used as a pharmacological tool to study the involvement of extracellular signal-regulated kinases in the induction of the acrosome reaction in human spermatozoa. (
  • These cocultures were treated with PD98059, a specific inhibitor of MAP/ERK kinase 1, or transfected with dominant-negative ERK-1 mutant containing expression vector. (
  • Strikingly, the abrogation of MAP kinase signaling by a dominant-negative ERK-1 mutant inhibited glial-induced capillary network formation by reducing VEGF levels and MMP-9 activity and increasing the levels of tissue inhibitor of metalloproteinase-1. (
  • Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2. (
  • Therefore, MAP kinase phosphatase-1 (MKP-1), a dual-specificity protein tyrosine phosphatase that exhibits catalytic activity toward both regulatory sites on MAP kinases, is suggested to be responsible for the downregulation of extracellular signal-regulated kinase (ERK), stress-activated protein kinase (SAPK), and p38 MAP kinase. (
  • In contrast to ERK, more recently described MAP kinases such as stress-activated protein kinase (SAPK), also referred to as c-Jun N-terminal kinase (JNK), and p38 MAP kinase are suggested to inhibit cellular proliferation and to induce apoptosis. (
  • Stress-activated protein kinase kinase (SEK1), an upstream kinase of JNK, was also activated within 5 min after HNE treatment and remained activated for up to 60 min. (
  • They are part of complex protein kinase cascades. (
  • Abstract -Mitogen-activated protein (MAP) kinase cascades are major signaling systems by which cells transduce extracellular cues into intracellular responses. (
  • Thus, highly specific protein kinase cascades lead to dual phosphorylation of tyrosine and threonine residues on these MAP kinases, inducing their full activation. (
  • The results demonstrate that for the first time that the small GTPase Ras family is involved in TLR signaling of avian heterophils with the TLR agonists LPS (Ras) and FLG (Rap1) inducing differential signaling cascades to activate the downstream ERK MAP kinase. (
  • Mitogen-activated protein kinase (MAP kinase) cascades are effectors for many growth factor signals implicated in developmental processes, including appendage outgrowth and organogenesis. (
  • Mitogen-activated protein kinase 1 (MAPK1) is also known as extracellular signal-regulated kinase 2 (ERK2). (
  • Two similar protein kinases with 85% sequence identity were originally called ERK1 and ERK2. (
  • APRTPGGRR is specific for MAP kinases: p44MAPK [extracellular signal-regulated kinase 1 (ERK1)] and p42MAPK (ERK2). (
  • Erk2, a serine/threonine kinase, phosphorylates microtubule associated protein-2 and myelin basic protein. (
  • ERK1 and ERK2 are structurally very similar and, unlike the RAF and MEK kinases, have a wide range of cytoplasmic and nuclear substrates (reviewed in ref. 5 ). (
  • Our goal is to study the mechanism of action and resistance of ERK inhibitors in lymphoma and to explore potential synergies between novel and already established inhibitors of cross-talking signaling networks. (
  • On the other hand, specific inhibitors of phosphatidylinositol 3-kinase (PI3K) suppressed TGF-β1-induced CTGF expression in a concentration-dependent manner. (
  • PI3K inhibitors dose-dependently suppressed TGF-β1-induced JNK, but not p38 MAP kinase activation. (
  • Whereas Hcys treatment increased protein kinase C (PKC) activity in Mo, pretreatment of Mo with PKC inhibitors totally suppressed Hcys-induced LPL mRNA expression. (
  • The JNK group of MAP kinases includes at least 10 members ( 4 ) that are activated in response to a wide array of cellular stresses, including osmotic shock, heat shock, lipopolysaccharide, protein synthesis inhibitors, UV irradiation, and certain cytokines ( 4 - 8 ). (
  • Finally, treatment of ERRα−/− myocytes with MEK inhibitors rescued normal ERK signaling and myogenesis. (
  • The signaling pathways that lead to MAP kinase activation are highly conserved and have been identified in many organisms, including yeast, worms, flies, and humans ( 3 ). (
  • Mitogen-activated protein kinase 6 is an enzyme that in humans is encoded by the MAPK6 gene . (
  • The report analyses the pipeline products from therapy areas Oncology and Musculoskeletal Disorders under development targeting Mitogen Activated Protein Kinase 1 (ERT1 or MAP Kinase Isoform p42 or Extracellular Signal Regulated Kinase 2 or Mitogen Activated Protein Kinase 2 or MAPK1 or EC (
  • The most promising approach to date appears to be the inhibition of mitogen-activated ERK kinase or MEK. (
  • 1] Mitogen-activated protein kinases (PRKMs, or MAPKs) are serine-threonine protein kinases that are activated in response to a wide variety of extracellular stimuli. (
  • We have studied the roles of mitogen-activated protein kinase family in the antiproliferative effect of GnRHa on the Caov-3 human ovarian cancer cell line. (
  • GnRHa also activated ERK kinase (mitogen-activated protein/ERK kinase) and resulted in an increase in phosphorylation of son of sevenless (Sos), and Shc. (
  • Previous reports indicated that LPS-induced mitogen-activated protein kinase activation is down-regulated by phosphatidylinositol 3-kinase through the activation of Akt. (
  • Mitogen-Activated Protein Kinase 3" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • This graph shows the total number of publications written about "Mitogen-Activated Protein Kinase 3" by people in Harvard Catalyst Profiles by year, and whether "Mitogen-Activated Protein Kinase 3" was a major or minor topic of these publication. (
  • Below are the most recent publications written about "Mitogen-Activated Protein Kinase 3" by people in Profiles. (
  • ACT-058362 also inhibits U-II-induced calcium mobilization and mitogen-activated protein kinase phosphorylation. (
  • This kinase functions as a mitogen-activated protein kinase (MAP kinase)- activated protein kinase. (
  • 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. (
  • The present study investigates the role of mitogen-activated protein (MAP) kinase in the expression of CTGF mRNA in the human lung fibroblast line, HFL-1. (
  • Specifically, we determined the effect of HNE on the activities of mitogen-activated protein (MAP) kinases involved in early signal transduction. (
  • On are 11 Mitogen-Activated Protein Kinase-Activated Protein Kinase 3 (MAPKAPK3) ELISA Kits from 4 different suppliers available. (
  • MKK4 is a member of the mitogen-activated protein kinase kinase group of dual specificity protein kinases that functions as an activator of the c-Jun NH 2 -terminal kinase (JNK) in vitro . (
  • i ) the mitogen-activated protein kinase kinase kinase MEKK1, and ( ii ) treatment with anisomycin or heat shock. (
  • Three distinct groups of mammalian enzymes closely related to mitogen-activated protein (MAP) kinases have been identified: extracellular signal-regulated kinase, p38 MAP kinase, and c-Jun NH 2 -terminal kinase (JNK) ( 1 ). (
  • This enzyme serves as a MAP (mitogen activated protein) kinase, it is a part of the dual specificity protein kinase family. (
  • 9 Mitogen-Activated Protein Kinase Kinase 6 (MAP2K6) ELISA Kits from 5 manufacturers are available on (
  • Mammalian mitogen-activated protein (MAP) kinases include extracellular signal-regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 subgroups. (
  • Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. (
  • The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. (
  • This kinase is known to play a critical role in mitogen growth factor signal transduction. (
  • Mitogen Activated Protein Kinases (MAPKs) play pivotal roles in mediating signal transduction from the cell surface to the nucleus. (
  • CT-1 intracellular signaling pathways include extracellular signal regulated kinases (ERK), mitogen activated protein (MAP) kinases, the janus kinase (JAK)/signal transducers and activators of transcription (STAT) system, and PI3-kinase/Akt. (
  • These findings provide evidence that β4 signaling promotes epidermal growth and wound healing through a previously unrecognized effect on nuclear translocation of NF-κB and mitogen-activated protein kinases. (
  • The protein encoded by this gene is a member of the Ser/Thr protein kinase family and is most closely related to mitogen-activated protein kinases (MAP kinases). (
  • It is an atypical member of the mitogen activated kinases family. (
  • 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. (
  • In the present study, we investigated whether interfering with the activation of this mitogen-activated protein (MAP) kinase would repress MMP-9 synthesis and inhibit capillary formation. (
  • In mosquito cells, signaling by PfGPIs and P. falciparum merozoites is mediated through Akt/protein kinase B (Akt/PKB), the mitogen-activated protein kinase kinase DSOR1, and extracellular signal-regulated kinase (ERK). (
  • Once MAPK3 is activated by phosphorylation by an upstream kinase, it translocates to the nucleus of the stimulated cell, where it phosphorylates target molecules. (
  • To investigate whether EGFR signaling has a functional effect on Jab1 activity, we performed immunoblotting and double-immunostaining for the Jab1 downstream target, p27. (
  • It would therefore be useful to identify markers that predict whether a specific cell line or tumor will undergo apoptosis when stimulated with CD40 and to identify targets downstream of CD40 that affect only the apoptotic arm of CD40 signaling. (
  • We propose that tight control of ERK signalling strength by MKP3 is important for the appropriate regulation of downstream cellular responses including the activation of scleraxis . (
  • These data demonstrate that the activators of p38 (MKK3 and MKK4), JNK (MKK4), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways. (
  • The protein encoded by this gene was identified as an interacting protein that binds specifically to MAP kinase kinase MAP2K1 /MEK1 and to MAP kinase MAPK2/ERK1. (
  • RAF kinases activate the dual specificity kinases MEK1 and MEK2 through phosphorylation at serine 218 and serine 222, respectively. (
  • Important FPR regulated pathways include: G protein dependent activation of phospholipase C (PLC) which results in the breakdown of the membrane constituent phospholipid, phosphatidylinositol (4,5)-bisphosphate (PIP2) into inositol (1,4,5)-trisphosphate (IP3) and diacyl glycerol (DAG). (
  • MAP kinases (e.g., extracellular signal-regulated kinases) integrate multiple biochemical signals and are involved in cell proliferation, differentiation, transcription, regulation and development. (
  • Extracellular signal-regulated kinases such as MAP kinases has an important role in assimilation of various biochemical signals. (
  • Given the importance of new gene expression for both LTP and learning, it is critical to elucidate the mechanisms by which glutamate regulates transcription in neurons. (
  • 15 16 Furthermore, the kinetics of gene expression and the cellular localization are consistent with a role for MKP-1 in the compensatory inactivation of stimulated MAP kinase-signaling pathways. (
  • PURPOSE: microRNAs (miRNAs) are non-coding RNAs composed of 20 to 22 nucleotides that regulate development and differentiation in various organs by silencing specific RNAs and regulating gene expression. (
  • c-Jun activation domain-binding protein-1 (Jab1) is a multifunctional signaling protein that previously has been shown to be a master regulator of a poor prognostic gene signature in invasive breast cancer and to mediate the action of S100A7. (
  • This gene encodes a member of the Ser/Thr protein kinase family. (
  • 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. (
  • A gene on chromosome 16p11.2 that encodes a protein of the MAP kinase family. (
  • The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. (
  • We are interested in how hormones act on gene expression and electrical activity of cells to regulate neurogenesis, and the functional significance of this striking form of adult brain plasticity. (
  • We have analyzed gene expression patterns in CD40-sensitive and CD40-resistant diffuse large B-cell lymphoma (DLBCL) cell lines to identify signaling pathways that are involved in CD40-mediated apoptosis. (
  • Consistent with these physiological phenotypes, RSK negatively regulates ERK-mediated developmental processes and gene expressions by blocking the nuclear localization of ERK in a kinase activity-independent manner. (
  • This fat metabolism switch in H3K4me3 methyltransferase-deficient worms is mediated at least in part by the downregulation of germline targets, including S6 kinase, and by the activation of an intestinal transcriptional network that upregulates delta-9 fatty acid desaturases. (
  • The in vivo role for ERRα in regulating energy metabolism has been most intensively studied in whole body ERRα knockout models ( 31 ), which have revealed its importance in mitochondrial energy generation in heart and brown adipose during metabolic stress ( 20 , 63 ). (
  • The extracellular face of the cell membrane is on top while the intracellular (cytoplasmic) face is on the bottom. (
  • 3 MEK, the specific activator of ERK, is a dual-specificity protein kinase that phosphorylates both threonine and tyrosine regulatory sites in ERK. (
  • The JNKs are activated by phosphorylation on Thr and Tyr ( 5 ) by the dual specificity protein kinase MKK4 (also known as SEK1/JNKK), a member of the MAP kinase kinase group ( 14 - 16 ). (
  • EP also attenuated the phosphorylation of extracellular signal-regulated kinase (ERK) in the neurons of L4-L5 spinal dorsal horn after formalin injection. (
  • Here we used immunohistochemistry and western blots to examine the effect of photoperiod on phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK) in male California mice (Peromyscus californicus) during resident-intruder tests. (
  • EGF causes significant phosphorylation of extracellular signal-regulated kinase (ERK) and Jun N-terminal protein kinase (JNK) and phosphorylation and degradation of IκB in β4 mutant cells adhering to laminin-5. (
  • Accordingly, recent advances in this area demonstrated that phagocytosis is a highly regulated process involving negative regulation by protein tyrosine phosphatases as well as inositol phosphatases ( 2 , 3 , 4 , 5 , 6 ). (
  • The functional role of the extracellular region has not been clearly defined and potential roles in ligand interaction, dimerization, and regulation of cell-cell contacts have been reported. (
  • ERK activation is a key signal step for the regulation of several biological responses like cell proliferation, cell differentiation and cell death. (
  • These MAP kinases phosphorylate distinct groups of substrates in vitro and have been implicated in the regulation of fundamental cellular processes ( 1 , 2 ). (
  • Even though intracellular signals underlying the regulation of microglia chemotaxis are still not well understood, many attempts focusing on revealing and understanding signaling pathways controlling microglia chemotaxis have been made in recent years. (
  • Signaling pathways reported to be involved in the regulation of microglia chemotaxis were depicted in a diagram ( Fig. 2 ). (
  • This translocation to the nucleus is essential to MAP kinase signalling because it enables the kinase to phosphorylate transcription factors. (
  • Data obtained in C. elegans indicate that the beneficial effect mediated via reduced IR/IGF-1R signaling might partially be induced via the forkhead-box O transcription factors (FoxO). (
  • Myocyte differentiation involves complex interactions between signal transduction pathways and transcription factors. (
  • To date, numerous reports have shown that signaling pathways and transcription factors could participate in osteoblastogenesis by regulating the production or activity of Runx2 [ 4 ]. (
  • PtdIn3,4,5P 3 , the lipid product of PtdIns3-kinase, is an important second messenger that is necessary for the activation of pleckstrin homology domain-containing enzymes such as the serine/threonine kinase Akt, the guanine nucleotide exchange factor Vav, and the Tec family tyrosine kinase Btk, involved in intracellular calcium mobilization ( 12 ). (
  • The RAF family of serine/threonine kinases consists of three family members: ARAF, BRAF, and CRAF. (
  • Cells were counted after 24 h and after inhibition of each signal, tyrosine phosphorylation or actin depolymerization. (
  • Inhibition of p38 MAP kinase or extracellular signal-regulated kinase (ERK) activation did not affect TGF-β1-induced CTGF expression. (
  • The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. (
  • Extracellular pressure stimulates colon cancer cell proliferation via a mechanism requiring PKC and tyrosine kinase signals. (
  • However, global tyrosine kinase blockade (genistein) and PKC blockade (calphostin C) negated pressure-induced proliferation. (
  • Indeed, this enzyme mediates the uptake of lipoproteins by Mo ( 15 - 17 ), promotes lipoprotein retention to the extracellular matrix ( 18 , 19 ), induces the expression of the proatherogenic cytokine tumor necrosis factor-α ( 20 , 21 ), increases monocyte adhesion to endothelial cells ( 22 - 24 ), and increases proliferation of vascular smooth muscle cells ( 25 ). (
  • We report that Gas6/Mer/RhoA signaling can induce the production of epithelial growth factor hepatic growth factor (HGF) in macrophages, which ultimately promotes epithelial cell proliferation and wound repair. (
  • The atypical protein kinase C (PKC) isotypes (λ/ιPKC and ζPKC) have been shown to be critically involved in important cell functions such as proliferation and survival. (
  • Although this makes CD40 an attractive target for antitumor therapies, the response of malignant B cells to CD40 signaling is variable, and CD40 stimulation can enhance proliferation and can increase chemoresistance in some cell lines. (
  • The p38 SAP kinase substrate MAP-kinase-activated protein kinase-2 (MAPKAP kinase-2) contains a putative nuclear localisation signal which we show is functional and required for activation by a variety of stimuli. (
  • Extracellular stimuli such as platelet-derived growth factor (PDGF), 12-O-tetradecanoylphorbol 13-acetate (TPA), and angiotensin II, which activated ERK but not SAPK/p38 MAP kinase, induced a transient induction of MKP-1 mRNA and its intracellular protein. (
  • We showed previously that SNB19 glioblastoma cells modulate bovine retinal endothelial cells in cocultures to form capillary-like network structures, that matrix metalloproteinase-9 (MMP-9) expression is critical for endothelial morphogenesis, and that MMP-9 expression in glioblastoma cells is regulated by extracellular signal-regulated kinase-1 (ERK-1). (
  • Following phosphorylation of MAPKAP kinase-2, nuclear p38 was exported to the cytoplasm in a complex with MAPKAP kinase-2. (
  • Nuclear export of p38 and MAPKAP kinase-2 may permit them to phosphorylate substrates in the cytoplasm. (
  • Surprisingly, RSK was found to be devoted to negatively regulate nuclear ERK function, restraining ERK in the cytoplasm during Drosophila eye and wing development, by physical association with ERK (Kim, 2006). (
  • The ability of MKK4 to activate JNK is not shared by any of the other MAP kinases kinases (MKK1, MKK2, MKK3, MKK5, and MKK6) that have been molecularly cloned ( 1 ). (
  • Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. (
  • Instead, cardiac myocyte-restricted knockout of gp130 in adult mice leads to left ventricular dilatation, myocyte apoptosis, and failure when the left ventricle is subjected to increased wall stress, 6 highlighting the cardioprotective effects of gp130 signaling. (
  • In addition, CD40-sensitive DLBCL cell lines also displayed constitutive activation of extracellular signal-regulated kinase (ERK) and failed to undergo apoptosis when ERK phosphorylation was inhibited. (
  • A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. (
  • This kinase is localized in the nucleus , and has been reported to be activated in fibroblasts upon treatment with serum or phorbol esters. (
  • These enzymes are activated by dual phosphorylation on Thr and Tyr within the motif Thr-Xaa-Tyr located in kinase subdomain VIII ( 3 ). (
  • MKK4 is, in turn, activated by dual phosphorylation on Ser and Thr within kinase subdomain VIII by MAP kinase kinase kinases, including MEKK1 ( 17 , 18 ). (
  • These MAP kinase isoforms are activated by dual phosphorylation on threonine and tyrosine. (
  • The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. (
  • In general, MAP kinases are activated by phosphorylation on tyrosine and threonine residues and inactivated by dephosphorylation. (
  • They regulate cellular processes as diverse as protein biosynthesis and intracellular membrane trafficking. (
  • Microglia respond to extracellular signals and engulf unwanted neuronal debris by phagocytosis, thereby maintaining normal cellular homeostasis in the CNS. (
  • These MKK isoforms did not activate the ERK subgroup of MAP kinases, but MKK4 did activate JNK. (
  • Signaling pathways that activate an epithelial growth program in macrophages are still poorly defined. (
  • A common feature for activation of all MAP kinase isoforms is the requirement for phosphorylation of both a threonine and a neighboring tyrosine regulatory site by a specific upstream protein kinase for activation. (
  • However, ERRα's role in regulating myocyte differentiation is not known. (
  • Collectively, these data demonstrate that ERRα is required for normal skeletal myocyte differentiation via modulation of MAP kinase signaling. (
  • In this study, the detailed signaling pathways in which ODN MT01 promoted the differentiation of osteoblasts were systematically examined. (
  • Stab2 morphants display reduced Erk phosphorylation in the arterial progenitors, which is a known transducer of VEGF signaling, previously associated with arterial-venous differentiation. (
  • We show that increased or decreased levels of phosphorylated ERK result in the loss of scleraxis transcripts and the loss of distal rib development, highlighting the importance of the MKP3-ERK-MAP kinase mediated feedback loop for cell specification and differentiation. (
  • Together with our previous findings, our data indicate that parasite signaling of innate immunity is conserved in mosquito and mammalian cells. (
  • Export of MAPKAP kinase-2 required phosphorylation by p38 but did not appear to require the kinase activity of MAPKAP kinase-2. (
  • Western Blot: MAPKAP Kinase 3 Antibody (3F4) [H00007867-M01] - MAPKAPK3 monoclonal antibody (M01), clone 3F4. (
  • Sandwich ELISA: MAPKAP Kinase 3 Antibody (3F4) [H00007867-M01] - Detection limit for recombinant GST tagged MAPKAPK3 is approximately 0.1ng/ml as a capture antibody. (
  • A total of 105 MAPKAP Kinase 3 products are currently listed. (
  • TNF-α and interleukin 1 are potent activators of protein kinase C ζ (ζPKC) in vivo ( 19 , 23 , 26 ). (
  • The developmental outcome of ERK signalling relies, at least in part, on the competing actions of upstream activators and inhibitory MAP kinase phosphatases (MKPs). (
  • In the present study, we examined the role of these MAP kinases in the induction of MKP-1 in vascular smooth muscle cells (VSMCs). (
  • We suggest that this pattern of MKP-1 induction may be a negative feedback mechanism in the control of MAP kinase activity in VSMCs. (
  • The transient induction of MAP kinase phosphatase-1 (MKP-1), which mediates ERK dephosphorylation at the onset of myogenesis, was lost in ERRα−/− myocytes and in XCT790-treated C2C12. (

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