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
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
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
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
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
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
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
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)

There are several types of MPDs, including:

1. Polycythemia vera (PV): This is a rare disorder characterized by an overproduction of red blood cells, white blood cells, and platelets.
2. Essential thrombocythemia (ET): This is a rare disorder characterized by an overproduction of platelets.
3. Primary myelofibrosis (PMF): This is a rare and severe disorder characterized by the accumulation of scar tissue in the bone marrow, leading to an overproduction of immature white blood cells.
4. Chronic myelogenous leukemia (CML): This is a type of cancer that affects the bone marrow and blood cells, characterized by the overproduction of immature white blood cells.

The symptoms of MPDs can vary depending on the specific disorder, but may include:

* Fatigue
* Weakness
* Shortness of breath
* Headaches
* Dizziness
* Pale skin
* Easy bruising or bleeding
* Swollen spleen
* Bone pain

The exact cause of MPDs is not known, but they are thought to be due to genetic mutations that occur in the bone marrow cells. Treatment options for MPDs include:

* Chemotherapy: This is a type of drug that kills cancer cells.
* Radiation therapy: This is a type of treatment that uses high-energy X-rays to kill cancer cells.
* Stem cell transplantation: This is a procedure in which healthy stem cells are transplanted into the body to replace damaged or diseased bone marrow cells.

Overall, MPDs are rare and complex disorders that can have a significant impact on quality of life. While there is no cure for these conditions, treatment options are available to help manage symptoms and improve outcomes.

PMF is a chronic disease that worsens over time, and it can lead to complications such as bleeding, infection, and bone damage. Treatment options include medications to reduce symptoms and slow the progression of the disease, as well as blood transfusions and splenectomy (removal of the spleen) in severe cases. The median age at diagnosis is around 60 years old, and the disease affects approximately 2-5 cases per million people per year.


* American Cancer Society. (2019). What is primary myelofibrosis? Retrieved from
* Leukemia and Lymphoma Society. (n.d.). Primary Myelofibrosis. Retrieved from

The exact cause of polycythemia vera is not known, but it is believed to be due to a genetic mutation in the JAK2 gene, which is involved in the signaling pathways that regulate blood cell production. The condition typically affects adults over the age of 60 and is more common in men than women.

Symptoms of polycythemia vera can include:

* Fatigue
* Weakness
* Shortness of breath
* Headaches
* Dizziness
* Itching
* Night sweats
* Weight loss

Diagnosis of polycythemia vera is typically made based on a combination of physical examination, medical history, and laboratory tests, including:

* Complete blood count (CBC) to measure the levels of red blood cells, white blood cells, and platelets
* Blood chemistry tests to assess liver function and other body chemicals
* Genetic testing to look for the JAK2 mutation
* Bone marrow biopsy to examine the bone marrow tissue for abnormalities

Treatment for polycythemia vera usually involves phlebotomy (the removal of blood from the body) to reduce the number of red blood cells and relieve symptoms such as itching and night sweats. In some cases, medications may be used to reduce the production of blood cells or to treat specific symptoms. Regular monitoring by a healthcare provider is important to detect any changes in the condition and to prevent complications.

Overall, polycythemia vera is a chronic and progressive disease that can have significant impact on quality of life if left untreated. Early diagnosis and appropriate treatment can help manage symptoms and improve outcomes for patients with this condition.

1. Primary essential thrombocythemia (PET): This is the more common form, usually occurring spontaneously without any identifiable cause. Symptoms may include headache, migraine, seizures, and stroke-like episodes.
2. Secondary essential thrombocythemia: This form is caused by another medical condition or medication that stimulates the production of platelets. Symptoms are similar to those of PET, but there may be an underlying cause such as a tumor or an adverse reaction to medication.

Treatment for essential thrombocythemia includes medications to reduce platelet count and prevent blood clots, as well as close monitoring and management of any underlying causes. In some cases, surgery may be necessary to remove a tumor or other contributing factor.

Explanation: Neoplastic cell transformation is a complex process that involves multiple steps and can occur as a result of genetic mutations, environmental factors, or a combination of both. The process typically begins with a series of subtle changes in the DNA of individual cells, which can lead to the loss of normal cellular functions and the acquisition of abnormal growth and reproduction patterns.

Over time, these transformed cells can accumulate further mutations that allow them to survive and proliferate despite adverse conditions. As the transformed cells continue to divide and grow, they can eventually form a tumor, which is a mass of abnormal cells that can invade and damage surrounding tissues.

In some cases, cancer cells can also break away from the primary tumor and travel through the bloodstream or lymphatic system to other parts of the body, where they can establish new tumors. This process, known as metastasis, is a major cause of death in many types of cancer.

It's worth noting that not all transformed cells will become cancerous. Some forms of cellular transformation, such as those that occur during embryonic development or tissue regeneration, are normal and necessary for the proper functioning of the body. However, when these transformations occur in adult tissues, they can be a sign of cancer.

See also: Cancer, Tumor

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1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.

2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.

3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.

4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.

5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.

6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.

7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.

8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.

9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.

10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.

The term splenomegaly is used to describe any condition that results in an increase in the size of the spleen, regardless of the underlying cause. This can be caused by a variety of factors, such as infection, inflammation, cancer, or genetic disorders.

Splenomegaly can be diagnosed through a physical examination, where the doctor may feel the enlarged spleen during an abdominal palpation. Imaging tests, such as ultrasound, computed tomography (CT) scans, or magnetic resonance imaging (MRI), may also be used to confirm the diagnosis and evaluate the extent of the splenomegaly.

Treatment for splenomegaly depends on the underlying cause. For example, infections such as malaria or mononucleosis are treated with antibiotics, while cancerous conditions may require surgical intervention or chemotherapy. In some cases, the spleen may need to be removed, a procedure known as splenectomy.

In conclusion, splenomegaly is an abnormal enlargement of the spleen that can be caused by various factors and requires prompt medical attention for proper diagnosis and treatment.

There are different types of Breast Neoplasms such as:

1. Fibroadenomas: These are benign tumors that are made up of glandular and fibrous tissues. They are usually small and round, with a smooth surface, and can be moved easily under the skin.

2. Cysts: These are fluid-filled sacs that can develop in both breast tissue and milk ducts. They are usually benign and can disappear on their own or be drained surgically.

3. Ductal Carcinoma In Situ (DCIS): This is a precancerous condition where abnormal cells grow inside the milk ducts. If left untreated, it can progress to invasive breast cancer.

4. Invasive Ductal Carcinoma (IDC): This is the most common type of breast cancer and starts in the milk ducts but grows out of them and invades surrounding tissue.

5. Invasive Lobular Carcinoma (ILC): It originates in the milk-producing glands (lobules) and grows out of them, invading nearby tissue.

Breast Neoplasms can cause various symptoms such as a lump or thickening in the breast or underarm area, skin changes like redness or dimpling, change in size or shape of one or both breasts, discharge from the nipple, and changes in the texture or color of the skin.

Treatment options for Breast Neoplasms may include surgery such as lumpectomy, mastectomy, or breast-conserving surgery, radiation therapy which uses high-energy beams to kill cancer cells, chemotherapy using drugs to kill cancer cells, targeted therapy which uses drugs or other substances to identify and attack cancer cells while minimizing harm to normal cells, hormone therapy, immunotherapy, and clinical trials.

It is important to note that not all Breast Neoplasms are cancerous; some are benign (non-cancerous) tumors that do not spread or grow.

... 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 ... Janus+Kinase+2 at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology (All articles with dead ...
... 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, ...
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] Kumar PJ, Clark ML (2005). "8". Clinical Medicine ...
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. ...
Hence drugs that inhibit the activity of these Janus kinases block cytokine signalling. More specifically, Janus kinases ... A Janus kinase inhibitor, also known as JAK inhibitor or jakinib, is a type of immune modulating medication, which inhibits the ... Janus kinase inhibitors can be classed in several overlapping classes: they are immunomodulators, they are DMARDs (disease- ... "Janus Kinase inhibitors (JAKi)". European Medicines Agency (EMA). 28 October 2022. Retrieved 28 October 2022. Furumoto Y, ...
A mutation in the JAK2 kinase (V617F) is strongly associated with polycythemia vera. JAK2 is a member of the Janus kinase ... Ruxolitinib, a Janus kinase 2 (JAK2) inhibitor, is also used to treat polycythemia. Ropeginterferon alfa-2b (Besremi) was ... PCV cells often carry activating mutation in the tyrosine kinase (JAK2) gene, which acts in signaling pathways of the EPO- ... "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders". Lancet. 365 (9464): 1054-61. doi:10.1016/ ...
... is a janus kinase inhibitor.It was developed and marketed by Incyte Corp in the US under the brand name Jakafi, and ... Ruxolitinib 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 ... It is the first topical janus kinase inhibitor approved in the United States. In July 2022, ruxolitinib cream (sold under the ...
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: ELP2, GNB2L1 IL6ST, Grb2, IL2RB, IRS1, IL10RA, PTPN11, STAM2, STAT3, STAT5A, ... Janus+Kinase+1 at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology (Genes on human ... 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 (1996). "Involvement of Janus kinases in the insulin signaling pathway ...
Janus kinase 2 and Tyrosine kinase 2 transduce the signal and phosphorylate STAT3 and STAT4. STATs dimerise and activate ... Receptor binding leads to recruitment of Janus kinase 2 and Tyrosine kinase 2 kinases. ... Adnectin-2 binds to IL-23 and competes with IL-23-IL-23R binding. The IL-23 heterodimer binds the receptor complex: the p19 ... 135 (2): 112-24. doi:10.1111/j.1365-2567.2011.03522.x. PMC 3277713. PMID 22044352. Zeng B, Shi S, Ashworth G, Dong C, Liu J, ...
... 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 ...
... 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 ...
... s work by inhibiting the action of the enzyme Janus kinase 3, so they interfere with the JAK-STAT ... Janus kinase 3 inhibitors, also called JAK3 inhibitors, are a new class of immunomodulatory agents that inhibit Janus kinase 3 ... "Identification of a potent Janus kinase 3 inhibitor with high selectivity within the Janus kinase family". Journal of Medicinal ... The Janus kinases are a family of four nonreceptor tyrosine-protein kinases, JAK1, JAK2, JAK3, and TYK2. They signal via the ...
... 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. ...
It is a macrocyclic protein kinase inhibitor. It mainly inhibits Janus kinase 2 (JAK2) and Fms-like tyrosine kinase 3\CD135 ( ... Non-receptor tyrosine kinase inhibitors, Orphan drugs, Pyrrolidines, Oxygen heterocycles, Nitrogen heterocycles, All stub ...
... 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 ...
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, ...
It acts as a highly selective allosteric inhibitor of non-receptor tyrosine-protein kinase 2 (TYK2). The chemical structure of ... October 2021). "Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 ... Non-receptor tyrosine kinase inhibitors, Triazoles, Cyclopropyl compounds, Pyridazines, Methoxy compounds, Carboxamides, All ...
"Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors". ... 2 April 2015. "Deudextromethorphan". AdisInsight. Retrieved 16 February 2017. Garde D (February 13, 2014). "Biotech IPOs roll ...
... 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 ...
... 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. S2CID 5419679. Voskarides, Konstantinos; Deltas, ...
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. Antiviral and ... Production of protein kinase R, for example, can be disrupted in cells infected with JEV. Some viruses escape the anti-viral ... The phosphatidylinositol 3-kinase (PI3K) signaling pathway is also regulated by both type I and type II IFNs. PI3K activates ...
... has been shown to interact with Janus kinase 3 and TRIB3. "Human PubMed Reference:". National Center for Biotechnology ... 6 (2): 97-105. doi:10.1038/ncb1086. PMID 14743216. S2CID 11683986. Schultz L, Khera S, Sleve D, Heath J, Chang NS (January 2004 ... "A novel protein MAJN binds to Jak3 and inhibits apoptosis induced by IL-2 deprival". Biochemical and Biophysical Research ... "A novel protein MAJN binds to Jak3 and inhibits apoptosis induced by IL-2 deprival". Biochemical and Biophysical Research ...
It (they) regulates signaling by: a) inhibiting the STAT3-Janus kinase pathway to block cellular pro-inflammatory responses; b ... 15-deoxy-Δ12,14-PGJ2 forms an adduct with the IKK-β subunit of IκB kinase thereby inhibiting the kinases activity thereby ... IKK-β subunit of IκB kinase: IκB serves to retain NFκB in the cell cytoplasm thereby inhibiting it from entering the nucleus ... 15-PGJ2 to inhibit the Phosphoinositide 3-kinase pathway of cell signaling. The direct injection of 15-d-Δ12,14-PGJ2 into the ...
Janus kinases are another notable example of drug enzyme targets. Inhibitors of Janus kinases block the production of ... Protein kinases can also be inhibited by competition at the binding sites where the kinases interact with their substrate ... A notable class of kinase drug targets is the receptor tyrosine kinases which are essential enzymes that regulate cell growth; ... As a consequence, if two protein kinase inhibitors both bind in the active site with similar affinity, but only one has to ...
Branscombe TL, Frankel A, Lee JH, Cook JR, Yang Z, Pestka S, Clarke S (August 2001). "PRMT5 (Janus kinase-binding protein 1) ... 74 (2): 137-49. doi:10.1016/0022-2836(73)90103-4. PMID 4689953. Chen F, Kan H, Castranova V (2010). "Methylation of Lysine 9 of ... 182 (2): 437-46. doi:10.1534/genetics.109.101899. PMC 2691753. PMID 19332880. GeneReviews/NCBI/NIH/UW entry on Kleefstra ... doi:10.1016/S0065-3233(04)67008-2. ISBN 0-12-034267-7. PMID 14969729. Sawan C, Herceg Z (2010). "Histone Modifications and ...
The reception of IFNγ activates Janus kinase 1, resulting in the stimulation of its association with Sxn8 above standard ... by allowing its association with the class III phosphatylinositol 3 kinase VPS34-containing translocon machinery to form the ... 1 (2): 191-198. PMC 3560458. PMID 22984654. Richards, Elliott G.; Zaveri, Hitisha P.; Wolf, Varina L.; Kang, Sung-Hae Lee; ... SNX8 acts as an adaptor or scaffolding protein by permitting the recruitment of the inhibitor of nuclear factor-kappa-B kinase ...
STAT proteins are activated by the Janus family (JAKs) tyrosine kinases in response to cytokine exposure. STAT6 is activated by ... 285 (1-2): 1-24. doi:10.1016/S0378-1119(02)00398-0. PMID 12039028. Hou J, Schindler U, Henzel WJ, Ho TC, Brasseur M, McKnight ... 2 (4): e25301. doi:10.4161/jkst.25301. PMC 3876430. PMID 24416647. Leek JP, Hamlin PJ, Bell SM, Lench NJ (1997). "Assignment of ... 32 (2): 969-978. doi:10.1096/fj.201700629R. ISSN 0892-6638. PMID 29066614. S2CID 3342014. Gong M, Zhuo X, Ma A (June 2017). " ...
Girault JA, Labesse G, Mornon JP, Callebaut I (December 1998). "Janus kinases and focal adhesion kinases play in the 4.1 band: ... Phosphorylation of the activation loop within this kinase domain is important for the kinase activity of FAK. FAK mRNA levels ... Lineage for Protein: Focal adhesion kinase 1 Q00944 "Entrez Gene: PTK2 PTK2 protein tyrosine kinase 2". Guan JL, Shalloway D ( ... "A scaffold protein in the c-Jun N-terminal kinase signaling pathway is associated with focal adhesion kinase and tyrosine- ...
Janus kinase 1, TNF-a, interleukin-6, heparin-binding growth factor-like growth factor, intracellular adhesion molecule 1, NF- ... c-src kinase, tyrosine kinase 2 mitogen-activated protein kinase kinase, tyrosine kinase 2, c-jun, JNK1, ... 3.0.CO;2-I. PMID 10751088. Ariel I, Lustig O, Schneider T, Pizov G, Sappir M, De-Groot N, Hochberg A (February 1995). "The ... 3.0.CO;2-B. PMID 9219849. Mirisola V, Mora R, Esposito AI, Guastini L, Tabacchiera F, Paleari L, Amaro A, Angelini G, ...
Isolated IgA deficiency Isolated primary IgM deficiency Janus kinase 3 deficiency Leukocyte adhesion molecule deficiency LIG4 ... 105 (2): 99-106, quiz 107-9, 117. doi:10.1016/j.anai.2009.10.002. PMID 20674819. Saint-Mezard P, Rosieres A, Krasteva M, et al ... 184 (1-2): 16-20. doi:10.1016/j.cbi.2009.10.009. PMID 19857474. Dempsey OJ, Paterson EW, Kerr KM, Denison AR (2009). " ... 44 (2): 144-9. doi:10.1515/CCLM.2006.027. PMID 16475898. S2CID 24967692. James, William D; et al. (2006). Andrews' Diseases of ...
In some instances, in epithelial-derived cells and cancer cell lines, this permits gp130-associated Janus kinases (JAK) ... 373 (2): 156-63. doi:10.1016/j.canlet.2016.01.004. PMID 26826523. Sims NA, Jenkins BJ, Nakamura A, Quinn JM, Li R, Gillespie MT ... 265 (2): 645-55. doi:10.1046/j.1432-1327.1999.00755.x. PMID 10504396. Mahboubi K, Biedermann BC, Carroll JM, Pober JS (April ... 283 (2): 199-202. doi:10.1016/0014-5793(91)80587-S. PMID 1828438. S2CID 1385397. Schafer S, Viswanathan S, Widjaja AA, Lim WW, ...
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. ... The 2 polypeptides differ by the presence or absence of 3 amino acids. Expression studies indicate that both have authentic ... "AXIS 2: AX200 for the Treatment of Ischemic Stroke - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Zhang Y, Wang L ...
Janus kinases (JAKs) and Signal Transducers and Activators of Transcription (STATs). IL-6 is probably the best-studied of the ... IL-6 activates the Phosphoinositide 3-kinase (PI3K) pathway, and a downstream target of this pathway is the protein kinase B ( ... At the cellular level, SP is noted to increase expression of interleukin-6 (IL-6) through PI-3K, p42/44 and p38 MAP kinase ... via phosphorylation of the nuclear localization sequence by the AKT kinase". Cancer Genomics & Proteomics. 4 (6): 387-398. PMID ...
JAK3 (Janus kinase 3) deficiency is a dysfunction in cytokine receptor signalling and their production of cytokines. JAK3 is a ... "Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell ... It is a kinase that is activated only by cytokines whose receptors contain the common gamma chain subunit (IL-2, IL-4, IL-7, IL ... The JAK3 tyrosine kinase is mutated in 10% to 16% of T-cell acute lymphoblastic leukemia (T-ALL) cases. Patients with JAK3- ...
... the common gamma subunit activates Janus Kinase 3 (JAK3), which leads to the phosphorylation of Signal Transducer and Activator ... Specifically, Interleukin 2 and Interleukin 7 are responsible for T-cell proliferation and survival. Likewise, the action of ... The most important receptors for X-SCID are those for Interleukin 2, Interleukin 4, Interleukin 7, and Interleukin 15. ... which is a cytokine receptor sub-unit that is part of the receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. People with X- ...
This family also includes Abl, Src, focal adhesion kinase and Janus kinase.) Fyn is located downstream of several cell surface ... Fyn is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been ... Janus kinase 2, KHDRBS1, Lck, LKB1, Nephrin, PAG1, PIK3R2, PRKCQ, PTK2B, PTK2, PTPRT UNC119, RICS, SH2D1A, SKAP1, Syk, TNK2, ... a kinase-inactive, dominant negative mutant form of Fyn (K299M); pharmacologic inhibitors of Src family kinases, such as PP2; ...
Stegmayr B, Brody I, Ronquist G (February 1982). "A biochemical and ultrastructural study on the endogenous protein kinase ... Ronquist G, Nilsson BO (2004). "The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive ... 30 (2): 98-106. doi:10.1002/(SICI)1097-0045(19970201)30:2. 3.0.CO;2-G. PMID 9051148. Arienti G, Carlini E, De Cosmo AM, Di ... 3.0.CO;2-D. PMID 9582086. Arienti G, Carlini E, Verdacchi R, Cosmi EV, Palmerini CA (October 1997). "Prostasome to sperm ...
The canonical pathway involves Janus kinase-signal transducer and activator of transcription-interferon regulatory factor (JAK- ... The noncanonical signaling pathway includes mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase thymoma ... 92 (2): 47. doi:10.1095/biolreprod.114.124156. PMID 25505203. Spencer TE, Ott TL, Bazer FW (May 1998). "Expression of ... doi:10.1016/b978-0-12-385157-4.00182-2. ISBN 978-0-12-385158-1. Choi Y, Johnson GA, Burghardt RC, Berghman LR, Joyce MM, Taylor ...
IL-13 and IL-31 which activate downstream Janus kinase (Jak) pathways. The active Jak pathways lead to inflammation and ... 21 (2): 59-61. doi:10.1111/j.1600-0781.2005.00141.x. ISSN 0905-4383. Gu S, Yang AW, Xue CC, Li CG, Pang C, Zhang W, Williams HC ... Retrieved 2 April 2015. Bao L, Shi VY, Chan LS (February 2013). "IL-4 up-regulates epidermal chemotactic, angiogenic, and pro- ... 70 (2): 338-51. doi:10.1016/j.jaad.2013.10.010. PMC 4410183. PMID 24290431. Brenninkmeijer EE, Schram ME, Leeflang MM, Bos JD, ...
Treatment with an inhibitor of the Janus kinase (JAK). This has been shown in vitro. Treatment with an inhibitor of the p38 MAP ... Using cultures of mouse neural stem cells, notch activation was shown to lead to the phosphorylation of several kinases (PI3K, ... An individual signal transduction pathway can regulate several proteins (e.g. kinases) as well as the activation of many genes ... kinase kinase. This has been shown in vitro. Treatment with cholera toxin. This has been shown in vitro. This particular ...
The JAK Janus kinase proteins on the cytoplasmic end of the receptors allows for the phosphorylation of STAT6, which then forms ... 2 (4): e25301. doi:10.4161/jkst.25301. PMC 3876430. PMID 24416647. Tu M, Wange W, Cai L, Zhu P, Gao Z, Zheng W (2016). "IL-13 ... IL-13 is a cytokine secreted by T helper type 2 (Th2) cells, CD4 cells, natural killer T cell, mast cells, basophils, ... IL-13 has been shown to induce a potent fibrogenic program during the course of diverse diseases marked by elevated Type 2 ...
... inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain". Genes Cells. ... inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain". Genes Cells. ... The SOCS3 protein can bind to JAK2 kinase, and inhibits the activity of JAK2 kinase. SOCS3 has been shown to interact with: ... Janus kinase 2, PTPN11, and RAS p21 protein activator 1. There is some evidence that the expression of SOCS3 is regulated by ...
It is an inhibitor of the kinases fms-like tyrosine kinase 3 (FLT3), Janus kinase 2 (JAK2), tropomyosin receptor kinase (trk) A ... Janus kinase inhibitor Shabbir M, Stuart R (2010). "Lestaurtinib, a multitargeted tyrosinse kinase inhibitor: from bench to ... Non-receptor tyrosine kinase inhibitors, Receptor tyrosine kinase inhibitors). ... Lestaurtinib was identified early on as a trk receptor tyrosine kinase (RTK) inhibitor, with a concentration inhibiting 50% of ...
There are some signaling pathways, such as LIF/JAK/STAT3 (Leukemia inhibitory factor/Janus kinase/Signal transducer and ... Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase) regulates gene transcription through successive kinase ... STAT (Signal Trandsducer and Activator of Transcription) is phosphorylated by JAK (Janus Kinase) and regulates gene ... Protein Kinase B). This kinase is involved in cell survival and inhibition of apoptosis, cellular growth and maintenance of ...
Janus tyrosine kinases (JAKs), cytoplasmic tyrosine kinases that are non-covalently associated with the cytoplasmic tails of ... Focal-adhesion kinases (FAKs), cytoplasmic protein tyrosine kinases involved in signalling through integrins. ... Non-receptor tyrosine-protein kinase TYK2. Protein-tyrosine phosphatases PTPN3 and PTPN4, enzymes that appear to act at ... 23 (8): 281-2. doi:10.1016/S0968-0004(98)01237-7. PMID 9757824. Pearson MA, Reczek D, Bretscher A, Karplus PA (April 2000). " ...
Janus kinase inhibitor tofacitinib is approved for the treatment of active ankylosing spondylitis in adult patients that show ... 1-2% of individuals with the HLA-B27 genotype develop the disease. Tumor necrosis factor-alpha (TNF α) and Interleukin 1 (IL-1 ... naproxen and COX-2 inhibitors, which reduce inflammation and pain. 2012 research showed that those with AS and elevated levels ... 2) insidious onset, (3) improvement with exercise, (4) no improvement with rest, and (5) pain at night (with improvement upon ...
Mutations in Janus kinase-2 (JAK2) occur in approximately 50% of patients. The only approved JAK2 inhibitor for myelofibrosis ... Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single- ... Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single- ... Claire N Harrison 1 , Nicolaas Schaap 2 , Alessandro M Vannucchi 3 , Jean-Jacques Kiladjian 4 , Ramon V Tiu 5 , Pierre Zachee 6 ...
Janus Kinase Inhibitors for Moderate to Severe COVID-19 Number of pages: 14 Posted: 09 Jun 2020 ...
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 ...
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 ...
7Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Changelian PS, Flanagan ME, Ball DJ, Kent CR, ... Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2. Johnston JA, Kawamura M, Kirken RA, Chen ... Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes. ... Unexpected effects of FERM domain mutations on catalytic activity of Jak3: structural implication for Janus kinases. Zhou YJ, ...
Our group has done extensive pre-clinical work with janus-kinase (JAK 1/2) inhibitors. This includes baricitinib, which is an ... In the ensuing 2 months, the investigators will make refinements based on participants data to produce LetSync v2.0. Then, ... Aim 2: Explore experiences of YLWH and staff/providers with the aDOT-CEI intervention and implementation facilitators and ... The 2 represents the level of each component:0 (receive) or (dont receive) four components: 1) Financial Literacy Training ( ...
RESULTS: Compounds targeting Janus kinase 2 (JAK2) were over-represented among HTS hits. Phosphomotif scans supported by mass ... Protein Kinase Inhibitors/analysis; Protein Kinase Inhibitors/chemistry; Protein Kinase Inhibitors/pharmacology; Protein ... Janus Kinase 2/metabolism*; Mice, Inbred C57BL; NAV1.6 Voltage-Gated Sodium Channel/metabolism*; Phosphorylation/drug effects; ... Regulation by top kinase targets was then explored using in vitro phosphorylation, biophysics, mass-spectrometry and patch- ...
Overexpression of Janus kinase 2 protein in extramammary Pagets disease.. Otsuka-Maeda S; Mijiddorj MT; Kajihara I; Sakamoto R ... 8. A rapidly expanding cutaneous tumour in the context of a Janus kinase inhibitor agent following allogeneic stem cell ... Kinase Inhibition as Treatment for Acute and Chronic Graft-. Braun LM; Zeiser R. Front Immunol; 2021; 12():760199. PubMed ID: ... Dual jak2/Aurora kinase A inhibition prevents human skin graft rejection by allo-inactivation and ILC2-mediated tissue repair. ...
Janus kinase-2 inhibition induces durable tolerance to alloantigen by human dendritic cell-stimulated T cells yet preserves ... Receptor Tyrosine Kinases and TLR/IL1Rs Unexpectedly Activate Myeloid Cell PI3Kγ, A Single Convergent Point Promoting Tumor ... Blockade of Phosphatidylinositol 3-Kinase (PI3K)δ or PI3Kγ Reduces IL-17 and Ameliorates Imiquimod-Induced Psoriasis-like ... Trusolino L, Bertotti A. Compensatory Pathways in Oncogenic Kinase Signaling and Resistance to Targeted Therapies: Six Degrees ...
Regarding kinase inhibitors (used by cases-patients 3 and 4), ruxolitinib is a selective Janus kinase (JAK)-1/2 inhibitor that ... An opportunistic infection associated with ruxolitinib, a novel janus kinase 1,2 inhibitor. Chest. 2013;143:1478-9. DOIPubMed ... Disseminated Infections with Talaromyces marneffei in Non-AIDS Patients Given Monoclonal Antibodies against CD20 and Kinase ... He had been given sorafenib (kinase inhibitor) 8 months earlier for chemotherapy-refractory acute myeloid leukemia (Table 1). ...
Protein-Tyrosine Kinases [D12.776.476.568] * Janus Kinases [D12.776.476.568.124] * Janus Kinase 1 [D12.776.476.568.124.100] ... Protein-Tyrosine Kinases [D08.811.913.696.620.682.725] * Janus Kinases [D08.811.913.696.620.682.725.124] * Janus Kinase 1 [ ... JAK2 Protein Tyrosine Kinase Registry Number. EC See Also. src Homology Domains. Public MeSH Note. 2007; JANUS KINASE ... Janus Kinase 2 Preferred Concept UI. M0203030. Registry Number. EC Scope Note. A Janus kinase subtype that is ...
Fedratinib is an oral kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 ( ... Another Janus Kinase (JAK)-inhibitor has increased the risk of MACE, including cardiovascular death, myocardial infarction, and ... INREBIC is a kinase inhibitor indicated for the treatment of adult patients with intermediate-2 or high-risk primary or ... INREBIC (fedratinib) is a kinase inhibitor with the chemical name N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy) ...
Emodin has a cytotoxic activity against human multiple myeloma as a Janus-activated kinase 2 inhibitor. Mol Cancer Ther 6(3): ... Table 2 The IC50 values (μmol/L) of EMO and CSO-SA/EMO against gastric cancer cells. Full size table. ... a protein-tyrosine kinase inhibitor. Biochem Biophys Res Commun 193(3):1152-1158 ... 2. In vitro cellular time-dependent uptake of CSO-SA micelles in MGC803 (a) and BGC823 (b) cells for 1, 4, 8, 12 h, ...
Janus kinase 2 is involved in lipopolysaccharide-induced activation of macrophages. Am. J. Physiol. Cell Physiol. ... Janus kinase 2 is involved in lipopolysaccharide-induced activation of macrophages. Am. J. Physiol. Cell Physiol. ... Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell. ... Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell. ...
... protein kinase cAMP-dependent (PKA)/adenosine monophosphate activated protein kinase (AMPK) pathway, against high-fat-diet- ... and mitogen-activated protein kinases (MAPKs)/c-jun N-terminal kinase (JNK) signaling pathways involved in pro-inflammatory ... eventually resulting in metabolic syndrome or overt type 2 diabetes. In this paper, we review the anti-inflammatory effects of ... via its receptor-associated Janus kinases (JAK)-1/2, form dimers and translocate to the nucleus where they bind to specific ...
... molecules including Janus kinase 2 (JAK2), and the signal transducer and activator of transcription (STAT5). In addition, EPO ... can activate the phosphoinositide 3-kinase/Akt pathway, protein kinase C isoforms, and the Ras-Raf-Mek pathway. It was ... 2. Cost Sharing or Matching This program does not require cost sharing as defined in the current NIH Grants Policy Statement.. ... and PI3-kinase/Akt pathways in small cell lung carcinoma cell lines. ...
... binds to receptors that associate with a class of protein tyrosine kinases termed Janus Kinases or JAKs (illustrated in Figure ... Janus kinases to jakinibs: from basic insights to clinical practice. Gadina M, Le MT, Schwartz DM, Silvennoinen O, Nakayamada S ... The NIH holds patents pertaining to Janus Kinases and identification of immune modulators (United States patents 7,070,972 and ... Protein kinases: drug targets for immunological disorders. Castelo-Soccio L, Kim H, Gadina M, Schwartzberg PL, Laurence A, ...
... which involve the Janus kinase 2 (JAK2) gene, are identified in almost all people with PV. JAK2 mutations are thought to ... Friday , 8:30am - 2:30pm. For medical advice after hours, call 402.484.4900 and leave a message with our answering service. The ... PV typically involves a high concentration of red blood cells and the presence of certain gene mutations in blood cells.2 These ... 2 Tefferi A. Polycythemia vera and essential thrombocythemia: 2013 update on diagnosis, risk-stratification, and management. ...
... which belongs to the Janus kinases (JAK) family of proteins. This enzyme plays a role in triggering the production of ... The active substance in Sotyktu, deucravacitinib, blocks the action of an enzyme inside cells called tyrosine kinase 2 (TYK2) ... and had a reduction of 2 points or more in their sPGA score. Around 33% of those treated with apremilast and around 8% in those ...
1 Somatic mutations in Janus kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia protein (MPL) are regarded as ... Cytokine production in myelofibrosis exhibits differential responsiveness to JAK-STAT, MAP kinase, and NFκB signaling. Leukemia ... Figure 2.Asxl1 deletion is associated with enhanced extramedullary hematopoiesis in Asxl1-/-Jak2VF mice. (A) Hemoglobin, white ... 2, P,0.05). (D) Relative expressions of Fos, Ccl4, Egr1 and Cxcl2 mRNA were measured in Asxl1-/-Jak2VF, Jak2VF, Asxl1-/- and WT ...
He recently examined a causal SNP for inflammatory bowel disease (IBD) in the promoter region of the Janus kinase 2 (JAK2) gene ...
Janus kinase-2 (JAK2) supports breast cancer growth, and clinical trials testing JAK2 inhibitors are under way. In addition to ... the JAK1/2 inhibitor ruxolitinib potently inhibited the anti-CD3-dependent production of IFN-γ, a marker of the differentiation ... 2 × 10(-16); n = 1,981) and with severe lymphocyte infiltration (P = 0.00003, n = 156). Moreover, ...
Protein-Tyrosine Kinases [D12.776.476.568] * Janus Kinases [D12.776.476.568.124] * Janus Kinase 1 [D12.776.476.568.124.100] ... Protein-Tyrosine Kinases [D08.811.913.696.620.682.725] * Janus Kinases [D08.811.913.696.620.682.725.124] * Janus Kinase 1 [ ... JAK2 Protein Tyrosine Kinase Registry Number. EC See Also. src Homology Domains. Public MeSH Note. 2007; JANUS KINASE ... Janus Kinase 2 Preferred Concept UI. M0203030. Registry Number. EC Scope Note. A Janus kinase subtype that is ...
19] Gual P, Baron V, Lequoy V, Van Obberghen E. Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the ... First, Ras binds to Raf (mitogen-activated protein kinase kinase kinase, MAPKKK), which in turn binds to and phosphorylates MEK ... MEK (mitogen-activated protein kinase kinase, MAPKK), is a dual specificity kinase that phosphoryles ERK at two residues ( ... stress activated protein kinases (SAPKs), such as the c-Jun N-terminal kinase (JNK) and the p38 MAPK [55], are kinases ...
Janus Kinase (JAK) 1 and 2 were required for STAT3 activation in these glioma stem-like cells, as was Vascular Endothelial ... 2. Methods and Materials 2.1. Cell Lines and Lifestyle HT-29, SW480, SW620 and HCT116 cancer of the colon cells were extracted ... 2.?Androgens An androgen is known as any molecule capable of inducing and maintaining the male phenotype in an organism (male ... Cells were washed with DPBS and resuspended in 1 twice.2 mL of glaciers frosty DPBS in polypropylene stream cytometry pipes. ...
The Janus kinase 2 (V617F) mutation was absent. Abdominal computed tomography scan showed a 8-mm left adrenal pheochromocytoma ... BACKGROUND: Mutations of genes related to Krebs cycle enzymes, kinases or to pseudohypoxic signaling pathways, including Von- ... tyrosine kinase inhibitors, immunomodulators, mammalian target of rapamycin), can induce SIADH-related hyponatremia and, less ... receptor and mechanistically involves protein kinase C (PKC), which can be substantially rescued by either valsartan (AT 1 ...
  • In 2005, researchers discovered a mutation in the Janus Tyrosine Kinase 2 gene (JAK2 (V617F)), which plays a pivotal role in the regulation of blood cell production (Levine et al. (cdc.gov)
  • He recently examined a causal SNP for inflammatory bowel disease (IBD) in the promoter region of the Janus kinase 2 (JAK2) gene. (chop.edu)
  • Activating alleles of Janus kinase 2 (JAK2) such as JAK2 V617F are central to the pathogenesis of myeloproliferative neoplasms (MPN), suggesting that small molecule inhibitors targeting JAK2 may be therapeutically useful. (elsevierpure.com)
  • We have identified an aminopyrimidine derivative (CYT387), which inhibits JAK1, JAK2, and tyrosine kinase 2 (TYK2) at low nanomolar concentrations, with few additional targets. (elsevierpure.com)
  • While the clinical benefit of JAK2 inhibitors may be substantial, not the least due to reduction of inflammatory cytokines and symptomatic improvement, our data add to increasing evidence that kinase inhibitor monotherapy of malignant disease is not curative, suggesting a need for drug combinations to optimally target the malignant cells. (elsevierpure.com)
  • Janus kinase 2 (JAK2) methylation and obesity: A Mendelian randomization study. (cdc.gov)
  • Polycythemia vera (PV) as a primary condition is a type of clonal disorder of bone marrow stem cells which is often caused by a mutation in exon 12 of the janus kinase 2 ( JAK2 ) tyrosine kinase gene [ 4 , 5 ]. (biomedcentral.com)
  • Increased secretion of both GH and IGF-1 activates pathways, such as Janus kinase 2/signal transducer and activator of transcription 5 (JAK2/STAT5), and mitogen-activated protein kinase (MAPK), involved in the development of tumors. (bvsalud.org)
  • It is an oral kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). (mpn-advocates.net)
  • The intact receptor lacks tyrosine kinase activity, but binding of GH and dimerization results in association with JAK2, a member of the Janus kinase family, which results in self-phosphorylation of the JAK2 and a cascade of phosphorylation of cellular proteins. (medscape.com)
  • We report disseminated T. marneffei infection in 4 hematology patients without AIDS who received targeted therapy with monoclonal antibodies against CD20 or kinase inhibitors during the past 2 years. (cdc.gov)
  • Oral Janus kinase inhibitors are known to be effective treating hypereosinophilic syndrome. (biomedcentral.com)
  • Janus kinase inhibitors have also demonstrated efficacy in alopecia. (biomedcentral.com)
  • This study demonstrates that longer eyelashes may be another effect of oral Janus kinase inhibitors. (biomedcentral.com)
  • Physicians and patients should be aware of the side effect of these Janus kinase inhibitors. (biomedcentral.com)
  • Las Vega (Nevada), United States //- As per DelveInsight's assessment, globally, Janus kinase (JAK) Inhibitors pipeline constitutes key companies continuously working towards developing Janus kinase (JAK) Inhibitors treatment therapies, analysis of Clinical Trials, Therapies, Mechanism of Action, Route of Administration, and Developments analyzes DelveInsight. (saurashtranews.com)
  • Janus kinase (JAK) inhibitors are small molecules approximately 400 Da that could be administered as oral medicines. (saurashtranews.com)
  • " Janus kinase (JAK) Inhibitors Pipeline Insight, 2023 " report by DelveInsight outlines comprehensive insights into the present clinical development scenario and growth prospects across the Janus kinase (JAK) Inhibitors Market. (saurashtranews.com)
  • The Janus kinase (JAK) Inhibitors Pipeline report embraces in-depth commercial and clinical assessment of the pipeline products from the pre-clinical developmental phase to the marketed phase. (saurashtranews.com)
  • Companies across the globe are diligently working toward developing novel Janus kinase (JAK) Inhibitors treatment therapies with a considerable amount of success over the years. (saurashtranews.com)
  • Janus kinase (JAK) Inhibitors pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. (saurashtranews.com)
  • With an increased worldwide focus on treating axial spondyloarthritis, the major market players are developing novel therapeutics, such as anti-janus kinase therapy, anti-interleukin therapy, and anti-tumor necrosis factor therapy, which is significantly impacting the growth of axial spondyloarthritis market.Due to the introduction of tumor necrosis factor inhibitors and interleukin 17 inhibitors, a new era of drug therapy was initiated for previously largely incurable diseases. (storiescover.com)
  • We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1-2 inhibitor, for the treatment of patients admitted to hospital with COVID-19. (ebsco.com)
  • BackgroundWe aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1-2 inhibitor, for the treatment of patients admitted to hospital with COVID-19.MethodsThis randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with COVID-19 in the UK. (ox.ac.uk)
  • Janus was the Roman god of gates and this protein regulates the production of red bloods cells. (gboncology.com)
  • In the present study, we characterized the E3 orthologues from sheeppox virus, yaba monkey tumor virus, swinepox virus, and myxoma virus for their ability to modulate protein kinase R (PKR) function, cytokine responses and virus pathogenicity. (mdm2-receptor.com)
  • TCDD for every step of the mechanism described for 2,3,7,8-TCDD carcinogenesis in humans including receptor binding, gene expression, protein activity changes, cellular replication, oxidative stress, promotion in initiation-promotion studies and complete carcinogenesis in laboratory animals. (who.int)
  • Methodology: Between September 2021 and February 2022, oropharyngeal and/or nasopharyngeal swab samples of consecutively selected COVID-19 symptomatic and apparently healthy workers from the Wahgnion mining site in the South-western Burkina Faso who consented to the study were collected according to the two weeks shift program and tested for SARS-CoV-2 using RT-PCR assay. (bvsalud.org)
  • Méthodologie: Entre septembre 2021 et février 2022, des écouvillonnages oropharyngés et/ou nasopharyngés de travailleurs symptomatiques COVID-19 et apparemment en bonne santé sélectionnés consécutivement du site minier de Wahgnion dans le sud-ouest du Burkina Faso qui ont consenti à l'étude ont été prélevés selon les deux programme de quart de semaines et testé pour le SRAS-CoV-2 à l'aide d'un test RT-PCR. (bvsalud.org)
  • Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. (ebsco.com)
  • The GH molecule binds to its specific cell surface receptor (GHR), which dimerizes with another GHR molecule so that the single GH molecule is enveloped by 2 GHR molecules. (medscape.com)
  • IGF binding involves 3 basic types of receptors: the structurally homologous insulin receptor and type 1 IGF receptor and the distinctive type 2 IGF-II/mannose-6-phosphate receptor. (medscape.com)
  • The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936) and is ongoing.FindingsBetween Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. (ox.ac.uk)
  • For instance, the tumor microenvironment modulates the immune response by selectively attracting and repolarizing immune cells (e.g. macrophages and neutrophils) from an anti-tumorigenic to a pro-tumorigenic phenotype ( 2 , 3 ). (frontiersin.org)
  • Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. (medscape.com)
  • Muscle subjected to functional overload mobilizes the mitotically-active satellite cells, in turn increasing myonuclei number of the recipient muscle cells and facilitating hypertrophy [2] -- an adaptation that will allow each nucleus to regulate more cytoplasm [3], and ultimately the enlarged muscles to undergo more forceful contractions (lift heavier loads). (bodybuilding.com)
  • Distinguishing between the two became much easier about ten years ago with the discovery and testing for Janus Kinase 2 (JAK-2) mutations. (gboncology.com)
  • The patients underwent bariatric surgery at a single center in France and were followed for 2 years. (bvsalud.org)
  • The average time in years from symptom onset to start of first treatment, and from first to second added treatment was 2;7/2;9 (females) and 5;1/5;2 (males). (braincirculation.org)
  • OPZELURA was studied in 2 double-blind, randomized, vehicle-controlled trials of identical design that enrolled 674 adult and adolescent patients with nonsegmental vitiligo ≥12 years of age. (opzelurahcp.com)
  • Real time polymerase chain reaction (RT-PCR) assay is the recommended confirmatory method for the diagnosis of SARS-CoV-2 infection. (bvsalud.org)
  • The aim of this study was to determine the prevalence of SARSCoV-2 infection in Burkina Faso and to use the initial cycle threshold (Ct) values of RT-PCR as a tool to monitor the dynamics of the viral load. (bvsalud.org)
  • The overall prevalence of SARS-CoV-2 infection was 14.3% (216/1506). (bvsalud.org)
  • Table 2 Plasma concentration of MP-10 and estimated target occupancy of PDE10A in monkeys 7.9, p 0.01,) and cortical (6, p 0.02) regions compared to vehicle treatment (Figure 1A-B). The magnitude of the increase was not different between the two doses of MP-10 despite a predicted 6-fold change in 7.9) or cortical (6) ROIs. (bioskinrevive.com)
  • INREBIC® (fedratinib) is indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF). (mpn-advocates.net)
  • In both trials, patients were randomized 2:1 to treatment with OPZELURA or vehicle cream twice daily (BID) for 24 weeks followed by a 28-week open-label extension, wherein patients originally assigned to vehicle could switch to OPZELURA. (opzelurahcp.com)
  • Background: To control the spread of coronavirus disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), it is necessary to adequately identify and isolate infectious patients particularly at the work place. (bvsalud.org)
  • Pregnant women are no more likely to contract coronavirus disease 2019 (COVID-19) than the background population and two-thirds of those testing positive are asymptomatic [ 1 , 2 ]. (ersjournals.com)
  • An estimated 2 million people in the United States are living with what's called posttreatment Lyme disease (PTLD) - a subset of patients with persistent or chronic Lyme disease - and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). (medscape.com)
  • Wet/dry mass ratio (W/D) of lung tissue of rats in each group was measured, and ELISA was used to assay interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), IL-6 content and rat plasma angiopoietin 2 (Ang2) content in bronchoalveolar lavage fluid (BALF). (bvsalud.org)
  • Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. (ebsco.com)
  • Contexte: Pour contrôler la propagation de la maladie à coronavirus 19 (COVID-19) causée par le syndrome respiratoire aigu sévère coronavirus-2 (SRAS-CoV-2), il est nécessaire d'identifier et d'isoler de manière adéquate les patients infectieux, en particulier sur le lieu de travail. (bvsalud.org)
  • 25 kg·m −2 , having a medical comorbidity, being in the Black, Asian and Minority Ethnicity (BAME) population, and socioeconomic deprivation [ 1 ]. (ersjournals.com)