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.
A Janus kinase subtype that is predominantly expressed in hematopoietic cell. It is involved in signaling from a broad variety of CYTOKINE RECEPTORS including ones that utilize the INTERLEUKIN RECEPTOR COMMON GAMMA SUBUNIT.
A family of intracellular tyrosine kinases that participate in the signaling cascade of cytokines by associating with specific CYTOKINE RECEPTORS. They act upon STAT TRANSCRIPTION FACTORS in signaling pathway referred to as the JAK/STAT pathway. The name Janus kinase refers to the fact the proteins have two phosphate-transferring domains.
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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.
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.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.
A family of transcription factors containing SH2 DOMAINS that are involved in CYTOKINE-mediated SIGNAL TRANSDUCTION. STAT transcription factors are recruited to the cytoplasmic region of CELL SURFACE RECEPTORS and are activated via PHOSPHORYLATION. Once activated they dimerize and translocate into the CELL NUCLEUS where they influence GENE expression. They play a role in regulating CELL GROWTH PROCESSES and CELL DIFFERENTIATION. STAT transcription factors are inhibited by SUPPRESSOR OF CYTOKINE SIGNALING PROTEINS and PROTEIN INHIBITORS OF ACTIVATED STAT.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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 family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS. The TYK2 kinase is considered the founding member of the janus kinase family and was initially discovered as a signaling partner for the INTERFERON ALPHA-BETA RECEPTOR. The kinase has since been shown to signal from several INTERLEUKIN RECEPTORS.
Agents that inhibit PROTEIN KINASES.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A family of structurally related proteins that are induced by CYTOKINES and negatively regulate cytokine-mediated SIGNAL TRANSDUCTION PATHWAYS. SOCS proteins contain a central SH2 DOMAIN and a C-terminal region of homology known as the SOCS box.
A signal transducer and activator of transcription that mediates cellular responses to INTERFERONS. Stat1 interacts with P53 TUMOR SUPPRESSOR PROTEIN and regulates expression of GENES involved in growth control and APOPTOSIS.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
A 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 signal transducer and activator of transcription that mediates cellular responses to a variety of CYTOKINES. Stat5 activation is associated with transcription of CELL CYCLE regulators such as CYCLIN KINASE INHIBITOR P21 and anti-apoptotic genes such as BCL-2 GENES. Stat5 is constitutively activated in many patients with acute MYELOID LEUKEMIA.
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.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
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 family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.
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.
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.
The major protein constituents of milk are CASEINS and whey proteins such as LACTALBUMIN and LACTOGLOBULINS. IMMUNOGLOBULINS occur in high concentrations in COLOSTRUM and in relatively lower concentrations in milk. (Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed, p554)
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A 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.
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.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A 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 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).
Established cell cultures that have the potential to propagate indefinitely.
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 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.
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.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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).
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.
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.
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 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.
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 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 cytokine receptor that acts through the formation of oligomeric complexes of itself with a variety of CYTOKINE RECEPTORS.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
A 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.
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.
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.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
A cell line derived from cultured tumor cells.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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 class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.
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 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.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A cell surface receptor that specifically mediates the biological effects of INTERLEUKIN-9. The functional IL9 receptor signals through interaction of its cytoplasm domain with JANUS KINASES and requires the INTERLEUKIN RECEPTOR COMMON GAMMA SUBUNIT for activity.
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.
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.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
Proteins prepared by recombinant DNA technology.
Conditions which cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. They all involve dysregulation of multipotent MYELOID PROGENITOR CELLS, most often caused by a mutation in the JAK2 PROTEIN TYROSINE KINASE.
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.
Cell surface proteins that bind cytokines and trigger intracellular changes influencing the behavior of cells.
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.
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 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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
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 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 rate dynamics in chemical or physical systems.
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.
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.
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 sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A group of phenyl benzopyrans named for having structures like FLAVONES.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A de novo myeloproliferation arising from an abnormal stem cell. It is characterized by the replacement of bone marrow by fibrous tissue, a process that is mediated by CYTOKINES arising from the abnormal clone.
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.
Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
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.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A signal transducer and activator of transcription that mediates cellular responses to TYPE I INTERFERONS. Stat2 protein is associated constitutively with INTERFERON REGULATORY FACTOR-9. After PHOSPHORYLATION Stat2 forms the IFN-STIMULATED GENE FACTOR 3 COMPLEX to regulate expression of target GENES.
Cell surface proteins that bind erythropoietin with high affinity and trigger intracellular changes influencing the behavior of 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.
Cell surface receptors with specificity for ONCOSTATIN M. Two subtypes of receptors have been identified and are defined by their subunit composition.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-4. Stat6 has been shown to partner with NF-KAPPA B and CCAAT-ENHANCER-BINDING PROTEINS to regulate GENETIC TRANSCRIPTION of interleukin-4 responsive GENES.
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 myeloproliferative disorder of unknown etiology, characterized by abnormal proliferation of all hematopoietic bone marrow elements and an absolute increase in red cell mass and total blood volume, associated frequently with splenomegaly, leukocytosis, and thrombocythemia. Hematopoiesis is also reactive in extramedullary sites (liver and spleen). In time myelofibrosis occurs.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Transport proteins that carry specific substances in the blood or across cell membranes.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
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.
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.
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.
Receptors present on a wide variety of hematopoietic and non-hematopoietic cell types that are specific for INTERLEUKIN-4. They are involved in signaling a variety of immunological responses related to allergic INFLAMMATION including the differentiation of TH2 CELLS and the regulation of IMMUNOGLOBULIN E production. Two subtypes of receptors exist and are referred to as the TYPE I INTERLEUKIN-4 RECEPTOR and the TYPE II INTERLEUKIN-4 RECEPTOR. Each receptor subtype is defined by its unique subunit composition.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
A 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
Cell surface receptors for obesity factor (LEPTIN), a hormone secreted by the WHITE ADIPOCYTES. Upon leptin-receptor interaction, the signal is mediated through the JAK2/STAT3 pathway to regulate food intake, energy balance and fat storage.
Elements of limited time intervals, contributing to particular results or situations.
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.
Labile proteins on or in prolactin-sensitive cells that bind prolactin initiating the cells' physiological response to that hormone. Mammary casein synthesis is one of the responses. The receptors are also found in placenta, liver, testes, kidneys, ovaries, and other organs and bind and respond to certain other hormones and their analogs and antagonists. This receptor is related to the growth hormone receptor.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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 ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
A 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.
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.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
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 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.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
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 clinical syndrome characterized by repeated spontaneous hemorrhages and a remarkable increase in the number of circulating platelets.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
A multimeric complex that functions as a ligand-dependent transcription factor. ISGF3 is assembled in the CYTOPLASM and translocated to the CELL NUCLEUS in response to INTERFERON signaling. It consists of ISGF3-GAMMA and ISGF3-ALPHA, and it regulates expression of many interferon-responsive GENES.
Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.
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.
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 serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
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.
An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.
A cytokine with both pro- and anti-inflammatory actions that depend upon the cellular microenvironment. Oncostatin M is a 28 kDa monomeric glycoprotein that is similar in structure to LEUKEMIA INHIBITORY FACTOR. Its name derives from the the observation that it inhibited the growth of tumor cells and augmented the growth of normal fibroblasts.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
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.
Cell surface proteins that bind GROWTH HORMONE with high affinity and trigger intracellular changes influencing the behavior of cells. Activation of growth hormone receptors regulates amino acid transport through cell membranes, RNA translation to protein, DNA transcription, and protein and amino acid catabolism in many cell types. Many of these effects are mediated indirectly through stimulation of the release of somatomedins.
An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
An enzyme that catalyzes the phosphorylation of the guanidine nitrogen of arginine in the presence of ATP and a divalent cation with formation of phosphorylarginine and ADP. EC 2.7.3.3.
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.
A ubiquitously expressed heterodimeric receptor that is specific for both INTERFERON-ALPHA and INTERFERON-BETA. It is composed of two subunits referred to as IFNAR1 and IFNAR2. The IFNAR2 subunit is believed to serve as the ligand-binding chain; however both chains are required for signal transduction. The interferon alpha-beta receptor signals through the action of JANUS KINASES such as the TYK2 KINASE.
An enzyme that catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside monophosphate, e.g., UMP, to form ADP and UDP. Many nucleoside monophosphates can act as acceptor while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.4.
Cell surface proteins that bind interleukins and trigger intracellular changes influencing the behavior of cells.
A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
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.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
A mitogen-activated protein kinase kinase with specificity for a subset of P38 MITOGEN-ACTIVATED PROTEIN KINASES that includes MITOGEN-ACTIVATED PROTEIN KINASE 12; MITOGEN-ACTIVATED PROTEIN KINASE 13; and MITOGEN-ACTIVATED PROTEIN KINASE 14.
A 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.
An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION.
Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
A non-receptor protein-tyrosine kinase that is expressed primarily in the BRAIN; OSTEOBLASTS; and LYMPHOID CELLS. In the CENTRAL NERVOUS SYSTEM focal adhesion kinase 2 modulates ION CHANNEL function and MITOGEN-ACTIVATED PROTEIN KINASES activity.
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.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.
An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.
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.
An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 2.7.1.20.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
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.
Serine protein kinases involved in the regulation of ACTIN polymerization and MICROTUBULE disassembly. Their activity is regulated by phosphorylation of a threonine residue within the activation loop by intracellular signaling kinases such as P21-ACTIVATED KINASES and by RHO KINASE.
5,7,4'-trihydroxy-flavone, one of the FLAVONES.
The process by which two molecules of the same chemical composition form a condensation product or polymer.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
An INTERLEUKIN-6 related cytokine that exhibits pleiotrophic effects on many physiological systems that involve cell proliferation, differentiation, and survival. Leukemia inhibitory factor binds to and acts through the lif receptor.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A lactogenic hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). It is a polypeptide of approximately 23 kD. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Prolactin receptors are present in the mammary gland, hypothalamus, liver, ovary, testis, and prostate.
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.

Granulocyte-macrophage colony-stimulating factor-activated signaling pathways in human neutrophils. Involvement of Jak2 in the stimulation of phosphatidylinositol 3-kinase. (1/1765)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates many of the biological activities of human neutrophils. The signaling pathways via which these effects are mediated are not fully understood. We have shown previously that GM-CSF treatment of human neutrophils activates the Janus kinase/signal transducers and activators of transcription (Jak/STAT) pathway and, more specifically, Jak2, STAT3, and STAT5B in neutrophils. GM-CSF also stimulates the activity of the phosphatidylinositol 3-kinase (PI3-kinase) in a tyrosine kinase-dependent manner. Here we report that pretreating the cells with a Jak2 inhibitor (AG-490) abolishes tyrosine phosphorylation of the p85 subunit of PI3-kinase induced by GM-CSF. Furthermore, p85 was found to associate with Jak2, but not with Lyn, in stimulated cells in situ and with its autophosphorylated form in vitro; however, Jak2 did not bind to either of the two Src homology 2 (SH2) domains of the p85 subunit of PI3-kinase. Although STAT5B bound to the carboxyl-terminal SH2 domain of p85, it was absent from the complex containing PI3-kinase and Jak2. These results suggest that stimulation of the activity of PI3-kinase induced by GM-CSF is mediated by Jak2 and that the association between Jak2 and p85 depends on an adaptor protein yet to be identified.  (+info)

Constitutive activation of JAK2 confers murine interleukin-3-independent survival and proliferation of BA/F3 cells. (2/1765)

The Janus tyrosine kinase 2 (JAK2) plays an essential role of cytokine receptor signaling, including that of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor. We reported earlier that the activation of JAK2 is essential for all the examined signals induced by human GM-CSF through the box1 region of betac, such as promotion of cell survival and proliferation. To elucidate the role of JAK2 in cell survival and proliferation, we generated an artificial activation system by constructing a chimeric molecule (beta/JAK2) consisting of betac extracellular and transmembrane regions fused with JAK2, and we analyzed various signaling events in interleukin-3-dependent mouse pro-B cell, BA/F3. The beta/JAK2 was constitutively phosphorylated in the absence of human GM-CSF and murine interleukin-3, and this led to proliferation and cell survival. Western blot analysis showed that STAT5, Shc, and SHP-2 were not phosphorylated in the cells, and the consistent activation of beta-casein and c-fos promoters was not enhanced. In contrast, c-myc transcription was constitutively activated. We propose that the activation of beta/JAK2 suffices for survival and proliferation and that the activation of STAT5 and mitogen-activated protein kinase cascade is not required for these activities in BA/F3 cells.  (+info)

Thrombopoietin-induced conformational change in p53 lies downstream of the p44/p42 mitogen activated protein kinase cascade in the human growth factor-dependent cell line M07e. (3/1765)

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

The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. (4/1765)

The Janus family of protein tyrosine kinases (JAKs) regulate cellular processes involved in cell growth, differentiation and transformation through their association with cytokine receptors. However, compared with other kinases, little is known about cellular regulators of the JAKs. We have recently identified a JAK-binding protein (JAB) that inhibits JAK signaling in cells. In the studies presented here we demonstrate that JAB specifically binds to the tyrosine residue (Y1007) in the activation loop of JAK2, whose phosphorylation is required for activation of kinase activity. Binding to the phosphorylated activation loop requires the JAB SH2 domain and an additional N-terminal 12 amino acids (extended SH2 subdomain) containing two residues (Ile68 and Leu75) that are conserved in JAB-related proteins. An additional N-terminal 12-amino-acid region (kinase inhibitory region) of JAB also contributes to high-affinity binding to the JAK2 tyrosine kinase domain and is required for inhibition of JAK2 signaling and kinase activity. Our studies define a novel type of regulation of tyrosine kinases and might provide a basis for the design of specific tyrosine kinase inhibitors.  (+info)

TGF-beta does not inhibit IL-12- and IL-2-induced activation of Janus kinases and STATs. (5/1765)

The immune system is an important target for the cytokine TGF-beta1, whose actions on lymphocytes are largely inhibitory. TGF-beta has been reported to inhibit IL-12- and IL-2-induced cell proliferation and IFN-gamma production by T cells and NK cells; however, the mechanisms of inhibition have not been clearly defined. It has been suggested by some studies that TGF-beta blocks cytokine-induced Janus kinase (JAK) and STAT activation, as in the case of IL-2. In contrast, other studies with cytokines like IFN-gamma have not found such an inhibition. The effect of TGF-beta on the IL-12-signaling pathway has not been addressed. We examined this and found that TGF-beta1 did not have any effect on IL-12-induced phosphorylation of JAK2, TYK2, and STAT4 although TGF-beta1 inhibited IL-2- and IL-12-induced IFN-gamma production. Similarly, but in contrast to previous reports, we found that TGF-beta1 did not inhibit IL-2-induced phosphorylation of JAK1, JAK3, and STAT5A. Furthermore, gel shift analysis showed that TGF-beta1 did not prevent activated STAT4 and STAT5A from binding to DNA. Our results demonstrate that the inhibitory effects of TGF-beta on IL-2- and IL-12-induced biological activities are not attributable to inhibition of activation of JAKs and STATs. Rather, our data suggest the existence of alternative mechanisms of inhibition by TGF-beta.  (+info)

Lineage-specific activation of STAT3 by interferon-gamma in human neutrophils. (6/1765)

Binding of interferon-gamma (IFN-gamma) to its heterodimeric receptor induces activation of the tyrosine kinases JAK1 and JAK2 followed by tyrosine phosphorylation of STAT1alpha. Selective activation of STAT1alpha at the IFN-gamma receptor is achieved by specific interaction between a cytosolic tyrosine motif including Y440 in the IFN-gamma receptor alpha-chain and the SH2 domain of STAT1alpha. We demonstrate that, in addition to STAT1alpha, STAT3 is also activated by IFN-gamma in human neutrophils. The activation of STAT3 was not found in human eosinophils, monocytes, and HL-60 cells, although the STAT3 protein was expressed in these cells. The cell type-specific activation of STAT3 by IFN-gamma was also observed in neutrophils that are differentiated in vitro from human CD34+ hematopoietic stem cells. These results indicate that a single cytokine receptor can activate different STAT family members in a cell-specific manner, which might result in cell-specific gene transcription.  (+info)

Growth hormone-dependent differentiation of 3T3-F442A preadipocytes requires Janus kinase/signal transducer and activator of transcription but not mitogen-activated protein kinase or p70 S6 kinase signaling. (7/1765)

The signals mediating growth hormone (GH)-dependent differentiation of 3T3-F442A preadipocytes under serum-free conditions have been studied. GH priming of cells was required before the induction of terminal differentiation by a combination of epidermal growth factor, tri-iodothyronine, and insulin. Cellular depletion of Janus kinase-2 (JAK-2) using antisense oligodeoxynucleotides (ODNs) prevented GH-stimulated JAK-2 and signal transducer and activator of transcription (STAT)-5 tyrosine phosphorylation and severely attenuated the ability of GH to promote differentiation. Although p42(MAPK)/p44(MAPK) mitogen-activated protein kinases were activated during GH priming, treatment of cells with PD 098059, which prevented activation of these kinases, did not block GH priming. However, antisense ODN-mediated depletion of mitogen-activated protein kinases from the cells showed that their expression was necessary for terminal differentiation. Similarly, although p70(s6k) was activated during GH priming, pretreatment of cells with rapamycin, which prevented the activation of p70(s6k), had no effect on GH priming. However, rapamycin did partially block epidermal growth factor, tri-iodothyronine, and insulin-stimulated terminal differentiation. By contrast, cellular depletion of STAT-5 with antisense ODNs completely abolished the ability of GH to promote differentiation. These results indicate that JAK-2, acting specifically via STAT-5, is necessary for GH-dependent differentiation of 3T3-F442A preadipocytes. Activation of p42(MAPK)/p44(MAPK) and p70(s6k) is not essential for the promotion of differentiation by GH, although these signals are required for GH-independent terminal differentiation.  (+info)

Constitutive activation of the JAK2/STAT5 signal transduction pathway correlates with growth factor independence of megakaryocytic leukemic cell lines. (8/1765)

The factor-independent Dami/HEL and Meg-01 and factor-dependent Mo7e leukemic cell lines were used as models to investigate JAK/STAT signal transduction pathways in leukemic cell proliferation. Although Dami/HEL and Meg-01 cell proliferation in vitro was independent of and unresponsive to exogenous cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), IL-6, thrombopoietin (TPO), and tumor necrosis factor-alpha (TNF-alpha), the growth of Mo7e cells was dependent on hematopoietic growth factors. When these cell lines were cultured in medium without cytokines, a constitutively activated STAT-like DNA-binding factor was detected in nuclear extracts from both Dami/HEL and Meg-01 cells. However, the STAT-like factor was not detectable in untreated Mo7e cells, but was activated transiently in Mo7e cells in response to cytokine treatments. The constitutively activated and cytokine-induced STAT-like DNA-binding factor in these three cell lines was identified as STAT5 by oligonucleotide competition gel mobility assays and by specific anti-STAT antibody gel supershift assays. Constitutive activation of JAK2 also was detected in the factor-independent cell lines, but not in Mo7e cells without cytokine exposure. Meg-01 cells express a p185 BCR/ABL oncogene, which may be responsible for the constitutive activation of STAT5. Dami/HEL cells do not express the BCR/ABL oncogene, but increased constitutive phosphorylation of Raf-1 oncoprotein was detected. In cytokine bioassays using growth factor-dependent Mo7e and TF-1 cells as targets, conditioned media from Dami/HEL and Meg-01 cells did not show stimulatory effects on cell proliferation. Our results indicate that the constitutive activation of JAK2/STAT5 correlates with the factor-independent growth of Dami/HEL and Meg-01 cells. The constitutive activation of JAK2/STAT5 in Dami/HEL cells is triggered by a mechanism other than autocrine cytokines or the BCR/ABL oncoprotein.  (+info)

BACKGROUND: The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), consisting of polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a heterogeneous group of neoplasms that harbor driver mutations in the JAK2, CALR, and MPL genes. The detection of these mutations has been incorporated into the recent World Health Organization (WHO) diagnostic criteria for MPN. Given a pressing clinical need to screen for these mutations in a routine diagnostic setting, a targeted next-generation sequencing (NGS) assay for the detection of MPN-associated mutations located in JAK2 exon 14, JAK2 exon 12, CALR exon 9, and MPL exon 10 was developed to provide a single platform alternative to reflexive, stepwise diagnostic algorithms ...
The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which include essential thrombocythemia, polycythemia vera, and myelofibrosis (MF), are in a new era of molecular diagnosis, ushered in by the identification of the JAK2 V617F and cMPL mutations in 2005 and 2006, respectively, and the CALR mutations in 2013. Coupled with increased knowledge of disease pathogenesis and refined diagnostic criteria and prognostic scoring systems, a more nuanced appreciation has emerged of the burden of MPN in the United States, including the prevalence, symptom burden, and impact on quality of life. Biological advances in MPN have translated into the rapid development of novel therapeutics, culminating in the approval of the first treatment for MF, the JAK1/JAK2 inhibitor ruxolitinib. However, certain practical aspects of care, such as those regarding diagnosis, prevention of vascular events, choice of cytoreductive agent, and planning for therapies, present challenges for ...
Janus kinase (JAK) is a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named just another kinase 1 and 2 (since they were just two of a large number of discoveries in a PCR-based screen of kinases,) but were ultimately published as Janus kinase. The name is taken from the two-faced Roman god of beginnings and endings, Janus, because the JAKs possess two near-identical phosphate-transferring domains. One domain exhibits the kinase activity, while the other negatively regulates the kinase activity of the first. The four JAK family members are: Janus kinase 1 (JAK1) Janus kinase 2 (JAK2) Janus kinase 3 (JAK3) Tyrosine kinase 2 (TYK2) Transgenic mice that do not express JAK1 have defective responses to some cytokines, such as interferon-gamma. JAK1 and JAK2 are involved in type II interferon (interferon-gamma) signalling, whereas JAK1 and TYK2 are involved in type I interferon signalling. Mice that do ...
TY - JOUR. T1 - Perspectives on the impact of JAK-inhibitor therapy upon inflammation-mediated comorbidities in myelofibrosis and related neoplasms. AU - Hasselbalch, Hans C.. PY - 2014/4. Y1 - 2014/4. N2 - Chronic inflammation is suggested to contribute to the Philadelphia- chromosome-negative myeloproliferative neoplasm (MPN) disease initiation and progression, as well as the development of premature atherosclerosis and may drive the development of other cancers in MPNs, both nonhematologic and hematologic. The MPN population has a substantial comorbidity burden, including cerebral, cardiovascular, pulmonary, abdominal, renal, metabolic, skeletal, autoimmune, and chronic inflammatory diseases. This review describes the comorbidities associated with MPNs and the potential impact of early intervention with anti-inflammatory and/or immunomodulatory agents such as JAK-inhibitors, statins, and IFN-α to inhibit cancer progression and reduce MPN-associated comorbidity impact. Early intervention may ...
Janus (Jak) tyrosine kinases contain a tyrosine kinase (JH1) domain adjacent to a catalytically inactive pseudokinase domain (JH2). The JH2 domain has been implicated in regulation of Jak activity, but its function remains poorly understood. Here, we found that the JH2 domain negatively regulates the activity of Jak2 and Jak3. Deletion of JH2 resulted in increased tyrosine phosphorylation of the Jak2- and Jak3-JH2 deletion mutants as well as of coexpressed STAT5. In cytokine receptor signaling, the deletion of the Jak2- and Jak3-JH2 domains resulted in interferon-gamma and interleukin-2-independent STAT activation, respectively. However, cytokine stimulations did not further induce the JH2 deletion mutant-mediated STAT activation. The deletion of the Jak2 JH2 domain also abolished interferon-gamma-inducible kinase activation, although it did not affect the reciprocal Jak1-Jak2 interaction in 293T cells. Chimeric constructs, where the JH2 domains were swapped between Jak2 and Jak3, retained low basal
Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF receptor family (IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g., IL-6R), and the single chain receptors (e.g. Epo-R, Tpo-R, GH-R, PRL-R). The distinguishing feature between janus kinase 2 and other JAK kinases is the lack of Src homology binding domains (SH2/SH3) and the presence of up to seven JAK homology domains (JH1-JH7). Nonetheless the terminal JH domains retain a high level of homology to tyrosine kinase domains. An interesting note is that only one of these carboxy-terminal JH domains retains full kinase function (JH1) while the other (JH2), previously thought to have no kinase functionality and accordingly termed a pseudokinase domain, has since been found to be catalytically active, albeit at only 10% that of the JH1 domain. Loss of ...
Global Markets Directs, Tyrosine Protein Kinase JAK3 (Janus Kinase 3 or Leukocyte Janus Kinase or JAK3 or EC 2.7.10.2) - Pipeline Review, H2
The IUPHAR/BPS Guide to Pharmacology. Janus kinase 1 - Janus kinase (JakA) family. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
It is not known at the moment how the kinase domains are regulated by JH2 or by JH2 V617F. The F739R mutation in helix F of the C-terminal lobe, which is predicted to disorganize the fold of the C-terminal lobe of JH2 only led to levels of activation that were much lower than those induced by the V617F mutation [20]. These data indicate that the V617F mutation activates JH1, and does not only remove the JH2 inhibition on JH1. JH2 domains might form heteromeric dimers with JH1 domains (in cis or in trans), or with themselves, and this could change between inactive and active states.. Two major theoretical models have been used to explore effects of V617F. One is the Lindauer-Kroemer model [37,38]. It was based on a dimer seen in the X-ray crystal structure of the FGFR1 (fibroblast growth factor receptor 1) kinase [39]. This is an antiparallel symmetric (anti-symmetrical) JH1-JH2 interaction in the inactive state (also having JH2 as an inactive kinase) and defined two interfaces, one between ...
JAKs (Janus kinases) are essential mediators of almost all biological signalling events initiated by haemopoietic and immune cytokines. However, aberrant and/or prolonged JAK-induced signalling is detrimental and can give rise to a number of inflammatory and proliferative pathologies. For this reason, the tyrosine kinase activity of the JAKs is carefully regulated at a number of different levels. Primarily, this is achieved by: (i) ensuring that the catalytic domain is switched off under basal conditions, and (ii) inhibiting the activity of JAK after it has been switched on. Whereas the first mode of inhibition is mediated by JAKs own pseudokinase domain as well as the action of phosphatases, the second is achieved by the action of the SOCS (suppressor of cytokine signalling) proteins, negative-feedback inhibitors of JAK-mediated signalling. The present review focuses on the mode of action of SOCS1 and SOCS3, the two most potent JAK inhibitors. ...
Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH2. Here we show that models of AMLs resulting from TET2 or IDH2 mutations combined with FLT3ITD mutations are sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-Azacytidine and AG-221 treatment induced an attenuation of aberrant DNA methylation and transcriptional output, and resulted in a reduction in leukemic blasts consistent with anti-leukemic activity. These therapeutic benefits were associated with restoration of leukemic cell differentiation, and the normalization of hematopoiesis was derived from mutant cells. By contrast, combining AG-221 or 5-Azacytidine with FLT3 inhibition resulted in a reduction in mutant allele burden, progressive recovery of normal hematopoiesis from non-mutant stem-progenitor cells, and reversal of dysregulated DNA methylation and transcriptional output. Together, our studies suggest combined targeting of ...
03); **represents significant difference between. group 1%FBS + 10 ng/ml TGF-β1′ and group 1%FBS (P = 0.044). Figure 6 The effects of TGF-β1 on expression levels of PKCα and p38 MAPK. BxPC3 cells were treated with 0.1, 1 and 10 ng/ml TGF-β1 for 10 min, 30 min and 24 h. Total cellular protein was extracted and subjected to western blotting analysis to detect expression of PKCα, phosphorylated-p38/total p38 MAPK and phosphorylated-ERK1/2/total ERK1/2. Bx represents BxPC3 cells and Bx/T represents the stably transfected BxPC3 cells with TGF-β1 plasmid. To determine whether the induced PKCα activity is Veliparib in vivo responsible for the TGF-β1-induced decrease in the sensitivity of BxPC3 cells to cisplatin, we treated the cells with a selective PKCα inhibitor, Gö6976, and assessed TGF-β1-induced drug resistance. We found that inhibition of PKCα. activity could partially reverse TGF-β1-induced drug resistance of BxPC3 cells to cisplatin RGFP966 solubility dmso (Figure 7). Figure ...
Reversible janus associated kinase (JAK) inhibitors such as tofacitinib and decernotinib block cytokine signaling and are efficacious in treating autoimmune diseases. However, therapeutic doses are limited due to inhibition of other JAK/signal transducer and activator of transcription pathways associated with hematopoiesis, lipid biogenesis, infection, and immune responses. A selective JAK3 inhibitor may have a better therapeutic index; however, until recently, no compounds have been described that maintain JAK3 selectivity in cells, as well as against the kinome, with good physicochemical properties to test the JAK3 hypothesis in vivo. To quantify the biochemical basis for JAK isozyme selectivity, we determined that the apparent Km value for each JAK isozyme ranged from 31.8 to 2.9 μM for JAK1 and JAK3, respectively. To confirm compound activity in cells, we developed a novel enzyme complementation assay that read activity of single JAK isozymes in a cellular context. Reversible JAK3 ...
|p|Direct and indirect inhibition of the JAKs has demonstrated rapid and sustained improvement in clinical measures of disease. Baricitinib phosphate (INCB 028050) is a selective JAK1 and JAK2 inhibitor. |/p| |p|In vitro: Baricitinib phosphate is a selec
Janus name meaning, Australian baby Girl name Janus meaning,etymology, history, presonality details. Janus Rhyming, similar names and popularity.
The JAK inhibitors pipeline has more than 35 drugs. In pipeline analysis, drugs are analyzed on the basis of route of administration and molecule type.
Pacritinib is a potent inhibitor of both wild-type JAK2 (IC50=23 nM) and JAK2V617F mutant (IC50=19 nM). Pacritinib also inhibits FLT3 (IC50=22 nM) and its mutant FLT3D835Y (IC50=6 nM). - Mechanism of Action & Protocol.
|p|CEP-33779, is a highly selective, orally active inhibitor of Janus kinase 2 (JAK2). When evaluate against the other members of the JAK family, CEP-33779 demonstrates varying degrees of selectivity from >40-fold versus JAK1 to >800-fold against TY
Prolactin (PRL), secreted by the pituitary, decidua, and lymphoid cells, has been shown to have a regulatory role in reproduction, immune function, and cell growth in mammals. The effects of PRL are mediated by a membrane-bound receptor that is a member of the superfamily of cytokine receptors. Formation of a trimer, consisting of one molecule of ligand and two molecules of receptor, appears to be a necessary prerequisite for biological activity. The function of these receptors is mediated, at least in part, by two families of signaling molecules: Janus tyrosine kinases (JAKs) and signal transducers and activators of transcription (STATs ...
克拉玛尔专业提供JAK3高品质试剂,可查询JAK3价格,提供JAK3技术资料,JAK3定制合成和大包装,是专业生产各种高端试剂的制造商和供应商.联系电话4001650900
An article in the Wall Street Journal compares the performance of the largest Janus fund with the performance of the S&P 500. The comparison is achieved by assuming that$10,000 was invested both in the Janus fund and in the S&P.
Karimatky, jak vybrat karimatku, karimatky a pomocn k pro v b r karimatek - spac ch podlo ek pro turisty, konstrukce a pou van materi ly
Your Search Returned No Results.. Sorry. There is currently no product that acts on isoform JAK1 together.. Please try each isoform separately.. ...
Hygiena p edko kov ho vaku - Na aludu a vnit n stran p edko ky se mi tvo jak si b l ka i kovit povlak, kter pon kud zap ch . Po umyt aludu se v ak vytvo povlak nov . N kdy je m j alud natolik podr d n , e p i jeho myt poci uji velice silnou ezavou bolest. Mohlo by se jednat o n jak z n t? Pora te mi pros m jak se toho zbavit... poradna zdravi predkozkovy vak, Zdravotn poradna
Background: This study was conducted to evaluate the frequency of JAK2, CALR and MPL mutations in with BCR-ABL myeloproliferative neoplasms and their association with demographic data and hematologic parameters in a referral center, in the Middle East. Methods: Seventy-one patients with BCR-ABL negative myeloproliferative neoplasms were evaluated for JAK2 V617F, CALR type 1, type 2, and MPL by allele-specific PCR and conventional PCR from 2018 to 2019. Results: Twenty three patients were categorized as polycythemia vera and demonstrated JAK2 V617F in 91.3 % of these cases. Thirty-eight patients were classified as essential thrombocythemia and showed JAK2 V617F in 52.6%, CALR type 1 in 18.4%, CALR type 2 in 7.9% and no mutation in 21.1%. Seven patients were recognized as primary myelofibrosis and exhibited JAK2 V617F mutation in 57.1%, CALR type 1 in 14.3 %, CALR type 2 in 14.3% and no mutation in 14.3%. Three patients were diagnosed as MPN, unclassifiable and revealed JAK2 V617F mutation in 33.3% and
Mutations in JAK2, MPL and CALR are highly relevant to the Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs). We performed high resolution melting analysis and Sanger sequencing together with T-A cloning to elucidate the unique mutation profile of these genes, in Chinese patients with MPNs. Peripheral blood DNA samples were obtained from 80 patients with polycythemia vera (PV), 80 patients with essential thrombocytosis (ET) and 50 patients with primary myelofibrosis (PMF). Ten PV patients were identified with diverse JAK2 exon 12 mutations. Five novel JAK2 Exon 12 mutation patterns (M532V/E543G, N533D, M535I/H538Y/K549I, E543G and D544N) were described. JAK2 V617F was detected in 140 samples (66 PV, 45 ET and 29 PMF). JAK2 Exon 12 mutations were prevalent (13%) and variable in the Chinese patients. Compared with PV patients with JAK2 V617F mutations, PV patients with JAK2 exon 12 mutations had an earlier median onset of disease (P = 0.0013). MPL W515L/K mutations were ...
The discovery of the JAK2 V617F mutation has undoubtedly revolutionised the diagnosis of the classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) with the mutation present in greater than 95% of polycythaemia vera (PV) patients, approximately 50% of patients with essential thrombocythaemia (ET) and primary myelofibrosis (PMF) and, to a lesser degree, in a number of other myeloid malignancies such as refractory anaemia with ringed sideroblasts with thrombocytosis, chronic myelomonocytic leukaemia and acute myeloid leukaemia. Detection of this mutation is beneficial in differentiating between a reactive haematological response and a true clonal disorder and can also serve as a target for therapeutic intervention.1 Current guidelines for the diagnosis of PV, ET and PMF maintain the requirement for inclusion and/or exclusion of numerous other clinical and laboratory parameters such as histopathological examination of a bone marrow biopsy.2-4 Molecular testing for the ...
Key words. Myelofibrosis (MF), including primary myelofibrosis (PMF) and MF secondary to essential thrombocythemia (ET) or polycythemia vera (PV), is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm associated with progressive bone marrow fibrosis.1 Many patients with MF experience new or worsening anemia during disease progression. Varying from study to study, 35% to 54% of patients with PMF have been reported to have anemia (i.e., hemoglobin ,10 g/dL) at the time of diagnosis.2-5 Anemia adversely affects overall survival (OS), and is included as a key negative prognostic factor in validated prognostic scoring systems for patients with PMF, which were developed before the introduction of Janus kinase (JAK) inhibitor therapy.2,3,5 Ruxolitinib, a JAK1/JAK2 inhibitor, improved OS compared with placebo and best available therapy in patients with intermediate-2 or high-risk MF5 in the phase 3 COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment (COMFORT) ...
We studied the relationship between JAK2 (V617F) mutant allele burden and clinical phenotype, disease progression and survival in patients with polycythemia vera (PV). The percentage of granulocyte mutant alleles was evaluated using a quantitative real-time polymerase chain reaction-based allelic discrimination assay. Of the 338 patients enrolled in this prospective study, 320 (94.7%) carried the JAK2 (V617F) mutation. Direct relationships were found between mutant allele burden and hemoglobin concentration (P=0.001), white blood cell count (P=0.001), spleen size (P=0.001) and age-adjusted bone marrow cellularity (P=0.002), while an inverse relationship was found with platelet count (P,0.001). During the study period, eight patients progressed to post-PV myelofibrosis (MF) (all carrying ,50% mutant alleles), while 10 patients developed acute myeloid leukemia (AML). The mutant allele burden was significantly related to the risk of developing myelofibrosis (P=0.029) and retained its significant ...
This study is investigating the efficacy and tolerability of givinostat [Italfarmaco] in the treatment of patients with JAK2V617F positive, chronic
Looking for online definition of LJAK, leukocyte Janus kinase in the Medical Dictionary? LJAK, leukocyte Janus kinase explanation free. What is LJAK, leukocyte Janus kinase? Meaning of LJAK, leukocyte Janus kinase medical term. What does LJAK, leukocyte Janus kinase mean?
Immediately following the 2010 annual American Society of Hematology (ASH) meeting, the 5th International Post-ASH Symposium on Chronic Myelogenous Leukemia and BCR-ABL1-Negative Myeloproliferative Neoplasms (MPNs) took place on 7-8 December 2010 in Orlando, Florida, USA. During this meeting, the most recent advances in laboratory research and clinical practice, including those that were presented at the 2010 ASH meeting, were discussed among recognized authorities in the field. The current paper summarizes the proceedings of this meeting in BCR-ABL1-negative MPN. We provide a detailed overview of new mutations with putative epigenetic effects (TET oncogene family member 2 (TET2), additional sex comb-like 1 (ASXL1), isocitrate dehydrogenase (IDH) and enhancer of zeste homolog 2 (EZH2)) and an update on treatment with Janus kinase (JAK) inhibitors, pomalidomide, everolimus, interferon-α, midostaurin and cladribine. In addition, the new Dynamic International Prognostic Scoring System ...
Bulgular: JAK-2 mutasyonu PV li hastalar n %86 s nda, ET li hastalar n %51,5 inde ve PMF li hastalar n %50,4 nde pozitif bulundu. Tan da tromboz ve kanama, PV li hastalar n s ras yla %20,6 ve %7,5 inde, ET li hastalar n %15,1 ve %9 unda ve PMF li hastalar n %9,5 ve %10,4 nde saptand . Alt y z sekiz hasta (%85,9) sitored ktif tedavi alm t . En s k kullan lan ila hidroksi re (%89,6) idi. L semik ve fibrotik transformasyon s kl %0,6 ve %13,2 idi. 10 y ll k hesaplanan toplam sa kal m PV, ET ve PMF hastalar nda s ras yla %89,7, %85 ve %82,5 idi. 10 y ll k toplam sa kal m a s ndan ET, PV ve PMF hastalar nda anlaml fark yoktu ...
Bulgular: leri ya , tan da y ksek l kosit say s JAK2 mutasyon pozitifli i tromboz i in risk fakt r olarak bulunmu tur. Trombosit say m n n 1000x109/L zerinde olmas kanama komplikasyonlar a s ndan risk fakt r d r. Hidroksi re tedavisi l semik d n mle ili kili bulunmam t r. Bu hastalarda: Medyan takip s resi 50 ay (22,2- 81,75 eyrekler) idi. Primer miyelofibrozisli hastalar ET i in 179 ay ve PV i in 231 ay olan ya am s releri ile kar la t r ld nda 137 ay ile en k sa ya am s resine sahip hastalard r. L semik transformasyon, tromboembolik olaylar, 60 ya st olmak ve anemi ya am s resinin etkileyen fakt rler olarak bulunmu tur ...
Myeloproliferative Neoplasms (MPNs): Diagnosis, Treatment and Side Effects Management This continuing education virtual lecture on myeloproliferative neoplasms diagnosis, treatment and side effects management is for nurses, nurse practitioners, and oncology social workers. Topics covered include types of myeloproliferative neoplasms tests for diagnosis, treatments and management of side effects.The material is presented by a physician, a pharmacist and a nurse practitioner. There is no fee for this educational activity.
Please join the RARE Portal to add diseases of interest to your personal profile. By creating a profile, you can receive news, resources and updates related to this disease as well as many other benefits. ...
Know more about the symptoms, causes, diagnosis and treatment for Myeloproliferative Neoplasms. mfine has the finest of Oncologist who will provide the best treatment.
The aim of this study is to investigate the differences of clinical and laboratory parameters between patients with JAK2-V617F positive myeloproliferative neoplasms (MPNs) and JAK2 wild type MPNs. DNA was isolated from peripheral blood...
Patients carrying mutations in JAK2 or MPL experienced a reduction in spleen size, in contrast with the absence of response among those carrying wild-type JAK2. Three out of the four patients with accelerated disease (10-19% blasts in the peripheral blood) displayed a marked reduction in blast burden during XL019 therapy. However, 21 (70%) out of 30 patients discontinued XL019 therapy, in some instances owing to nerve conduction abnormalities and/or altered mental status. The unacceptable rate of neurological toxicity has precluded further development of XL019 for the treatment of patients with MPNs.. NOVEL JAK INHIBITORS. The promising preliminary results obtained with first-generation JAK inhibitors stimulated the development of novel JAK inhibitors by several biotechnology companies. These agents are in different stages of development, with some of them (SB1518, AZD1480 and CYT387) already being tested in clinical trials in patients with MPNs and others (INCB16562 and NVP BSK805) still being ...
Patients carrying mutations in JAK2 or MPL experienced a reduction in spleen size, in contrast with the absence of response among those carrying wild-type JAK2. Three out of the four patients with accelerated disease (10-19% blasts in the peripheral blood) displayed a marked reduction in blast burden during XL019 therapy. However, 21 (70%) out of 30 patients discontinued XL019 therapy, in some instances owing to nerve conduction abnormalities and/or altered mental status. The unacceptable rate of neurological toxicity has precluded further development of XL019 for the treatment of patients with MPNs.. NOVEL JAK INHIBITORS. The promising preliminary results obtained with first-generation JAK inhibitors stimulated the development of novel JAK inhibitors by several biotechnology companies. These agents are in different stages of development, with some of them (SB1518, AZD1480 and CYT387) already being tested in clinical trials in patients with MPNs and others (INCB16562 and NVP BSK805) still being ...
ETV6-ABL1 is a rare gene fusion with oncogenic properties, reported so far in 28 patients presenting a variety of haematological malignancies associated with clinical outcome, including chronic myeloid leukaemia (CML), acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) and chronic myeloproliferative neoplasm (cMPN). Here we report on a 46-year-old female who presented with Philadelphia negative CML, positive for the ETV6-ABL1 fusion. Whole genome screening carried out with oligonucleotide arrays showed a subtle loss at 12p13 and cryptic imbalances within the 9q34.3 region in a highly unstable genome. FISH mapping with custom BAC probes identified two breakpoints 5 Mb apart within the 9q34 region, together with a break at 12p13. While FISH with commercial BCR-ABL1 probes failed to detect any ABL1 changes, the ETV6 break-apart probe conclusively identified the ETV6-ABL1 fusion thus determining the probes role as the primary diagnostic FISH test for this chimeric oncogene. In addition, we
Abstract: The major complications of Philadelphia‐negative (Ph‐Negative) myeloproliferative neoplasms (MPNs) are thrombosis, haemorrhage and leukemic transformation. As systemic and haematological diseases, MPNs have the potential to affect many tissues and organs. Some complications lead to the diagnosis of MPNs, but other signs and symptoms are often misdiagnosed or neglected as a sign of MPN disease. […]. ...
The gain-of-function mutation in the gene encoding Janus kinase 2 (JAK2) is frequently found in patients with myeloproliferative neoplasms (MPNs). Those patients performed resistent to therapy that targeting JAK and its downstream signaling, such as signal transducer and activator of transcription (STAT). Winter et al. identified the underlying mechanism of the emerging therapy resistance, and found the guanosine triphosphatase (GTPase) RAS and pathways mediated by AKT and ERK contribute to the resistance. The article was published in Science Signaling.. Reaserchers performed pathway-centric screens in hematopoietic cells containing JAK2V617F mutation, found GTPase RAS and its effector pathways mediated by AKT and ERK are involved in generation of resistance to JAK inhibition. Mechanistically, the JAK2 mediated phosphorylation inactivates B cell lymphoma 2-associated death promoter (BAD), which regulates cell apoptosis, to promote cell growth and proliferation. In sensitive cells, BAD is ...
V617F driver mutation of JAK2 is the leading cause of the Philadelphia-chromosome-negative myeloproliferative neoplasms (MPNs). Although thrombosis is a leading cause of mortality and morbidity in MPNs, the mechanisms underlying their pathogenesis are unclear. Here, we identified pleckstrin-2 (Plek2) as a downstream target of the JAK2/STAT5 pathway in erythroid and myeloid cells, and showed that it is upregulated in a JAK2V617F-positive MPN mouse model and in patients with MPNs. Loss of Plek2 ameliorated JAK2V617F-induced myeloproliferative phenotypes including erythrocytosis, neutrophilia, thrombocytosis, and splenomegaly, thereby reverting the widespread vascular occlusions and lethality in JAK2V617F-knockin mice. Additionally, we demonstrated that a reduction in red blood cell mass was the main contributing factor in the reversion of vascular occlusions. Thus, our study identifies Plek2 as an effector of the JAK2/STAT5 pathway and a key factor in the pathogenesis of JAK2V617F-induced MPNs, ...
Coherent Market Insights recently published a detailed study of Myeloproliferative Neoplasms Treatment Market covering interesting aspects of the market with supporting development scenarios ranging from 2018-2026. The report delivers the clean elaborated structure of the Market comprising each and every business-related information of the market at a global level. The complete range of information related to the Global Market is obtained through various sources and this obtained bulk of the information is arranged, processed, and represented by a group of specialists through the application of different methodological techniques and analytical tools such as SWOT analysis to generate a whole set of trade-based study regarding the Myeloproliferative Neoplasms Treatment.. Get Free Download PDF Brochure: https://www.coherentmarketinsights.com/insight/request-pdf/930. This report assesses the growth rate and the market value on the basis of the key market dynamics, as well as the growth inducing ...
Myeloproliferative Neoplasm Causes, Types, Treatment, Symptoms & Signs. Click for basic information about myeloproliferative neoplasm, its symptoms and treatment.
Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The
In November 2013, CTI and Baxter International (Baxter) entered into a worldwide license agreement to develop and commercialize pacritinib in which CTI and Baxter will jointly commercialize pacritinib in the U.S. and Baxter has exclusive commercialization rights for all indications outside the U.S.. About Myelofibrosis. Myelofibrosis is classified as a myeloproliferative neoplasm and is a chronic bone marrow disorder. Myelofibrosis is caused by the accumulation of malignant bone marrow cells that triggers an inflammatory response, scarring the bone marrow and limiting its ability to produce red blood cells, prompting the spleen and liver to take over this function. Symptoms that arise from this disease include enlargement of the spleen, anemia, extreme fatigue and pain. About CTI BioPharma. CTI BioPharma Corp. (NASDAQ and MTA: CTIC) is a biopharmaceutical company focused on the acquisition, development and commercialization of novel targeted therapies covering a spectrum of blood-related cancers ...
Constitutive JAK2 activation in hematopoietic cells by the JAK2V617F mutation recapitulates myeloproliferative neoplasm (MPN) phenotypes in mice, establishing J
Abdominal venous thrombosis presenting in myeloproliferative neoplasm with JAK2 V617F mutation: a case report. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Glandular MPNs or Myeloproliferative Neoplasms are blood cancers that develop when the body(bone marrow) produces excessive mature WBCs, RBCs, and platelets
Chronic Myeloproliferative Neoplasms (MPN) treatment varies widely depending on the specific diagnosis. Treatment options may include observation, phlebotomy, steroids, chemotherapy, immunotherapy, and stem cell transplant. Get detailed information about MPNs in this summary for clinicians.
Polycythemia Vera Patients with polycythemia vera (PV) experience significant symptoms characterized by fatigue, itching, night sweats, bone pain, fever, and undesired weight loss; these symptoms contribute to a poor quality of life, which is often under appreciated by family and providers. Until recently, PV patients only treatment options were phle-botomy and hydroxyurea (HU). However, the development and approval of the JAK2 inhibitor Jakafi® (ruxolitinib) has led to an effective alleviation of these symptoms in many patients.. Jakafi has mainly been used to reduce symptoms in individuals with severe PV who have three or more of these debilitating symptoms. An international study was presented at the American Society of Hematology demonstrating that many PV symptoms remain severe independent of the total number of features present.8 The results of this study demonstrate that the symptom burden in patients with PV is substantial, independent of whether a patient has used HU, has received ...
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases 2 and 3. Protein Tyrosine Kinase (PTK) family; Janus kinase 2 (Jak2) and Jak3; catalytic (c) domain (repeat 2). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 and Jak3 are members of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal ...
DO YOU KNOW JAK?. One of the most important new treatments that many people in the trichological field are talking about are JAK inhibitors. As Dr. Brett King, MD, PhD said at the summer 2018 American Academy of Dermatology meeting in Chicago, Illinois, JAK inhibitors will be a very important - maybe the most important - drug class in dermatology because of their broad applicability across numerous conditions that patients commonly, and uncommonly, present within our clinics.. With this in mind, I thought it fitting to devote this article explaining what a JAK is and why inhibiting it may help many of our trichological clients.. What does JAK stand for and what is it?. JAK is short for Janus Kinase. There are four types of Janus Kinases.. Janus kinases are involved in the process of signaling between cells (known as the JAK-STAT pathway). Cell signaling is important in how cells function and in coordinating important actions of cells.. Immune Disorders.. Examples of the role of JAK-STAT ...
In the following video, Fool contributor Maxx Chatsko updates AbbVie (NYSE:ABBV) investors on momentum-building developments around promising drug collaboration. AbbVie and Belgium pharma company Galapagos were already partnered to develop a selective JAK1 inhibitor for rheumatoid arthritis, but why stop there? The two announced that the potential-packed therapy under development would also be expanded to include Crohns disease.. What the heck is a JAK inhibitor, and why does it matter? JAK inhibitors are small molecules that transcend the cell membrane and cell communication process to regulate immune response for inflammatory diseases. Given the success of biologics in treating inflammatory diseases and cancers, pharmaceutical companies are racing to develop JAK inhibitors. Could bringing such a drug to market help AbbVie survive Humiras fall over the patent cliff? Get more details in the video below.. ...
MPN expert Dr. Mark Heaney explores risk factors that contribute to progression in MPNs and discusses treatment options and the role that lifestyle choices play in reducing risks of the disease.
Myeloproliferative neoplasms (MPNs) are a group of blood cancers that cause excess blood cell production in the bone marrow and often in the peripheral blood, and are characterized by clonal genetic changes. MPNs include chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), chronic neutrophilic leukemia (CNL), and chronic eosinophilic leukemia (CEL).
How does MDM2 inhibition work to treat MPNs? Watch as experts Dr. Srdan Verstovsek and Dr. Jason Gotlib discuss an upcoming MDM2 inhibitor clinical trial for patients living with MF and PV.
The actual Janus kinases (Jak) will be men and women of your list of intra cellular tyrosine kinases that will enjoy essential tasks within cytokine receptor-mediated indicate transduction by using initial involving downstream indicate transducers as well as activators of transcribing (STAT), phosphatidylinositol 3-kinase (PI3K), and mitogen-triggered protein kinase (MAPK) pathways. Youll find four kinases within the Jak loved ones [Jak1, Jak2, Jak3, plus tyrosine kinase Two (Tyk2), and Jak2 possesses come forth not too long ago like a likely healing goal. A considerable proportion of affected individuals along with myeloproliferative problems (MPD), including polycythemia observara (P v), critical thrombocythemia (ET), and also main myelofibrosis (MF), are shown to have some sort of mutation inside the pseudokinase area regarding Jak2 (V617F), which often provides your kinase constitutively effective as well as points too inhibition regarding Jak2 can be quite a successful way of healing MPD. ...
Has anyone else been given a diagnosis of an Unclassified Myeloproliferative Neoplasm? Originally my diagnosis was PV however was tested for JAK2 and EXON12 mutations which were both negative. I...
Cytoplasmic Janus protein tyrosine kinases (JAKs) are crucial components of diverse signal transduction pathways that govern cellular survival, proliferation, differentiation and apoptosis. Evidence to date, indicates that JAK kinase function may integrate components of diverse signaling cascades. While it is likely that activation of STAT proteins may be an important function attributed to the JAK kinases, it is certainly not the only function performed by this key family of cytoplasmic tyrosine kinases. Emerging evidence indicates that phosphorylation of cytokine and growth factor receptors may be the primary functional attribute of JAK kinases. The JAK-triggered receptor phosphorylation can potentially be a rate-limiting event for a successful culmination of downstream signaling events. In support of this hypothesis, it has been found that JAK kinase function is required for optimal activation of the Src-kinase cascade, the Ras-MAP kinase pathway, the PI3K-AKT pathway and STAT signaling following the
The primary myelofibrosis prognosis tool helps evaluate whether a patients diagnosis is consistent with the World Health Organization (WHO) criteria for a diagnosis of PMF.
Recognize an individual who has made a difference in the life of someone with a Myeloproliferative Neoplasm. Visit VoicesofMPN.com and submit a story and photo today!
Coping with a Myeloproliferative Neoplasm (MPN) alone can be difficult. Share your story with friends, family, and your MPN healthcare providers.
In this second part of our two-part review, we discuss the use of mutation profiling in the diagnosis, prognosis, and treatment of patients with myeloproliferative neoplasms and other myeloid diseases.
Study 4 BL MDS & Myeloproliferative Neoplasms flashcards from Nebuchadnezzer II's University of Colorado School of Medicine class online, or in Brainscape's iPhone or Android app. ✓ Learn faster with spaced repetition.
Janus kinase and microtubule interacting protein 2 is a protein that in humans is encoded by the JAKMIP2 gene. The protein ... "Entrez Gene: Janus kinase and microtubule interacting protein 2". Retrieved 2017-05-31. Cruz-Garcia D, Vazquez-Martinez R, ...
Extremely high platelet counts can be treated with hydroxyurea (a cytoreducing agent) or anagrelide (Agrylin). In Janus kinase ... 2 positive disorders, ruxolitinib (Jakafi) can be effective.[citation needed] Schafer AI (March 2004). "Thrombocytosis". N. ...
Examples of the P-type ATPase include Na+/K+-ATPase that is regulated by Janus Kinase-2 as well as Ca2+ ATPase which exhibits ... channel ENaC by Janus kinase 2". The Journal of Membrane Biology. 247 (4): 331-8. doi:10.1007/s00232-014-9636-1. PMID 24562791 ... Using protein kinases to add a phosphate group or phosphatases to dephosphorylate the protein can change the activity of the ... channel functional regulation by phosphorylation of focal adhesion kinase at tyrosine 407 in osmosensitive ion transporting ...
It is a semi-selective inhibitor of Janus kinase 2 (JAK-2). It was approved by the FDA on 16 August 2019. Myelofibrosis is a ... who are Janus kinase (JAK) inhibitor naïve or have been treated with ruxolitinib. Fedratinib acts as a competitive inhibitor of ... Significantly less activity was observed against other tyrosine kinases including JAK3 (IC50=169 nM). In treated cells the ... related kinases FLT3 and RET are also sensitive, with IC50=25 nM and IC50=17 nM, respectively. ...
... is a janus kinase inhibitor (JAK inhibitor) with selectivity for subtypes JAK1 and JAK2. Ruxolitinib inhibits ... Wysham NG, Sullivan DR, Allada G (May 2013). "An opportunistic infection associated with ruxolitinib, a novel janus kinase 1,2 ... "Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors".[full citation needed][ ... "Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors" at ClinicalTrials.gov " ...
Janus kinase 1, Janus kinase 2, LAIR1, LRP1, PDGFRB, PI3K → Akt PLCG2, PTK2B, Ras SLAMF1, SOCS3, SOS1, STAT3, STAT5A, and ... Saito Y, Hojo Y, Tanimoto T, Abe J, Berk BC (June 2002). "Protein kinase C-alpha and protein kinase C-epsilon are required for ... "SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates". Biochem. Biophys. Res. Commun. ... Tang H, Zhao ZJ, Huang XY, Landon EJ, Inagami T (April 1999). "Fyn kinase-directed activation of SH2 domain-containing protein- ...
... has been shown to interact with PPP2R3A, CCNG1 and Janus kinase 2. GRCh38: Ensembl release 89: ENSG00000119383 - Ensembl ... 1997). "Regulation of protein phosphatase 2A by direct interaction with casein kinase 2alpha". Science. 276 (5314): 952-5. doi: ... 2: 11. doi:10.1186/1742-4690-2-11. PMC 554975. PMID 15725353. Zhao RY, Elder RT (2005). "Viral infections and cell cycle G2/M ... 224 (2): 289-96. doi:10.1006/bbrc.1996.1023. ISSN 0006-291X. PMID 8702385. Andersen JL, Planelles V (2005). "The role of Vpr in ...
... has been shown to interact with Janus kinase 2, CTNND1, RPL10 and Occludin. GRCh38: Ensembl release 89: ENSG00000176105 - ... Proto-oncogene tyrosine-protein kinase Yes is a non-receptor tyrosine kinase that in humans is encoded by the YES1 gene. This ... "Autophosphorylation activity and association with Src family kinase of Sky receptor tyrosine kinase". Biochem. Biophys. Res. ... The encoded protein has tyrosine kinase activity and belongs to the src family. This gene lies in close proximity to ...
... is a macrocyclic Janus kinase inhibitor that is being developed for the treatment of myelofibrosis. It mainly inhibits Janus ... and Fms-like tyrosine kinase 3 (FLT3). The drug was in Phase III clinical trials as of 2013[update]. The drug was given fast- ... "PERSIST-2" trial. The clinical hold was lifted in January 2017. "International Nonproprietary Names for Pharmaceutical ...
... has been shown to interact with HGS, Janus kinase 2. MAP3K1, STAMBP, and TIMM8A. GRCh38: ... is associated with Janus kinases and involved in signaling for cell growth and c-myc induction". Immunity. 6 (4): 449-57. doi: ... is associated with Janus kinases and involved in signaling for cell growth and c-myc induction". Immunity. 6 (4): 449-57. doi: ... binding to the Janus kinases". FEBS Letters. 477 (1-2): 55-61. doi:10.1016/S0014-5793(00)01760-9. PMID 10899310. S2CID 31811757 ...
... has been shown to interact with: Grb2, Insulin receptor, Janus kinase 2, and TrkA. Variations close to or in the SH2B1 ... Nishi M, Werner ED, Oh BC, Frantz JD, Dhe-Paganon S, Hansen L, Lee J, Shoelson SE (2005). "Kinase activation through ... O'Brien KB, O'Shea JJ, Carter-Su C (2002). "SH2-B family members differentially regulate JAK family tyrosine kinases". J. Biol ... "Identification of SH2-Bbeta as a substrate of the tyrosine kinase JAK2 involved in growth hormone signaling". Mol. Cell. Biol. ...
Fortunately, this previously-lethal condition was recently demonstrated to be curable with a Janus kinase inhibitor and ... leading to the displacement of Janus kinase 1. and the dissociation of the cytokine-receptor complex. This process requires ... 38 (2): 79-93. doi:10.1016/j.it.2016.11.001. PMID 27887993. Zhang X, Bogunovic D, Payelle-Brogard B, Francois-Newton V, Speer ... 267 (2): 233-42. doi:10.1016/S0378-1119(01)00384-5. PMID 11313150. Tokarz S, Berset C, La Rue J, Friedman K, Nakayama K, ...
... has been shown to interact with: Glucocorticoid receptor, Janus kinase 1, Janus kinase 2, and PTPN11. STAT5 GRCh38: ... In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and ... Reconstitution of interleukin-2-induced Stat5A and Stat5B DNA binding activity in COS-7 cells". J. Biol. Chem. 271 (18): 10738- ... 285 (1-2): 1-24. doi:10.1016/S0378-1119(02)00398-0. PMID 12039028. This article incorporates text from the United States ...
This results in the activation of Janus kinase 2, a tyrosine kinase that initiates the JAK-STAT pathway. Activation also ... results in the activation of mitogen-activated protein kinases and Src kinase. Human prolactin receptors are insensitive to ... Table 2 Archived 9 November 2011 at the Wayback Machine in Beltran L, Fahie-Wilson MN, McKenna TJ, Kavanagh L, Smith TP ( ... 88 (2): 689-96. doi:10.1210/jc.2002-021255. PMID 12574200. Kulick RS, Chaiseha Y, Kang SW, Rozenboim I, El Halawani ME (July ...
... and SH2B2alpha-promoted Janus kinase-2 activation and insulin signaling". Endocrinology. 148 (4): 1615-21. doi:10.1210/en.2006- ... O'Brien KB, O'Shea JJ, Carter-Su C (2002). "SH2-B family members differentially regulate JAK family tyrosine kinases". J. Biol ... "Cross-talk between the two divergent insulin signaling pathways is revealed by the protein kinase B (Akt)-mediated ... SH2B adapter protein 2 is a protein that in humans is encoded by the SH2B2 gene. The protein encoded by this gene is expressed ...
Witthuhn BA, Silvennoinen O, Miura O, Lai KS, Cwik C, Liu ET, Ihle JN (July 1994). "Involvement of the Jak-3 Janus kinase in ... Verbsky JW, Bach EA, Fang YF, Yang L, Randolph DA, Fields LE (June 1996). "Expression of Janus kinase 3 in human endothelial ... a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes". Proceedings of the National ... binding to the Janus kinases". FEBS Letters. 477 (1-2): 55-61. doi:10.1016/S0014-5793(00)01760-9. PMID 10899310. S2CID 31811757 ...
Huang LJ, Constantinescu SN, Lodish HF (Dec 2001). "The N-terminal domain of Janus kinase 2 is required for Golgi processing ... Erythropoietin receptor has been shown to interact with: CRKL, Erythropoietin, Grb2, Janus kinase 2, LYN, PIK3R1, PTPN6, SOCS2 ... 3-kinase and for EpR-associated PI 3-kinase activity". The Journal of Biological Chemistry. 270 (40): 23402-8. doi:10.1074/jbc. ... In addition to activating Ras/AKT and ERK/MAP kinase, phosphatidylinositol 3-kinase/AKT pathway and STAT transcription factors ...
Gual P, Baron V, Lequoy V, Van Obberghen E (March 1998). "Interaction of Janus kinases JAK-1 and JAK-2 with the insulin ... Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E (December 1995). "Involvement of Janus kinases in the insulin ... PI3K, involved in interaction with IRS-1, produces PIP3, which, in turn, recruits Akt kinase. Further, Akt kinase is activated ... Xia X, Serrero G (August 1999). "Multiple forms of p55PIK, a regulatory subunit of phosphoinositide 3-kinase, are generated by ...
... has been shown to interact with SGTA, PTPN11, Janus kinase 2, Suppressor of cytokine signaling 1 and ... "Regions of the JAK2 tyrosine kinase required for coupling to the growth hormone receptor". The Journal of Biological Chemistry ... whereas the intracellular domain contains tyrosine Kinase JAK2 binding sites for SH2 proteins. JAK2 is the primary signal ... "Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase". The Journal of ...
This protein associates constitutively with Janus kinase 2 (JAK2), and also binds to transcription activator STAT3 in a ligand- ... 80 (2): 273-90. doi:10.1086/511051. PMC 1785338. PMID 17236132. Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A ... 154 (2): 452-64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131. "Infection and Immunity Immunophenotyping (3i) ... 5 (8): 977-81, 981.e1-2. doi:10.1016/j.cgh.2007.05.002. hdl:10261/75893. PMID 17678845. Raelson JV, Little RD, Ruether A, ...
The method has been used to detect mutations in epidermal-growth-factor-receptor (EGFR), Janus Kinase 2 (JAK2), p53 and others ... doi:10.1007/978-1-60761-753-2_15. ISBN 978-1-60761-752-5. ISSN 1940-6029. PMID 20680839. Ran, F. Ann; Hsu, Patrick D.; Lin, ... 30 (2): 264-273. doi:10.1002/humu.20842. ISSN 1098-1004. PMID 18837007. Voskarides, Konstantinos; Deltas, Constantinos (2009-07 ...
Li J, Feltzer RE, Dawson KL, Hudson EA, Clark BJ (December 2003). "Janus kinase 2 and calcium are required for angiotensin II- ... 978 (1-2): 245-9. doi:10.1016/s0006-8993(03)02840-3. PMID 12834921. S2CID 32869169. Kohen P, Castro O, Palomino A, Muñoz A, ... steroidogenic response to gonadotropins in human and rat preovulatory granulosa cells involves mitogen-activated protein kinase ...
... such as PDGF receptor pathways and Janus kinase 2 (JAK2) signaling pathway. Anti-Müllerian hormone (AMH), a glycoprotein ... The activation of protein kinase C by phorbol ester PMA also decreased fetal gonocyte mitotic activity. There are a number of ... 75 (2): 130-141. doi:10.1002/bdrc.20041. ISSN 1542-975X. PMID 16035044. Wu, Ray-Chang; Zeng, Yang; Chen, Yu-Fang; Lanz, Rainer ... 89 (2): 46. doi:10.1095/biolreprod.113.110544. ISSN 0006-3363. PMID 23843237. Yang, Qi-En; Oatley, Jon M. (2014-01-01), Rendl, ...
It is a selective inhibitor of the enzyme janus kinase 1 (JAK1). Abrocitinib is quickly absorbed from the gut and generally ... Abrocitinib (code name PF-04965842) is a Janus kinase inhibitor drug which is currently under investigation for the treatment ... October 2019). "Efficacy and Safety of Oral Janus Kinase 1 Inhibitor Abrocitinib for Patients With Atopic Dermatitis: A Phase 2 ... August 2018). "Evaluation of a Janus kinase 1 inhibitor, PF-04965842, in healthy subjects: A phase 1, randomized, placebo- ...
JAK2 (Janus-activated kinase 2), STAT3 and kinases increases regulated by extracellular signals have also been observed in the ... Brown, D.; Yallampalli, U.; Owlia, A.; Singh, P. (2003-01-01). "pp60c-Src Kinase Mediates Growth Effects of the Full-Length ... "Activation of the pp60c-src protein kinase is an early event in colonic carcinogenesis". Proceedings of the National Academy of ... Binding was not influenced by the presence of the classical CCK-2 receptor. It is clear from these two studies that there is a ...
Janus kinase 1, Janus kinase 2, MAPK1 NMI, and PTPN11. CBX5, STAT5 GRCh38: Ensembl release 89: ENSG00000126561 - Ensembl, May ... Schulze WX, Deng L, Mann M (2005). "Phosphotyrosine interactome of the ErbB-receptor kinase family". Mol. Syst. Biol. 1 (1): E1 ... In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and ... Pircher TJ, Petersen H, Gustafsson JA, Haldosén LA (April 1999). "Extracellular signal-regulated kinase (ERK) interacts with ...
... activating such kinases as Janus kinase and tyrosine kinase 2. IL-10R2 receptor is presented in most cells, when IL-10R1 ... 23 (2): 89-96. doi:10.1016/S1471-4906(01)02149-4. ISSN 1471-4906. PMID 11929132. Trivella, Daniela Barretto Barbosa; Ferreira- ... 179 (2): 300-308. doi:10.1111/cei.12449. PMC 4298407. PMID 25178435. v t e. ...
Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2). The biological effects of IFNs are mediated through the Janus kinase/signal ... STAT1 and STAT2 are activated by these tyrosine kinases, and STAT1 and STAT2 mediate the antiviral and inflammatory effects of ... Two cytoplasmic tyrosine kinases provide downstream signaling after type I IFN binds to the IFNAR receptor, ... the pathway involving mitogen-activated protein kinases (MAPKs) and IRF pathways, depending on the stimulus and the responding ...
... associations between the cytoplasmic regions of the interleukin-12 receptor subunits beta1 and beta2 and JAK kinases". J. Biol ... 257 (2): 400-4. doi:10.1006/bbrc.1999.0479. ISSN 0006-291X. PMID 10198225. Airoldi I, Guglielmino R, Carra G, et al. (2002). " ... 257 (2): 400-4. doi:10.1006/bbrc.1999.0479. PMID 10198225. Yao BB, Niu P, Surowy CS, Faltynek CR (1999). "Direct interaction of ... 266 (2): 551-5. doi:10.1006/bbrc.1999.1859. PMID 10600539. van Rietschoten JG, Smits HH, Westland R, et al. (2000). "Genomic ...
This leads to the activation of Janus kinases JAK1 and JAK3 which subsequently phosphorylate T338 on CD122. This ... IL-2 is a member of a cytokine family, each member of which has a four alpha helix bundle; the family also includes IL-4, IL-7 ... The IL-2 receptor (IL-2R) α subunit binds IL-2 with low affinity (Kd~ 10−8 M). Interaction of IL-2 and CD25 alone does not lead ... Low-dose IL-2 has been reported to reduce hepatitis C and B infection. IL-2 has been used in clinical trials for the treatment ...
Tyrosine-kinase inhibitors ("-nib"). Receptor tyrosine kinase. *ErbB: HER1/EGFR (Brigatinib. *Erlotinib ... 3 (2): 86-90. doi:10.1186/bcr276. PMC 138676. PMID 11250751.. *^ Maverakis E, Kim K, Shimoda M, Gershwin M, Patel F, Wilken R, ... 4 (2): 107. doi:10.1016/s1548-5315(11)70061-4. Archived (PDF) from the original on 2007-09-29.. CS1 maint: Multiple names: ... Lahiri, Diptendu; Osterman, Cynthia (2 November 2018). "Novartis abandons effort for U.S. approval of biosimilar rituximab". ...
... kinases. Afatinib is not only active against EGFR mutations targeted by first generation tyrosine-kinase inhibitors (TKIs) like ... Like lapatinib and neratinib, afatinib is a protein kinase inhibitor that also irreversibly inhibits human epidermal growth ... Minkovsky N, Berezov A (December 2008). "BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors ... It belongs to the tyrosine kinase inhibitor family of medications.[4] It is taken by mouth.[4] ...
positive regulation of MAP kinase activity. • positive regulation of catalytic activity. • mitochondrial transport. • post- ... Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P (September 2000). "Nicastrin modulates ... negative regulation of protein kinase activity. • cell fate specification. • skeletal system morphogenesis. • regulation of ... positive regulation of protein kinase activity. • T cell activation involved in immune response. • cellular protein metabolic ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... 2. [. ES. ]. =. k. 2. K. i. [. S. ]. [. E. ]. 0. K. m. K. i. +. K. i. [. S. ]. +. K. m. [. I. ]. {\displaystyle V_{0}=k_{2}[{\ ... 2. [. E. ]. 0. [. S. ]. K. m. +. [. S. ]. +. K. m. [. I. ]. K. i. {\displaystyle V_{0}={\frac {k_{2}[{\ce {E}}]_{0}[{\ce {S ... 2. [. ES. ]. −. k. 3. [. E. ]. [. I. ]. +. k. −. 3. [. EI. ]. {\displaystyle {\frac {d[{\ce {E}}]}{dt}}=0=-k_{1}[{\ce {E}}][{\ ...
2010). "Extended kinase profile and properties of the protein kinase inhibitor nilotinib". Biochimica et Biophysica Acta (BBA ... Nilotinib inhibits the kinases BCR-ABL,[16] KIT, LCK, EPHA3, EPHA8, DDR1, DDR2, PDGFRB, MAPK11 and ZAK.[17] ... See also: Discovery and development of Bcr-Abl tyrosine kinase inhibitors. Nilotinib was developed by Novartis.[3] It was ... Structurally related to imatinib,[18] It is 10-30 fold more potent than imatinib in inhibiting Bcr-Abl tyrosine kinase activity ...
Branscombe TL, Frankel A, Lee JH, Cook JR, Yang Z, Pestka S, Clarke S (August 2001). "PRMT5 (Janus kinase-binding protein 1) ... 2][3][4] In both types of histone methyltransferases, S-Adenosyl methionine (SAM) serves as a cofactor and methyl donor group.[ ...
Upon binding IL-15β subunit activates Janus kinase 1 (Jak1) and γc subunit Janus kinase 3 (Jak3), which leads to ... Upon binding IL-15β subunit activates Janus kinase 1 (Jak1) and γc subunit Janus kinase 3 (Jak3), which leads to ... kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) and Syk (spleen tyrosine kinase) ... kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) and Syk (spleen tyrosine kinase) ...
Structural requirements of the interleukin-6 signal transducer gp130 for its interaction with Janus kinase 1: the receptor is ... 1993). „IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase.". Science. 260 (5115): 1808-10. ... On interaguje sa Janus kinazom da bi izazvao intracelularni signal nakon interakcije receptora sa ligandom. Strukturno, gp130 ... 2000). „Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines.". ...
Janus kinases (JAKs) are non-receptor tyrosine kinases essential for the activation of signaling that is mediated by cytokine ... Fibrosis grade 2 or 3 defines overt PMF whereas grade 0 or 1 defines prefibrotic primary myelofibrosis. ... In August 2019, the FDA approved fedratinib as a treatment for adults with intermediate-2 or high-risk primary or secondary ( ... Ruxolitinib serves as an inhibitor of JAK 1 and 2. The New England Journal of Medicine (NEJM) published results from two Phase ...
Zhang J, Yang PL, Gray NS (Jan 2009). "Targeting cancer with small molecule kinase inhibitors". Nature Reviews. Cancer. 9 (1): ... doi:10.1016/0163-7258(91)90086-2.. *^ a b c d Yue QX, Liu X, Guo DA (Aug 2010). "Microtubule-binding natural products for ... 56 (2): 185-229. PMID 15169927. doi:10.1124/pr.56.2.6.. *^ Sobell HM (Aug 1985). "Actinomycin and DNA transcription". ... 2 (10): 750-63. PMID 12360278. doi:10.1038/nrc903.. *^ Chen HX, Cleck JN (Aug 2009). "Adverse effects of anticancer agents that ...
"Janus kinases and focal adhesion kinases play in the 4.1 band: a superfamily of band 4.1 domains important for cell structure ... protein kinase activity. • JUN kinase binding. • non-membrane spanning protein tyrosine kinase activity. • transferase activity ... FAK(focal adhesion kinase、フォーカルアドヒージョンキナーゼ、焦点接着キナーゼ、接着斑キナーゼ)またはPTK2(protein tyrosine kinase 2)は、ヒトではPTK2遺伝子にコードされるタンパク質である[4]。 ... "Regulation of the PH-domain-containing tyrosine kinase
Janus kinase 2,[24]. *SNRPD3,[23]. *SUPT5H,[25] and. *WD repeat-containing protein 77.[21] ... "Interaction of the somatostatin receptor subtype 1 with the human homolog of the Shk1 kinase-binding protein from yeast". J. ... "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase ... "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase ...
Over 50% of resistance is caused by a mutation in the ATP binding pocket of the EGFR kinase domain involving substitution of a ... JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial ... As with other ATP competitive small molecule tyrosine kinase inhibitors, such as imatinib (Gleevec) in CML, patients rapidly ... Blum G, Gazit A, Levitzki A (2000). "Substrate competitive inhibitors of IGF-1 receptor kinase". Biochemistry. 39 (51): 15705- ...
G-CSF regulates them using Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and Ras/mitogen-activated ... protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal transduction pathway.. ... positive regulation of protein kinase B signaling. • positive regulation of actin filament polymerization. • cellular response ... positive regulation of phosphatidylinositol 3-kinase signaling. • positive regulation of protein binding. • cellular response ...
The active sites of tyrosine kinases each have a binding site for ATP. The enzymatic activity catalyzed by a tyrosine kinase is ... Some tumor cells, however, have a dependence on bcr-abl.[28] Inhibition of the bcr-abl tyrosine kinase also stimulates its ... Schiffer CA (July 2007). "BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia". N. Engl. J. Med. 357 (3): 258- ... As this is now a constitutively active tyrosine kinase, imatinib is used to decrease bcr-abl activity. ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... 17 (2): 197-208. doi:10.1517/13543784.17.2.197. PMID 18230053.. *^ Schönthal AH (2006). "Antitumor properties of dimethyl- ... "COX-2 Inhibitors and Cancer". Fact Sheet. United States National Cancer Institute. Archived from the original on May 9, 2008.. ... 165 (2): 171-7. doi:10.1001/archinte.165.2.171. PMID 15668363.. *. Solomon DH, Avorn J (Jan 2005). "Coxibs, science, and the ...
... a process regulated by phosphorylation of the lamins by protein kinases such as the CDC2 protein kinase.[63] Towards the end of ... "Coiled bodies and gems: Janus or gemini?". American Journal of Human Genetics. 63 (2): 317-21. doi:10.1086/301992. PMC 1377332 ... Observations that myxobacteria are motile, can form multicellular complexes, and possess kinases and G proteins similar to ... 978-0-7216-3360-2. .. *^ a b c Dundr M, Misteli T (June 2001). "Functional architecture in the cell nucleus". The Biochemical ...
에리트로포이에틴이 붙는 수용체는 적혈구 전구체에 있고 JAK2(janus kinase 2) 신호체계를 활성화시킨다. 에리트로포이에틴 수용체는 골수, 말초신경/중추신경계 등 여러 조직에서 발현된다. 혈액내에서는 적혈구는 스스로 ... 예를 들면, 신경 손상에 대한 뇌의 반응에 중요한 역할을 한다고 알려졌다.[1] 에리트로포이에틴은 또한 상처의 회복과정에도 포함된다고 알려졌다.[2] ... Genc S, Koroglu TF, Genc K (2004). "Erythropoietin and the nervous system". 《Brain Res.》 1000 (1-2): 19-31. PMID 15053948. doi: ... 2005). "Brain and cancer: the protective role of erythropoietin". 《Med Res Rev》 25 (2): 245-59. PMID 15389732. doi:10.1002/med. ...
Protein kinase *Tyrosine kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... ISBN 0-9578521-4-2 *^ a b c Azzouni F, Godoy A, Li Y, Mohler J, et al. (2012). "The 5 alpha-reductase isozyme family: a review ... 978-3-11-015793-2. .. *^ Mutschler, Ernst; Gerd Geisslinger; Heyo K. Kroemer; Monika Schäfer-Korting (2001). ... D2 receptor antagonists (prolactin releasers) (e.g., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... 302 (2): 497-519. doi:10.1006/jmbi.2000.4075. PMID 10970748.. *. Bretscher LE, Abel RL, Raines RT (Apr 2000). "A ribonuclease A ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... ISBN 0-9578521-4-2 *^ a b c Azzouni F, Godoy A, Li Y, Mohler J, et al. (2012). "The 5 alpha-reductase isozyme family: a review ... ISBN 3-8047-1763-2.. *^ a b c Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS (2016). "Adverse Effects and ... 2 (3): 293-299. doi:10.1515/hmbci.2010.035.. *^ McConnell J. D.; Wilson J. D.; George F. W.; Geller J.; Pappas F.; Stoner E. ( ...
STAT activation initiates the most well-defined cell signaling pathway for all IFNs, the classical Janus kinase-STAT (JAK-STAT ... Type I IFNs further activate p38 mitogen-activated protein kinase (MAP kinase) to induce gene transcription.[17] Antiviral and ... The phosphatidylinositol 3-kinase (PI3K) signaling pathway is also regulated by both type I and type II IFNs. PI3K activates ... Production of protein kinase R, for example, can be disrupted in cells infected with JEV.[22] Some viruses escape the anti- ...
JAK inhibitors: Janus kinase inhibitors, previously used in the treatment of cancer and other diseases, such as arthritis, have ... 79 (2): 138-40. PMID 17388216.. *^ "Hairless Man Grows Full Head Of Hair In Yale Arthritis Drug Trial". boston.cbslocal.com. ... Genetic factors may contribute to AU, as about 20% of those affected have a family member with alopecia.[2] ... 10 (2): 51-60. doi:10.4103/ijt.ijt_99_17. ISSN 0974-7753. PMC 5939003. PMID 29769777.. ...
Uckun F. M., Qazi S., Ma H., Tuel-Ahlgren L., Ozer Z. STAT3 is a substrate of SYK tyrosine kinase in B-lineage leukemia/ ... STAT3, в зависимости от типа клеток и конкретных условий, могут фосфорилировать киназы Janus (JAK1, JAK2, JAK3), SYK и другие[4 ... protein kinase binding. • ДНК-связывающий. • sequence-specific DNA binding. • transcriptional activator activity, RNA ... 1 2 3 4 Subramaniam A., Shanmugam M. K., Perumal E., Li F., Nachiyappan A., Dai X., Swamy S. N., Ahn K. S., Kumar A. P., Tan B ...
It is an inhibitor of the enzyme janus kinase 1 (JAK1) and janus kinase 3 (JAK 3), which means that it interferes with the JAK- ... Tofacitinib (INN) is a drug of the janus kinase (JAK) inhibitor class, discovered and developed by the National Institutes of ... 7 July 2015). "Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two, ... Levy LL, Urban J, King BA (2015). "Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib ...
... phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or Ikappa B kinase ... 280 (2): 273-82. doi:10.1006/viro.2000.0782. PMID 11162841.. *^ Zhou Q, Lavorgna A, Bowman M, Hiscott J, Harhaj EW (June 2015 ... 280 (2): 273-82. doi:10.1006/viro.2000.0782. PMID 11162841.. *. Lu R, Moore PA, Pitha PM (May 2002). "Stimulation of IRF-7 gene ... 9 (2): 191-7. doi:10.1038/nm822. PMID 12539042.. *. Yang H, Lin CH, Ma G, Baffi MO, Wathelet MG (May 2003). "Interferon ...
Monitoring liver enzymes and creatine kinase is especially prudent in those on high-dose statins or in those on statin/fibrate ... 114 (2): 99-108. doi:10.7556/jaoa.2014.023. PMID 24481802.. *^ Ramasamy I (February 2016). "Update on the molecular biology of ... 36 (2): 288-95. doi:10.1345/aph.1A289. PMID 11847951.. *^ Armitage J (November 2007). "The safety of statins in clinical ... 172 (2): 144-52. doi:10.1001/archinternmed.2011.625. PMID 22231607.. *^ Jukema JW, Cannon CP, de Craen AJ, Westendorp RG, ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... medium (1-2 hrs.)[21] neuromuscular junction[21] *Reverse neuromuscular block (intravenously)[21] ... medium (2-3 hrs.)[21] neuromuscular junction[21] *Treat myasthenia gravis (orally)[21] ... Consumer Reports: 2. Archived (PDF) from the original on 5 September 2012. Retrieved 1 May 2013.. , which claims Alzheimer's ...
... as quinases Janus (JAKs) e Transdutores de Sinais e Activadores de Transcrición (Signal Transducers and Activators of ... via phosphorylation of the nuclear localization sequence by the AKT kinase". Cancer Genomics Proteomics 4 (6): 387-98. PMID ... Neurosci. 11 (2): 100-13. PMID 20087360. doi:10.1038/nrn2774.. *↑ 52,0 52,1 52,2 Sharma RP, Tun N, Grayson DR (2008). " ... 334 ( Pt 2) (Pt 2): 297-314. PMC 1219691. PMID 9716487.. *↑ Kishimoto T, Akira S, Narazaki M, Taga T (1995). "Interleukin-6 ...
... inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain". Genes to ... is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of ... Janus kinase 2 has been shown to interact with: DNAJA3 EGFR EPOR FYN Grb2 GHR IRS1 IL12RB2 IL5RA PIK3R1 PPP2R4 PTK2 PTPN11 ... Gual P, Baron V, Lequoy V, Van Obberghen E (March 1998). "Interaction of Janus kinases JAK-1 and JAK-2 with the insulin ...
Janus Kinase 2: A Critical Target in Chronic Myelogenous Leukemia. Ajoy K. Samanta, Hui Lin, Tong Sun, Hagop Kantarjian and ... Janus Kinase 2: A Critical Target in Chronic Myelogenous Leukemia. Ajoy K. Samanta, Hui Lin, Tong Sun, Hagop Kantarjian and ... Janus Kinase 2: A Critical Target in Chronic Myelogenous Leukemia. Ajoy K. Samanta, Hui Lin, Tong Sun, Hagop Kantarjian and ... Janus Kinase 2: A Critical Target in Chronic Myelogenous Leukemia Message Subject (Your Name) has forwarded a page to you from ...
Insufficiency of Janus Kinase 2-Autonomous Leptin Receptor Signals for Most Physiologic Leptin Actions. ... Insufficiency of Janus Kinase 2-Autonomous Leptin Receptor Signals for Most Physiologic Leptin Actions ... Insufficiency of Janus Kinase 2-Autonomous Leptin Receptor Signals for Most Physiologic Leptin Actions ... Insufficiency of Janus Kinase 2-Autonomous Leptin Receptor Signals for Most Physiologic Leptin Actions ...
The role of proto-oncogene Janus kinase-2 (JAK-2) in proliferation and survival of gastric cancer has been... ... Preliminary study on the effect of nucleolin specific aptamer-miRNA let-7d chimera on Janus kinase-2 expression level and ... The role of proto-oncogene Janus kinase-2 (JAK-2) in proliferation and survival of gastric cancer has been previously ... Nucleolin specific aptamer (NCL-Apt) MiRNA let-7d Janus kinase-2 (JAK-2) Gastric cancer ...
The chemokine monocyte chemotactic protein 1 triggers Janus kinase 2 activation and tyrosine phosphorylation of the CCR2B ... triggers activation of the Janus kinase 2 (JAK2)/STAT3 pathway and CCR2 receptor tyrosine phosphorylation. Both Ca2+ ... These results implicate the tyrosine kinase pathway in early chemokine signaling, suggesting a key role for this kinase in ... mobilization and cell migration are blocked in Mono Mac 1 cells by tyrphostin B42, a specific JAK2 kinase inhibitor. Within ...
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of ... "Janus Kinase 2" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE ... This graph shows the total number of publications written about "Janus Kinase 2" by people in this website by year, and whether ...
WP1066 Disrupts Janus Kinase-2 and Induces Caspase-Dependent Apoptosis in Acute Myelogenous Leukemia Cells. Alessandra ... Janus kinase 2: a critical target in chronic myelogenous leukemia. Cancer Res 2006; 66: 6468-72. ... Janus kinases and their role in growth and disease. Life Sci 1999; 64: 2173-86. ... WP1066 Disrupts Janus Kinase-2 and Induces Caspase-Dependent Apoptosis in Acute Myelogenous Leukemia Cells ...
Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis ... Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis ... Objective Angiotensin II (AngII) activates via angiotensin-II-type-I receptor (AT1R) Janus-kinase-2 (JAK2)/Arhgef1 pathway and ... 2Institute for Cell Biology, University of Bonn, Bonn, Germany. *. 3Department of Liver and Biliopancreatic Disorders, ...
... a small molecule Janus kinase 2 (JAK2)-inhibitor, i ... Phase 2. Minimum Age:. 18 Years. Maximum Age:. N/A. Enrollment ... A Phase 2, Two Stage, Open-label, Clinical Trial to Determine the Therapeutic Effect and Safety of an Oral JAK2-inhibitor ( ... A Phase 2, Two Stage, Open-label, Clinical Trial to Determine the Therapeutic Effect and Safety of an Oral JAK2-inhibitor ( ... Day 1 of Cycles 2, 3, and 4 and then every 3 months thereafter (up to 25 months). ...
... terminal kinase and p38 mitogen‑activated protein kinase in colon cancer cells. Conversely, the phosphorylation of Janus kinase ... p-JAK2, phosphorylated Janus kinase 2; p-STAT3, phosphorylated signal transducer and activator of transcription 3. ... Dihydroartemisinin increases apoptosis of colon cancer cells through targeting Janus kinase 2/signal transducer and activator ... p-ERK, phosphorylated extracellular-signal-related kinase; p-JNK, phosphorylated c-Jun N-terminal kinase; p-p38, phosphorylated ...
... ... Growth hormone (GH), Janus kinase 2 (Jak2), Signal transducer and activator of transcription (Stat), Protein phosphorylation, ... In vitro growth hormone (GH) stimulation of Janus kinase 2 (Jak2) tyrosine phosphorylation and activation has been detected in ... In vitro growth hormone (GH) stimulation of Janus kinase 2 (Jak2) tyrosine phosphorylation and activation has been detected in ...
Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate ... Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate ... Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate ... Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate ...
In 2005, a mutation located at exon 14 of the Janus Kinase gene on chromosome 9 was discovered in patients with Polycythaenia ... Detection of the Janus kinase 2 V617F mutation using molecular methods. Login ... Detection of the Janus kinase 2 V617F mutation using molecular methods. Senamela, Tshiphiri ...
Janus kinase (JakA) family. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of ... Janus kinase (JakA) family: tyrosine kinase 2. Last modified on 16/06/2020. Accessed on 24/09/2020. IUPHAR/BPS Guide to ... rather than the functional kinase (or JH1) domain which shares a high degree of homology across all members of the Janus kinase ... TYK2 was the first member of the Janus kinase family to be identified. It associates with the cytoplasmic domain of type I and ...
Janus kinase 2 mutations in Philadelphia negative chronic myeloproliferative disorders: clinical implications.. *. Anna D. ... article{Panani2009JanusK2, title={Janus kinase 2 mutations in Philadelphia negative chronic myeloproliferative disorders: ...
Hematopoietic cytokine receptor signaling is mediated by Janus kinases (JAKs) and their downstream transcription factor, signal ... The ABL kinase inhibitor imatinib is highly effective in treating most, but not all, patients with chronic myeloid leukemia ( ... Janus kinases (JAKs) are a family of intracellular, non-receptor tyrosine kinases including four family members such as JAK1, ... Combination of the ABL kinase inhibitor imatinib with the Janus kinase 2 inhibitor TG101348 for targeting residual BCR-ABL- ...
Ltd., Janus Kinase 2 test at home is available in Delhi India ... Janus Kinase 2 test is conducted by experienced pathologists ...
The discovery of an activating Janus kinase 2 (JAK2) activating mutation (JAK2V617F) that is present in almost all patients ... The discovery of an activating Janus kinase 2 (JAK2) activating mutation (JAK2V617F) that is present in almost all patients ... Ghoreschi K, Laurence A, OShea JJ: Janus kinases in immune cell signaling. Immunol Rev. 2009, 228: 273-287. 10.1111/j.1600- ... Verstovsek S: Therapeutic potential of Janus-activated kinase-2 inhibitors for the management of myelofibrosis. Clin Cancer Res ...
HCA RNA Cell Line for Janus kinase and microtubule-interacting protein 2. ...
You search for a phrase "Janus Kinase 2 genetics" according to the criterion: Subject Terms ...
The V617F mutation in the JAK-2 gene is associated with myeloproliferative disorders (MPDs). This mutation was found in more ...
Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinase 2/Signal Transducer and Activation ... Additionally, tubulosine suppressed IL-6-induced Janus kinase 2 (JAK2)/STAT3 signaling, resulting in decreased viability and ... Janus Kinase 2 , Phosphorylation , Phosphotransferases , Polymerase Chain Reaction , Receptors, Interleukin-6 , Reverse ... Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinas ...
Janus kinase 2 and signal transducer and activator of transcription 3 activation is not essential for CCL3-, CCL5- or CCL8- ... Janus kinase 2 and signal transducer and activator of transcription 3 activation is not essential for CCL3-, CCL5- or CCL8- ... Khabbazi S., Jacques R.O., Moyano Cardaba C. and Mueller A. (2013) Janus kinase 2 and signal transducer and activator of ... we show that chemokine-induced cell migration is not dependent on activation of Janus kinase 2 or STAT3. ...
Association of factor V Leiden, Janus kinase 2, prothrombin, and MTHFR mutations with primary Budd-Chiari syndrome in Egyptian ... Association of factor V Leiden, Janus kinase 2, prothrombin, and MTHFR mutations with primary Budd-Chiari syndrome in Egyptian ... This study aimed to evaluate the association of factor V Leiden (FVL), Janus kinase 2 (JAK2), prothrombin, and methylene ... Hatem M El Sebay 1 , Manal A Safan 1 , Ashraf A Daoud 1 , Safaa I Tayel 1 , Mohamed A Nouh 2 , Shymaa El Shafie 1 ...
Hepatic deletion of Janus Kinase 2 counteracts oxidative stress in mice. Madeleine Themanns, Kristina M. Mueller, Sonja M. ... Fingerprint Dive into the research topics of Hepatic deletion of Janus Kinase 2 counteracts oxidative stress in mice. ...
Janus kinase 3 is a tyrosine kinase that belongs to the janus family of kinases. Other members of the Janus family include JAK1 ... Janus kinases (JAKs) are relatively large kinases of approximately 1150 amino acids with apparent molecular weights of 120-130 ... Janus+Kinase+3 at the US National Library of Medicine Medical Subject Headings (MeSH) Overview of all the structural ... Janus kinase 3 has been shown to interact with CD247, TIAF1 and IL2RG. GRCh38: Ensembl release 89: ENSG00000105639 - Ensembl, ...
야누스키나아제(janus kinase 2, JAK2)는 티로신인산화효소(tyrosine kinase)의 일종으로 조혈기능에 관여하는 유전자로, JAK2 유전자의 valine-to-phenylalanine (V617F) 돌연변이는 ... Should we screen for Janus kinase 2 V617F mutation in cerebral venous thrombosis? Cerebrovasc Dis 2017;44:97-104.. ... Cerebral Venous Thrombosis Presenting in Pregnancy with Thrombocytosis and Janus Kinase 2 Valine-to-Phenylalanine Mutation. 임신 ... Cerebral Venous Thrombosis Presenting in Pregnancy with Thrombocytosis and Janus Kinase 2 Valine-to-Phenylalanine Mutation. ...
Janus kinase 2 To use the sharing features on this page, please enable JavaScript.. ... Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome. Gastroenterology. 2006 Jun;130(7 ... 2010 Mar 2;152(5):300-6. doi: 10.7326/0003-4819-152-5-201003020-00008. Review. Citation on PubMed ...
JAK3: Janus kinase 3. *JPH3: junctophilin 3. *JUP: junction plakoglobin. Genetics Home Reference has merged with MedlinePlus. ...
STAT3 is phosphorylated by the non-receptor protein tyrosine kinases janus kinase 2 (JAK2), leading to the formation of STAT3 ... Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis. Nat Med. 2017;23:291- ... Epidermal growth factor receptor tyrosine kinase inhibitors in advanced squamous cell lung cancer. Clin Lung Cancer. 2016;17: ... binds to specific transmembrane type I and type II serine/threonine kinase receptors (TGF-βR1 and TGF-βR2) [42], resulting in ...
  • Treatment of CML cell lines and mouse Bcr-Abl+ 32D cells with either Jak2 short interfering RNA or Jak2 kinase inhibitor AG490 inhibited pTyr Gab2 and pSer Akt formation, inhibited the activation of nuclear factor-κB, and caused the activation of GSK-3β, leading to the reduction of c-Myc. (aacrjournals.org)
  • Imatinib mesylate is a selective inhibitor of the Bcr-Abl tyrosine kinase, and this drug is the frontline treatment for CML patients ( 4 ). (aacrjournals.org)
  • AG490, a member of the tyrphostin family of protein kinase inhibitors, is a potent and specific inhibitor of Jak2 kinase ( 6 ). (aacrjournals.org)
  • Both Ca2+ mobilization and cell migration are blocked in Mono Mac 1 cells by tyrphostin B42, a specific JAK2 kinase inhibitor. (uniprot.org)
  • Because ( E )-3(6-bromopyridin-2-yl)-2-cyano- N -((S0-1-phenylethyl)acrylamide) (WP1066) is a novel analogue of the JAK2 inhibitor AG490, we tested its activity in AML cells and investigated its mechanism of action. (aacrjournals.org)
  • The ABL kinase inhibitor imatinib is highly effective in treating most, but not all, patients with chronic myeloid leukemia (CML). (biomedcentral.com)
  • Hematopoietic cytokine receptor signaling is mediated by Janus kinases (JAKs) and their downstream transcription factor, signal transducer and activator of transcription (STAT). TG101348 (SAR302503) is an oral inhibitor of JAK2. (biomedcentral.com)
  • Background Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen quantity, symptoms, and success more than placebo and very best available therapy in intermediate-2 or high-risk myelofibrosis individuals with baseline platelet matters 100? (biologyexperimentideas.net)
  • strong course="kwd-title" Keywords: Janus kinase inhibitor, Myelofibrosis, Stage II, Platelet count number, Ruxolitinib, Spleen quantity, Total indicator rating Background Myelofibrosis (MF) can be a Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), including major MF (PMF), post-polycythemia vera MF (PPV-MF) and post-essential thrombocythemia MF (PET-MF) [1]. (biologyexperimentideas.net)
  • Ruxolitinib treatment decreased spleen quantity and improved MF-related symptoms and QoL procedures in sufferers with intermediate-2 or high-risk MF, as described with the International Prognostic Credit scoring Program (IPSS) [6], in the stage III Managed MyeloFibrosis Research with Dental JAK Inhibitor Treatment (Convenience)-I and COMFORT-II research [7,8]. (biologyexperimentideas.net)
  • Results of enzymatic assays revealed that against a panel of kinases, compound NSC13626 is a JAK2 inhibitor and has high selectivity toward the JAK2 and JAK3 isozymes. (frontiersin.org)
  • Importantly, after comparing the proliferation, migration, and invasion of LUAD to the corresponding control groups treated in STAT3 inhibitor ADZ1480, we found that STEAP1 regulates EMT via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. (portlandpress.com)
  • Baricitinib is a selective inhibitor Janus kinase 1 and 2. (medscape.com)
  • Baricitinib is an orally administered inhibitor of janus kinase 1 and 2. (meduniwien.ac.at)
  • TG 101348, is a potent inhibitor of Janus kinase 2 (JAK-2). (fiercebiotech.com)
  • The binding mode was corroborated by solving the structure of the kinase-inhibitor complex. (aacrjournals.org)
  • Ruxolitinib is a Janus kinases (JAK) 1/2 inhibitor, an enzyme-blocker that affects blood cell production. (eurekalert.org)
  • The purpose of this study is to evaluate the percentage of spleen (largest lymph organ in the body) response and symptom response of 2 dose regimens of imetelstat in participants with intermediate-2 or high-risk myelofibrosis (MF) who are relapsed after or refractory to Janus Kinase (JAK) inhibitor treatment. (clinicaltrials.gov)
  • This is a randomized (study medication assigned to participants by chance), multicenter (more than one hospital, medical school team or medical clinic work on a medical research study) study of 2 dosing regimens (treatment arms) of single-agent imetelstat in participants with intermediate-2 or high risk myelofibrosis (MF) whose disease is relapsed after or refractory to Janus Kinase (JAK) inhibitor treatment. (clinicaltrials.gov)
  • In the present study, it was identified that dihydroartemisinin inhibited cell viability, promoted cell apoptosis, increased B‑cell lymphoma‑2‑associated X‑protein expression, increased caspase‑3/9 activities, decreased poly(ADP‑ribose) polymerase levels, decreased phosphorylation of extracellular‑signal‑regulated kinase, and increased phosphorylation of c‑Jun N‑terminal kinase and p38 mitogen‑activated protein kinase in colon cancer cells. (spandidos-publications.com)
  • However, accumulation of activated extracellular signal-regulated kinase (ERK)1 and ERK2 were the only transducers measured in the study not affected by the 1% replacement pulse of growth hormone and were elevated 2- to 3-fold above normal when the pulse was renaturalized to 10% of physiological amplitude, suggesting the possible involvement of mitogen-activated protein kinase in episodic growth hormone regulation of CYP2C11. (aspetjournals.org)
  • GH-stimulated activation of signal transducers and activators of transcription (STATs), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3' kinase (PI3K) cascades have been shown to regulate the transcription of GH-responsive genes. (biomedsearch.com)
  • Mitogen-activated protein kinase plays an essential role in the erythropoietin-dependent proliferation of CTLL-2 cells. (biomedsearch.com)
  • The JAK proteins are a family of four cytosolic tyrosine kinases (JAK1, JAK2, JAK3, and TYK2). (aacrjournals.org)
  • Structural and thermodynamic characterization of the TYK2 and JAK3 kinase domains in complex with CP-690550 and CMP-6. (guidetopharmacology.org)
  • Janus kinases (JAKs) are a family of intracellular, non-receptor tyrosine kinases including four family members such as JAK1, JAK2, JAK3, and Tyk2. (biomedcentral.com)
  • Tyrosine-protein kinase JAK3 is a tyrosine kinase enzyme that in humans is encoded by the JAK3 gene. (wikipedia.org)
  • Functional reconstitution of kinase activity by recombinant Jak3 using Jak3-wt or villin/gelsolin-wt as substrate showed that Jak3 autophosphorylation was the rate-limiting step during interactions between Jak3 and cytoskeletal proteins. (wikipedia.org)
  • while TNF-alpha levels in LPS + 50 mmol/L CORM-2 and LPS + 100 mmol/L CORM-2 groups decreased obviously as compared with that of LPS group [(5.7 +/- 1.4), (3.2 +/- 0.9) pg/mL, with t value respectively 2.104 and 2.363, P values all below 0.05], and it was the same with phosphorylation levels of JAK1, JAK3 in a dose -dependent manner. (bvsalud.org)
  • while plasma levels of TNF-alpha and IL-1beta and the phosphorylation levels of JAK1, JAK3 in liver tissue decreased significantly in CLP + CORM-2 group (with t value respectively 2.115 and 2.398, and P values all below 0.05). (bvsalud.org)
  • The four JAK family members are: Janus kinase 1 (JAK1) Janus kinase 2 (JAK2) Janus kinase 3 (JAK3) Tyrosine kinase 2 (TYK2) Transgenic mice that do not express JAK1 have defective responses to some cytokines, such as interferon-gamma. (wikipedia.org)
  • Global Markets Direct's, 'Tyrosine Protein Kinase JAK3 (Janus Kinase 3 or Leukocyte Janus Kinase or JAK3 or EC 2.7.10.2) - Pipeline Review, H2 2016', provides in depth analysis on Tyrosine Protein Kinase JAK3 (Janus Kinase 3 or Leukocyte Janus Kinase or JAK3 or EC 2.7.10.2) targeted pipeline therapeutics. (globalmarketsdirect.com)
  • The report provides comprehensive information on the Tyrosine Protein Kinase JAK3 (Janus Kinase 3 or Leukocyte Janus Kinase or JAK3 or EC 2.7.10.2), targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (globalmarketsdirect.com)
  • Additionally, the report provides an overview of key players involved in Tyrosine Protein Kinase JAK3 (Janus Kinase 3 or Leukocyte Janus Kinase or JAK3 or EC 2.7.10.2) targeted therapeutics development and features dormant and discontinued projects. (globalmarketsdirect.com)
  • Second, Jak3 is widely believed to be expressed only in cells of the lymphoid and myeloid lineages, while Jak1, Jak2, and tyrosine kinase 2 are ubiquitously expressed ( 2 , 4 , 5 ). (jimmunol.org)
  • In the present study, we investigated a novel AG490 analogue, ( E )-3(6-bromopyridin-2-yl)-2-cyano- N -((S0-1-phenylethyl)acrylamide) (WP1066), whose solubility and protein kinase-inhibitory profile suggested that this compound might be a good candidate for clinical development. (aacrjournals.org)
  • In addition, HG increases the de novo synthesis of the protein kinase C activator diacylglycerol ( 3 ). (diabetesjournals.org)
  • Thus, a mechanism by which HG induces GMC production of TGF-β and extracellular matrix molecules may be through the chronic activation of one or more isoforms of protein kinase C ( 4 ). (diabetesjournals.org)
  • Additionally, TM increased the expression of nuclear respiratory factor 2 (Nrf2), catalase, heme oxygenase 1, heme oxygenase 2, and manganese superoxide dismutase 2 and decreased the expression of protein kinase C alpha, phosphor-janus kinase 2, phosphor-signal transducer and activator of transcription 3, and phosphor-nuclear factor- κ B in the kidneys. (hindawi.com)
  • However, greater activation of protein kinase C and loss of Akt and endothelial nitric oxide synthase phosphorylation occurred in the Akita/ACE2KO hearts. (ahajournals.org)
  • Tyrosine-protein kinase Tec is an enzyme that in humans is encoded by the TEC gene . (wn.com)
  • The V617F mutation in the JAK-2 gene is associated with myeloproliferative disorders (MPDs). (5minuteconsult.com)
  • The role of Janus Kinase 2 V617F mutation in extramedullary hematopoiesis of the spleen in neoplastic myeloid disorders. (cdc.gov)
  • She had thrombocytosis in the peripheral blood, and a genetic test for thrombocytosis revealed the presence of the valine-to-phenylalanine (V617F) mutation of the Janus kinase 2 (JAK2) gene. (jkna.org)
  • 야누스키나아제(janus kinase 2, JAK2)는 티로신인산화효소(tyrosine kinase)의 일종으로 조혈기능에 관여하는 유전자로, JAK2 유전자의 valine-to-phenylalanine (V617F) 돌연변이는 진성적혈구증가증, 본태혈소판증가증과 같은 골수증식성질환을 초래하고 혈전색전증의 위험을 높이는 것으로 알려져 있다[ 1 ]. (jkna.org)
  • Jak2 +/VF mice have an inverted exon 14, carrying a valine to phenylalanine mutation (V617F), downstream of the endogenous exon 14 of the Janus kinase 2 ( Jak2 ) gene. (jax.org)
  • The V617F mutation results in constitutive activation of JAK2 kinase signaling. (jax.org)
  • A screen of 72 inhibitors against 456 human kinases. (guidetopharmacology.org)
  • The discovery of an activating Janus kinase 2 (JAK2) activating mutation (JAK2V617F) that is present in almost all patients with PV and in about 50-60 % of patients with ET and PMF led to the initiation of several trials investigating the clinical effectiveness of various JAK2 (or JAK1/JAK2) inhibitors for the treatment of patients with ET, PV, and MF. (biomedcentral.com)
  • However, for inhibitors that do not affect the actin cytoskeleton or induce cell death, we show that chemokine-induced cell migration is not dependent on activation of Janus kinase 2 or STAT3. (edu.au)
  • The similarity between the ATP binding site of protein kinases has made development of specific inhibitors difficult. (frontiersin.org)
  • It is thought that increasing selectivity of kinase inhibitors may reduce the side effects seen with current treatment options. (frontiersin.org)
  • Molecular modeling-driven approach for identification of Janus kinase 1 inhibitors through 3D-QSAR, docking and molecular dynamics simulations. (nih.gov)
  • We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib). (bmj.com)
  • Paris, France - June 30, 2010 - Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today that it has signed an agreement for the acquisition of TargeGen Inc., ("TargeGen") a privately held US biopharmaceutical company developing small molecule kinase inhibitors for the treatment of certain forms of leukemia, lymphoma and other hematological malignancies and blood disorders. (fiercebiotech.com)
  • TargeGen is a privately held US biopharmaceutical company based in San Diego, CA, USA, developing small molecule kinase inhibitors for the treatment of hematological malignancies and certain other disorders. (fiercebiotech.com)
  • As Janus kinase inhibitors alter the immune response they increase the risk of serious infections. (nps.org.au)
  • The driving force for the leukemia is the activated tyrosine kinase of Bcr-Abl, which stimulates several signal transduction pathways ( 1 ), including the Janus kinase (Jak) 2 pathway ( 2 ) and, separately, the signal transducer and activator of transcription 5 (STAT5) pathway ( 3 ). (aacrjournals.org)
  • Using the Mono Mac 1 monocytic cell line, we show that monocyte chemotactic protein 1 (MCP-1) triggers activation of the Janus kinase 2 (JAK2)/STAT3 pathway and CCR2 receptor tyrosine phosphorylation. (uniprot.org)
  • These results implicate the tyrosine kinase pathway in early chemokine signaling, suggesting a key role for this kinase in later events. (uniprot.org)
  • Objective Angiotensin II (AngII) activates via angiotensin-II-type-I receptor (AT1R) Janus-kinase-2 (JAK2)/Arhgef1 pathway and subsequently RHOA/Rho-kinase (ROCK), which induces experimental and probably human liver fibrosis. (bmj.com)
  • A considerable number of reports have indicated that episodic growth hormone effects are mediated by the activation of the Janus kinase 2 (Jak2)/signal transducer and activator of transcription (Stat)5B signal transduction pathway. (aspetjournals.org)
  • Several studies have established a role for the Janus tyrosine kinase/signal transducer and activator of transcription (Jak/Stat) signal transduction pathway in mediating the actions of GH. (aspetjournals.org)
  • Therefore, we investigated here the molecular mechanisms of CCL3-, CCL5- and CCL8-induced cells migration and investigated whether the Janus kinase/signal transducer and activator of transcription (STAT) signalling pathway is involved. (edu.au)
  • To study the inhibitive effect of exogenous carbon monoxide -releasing molecules 2 (CORM-2) on the activation of Janus kinase /signal transducer and activator of transcription (JAK/STAT) pathway in sepsis . (bvsalud.org)
  • Exogenous CORM-2 can obviously inhibit the phosphorylation of JAKs molecules and then inhibit the activation of JAK/STAT signal pathway in sepsis , and decrease the expression of downstream cytokines to effectively prevent cascade reaction in the inflammatory response after severe infection . (bvsalud.org)
  • Non-coding RNA 886 promotes renal cell carcinoma growth and metastasis through the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. (bvsalud.org)
  • Janus kinase ( JAK ) is a family of intracellular non-receptor tyrosine kinases , ranging from 120-140 kDa in size, that transduce cytokine -mediated signals via the JAK-STAT pathway . (wikidoc.org)
  • Janus kinase 2, the downstream signal pathway of growth hormone receptor, was activated time-dependently by stimulating the BPC 157-treated tendon fibroblasts with growth hormone. (mdpi.com)
  • We have recently shown that in vascular smooth muscle cells (VSMCs), exposure to HG results in the activation of the janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. (diabetesjournals.org)
  • In addition, we have shown that the activation of JAK2 was essential for both the Ang II and platelet-derived growth factor-induced MAP kinase pathway activation and VSMC growth ( 8 ). (diabetesjournals.org)
  • Although the explicit pathogenesis of SLE remains unclear, increasing evidence suggests that dysregulation of cytokine signals contributes to the progression of SLE through the Janus kinase/signal transducer and activator of transcription (STAT) signaling pathway. (frontiersin.org)
  • Many cytokines can activate the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 1 (STAT1) signaling pathway. (frontiersin.org)
  • JAK2 is a member of the Janus kinase (JAK) family and aberrant JAK2/STAT is involved with various diseases, making the pathway a therapeutic target. (frontiersin.org)
  • Our results suggest that MAP kinase activation is, at least in part, an important component for mitotic signal from the EPOR, and CTLL-2 cells probably lack signaling molecule(s) in JAK2 and the Ras-MAP kinase pathway. (biomedsearch.com)
  • Janus kinase (JAK) is a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. (wikipedia.org)
  • It inhibits the intracellular signalling pathway of cytokines such as IL-2, IL-6, IL-10, interferon-γ, and granulocyte macrophage colony-stimulating factor. (medscape.com)
  • The present study was designed to investigate the specific role of IL‑23 in myocardial I/R injury, and whether the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2‑STAT3) signaling pathway, one of the important downstream signaling pathways of IL‑23, and the IL‑17A downstream pro‑inflammatory cytokine, were involved. (spandidos-publications.com)
  • The present study attempted to test the hypothesis that IL-23 aggravates myocardial I/R injury by promoting inflammatory responses and myocardial apoptosis, which may be associated with the high expression of IL-17A and upregulation of the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2-STAT3) signaling pathway. (spandidos-publications.com)
  • Renal protein levels of Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway components were determined by western blot assay. (spandidos-publications.com)
  • The Janus kinase 2 (JAK2)/STAT3 pathway is well known to be involved in the immune response of numerous cytokines, including TNF-α and IL-6 ( 6 ). (spandidos-publications.com)
  • Frequent subversion of the PI3K (phosphoinositide 3-kinase) pathway during neoplastic transformation contributes to several hallmarks of cancer that result in a competitive advantage for cancer cells. (biochemsoctrans.org)
  • Deregulation of this pathway can be the result of genomic alterations such as PIK3CA mutation, PTEN (phosphatase and tensin homologue deleted on chromosome 10) loss or the activation of upstream protein tyrosine kinases. (biochemsoctrans.org)
  • There are two large subgroups of cytokine-receptor interactions that cause signal transduction via the Janus kinase-Signal Transducer and Activation of Transcription (JAK-STAT) pathway. (nps.org.au)
  • We have shown that Bcr-Abl is associated with a cluster of signaling proteins, including Janus kinase (Jak) 2, growth factor receptor binding protein 2-associated binder (Gab) 2, Akt, and glycogen synthase kinase (GSK)-3β. (aacrjournals.org)
  • Each LepRb tyrosine phosphorylation site recruits specific Src homology 2 (SH2) domain-containing effector proteins: Tyr 985 recruits Src homology phosphatase-2 (SHP-2) and suppressor of cytokine signaling 3 and attenuates LepRb signaling, but does not appear to play other roles in leptin action in vivo ( 13 - 15 ). (diabetesjournals.org)
  • Upon binding to their cellular receptors, hematopoietic growth factors and cytokines activate Janus-activated kinase (JAK) proteins. (aacrjournals.org)
  • The differential tyrosine phosphorylation of these proteins suggests involvement of a kinase other than Jak2 in Stat5A activation. (lu.se)
  • Since members of the type I and type II cytokine receptor families possess no catalytic kinase activity, they rely on the JAK family of tyrosine kinases to phosphorylate and activate downstream proteins involved in their signal transduction pathways. (wikidoc.org)
  • The encoded kinase phosphorylates STAT proteins (signal transducers and activators of transcription) and plays a key role in interferon-alpha/beta and interferon-gamma signal transduction. (nih.gov)
  • The activation step involves phosphorylation of critical Tyr 1007 ( 2 , 5 ). (aacrjournals.org)
  • Leptin binding to LepRb initiates signaling by activating the associated Janus kinase 2 (Jak2) tyrosine kinase, which promotes the phosphorylation of tyrosine residues on the intracellular tail of LepRb. (diabetesjournals.org)
  • The chemokine monocyte chemotactic protein 1 triggers Janus kinase 2 activation and tyrosine phosphorylation of the CCR2B receptor. (uniprot.org)
  • Mashili F, Chibalin AV, Krook A, Zierath JR. Constitutive STAT3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. (umassmed.edu)
  • Similar to its parent compound AG490, WP1066 inhibited the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein, thereby blocking its downstream signal transducer and activator of transcription (STAT) and phosphoinositide-3-kinase pathways. (aacrjournals.org)
  • Conversely, the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was suppressed by dihydroartemisinin in colon cancer cells. (spandidos-publications.com)
  • In vitro growth hormone (GH) stimulation of Janus kinase 2 (Jak2) tyrosine phosphorylation and activation has been detected in rat adipocytes where GH exerts both chronic diabetogenic and acute insulin-like effects but not in adipocytes where only chronic diabetogenic effects are exerted. (lu.se)
  • The interaction of GH with GH receptors (GHR) on target cells promotes the association of the cellular tyrosine kinase JAK2 with the GHR, initiating tyrosine phosphorylation of GHR and JAK2, and activation of multiple signaling cascades. (biomedsearch.com)
  • The kinase inhibitory region of SOCS1 targets the substrate binding groove of JAK1 and JAK2 with high specificity and thereby blocks any subsequent phosphorylation. (nih.gov)
  • This is mediated by phosphorylation of latent cytoplasmic STAT3 on specific residues (Y705, Ser727) by a variety of tyrosine and serine kinases leading to its dimerization and nuclear translocation, where it acts as a transcription factor for a plethora of genes governing the malignant properties of the tumor cell. (mdpi.com)
  • Janus kinase 2 mutations in Philadelphia negative chronic myeloproliferative disorders: clinical implications. (semanticscholar.org)
  • This study aimed to evaluate the association of factor V Leiden (FVL), Janus kinase 2 (JAK2), prothrombin, and methylene tetrahydrofolate reductase (MTHFR) mutations with primary BCS. (cdc.gov)
  • Mutations that abrogate Janus kinase 3 function cause an autosomal SCID (severe combined immunodeficiency disease), while activating Janus kinase 3 mutations lead to the development of leukemia. (wikipedia.org)
  • Dysregulated Janus kinase (JAK)-sign transducer and activator of transcription (STAT) signaling, aswell as mutations in JAK2, are normal in Philadelphia chromosome-negative MPNs [3]. (biologyexperimentideas.net)
  • Janus kinase 2 ( JAK2 ) mutations define polycythemia vera (PV). (bloodjournal.org)
  • Fms-like tyrosine kinase 3 (Flt3), PI3K, and signal transducer and activator of transcription (Stat)] are dysregulated by these mutations in Cbl has helped to identify potential targets for therapy of myeloid neoplasms. (curehunter.com)
  • MF is a chronic and progressive disorder in which there is a proliferation of certain cells of the bone marrow resulting in bone marrow fibrosis and is associated with activating mutations of JAK-2. (fiercebiotech.com)
  • Additionally, tubulosine suppressed IL-6-induced Janus kinase 2 (JAK2)/STAT3 signaling, resulting in decreased viability and induction of apoptotic cell death in breast cancer cells. (bvsalud.org)
  • Furthermore, whether nc886 exerts its function on RCC via Janus kinase 2 / signal transducer and activator of transcription 3 (JAK2/STAT3) signaling was investigated. (bvsalud.org)
  • We recently found that exposure of cells to HG also activates the growth-promoting enzyme janus kinase 2 (JAK2) and its latent signal transducers and activators of transcription (STAT) transcription factors (STAT1, STAT3, and STAT5). (diabetesjournals.org)
  • Mice with hepatocyte -specific deletion of Janus kinase 2 (L-JAK2 KO mice ) develop spontaneous steatosis as early as 2 weeks of age. (bvs.br)
  • Thirty-five male BALB/c mice were divided into normal control group , cecal ligation and puncture (CLP) group, CLP + iCORM-2 (8.0 mg/kg) group and CLP + CORM-2 group (8.0 mg/kg) according to the random number table. (bvsalud.org)
  • Mice in CLP + CORM-2 group were treated the same as mice in CLP group except for administration of CORM-2 after CLP. (bvsalud.org)
  • In December 2019, the first known cases of the coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were identified in humans in Wuhan, China. (jmir.org)
  • Ruxolitinib and baracitinib mainly inhibit Janus kinase 1 and 2. (nps.org.au)
  • Janus kinases (JAKs) are relatively large kinases of approximately 1150 amino acids with apparent molecular weights of 120-130 kDa. (wikipedia.org)
  • The JH3-JH4 domain of JAKs shares homology with Src-homology -2 (SH2) domains. (wikidoc.org)
  • this domain is also found in the focal adhesion kinase (FAK) family and is involved in association of JAKs with cytokine receptors and/or other kinases [2] . (wikidoc.org)
  • The name is taken from the two-faced Roman god of beginnings and endings, Janus, because the JAKs possess two near-identical phosphate-transferring domains. (wikipedia.org)
  • JAKs range from 120-140 kDa in size and have seven defined regions of homology called Janus homology domains 1 to 7 (JH1-7). (wikipedia.org)
  • An interesting note is that only one of these carboxy-terminal JH domains retains full kinase function (JH1) while the other (JH2), previously thought to have no kinase functionality and accordingly termed a pseudokinase domain, has since been found to be catalytically active, albeit at only 10% that of the JH1 domain. (wikipedia.org)
  • We review evidence that the pseudokinase STRAD controls the function of the tumour suppressor kinase LKB1 and that a single amino acid substitution within the pseudokinase domain of the tyrosine kinase JAK2 leads to several malignant myeloproliferative disorders. (nih.gov)
  • JH2 is a pseudokinase domain , a domain structurally similar to a tyrosine kinase and is essential for a normal kinase activity yet lacks enzymatic activity. (wikidoc.org)
  • Signal transducers and activators of transcription (STATs), a protein family comprised of seven members (STAT1, −2, −3, −4, −5a, −5b and −6), generally transduce signals from activated receptors or intracellular kinases to the nucleus, thus activating and regulating gene transcription ( 5 ). (spandidos-publications.com)
  • Tec family kinases are involved in the intracellular signaling mechanisms of cytokine receptors, lymphocyte surface antigens, heterotrimeric G-protein-coupled receptors, and integrin molecules. (wn.com)
  • Khabbazi S., Jacques R.O., Moyano Cardaba C. and Mueller A. (2013) Janus kinase 2 and signal transducer and activator of transcription 3 activation is not essential for CCL3-, CCL5- or CCL8-induced chemotaxis. (edu.au)
  • The Jak2 VF targeting vector was designed to insert an inverted mutated exon 14 downstream of endogenous exon 14 of the Janus kinase 2 ( Jak2 ) gene. (jax.org)
  • Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS. (umassmed.edu)
  • Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. (labcorp.com)
  • The JAK2V617F tyrosine kinase mutation in myeloproliferative disorders: Status report and immediate implications for disease classification and diagnosis. (labcorp.com)
  • It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF receptor family (IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g. (wikipedia.org)
  • Like other type I cytokine receptors ( 11 ), LepRb (which is required for physiologic leptin action) contains no intrinsic enzymatic activity, but associates with and activates the Janus kinase 2 (Jak2) tyrosine kinase to mediate leptin signaling. (diabetesjournals.org)
  • They are cytosolic tyrosine kinases that are specifically associated with cytokine receptors. (wikipedia.org)
  • Several distinct classes of cytokine receptors engage Jak kinases as primary effectors. (unh.edu)
  • Among type 1 receptors, Janus-activated kinase (Jak) recruitment is mediated by membrane-proximal cytoplasmic domains, which typically contain conserved box motifs. (unh.edu)
  • Tyrosine kinases of the Janus kinase (Jak) family transduce signals from the type I and type II cytokine receptors. (jimmunol.org)
  • The type I receptor (cytokine/hematopoietic growth factor receptor) family and the type II receptor (IFNR) family use Janus kinase (Jak) 3 protein tyrosine kinases and STAT transcription factors to transduce signals from the receptors to the nucleus ( 1 , 2 , 3 , 4 , 5 , 6 ). (jimmunol.org)
  • It appears to be essential for responsiveness of receptors that use this subunit, including the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. (jimmunol.org)
  • The Janus kinase family of enzymes are associated with cytokine receptors on the surface of cells. (nps.org.au)
  • The box1 domain of the erythropoietin receptor specifies Janus kinase 2 activation and functions mitogenically within an interleukin 2 beta-receptor chimera. (unh.edu)
  • It has been shown that the ectopic expression of EPOR confers EPO-dependent proliferation on an interleukin 3 (IL3)-dependent cell line, Ba/F3, whereas the IL2-dependent T cell line, CTLL-2 expressing the EPOR (T-ER), fails to proliferate in response to EPO. (biomedsearch.com)
  • Myocardial I/R can induce local myocardial inflammation, including promoting the release of various cytokines, including interleukin (IL)-17A, tumor necrosis factor-α (TNF-α) and IL-6, and promoting the activation of inflammatory cells, including neutrophils, which is one of the crucial pathophysiological processes in myocardial I/R injury ( 2 - 4 ). (spandidos-publications.com)
  • Increasing evidence has indicated that pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, have an important role in the pathological mechanisms of SAP and SAP-associated organ failure ( 2 - 4 ). (spandidos-publications.com)
  • For example, the cytokine interleukin-2 stimulates the production of T cells. (nps.org.au)
  • In 2005, a mutation located at exon 14 of the Janus Kinase gene on chromosome 9 was discovered in patients with Polycythaenia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF). (up.ac.za)
  • TG 101348 has completed a multicenter clinical Phase 1/2 trial in patients with myelofibrosis. (fiercebiotech.com)
  • JAK2 is a protein tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways and is misregulated or mutated in some myeloproliferative diseases and cancers. (jax.org)
  • These mechanisms include the nonenzymatic modification of macromolecules to form advanced glycation end products, changes in sorbitol and myoinositol metabolism, increased oxidant formation, and activation of mitogen-activated protein (MAP) kinase pathways ( 5 , 6 ). (diabetesjournals.org)
  • these are called Janus homology domain 1-7 (JH1-7). (wikidoc.org)
  • Description: In an assay using the kinase domain of the recombinant human enzyme, a biotinylated peptide substrate, and [ 33 P]ATP. (guidetopharmacology.org)
  • TM promoted glucose metabolism by increasing the levels of pyruvate kinase and hepatic glycogen. (hindawi.com)
  • Janus kinase 3 regulates renal 25-hydroxyvitamin D 1α-hydroxylase expression, calcitriol formation, and phosphate metabolism. (xenbase.org)
  • Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. (wikipedia.org)
  • Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. (uniprot.org)
  • Non-receptor tyrosine kinase involved in various processes such as cell cycle progression, apoptosis, mitotic recombination, genetic instability and histone modifications. (abcam.com)
  • A receptor tyrosine kinase that is involved in HEMATOPOIESIS. (curehunter.com)
  • NVP-BSK805 displays more than 20-fold selectivity over the other JAK family members and more than 100-fold selectivity over a panel of kinases in vitro . (aacrjournals.org)
  • Initially discovered in a PCR-based screen of kinases [1] and named ironically as "just another kinase" 1 & 2 (since they were two of a large number of new kinases discovered in the screen) JAK1 and JAK2 were ultimately published as Janus kinase 1 and Janus kinase 2. (wikidoc.org)
  • Bcr-Abl activates the Jak2 tyrosine kinase ( 2 , 5 ), a member of the Jak family. (aacrjournals.org)
  • Pulse amplitudes that decline to ∼2% or less of normal become incapable of inducing CYP2C11 expression ( Agrawal and Shapiro, 2000 ). (aspetjournals.org)
  • Fc receptor-mediated opsonization also enhances expression of costimulatory molecules such as CD40, B7-1 (CD80), and B7-2 (CD86) on the DC surface, promoting T cell activation. (nih.gov)
  • Expression of Janus Kinase 1 in vitiligo & psoriasis before and after narrow band UVB: a case-control study. (nih.gov)
  • Angiotensin-converting enzyme-2 (ACE2) is a negative regulator of the renin-angiotensin system. (ahajournals.org)
  • 8 - 11 Angiotensin-converting enzyme-2 (ACE2) is a carboxypeptidase that metabolizes angiotensin II (Ang II) to yield angiotensin 1 to 7 (Ang 1-7), essentially negatively regulating the RAS. (ahajournals.org)
  • After a cytokine binds to its receptor, an enzyme called Janus kinase (JAK) contributes to the processes within the cell to produce an immune or inflammatory response. (nps.org.au)
  • Several cytokines and growth factors that stimulate the proliferation of acute myelogenous leukemia (AML) cells transduce their signals by activating the transcription factor Janus-activated kinase 2 (JAK2). (aacrjournals.org)
  • Janus kinase 2 (JAK2) is associated with the embryonic development of normal individuals and is widely expressed in various types of cell, catalyzing the immune responses induced by cytokines ( 7 ). (spandidos-publications.com)
  • Growth factors and cytokines produced by the cells of hematopoietic origin use Jak kinases for signal transduction in both immune and nonimmune cells. (wikipedia.org)
  • These cytokines are secreted by activated T cells and macrophages that infiltrate the islets (referred to as the insulitis lesion) during the autoimmune reaction ( 2 ). (jimmunol.org)
  • Furthermore, chromosomal translocations that involve the JAK2 kinase, such as the t(9;12) TEL-JAK2 fusion in rare cases of T-cell acute lymphoblastic leukemia, can also cause constitutive kinase activation ( 13 ). (aacrjournals.org)
  • Up-Regulation of the Large-Conductance Ca2+-Activated K+ Channel by Glycogen Synthase Kinase GSK3β. (xenbase.org)
  • by Lithium Sensitive Glycogen Synthase Kinase GSK3ß. (xenbase.org)
  • SLC6A8) by Glycogen Synthase Kinase GSK3ß. (xenbase.org)
  • One domain exhibits the kinase activity, while the other negatively regulates the kinase activity of the first. (wikipedia.org)
  • One of the basic underlying mechanisms of diabetic nephropathy seems to involve high glucose (HG)-induced production of transforming growth factor-β (TGF-β) and extracellular matrix molecules such as fibronectin ( 1 , 2 ). (diabetesjournals.org)
  • Glomerular mesangial cells (GMCs) cultured under HG conditions produce TGF-β and extracellular matrix molecules at a significantly faster rate than those cultured under normal glucose (NG) conditions ( 1 , 2 ). (diabetesjournals.org)
  • Epo-R, Tpo-R, GH-R, PRL-R). The distinguishing feature between janus kinase 2 and other JAK kinases is the lack of Src homology binding domains (SH2/SH3) and the presence of up to seven JAK homology domains (JH1-JH7). (wikipedia.org)
  • OBJECTIVE: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity. (bireme.br)
  • Janus kinase 2 influences growth hormone receptor metalloproteolysis. (semanticscholar.org)
  • Janus kinase 2 enhances the stability of the mature growth hormone receptor. (semanticscholar.org)