Janus Kinase 2
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.
Janus Kinase 3
Janus Kinases
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.
Janus Kinase 1
Protein-Tyrosine Kinases
Phosphatidylinositol 3-Kinases
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.
MAP Kinase Signaling System
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.
STAT3 Transcription Factor
STAT Transcription Factors
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.
Protein-Serine-Threonine Kinases
Signal Transduction
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.
Protein Kinases
TYK2 Kinase
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.
Phosphorylation
Suppressor of Cytokine Signaling Proteins
STAT1 Transcription Factor
src-Family Kinases
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.
Calcium-Calmodulin-Dependent Protein Kinases
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)
STAT5 Transcription Factor
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.
Proto-Oncogene Proteins
Trans-Activators
p38 Mitogen-Activated Protein Kinases
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Tyrphostins
Mitogen-Activated Protein Kinase 1
Protein Kinase C
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.
Milk Proteins
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)
Tyrosine
JNK Mitogen-Activated Protein Kinases
Cyclic AMP-Dependent Protein Kinases
Mitogen-Activated Protein Kinase Kinases
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.
Mitogen-Activated Protein Kinase 3
DNA-Binding Proteins
Enzyme Activation
p21-Activated Kinases
Mitogen-Activated Protein Kinases
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).
Creatine Kinase
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.
Extracellular Signal-Regulated MAP Kinases
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.
CDC2 Protein Kinase
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.
Cyclin-Dependent Kinases
Enzyme Inhibitors
MAP Kinase Kinase Kinases
Transfection
Mutation
eIF-2 Kinase
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
Casein Kinase II
Casein Kinases
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, Cultured
Cytokine Receptor gp130
Pyruvate Kinase
Ribosomal Protein S6 Kinases
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.
Protein Binding
Blotting, Western
Intracellular Signaling Peptides and Proteins
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.
Proto-Oncogene Proteins c-akt
MAP Kinase Kinase 1
Molecular Sequence Data
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.
Receptor Protein-Tyrosine Kinases
Thymidine Kinase
Phosphotyrosine
MAP Kinase Kinase 4
RNA, Messenger
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.
Receptors, Interleukin-9
1-Phosphatidylinositol 4-Kinase
Apoptosis
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.
Phosphotransferases (Alcohol Group Acceptor)
Myeloproliferative Disorders
CDC2-CDC28 Kinases
Receptors, Cytokine
Tumor Cells, Cultured
Gene Expression Regulation
I-kappa B Kinase
Cell Division
Isoenzymes
Glycogen Synthase Kinase 3
Aurora Kinases
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.
rho-Associated Kinases
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.
Interleukin-6
Amino Acid Sequence
Protein Kinase C-delta
Protein Kinase C-alpha
Proteins
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.
Protein Structure, Tertiary
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.
Base Sequence
Recombinant Fusion Proteins
Primary Myelofibrosis
Precipitin Tests
src Homology Domains
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.
Diacylglycerol Kinase
Serine
AMP-Activated Protein Kinases
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.
Dose-Response Relationship, Drug
STAT2 Transcription Factor
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.
Receptors, Erythropoietin
Down-Regulation
Receptors, Oncostatin M
Substrate Specificity
Transcription Factors
Binding Sites
STAT6 Transcription Factor
Focal Adhesion Kinase 1
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.
Polycythemia Vera
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.
Gene Expression Regulation, Enzymologic
Carrier Proteins
Pyrimidines
Myosin-Light-Chain Kinase
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.
Models, Biological
3T3 Cells
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, Interleukin-4
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.
Immunoblotting
Adaptor Proteins, Signal Transducing
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
Receptors, Leptin
Focal Adhesion Protein-Tyrosine Kinases
RNA, Small Interfering
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.
Receptors, Prolactin
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.
Transcription, Genetic
Sequence Homology, Amino Acid
Mice, Knockout
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.
Ribosomal Protein S6 Kinases, 90-kDa
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.
Cell Survival
Protein Kinase C-epsilon
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.
Up-Regulation
Reverse Transcriptase Polymerase Chain Reaction
Androstadienes
MAP Kinase Kinase Kinase 1
Calcium-Calmodulin-Dependent Protein Kinase Type 2
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.
Pyridines
Cell Nucleus
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)
Thrombocythemia, Essential
Protein Kinase C beta
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.
Repressor Proteins
Tetradecanoylphorbol Acetate
MAP Kinase Kinase 2
Cell Differentiation
Calcium
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.
Cyclin-Dependent Kinase 2
Cyclic GMP-Dependent Protein Kinases
Interferon-Stimulated Gene Factor 3
TOR Serine-Threonine Kinases
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.
NF-kappa B
Cyclin-Dependent Kinase 5
HeLa Cells
Phosphoglycerate Kinase
Oncostatin M
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.
Cell Line, Transformed
Rats, Sprague-Dawley
Receptors, Somatotropin
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.
Phosphorylase Kinase
Cytokines
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.
Fibroblasts
Arginine Kinase
Cell Cycle Proteins
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.
Receptor, Interferon alpha-beta
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.
Nucleoside-Phosphate Kinase
Receptors, Interleukin
MAP Kinase Kinase 6
Gene Expression
Transcriptional Activation
Promoter Regions, Genetic
Interferon-gamma
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.
Casein Kinase I
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.
Receptor, Epidermal Growth Factor
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.
Interleukin-4
MAP Kinase Kinase 3
Mitogen-Activated Protein Kinase 8
Aurora Kinase A
3-Phosphoinositide-Dependent Protein Kinases
Mutagenesis, Site-Directed
Focal Adhesion Kinase 2
Cyclic AMP
DNA Primers
Membrane Proteins
Phosphatidylinositol 3-Kinase
Genistein
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.
Protein Processing, Post-Translational
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.
Adenosine Kinase
Tumor Suppressor Proteins
Nitriles
Cell Cycle
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.
Lim Kinases
Dimerization
Cell Movement
Leukemia Inhibitory Factor
Protein Transport
Cell Membrane
DNA
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).
Prolactin
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.
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)
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JAKMIP2
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, ...
Thrombocythemia
Extremely high platelet counts can be treated with hydroxyurea (a cytoreducing agent) or anagrelide (Agrylin). In Janus kinase ... 2 positive disorders, ruxolitinib (Jakafi) can be effective.[citation needed] Schafer AI (March 2004). "Thrombocytosis". N. ...
Ion transporter
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 ...
Fedratinib
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. ...
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 ... "Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors".[full citation needed][ ... "Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors" at ClinicalTrials.gov " ...
PTPN11
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- ...
PPP2R4
... 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 ...
YES1
... 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 ...
Pacritinib
... is a macrocyclic Janus kinase inhibitor that is being developed for the treatment of myelofibrosis. It mainly inhibits Janus ... and Fms-like tyrosine kinase 3 (FLT3). The drug was in Phase III clinical trials as of 2013[update]. The drug was given fast- ... "PERSIST-2" trial. The clinical hold was lifted in January 2017. "International Nonproprietary Names for Pharmaceutical ...
Signal transducing adaptor molecule
... 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 ...
SH2B1
... 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. ...
USP18
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, ...
STAT5B
... 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 ...
Prolactin
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 ...
SH2B2
... 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 ...
INSL3
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 ...
Erythropoietin receptor
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 ...
IRS1
Gual P, Baron V, Lequoy V, Van Obberghen E (March 1998). "Interaction of Janus kinases JAK-1 and JAK-2 with the insulin ... Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E (December 1995). "Involvement of Janus kinases in the insulin ... PI3K, involved in interaction with IRS-1, produces PIP3, which, in turn, recruits Akt kinase. Further, Akt kinase is activated ... Xia X, Serrero G (August 1999). "Multiple forms of p55PIK, a regulatory subunit of phosphoinositide 3-kinase, are generated by ...
Growth hormone receptor
... 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 ...
Interleukin-23 receptor
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, ...
Surveyor nuclease assay
The method has been used to detect mutations in epidermal-growth-factor-receptor (EGFR), Janus Kinase 2 (JAK2), p53 and others ... doi:10.1007/978-1-60761-753-2_15. ISBN 978-1-60761-752-5. ISSN 1940-6029. PMID 20680839. Ran, F. Ann; Hsu, Patrick D.; Lin, ... 30 (2): 264-273. doi:10.1002/humu.20842. ISSN 1098-1004. PMID 18837007. Voskarides, Konstantinos; Deltas, Constantinos (2009-07 ...
STAR (gene)
Li J, Feltzer RE, Dawson KL, Hudson EA, Clark BJ (December 2003). "Janus kinase 2 and calcium are required for angiotensin II- ... 978 (1-2): 245-9. doi:10.1016/s0006-8993(03)02840-3. PMID 12834921. S2CID 32869169. Kohen P, Castro O, Palomino A, Muñoz A, ... steroidogenic response to gonadotropins in human and rat preovulatory granulosa cells involves mitogen-activated protein kinase ...
Gonocyte
... such as PDGF receptor pathways and Janus kinase 2 (JAK2) signaling pathway. Anti-Müllerian hormone (AMH), a glycoprotein ... The activation of protein kinase C by phorbol ester PMA also decreased fetal gonocyte mitotic activity. There are a number of ... 75 (2): 130-141. doi:10.1002/bdrc.20041. ISSN 1542-975X. PMID 16035044. Wu, Ray-Chang; Zeng, Yang; Chen, Yu-Fang; Lanz, Rainer ... 89 (2): 46. doi:10.1095/biolreprod.113.110544. ISSN 0006-3363. PMID 23843237. Yang, Qi-En; Oatley, Jon M. (2014-01-01), Rendl, ...
Abrocitinib
It is a selective inhibitor of the enzyme janus kinase 1 (JAK1). Abrocitinib is quickly absorbed from the gut and generally ... Abrocitinib (code name PF-04965842) is a Janus kinase inhibitor drug which is currently under investigation for the treatment ... October 2019). "Efficacy and Safety of Oral Janus Kinase 1 Inhibitor Abrocitinib for Patients With Atopic Dermatitis: A Phase 2 ... August 2018). "Evaluation of a Janus kinase 1 inhibitor, PF-04965842, in healthy subjects: A phase 1, randomized, placebo- ...
HPG80
JAK2 (Janus-activated kinase 2), STAT3 and kinases increases regulated by extracellular signals have also been observed in the ... Brown, D.; Yallampalli, U.; Owlia, A.; Singh, P. (2003-01-01). "pp60c-Src Kinase Mediates Growth Effects of the Full-Length ... "Activation of the pp60c-src protein kinase is an early event in colonic carcinogenesis". Proceedings of the National Academy of ... Binding was not influenced by the presence of the classical CCK-2 receptor. It is clear from these two studies that there is a ...
STAT5A
Janus kinase 1, Janus kinase 2, MAPK1 NMI, and PTPN11. CBX5, STAT5 GRCh38: Ensembl release 89: ENSG00000126561 - Ensembl, May ... Schulze WX, Deng L, Mann M (2005). "Phosphotyrosine interactome of the ErbB-receptor kinase family". Mol. Syst. Biol. 1 (1): E1 ... In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and ... Pircher TJ, Petersen H, Gustafsson JA, Haldosén LA (April 1999). "Extracellular signal-regulated kinase (ERK) interacts with ...
IL-10 family
... activating such kinases as Janus kinase and tyrosine kinase 2. IL-10R2 receptor is presented in most cells, when IL-10R1 ... 23 (2): 89-96. doi:10.1016/S1471-4906(01)02149-4. ISSN 1471-4906. PMID 11929132. Trivella, Daniela Barretto Barbosa; Ferreira- ... 179 (2): 300-308. doi:10.1111/cei.12449. PMC 4298407. PMID 25178435. v t e. ...
Interferon alpha-1
Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2). The biological effects of IFNs are mediated through the Janus kinase/signal ... STAT1 and STAT2 are activated by these tyrosine kinases, and STAT1 and STAT2 mediate the antiviral and inflammatory effects of ... Two cytoplasmic tyrosine kinases provide downstream signaling after type I IFN binds to the IFNAR receptor, ... the pathway involving mitogen-activated protein kinases (MAPKs) and IRF pathways, depending on the stimulus and the responding ...
Interleukin 12 receptor, beta 2 subunit
... 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 ...
Interleukin 2
This leads to the activation of Janus kinases JAK1 and JAK3 which subsequently phosphorylate T338 on CD122. This ... IL-2 is a member of a cytokine family, each member of which has a four alpha helix bundle; the family also includes IL-4, IL-7 ... The IL-2 receptor (IL-2R) α subunit binds IL-2 with low affinity (Kd~ 10−8 M). Interaction of IL-2 and CD25 alone does not lead ... Low-dose IL-2 has been reported to reduce hepatitis C and B infection. IL-2 has been used in clinical trials for the treatment ...
Rituximab
Tyrosine-kinase inhibitors ("-nib"). Receptor tyrosine kinase. *ErbB: HER1/EGFR (Brigatinib. *Erlotinib ... 3 (2): 86-90. doi:10.1186/bcr276. PMC 138676. PMID 11250751.. *^ Maverakis E, Kim K, Shimoda M, Gershwin M, Patel F, Wilken R, ... 4 (2): 107. doi:10.1016/s1548-5315(11)70061-4. Archived (PDF) from the original on 2007-09-29.. CS1 maint: Multiple names: ... Lahiri, Diptendu; Osterman, Cynthia (2 November 2018). "Novartis abandons effort for U.S. approval of biosimilar rituximab". ...
Afatinib
... kinases. Afatinib is not only active against EGFR mutations targeted by first generation tyrosine-kinase inhibitors (TKIs) like ... Like lapatinib and neratinib, afatinib is a protein kinase inhibitor that also irreversibly inhibits human epidermal growth ... Minkovsky N, Berezov A (December 2008). "BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors ... It belongs to the tyrosine kinase inhibitor family of medications.[4] It is taken by mouth.[4] ...
PSEN1
positive regulation of MAP kinase activity. • positive regulation of catalytic activity. • mitochondrial transport. • post- ... Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P (September 2000). "Nicastrin modulates ... negative regulation of protein kinase activity. • cell fate specification. • skeletal system morphogenesis. • regulation of ... positive regulation of protein kinase activity. • T cell activation involved in immune response. • cellular protein metabolic ...
Competitive inhibition
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... 2. [. ES. ]. =. k. 2. K. i. [. S. ]. [. E. ]. 0. K. m. K. i. +. K. i. [. S. ]. +. K. m. [. I. ]. {\displaystyle V_{0}=k_{2}[{\ ... 2. [. E. ]. 0. [. S. ]. K. m. +. [. S. ]. +. K. m. [. I. ]. K. i. {\displaystyle V_{0}={\frac {k_{2}[{\ce {E}}]_{0}[{\ce {S ... 2. [. ES. ]. −. k. 3. [. E. ]. [. I. ]. +. k. −. 3. [. EI. ]. {\displaystyle {\frac {d[{\ce {E}}]}{dt}}=0=-k_{1}[{\ce {E}}][{\ ...
Nilotinib
2010). "Extended kinase profile and properties of the protein kinase inhibitor nilotinib". Biochimica et Biophysica Acta (BBA ... Nilotinib inhibits the kinases BCR-ABL,[16] KIT, LCK, EPHA3, EPHA8, DDR1, DDR2, PDGFRB, MAPK11 and ZAK.[17] ... See also: Discovery and development of Bcr-Abl tyrosine kinase inhibitors. Nilotinib was developed by Novartis.[3] It was ... Structurally related to imatinib,[18] It is 10-30 fold more potent than imatinib in inhibiting Bcr-Abl tyrosine kinase activity ...
Histone methyltransferase
Branscombe TL, Frankel A, Lee JH, Cook JR, Yang Z, Pestka S, Clarke S (August 2001). "PRMT5 (Janus kinase-binding protein 1) ... 2][3][4] In both types of histone methyltransferases, S-Adenosyl methionine (SAM) serves as a cofactor and methyl donor group.[ ...
Interleukin 15
Upon binding IL-15β subunit activates Janus kinase 1 (Jak1) and γc subunit Janus kinase 3 (Jak3), which leads to ... Upon binding IL-15β subunit activates Janus kinase 1 (Jak1) and γc subunit Janus kinase 3 (Jak3), which leads to ... kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) and Syk (spleen tyrosine kinase) ... kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) and Syk (spleen tyrosine kinase) ...
Glikoprotein 130 - Википедија, слободна енциклопедија
Structural requirements of the interleukin-6 signal transducer gp130 for its interaction with Janus kinase 1: the receptor is ... 1993). „IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase.". Science. 260 (5115): 1808-10. ... On interaguje sa Janus kinazom da bi izazvao intracelularni signal nakon interakcije receptora sa ligandom. Strukturno, gp130 ... 2000). „Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines.". ...
Primary myelofibrosis
Janus kinases (JAKs) are non-receptor tyrosine kinases essential for the activation of signaling that is mediated by cytokine ... Fibrosis grade 2 or 3 defines overt PMF whereas grade 0 or 1 defines prefibrotic primary myelofibrosis. ... In August 2019, the FDA approved fedratinib as a treatment for adults with intermediate-2 or high-risk primary or secondary ( ... Ruxolitinib serves as an inhibitor of JAK 1 and 2. The New England Journal of Medicine (NEJM) published results from two Phase ...
Chemotherapy
Zhang J, Yang PL, Gray NS (Jan 2009). "Targeting cancer with small molecule kinase inhibitors". Nature Reviews. Cancer. 9 (1): ... doi:10.1016/0163-7258(91)90086-2.. *^ a b c d Yue QX, Liu X, Guo DA (Aug 2010). "Microtubule-binding natural products for ... 56 (2): 185-229. PMID 15169927. doi:10.1124/pr.56.2.6.. *^ Sobell HM (Aug 1985). "Actinomycin and DNA transcription". ... 2 (10): 750-63. PMID 12360278. doi:10.1038/nrc903.. *^ Chen HX, Cleck JN (Aug 2009). "Adverse effects of anticancer agents that ...
FAK
"Janus kinases and focal adhesion kinases play in the 4.1 band: a superfamily of band 4.1 domains important for cell structure ... protein kinase activity. • JUN kinase binding. • non-membrane spanning protein tyrosine kinase activity. • transferase activity ... FAK(focal adhesion kinase、フォーカルアドヒージョンキナーゼ、焦点接着キナーゼ、接着斑キナーゼ)またはPTK2(protein tyrosine kinase 2)は、ヒトではPTK2遺伝子にコードされるタンパク質である[4]。 ... "Regulation of the PH-domain-containing tyrosine kinase
Protein arginine methyltransferase 5
Janus kinase 2,[24]. *SNRPD3,[23]. *SUPT5H,[25] and. *WD repeat-containing protein 77.[21] ... "Interaction of the somatostatin receptor subtype 1 with the human homolog of the Shk1 kinase-binding protein from yeast". J. ... "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase ... "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase ...
Erlotinib
Over 50% of resistance is caused by a mutation in the ATP binding pocket of the EGFR kinase domain involving substitution of a ... JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial ... As with other ATP competitive small molecule tyrosine kinase inhibitors, such as imatinib (Gleevec) in CML, patients rapidly ... Blum G, Gazit A, Levitzki A (2000). "Substrate competitive inhibitors of IGF-1 receptor kinase". Biochemistry. 39 (51): 15705- ...
Granulocyte colony-stimulating factor
G-CSF regulates them using Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and Ras/mitogen-activated ... protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal transduction pathway.. ... positive regulation of protein kinase B signaling. • positive regulation of actin filament polymerization. • cellular response ... positive regulation of phosphatidylinositol 3-kinase signaling. • positive regulation of protein binding. • cellular response ...
Imatinib
The active sites of tyrosine kinases each have a binding site for ATP. The enzymatic activity catalyzed by a tyrosine kinase is ... Some tumor cells, however, have a dependence on bcr-abl.[28] Inhibition of the bcr-abl tyrosine kinase also stimulates its ... Schiffer CA (July 2007). "BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia". N. Engl. J. Med. 357 (3): 258- ... As this is now a constitutively active tyrosine kinase, imatinib is used to decrease bcr-abl activity. ...
COX-2 inhibitor
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... 17 (2): 197-208. doi:10.1517/13543784.17.2.197. PMID 18230053.. *^ Schönthal AH (2006). "Antitumor properties of dimethyl- ... "COX-2 Inhibitors and Cancer". Fact Sheet. United States National Cancer Institute. Archived from the original on May 9, 2008.. ... 165 (2): 171-7. doi:10.1001/archinte.165.2.171. PMID 15668363.. *. Solomon DH, Avorn J (Jan 2005). "Coxibs, science, and the ...
Cell nucleus
... a process regulated by phosphorylation of the lamins by protein kinases such as the CDC2 protein kinase.[63] Towards the end of ... "Coiled bodies and gems: Janus or gemini?". American Journal of Human Genetics. 63 (2): 317-21. doi:10.1086/301992. PMC 1377332 ... Observations that myxobacteria are motile, can form multicellular complexes, and possess kinases and G proteins similar to ... 978-0-7216-3360-2. .. *^ a b c Dundr M, Misteli T (June 2001). "Functional architecture in the cell nucleus". The Biochemical ...
에리트로포이에틴 - 위키백과, 우리 모두의 백과사전
에리트로포이에틴이 붙는 수용체는 적혈구 전구체에 있고 JAK2(janus kinase 2) 신호체계를 활성화시킨다. 에리트로포이에틴 수용체는 골수, 말초신경/중추신경계 등 여러 조직에서 발현된다. 혈액내에서는 적혈구는 스스로 ... 예를 들면, 신경 손상에 대한 뇌의 반응에 중요한 역할을 한다고 알려졌다.[1] 에리트로포이에틴은 또한 상처의 회복과정에도 포함된다고 알려졌다.[2] ... Genc S, Koroglu TF, Genc K (2004). "Erythropoietin and the nervous system". 《Brain Res.》 1000 (1-2): 19-31. PMID 15053948. doi: ... 2005). "Brain and cancer: the protective role of erythropoietin". 《Med Res Rev》 25 (2): 245-59. PMID 15389732. doi:10.1002/med. ...
5α-Reductase inhibitor
Protein kinase *Tyrosine kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... ISBN 0-9578521-4-2 *^ a b c Azzouni F, Godoy A, Li Y, Mohler J, et al. (2012). "The 5 alpha-reductase isozyme family: a review ... 978-3-11-015793-2. .. *^ Mutschler, Ernst; Gerd Geisslinger; Heyo K. Kroemer; Monika Schäfer-Korting (2001). ... D2 receptor antagonists (prolactin releasers) (e.g., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, ...
Ribonuclease inhibitor
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... 302 (2): 497-519. doi:10.1006/jmbi.2000.4075. PMID 10970748.. *. Bretscher LE, Abel RL, Raines RT (Apr 2000). "A ribonuclease A ...
5α-Reductase inhibitor
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... ISBN 0-9578521-4-2 *^ a b c Azzouni F, Godoy A, Li Y, Mohler J, et al. (2012). "The 5 alpha-reductase isozyme family: a review ... ISBN 3-8047-1763-2.. *^ a b c Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS (2016). "Adverse Effects and ... 2 (3): 293-299. doi:10.1515/hmbci.2010.035.. *^ McConnell J. D.; Wilson J. D.; George F. W.; Geller J.; Pappas F.; Stoner E. ( ...
Interferon
STAT activation initiates the most well-defined cell signaling pathway for all IFNs, the classical Janus kinase-STAT (JAK-STAT ... Type I IFNs further activate p38 mitogen-activated protein kinase (MAP kinase) to induce gene transcription.[17] Antiviral and ... The phosphatidylinositol 3-kinase (PI3K) signaling pathway is also regulated by both type I and type II IFNs. PI3K activates ... Production of protein kinase R, for example, can be disrupted in cells infected with JEV.[22] Some viruses escape the anti- ...
Alopecia universalis
JAK inhibitors: Janus kinase inhibitors, previously used in the treatment of cancer and other diseases, such as arthritis, have ... 79 (2): 138-40. PMID 17388216.. *^ "Hairless Man Grows Full Head Of Hair In Yale Arthritis Drug Trial". boston.cbslocal.com. ... Genetic factors may contribute to AU, as about 20% of those affected have a family member with alopecia.[2] ... 10 (2): 51-60. doi:10.4103/ijt.ijt_99_17. ISSN 0974-7753. PMC 5939003. PMID 29769777.. ...
STAT3 - Википедия
Uckun F. M., Qazi S., Ma H., Tuel-Ahlgren L., Ozer Z. STAT3 is a substrate of SYK tyrosine kinase in B-lineage leukemia/ ... STAT3, в зависимости от типа клеток и конкретных условий, могут фосфорилировать киназы Janus (JAK1, JAK2, JAK3), SYK и другие[4 ... protein kinase binding. • ДНК-связывающий. • sequence-specific DNA binding. • transcriptional activator activity, RNA ... 1 2 3 4 Subramaniam A., Shanmugam M. K., Perumal E., Li F., Nachiyappan A., Dai X., Swamy S. N., Ahn K. S., Kumar A. P., Tan B ...
Tofacitinib
It is an inhibitor of the enzyme janus kinase 1 (JAK1) and janus kinase 3 (JAK 3), which means that it interferes with the JAK- ... Tofacitinib (INN) is a drug of the janus kinase (JAK) inhibitor class, discovered and developed by the National Institutes of ... 7 July 2015). "Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two, ... Levy LL, Urban J, King BA (2015). "Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib ...
IRF7
... phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or Ikappa B kinase ... 280 (2): 273-82. doi:10.1006/viro.2000.0782. PMID 11162841.. *^ Zhou Q, Lavorgna A, Bowman M, Hiscott J, Harhaj EW (June 2015 ... 280 (2): 273-82. doi:10.1006/viro.2000.0782. PMID 11162841.. *. Lu R, Moore PA, Pitha PM (May 2002). "Stimulation of IRF-7 gene ... 9 (2): 191-7. doi:10.1038/nm822. PMID 12539042.. *. Yang H, Lin CH, Ma G, Baffi MO, Wathelet MG (May 2003). "Interferon ...
Statin
Monitoring liver enzymes and creatine kinase is especially prudent in those on high-dose statins or in those on statin/fibrate ... 114 (2): 99-108. doi:10.7556/jaoa.2014.023. PMID 24481802.. *^ Ramasamy I (February 2016). "Update on the molecular biology of ... 36 (2): 288-95. doi:10.1345/aph.1A289. PMID 11847951.. *^ Armitage J (November 2007). "The safety of statins in clinical ... 172 (2): 144-52. doi:10.1001/archinternmed.2011.625. PMID 22231607.. *^ Jukema JW, Cannon CP, de Craen AJ, Westendorp RG, ...
Acetylcholinesterase inhibitor
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... medium (1-2 hrs.)[21] neuromuscular junction[21] *Reverse neuromuscular block (intravenously)[21] ... medium (2-3 hrs.)[21] neuromuscular junction[21] *Treat myasthenia gravis (orally)[21] ... Consumer Reports: 2. Archived (PDF) from the original on 5 September 2012. Retrieved 1 May 2013.. , which claims Alzheimer's ...
Interleucina 6, a enciclopedia libre
... as quinases Janus (JAKs) e Transdutores de Sinais e Activadores de Transcrición (Signal Transducers and Activators of ... via phosphorylation of the nuclear localization sequence by the AKT kinase". Cancer Genomics Proteomics 4 (6): 387-98. PMID ... Neurosci. 11 (2): 100-13. PMID 20087360. doi:10.1038/nrn2774.. *↑ 52,0 52,1 52,2 Sharma RP, Tun N, Grayson DR (2008). " ... 334 ( Pt 2) (Pt 2): 297-314. PMC 1219691. PMID 9716487.. *↑ Kishimoto T, Akira S, Narazaki M, Taga T (1995). "Interleukin-6 ...
Janus kinase 2 - Wikipedia
... inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain". Genes to ... is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of ... Janus kinase 2 has been shown to interact with: DNAJA3 EGFR EPOR FYN Grb2 GHR IRS1 IL12RB2 IL5RA PIK3R1 PPP2R4 PTK2 PTPN11 ... Gual P, Baron V, Lequoy V, Van Obberghen E (March 1998). "Interaction of Janus kinases JAK-1 and JAK-2 with the insulin ...
Janus Kinase 2: A Critical Target in Chronic Myelogenous Leukemia | Cancer Research
Janus Kinase 2: A Critical Target in Chronic Myelogenous Leukemia. Ajoy K. Samanta, Hui Lin, Tong Sun, Hagop Kantarjian and ... Janus Kinase 2: A Critical Target in Chronic Myelogenous Leukemia. Ajoy K. Samanta, Hui Lin, Tong Sun, Hagop Kantarjian and ... Janus Kinase 2: A Critical Target in Chronic Myelogenous Leukemia. Ajoy K. Samanta, Hui Lin, Tong Sun, Hagop Kantarjian and ... Janus Kinase 2: A Critical Target in Chronic Myelogenous Leukemia Message Subject (Your Name) has forwarded a page to you from ...
Insufficiency of Janus Kinase 2-Autonomous Leptin Receptor Signals for Most Physiologic Leptin Actions | Diabetes
Insufficiency of Janus Kinase 2-Autonomous Leptin Receptor Signals for Most Physiologic Leptin Actions. ... Insufficiency of Janus Kinase 2-Autonomous Leptin Receptor Signals for Most Physiologic Leptin Actions ... Insufficiency of Janus Kinase 2-Autonomous Leptin Receptor Signals for Most Physiologic Leptin Actions ... Insufficiency of Janus Kinase 2-Autonomous Leptin Receptor Signals for Most Physiologic Leptin Actions ...
Preliminary study on the effect of nucleolin specific aptamer -miRNA let -7d chimera on Janus kinase -2 expression level and...
The role of proto-oncogene Janus kinase-2 (JAK-2) in proliferation and survival of gastric cancer has been... ... Preliminary study on the effect of nucleolin specific aptamer-miRNA let-7d chimera on Janus kinase-2 expression level and ... The role of proto-oncogene Janus kinase-2 (JAK-2) in proliferation and survival of gastric cancer has been previously ... Nucleolin specific aptamer (NCL-Apt) MiRNA let-7d Janus kinase-2 (JAK-2) Gastric cancer ...
The chemokine monocyte chemotactic protein 1 triggers Janus kinase 2 activation and tyrosine phosphorylation of the CCR2B...
The chemokine monocyte chemotactic protein 1 triggers Janus kinase 2 activation and tyrosine phosphorylation of the CCR2B ... triggers activation of the Janus kinase 2 (JAK2)/STAT3 pathway and CCR2 receptor tyrosine phosphorylation. Both Ca2+ ... These results implicate the tyrosine kinase pathway in early chemokine signaling, suggesting a key role for this kinase in ... mobilization and cell migration are blocked in Mono Mac 1 cells by tyrphostin B42, a specific JAK2 kinase inhibitor. Within ...
Janus Kinase 2 | Profiles RNS
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of ... "Janus Kinase 2" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE ... This graph shows the total number of publications written about "Janus Kinase 2" by people in this website by year, and whether ...
WP1066 Disrupts Janus Kinase-2 and Induces Caspase-Dependent Apoptosis in Acute Myelogenous Leukemia Cells | Cancer Research
WP1066 Disrupts Janus Kinase-2 and Induces Caspase-Dependent Apoptosis in Acute Myelogenous Leukemia Cells. Alessandra ... Janus kinase 2: a critical target in chronic myelogenous leukemia. Cancer Res 2006; 66: 6468-72. ... Janus kinases and their role in growth and disease. Life Sci 1999; 64: 2173-86. ... WP1066 Disrupts Janus Kinase-2 and Induces Caspase-Dependent Apoptosis in Acute Myelogenous Leukemia Cells ...
Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis | Gut
Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis ... Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis ... Objective Angiotensin II (AngII) activates via angiotensin-II-type-I receptor (AT1R) Janus-kinase-2 (JAK2)/Arhgef1 pathway and ... 2Institute for Cell Biology, University of Bonn, Bonn, Germany. *. 3Department of Liver and Biliopancreatic Disorders, ...
A Study to Determine the Effect and Safety of an Oral Janus Kinase 2 (JAK2)-Inhibitor (Ruxolitinib; INBC018424) in Patients...
... a small molecule Janus kinase 2 (JAK2)-inhibitor, i ... Phase 2. Minimum Age:. 18 Years. Maximum Age:. N/A. Enrollment ... A Phase 2, Two Stage, Open-label, Clinical Trial to Determine the Therapeutic Effect and Safety of an Oral JAK2-inhibitor ( ... A Phase 2, Two Stage, Open-label, Clinical Trial to Determine the Therapeutic Effect and Safety of an Oral JAK2-inhibitor ( ... Day 1 of Cycles 2, 3, and 4 and then every 3 months thereafter (up to 25 months). ...
Dihydroartemisinin increases apoptosis of colon cancer cells through targeting Janus kinase 2/signal transducer and activator...
... terminal kinase and p38 mitogen‑activated protein kinase in colon cancer cells. Conversely, the phosphorylation of Janus kinase ... p-JAK2, phosphorylated Janus kinase 2; p-STAT3, phosphorylated signal transducer and activator of transcription 3. ... Dihydroartemisinin increases apoptosis of colon cancer cells through targeting Janus kinase 2/signal transducer and activator ... p-ERK, phosphorylated extracellular-signal-related kinase; p-JNK, phosphorylated c-Jun N-terminal kinase; p-p38, phosphorylated ...
Differential phosphorylation of Janus kinase 2, Stat5A and Stat5B in response to growth hormone in primary rat adipocytes
... ... Growth hormone (GH), Janus kinase 2 (Jak2), Signal transducer and activator of transcription (Stat), Protein phosphorylation, ... In vitro growth hormone (GH) stimulation of Janus kinase 2 (Jak2) tyrosine phosphorylation and activation has been detected in ... In vitro growth hormone (GH) stimulation of Janus kinase 2 (Jak2) tyrosine phosphorylation and activation has been detected in ...
Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate...
Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate ... Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate ... Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate ... Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate ...
Detection of the Janus kinase 2 V617F mutation using molecular methods
In 2005, a mutation located at exon 14 of the Janus Kinase gene on chromosome 9 was discovered in patients with Polycythaenia ... Detection of the Janus kinase 2 V617F mutation using molecular methods. Login ... Detection of the Janus kinase 2 V617F mutation using molecular methods. Senamela, Tshiphiri ...
tyrosine kinase 2 | Janus kinase (JakA) family | IUPHAR/BPS Guide to PHARMACOLOGY
Janus kinase (JakA) family. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of ... Janus kinase (JakA) family: tyrosine kinase 2. Last modified on 16/06/2020. Accessed on 24/09/2020. IUPHAR/BPS Guide to ... rather than the functional kinase (or JH1) domain which shares a high degree of homology across all members of the Janus kinase ... TYK2 was the first member of the Janus kinase family to be identified. It associates with the cytoplasmic domain of type I and ...
Janus kinase 2 mutations in Philadelphia negative chronic myeloproliferative disorders: clinical implications. - Semantic...
Combination of the ABL kinase inhibitor imatinib with the Janus kinase 2 inhibitor TG101348 for targeting residual BCR-ABL...
Hematopoietic cytokine receptor signaling is mediated by Janus kinases (JAKs) and their downstream transcription factor, signal ... The ABL kinase inhibitor imatinib is highly effective in treating most, but not all, patients with chronic myeloid leukemia ( ... Janus kinases (JAKs) are a family of intracellular, non-receptor tyrosine kinases including four family members such as JAK1, ... Combination of the ABL kinase inhibitor imatinib with the Janus kinase 2 inhibitor TG101348 for targeting residual BCR-ABL- ...
Janus Kinase 2
Splenomegaly in myelofibrosis-new options for therapy and the therapeutic potential of Janus kinase 2 inhibitors | Journal of...
The discovery of an activating Janus kinase 2 (JAK2) activating mutation (JAK2V617F) that is present in almost all patients ... The discovery of an activating Janus kinase 2 (JAK2) activating mutation (JAK2V617F) that is present in almost all patients ... Ghoreschi K, Laurence A, OShea JJ: Janus kinases in immune cell signaling. Immunol Rev. 2009, 228: 273-287. 10.1111/j.1600- ... Verstovsek S: Therapeutic potential of Janus-activated kinase-2 inhibitors for the management of myelofibrosis. Clin Cancer Res ...
Janus kinase and microtubule-interacting protein 2
Subject Terms: 'Janus Kinase 2 genetics' - OpacWWW - Prolib Integro
Janus Kinase-2 (JAK2) DNA Mutation Assay | Lab Tests | 5MinuteConsult
Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinase 2/Signal Transducer and Activation...
Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinase 2/Signal Transducer and Activation ... Additionally, tubulosine suppressed IL-6-induced Janus kinase 2 (JAK2)/STAT3 signaling, resulting in decreased viability and ... Janus Kinase 2 , Phosphorylation , Phosphotransferases , Polymerase Chain Reaction , Receptors, Interleukin-6 , Reverse ... Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinas ...
Janus kinase 2 and signal transducer and activator of transcription 3 activation is not essential for CCL3-, CCL5- or CCL8...
Janus kinase 2 and signal transducer and activator of transcription 3 activation is not essential for CCL3-, CCL5- or CCL8- ... Janus kinase 2 and signal transducer and activator of transcription 3 activation is not essential for CCL3-, CCL5- or CCL8- ... Khabbazi S., Jacques R.O., Moyano Cardaba C. and Mueller A. (2013) Janus kinase 2 and signal transducer and activator of ... we show that chemokine-induced cell migration is not dependent on activation of Janus kinase 2 or STAT3. ...
Association of factor V Leiden, Janus kinase 2, prothrombin, and MTHFR mutations with primary Budd-Chiari syndrome in Egyptian...
Association of factor V Leiden, Janus kinase 2, prothrombin, and MTHFR mutations with primary Budd-Chiari syndrome in Egyptian ... Association of factor V Leiden, Janus kinase 2, prothrombin, and MTHFR mutations with primary Budd-Chiari syndrome in Egyptian ... This study aimed to evaluate the association of factor V Leiden (FVL), Janus kinase 2 (JAK2), prothrombin, and methylene ... Hatem M El Sebay 1 , Manal A Safan 1 , Ashraf A Daoud 1 , Safaa I Tayel 1 , Mohamed A Nouh 2 , Shymaa El Shafie 1 ...
Hepatic deletion of Janus Kinase 2 counteracts oxidative stress in mice - Fingerprint
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Janus kinase 3 - Wikipedia
Janus kinase 3 is a tyrosine kinase that belongs to the janus family of kinases. Other members of the Janus family include JAK1 ... Janus kinases (JAKs) are relatively large kinases of approximately 1150 amino acids with apparent molecular weights of 120-130 ... Janus+Kinase+3 at the US National Library of Medicine Medical Subject Headings (MeSH) Overview of all the structural ... Janus kinase 3 has been shown to interact with CD247, TIAF1 and IL2RG. GRCh38: Ensembl release 89: ENSG00000105639 - Ensembl, ...
Cerebral Venous Thrombosis Presenting in Pregnancy with Thrombocytosis and Janus Kinase 2 Valine-to-Phenylalanine Mutation
야누스키나아제(janus kinase 2, JAK2)는 티로신인산화효소(tyrosine kinase)의 일종으로 조혈기능에 관여하는 유전자로, JAK2 유전자의 valine-to-phenylalanine (V617F) 돌연변이는 ... Should we screen for Janus kinase 2 V617F mutation in cerebral venous thrombosis? Cerebrovasc Dis 2017;44:97-104.. ... Cerebral Venous Thrombosis Presenting in Pregnancy with Thrombocytosis and Janus Kinase 2 Valine-to-Phenylalanine Mutation. 임신 ... Cerebral Venous Thrombosis Presenting in Pregnancy with Thrombocytosis and Janus Kinase 2 Valine-to-Phenylalanine Mutation. ...
JAK2 gene: MedlinePlus Genetics
Janus kinase 2 To use the sharing features on this page, please enable JavaScript.. ... Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome. Gastroenterology. 2006 Jun;130(7 ... 2010 Mar 2;152(5):300-6. doi: 10.7326/0003-4819-152-5-201003020-00008. Review. Citation on PubMed ...
MedlinePlus: Genes: J
CD109 and squamous cell carcinoma | SpringerLink
STAT3 is phosphorylated by the non-receptor protein tyrosine kinases janus kinase 2 (JAK2), leading to the formation of STAT3 ... Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis. Nat Med. 2017;23:291- ... Epidermal growth factor receptor tyrosine kinase inhibitors in advanced squamous cell lung cancer. Clin Lung Cancer. 2016;17: ... binds to specific transmembrane type I and type II serine/threonine kinase receptors (TGF-βR1 and TGF-βR2) [42], resulting in ...
InhibitorMitogen-activaJAK3Protein kinaseV617FInhibitorsPathwayProteinsPhosphorylationMutationsTYK2STAT3MiceHumansRuxolitinibJAKsPseudokinase domainIntracellularTransducer and activator of transcriptionDownstreamMyeloproliferative disordersRECEPTORSInterleukinMyelofibrosisPathwaysCalled Janus homologyRecombinantMetabolismReceptor tyrosiPanel of kinasesAnother kinaseActivatesExpressionEnzymeCytokinesConstitutiveGlycogenRegulatesExtracellularHomology bindingGrowth
Inhibitor19
- Treatment of CML cell lines and mouse Bcr-Abl+ 32D cells with either Jak2 short interfering RNA or Jak2 kinase inhibitor AG490 inhibited pTyr Gab2 and pSer Akt formation, inhibited the activation of nuclear factor-κB, and caused the activation of GSK-3β, leading to the reduction of c-Myc. (aacrjournals.org)
- Imatinib mesylate is a selective inhibitor of the Bcr-Abl tyrosine kinase, and this drug is the frontline treatment for CML patients ( 4 ). (aacrjournals.org)
- AG490, a member of the tyrphostin family of protein kinase inhibitors, is a potent and specific inhibitor of Jak2 kinase ( 6 ). (aacrjournals.org)
- Both Ca2+ mobilization and cell migration are blocked in Mono Mac 1 cells by tyrphostin B42, a specific JAK2 kinase inhibitor. (uniprot.org)
- Because ( E )-3(6-bromopyridin-2-yl)-2-cyano- N -((S0-1-phenylethyl)acrylamide) (WP1066) is a novel analogue of the JAK2 inhibitor AG490, we tested its activity in AML cells and investigated its mechanism of action. (aacrjournals.org)
- The ABL kinase inhibitor imatinib is highly effective in treating most, but not all, patients with chronic myeloid leukemia (CML). (biomedcentral.com)
- Hematopoietic cytokine receptor signaling is mediated by Janus kinases (JAKs) and their downstream transcription factor, signal transducer and activator of transcription (STAT). TG101348 (SAR302503) is an oral inhibitor of JAK2. (biomedcentral.com)
- Background Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen quantity, symptoms, and success more than placebo and very best available therapy in intermediate-2 or high-risk myelofibrosis individuals with baseline platelet matters 100? (biologyexperimentideas.net)
- strong course="kwd-title" Keywords: Janus kinase inhibitor, Myelofibrosis, Stage II, Platelet count number, Ruxolitinib, Spleen quantity, Total indicator rating Background Myelofibrosis (MF) can be a Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), including major MF (PMF), post-polycythemia vera MF (PPV-MF) and post-essential thrombocythemia MF (PET-MF) [1]. (biologyexperimentideas.net)
- Ruxolitinib treatment decreased spleen quantity and improved MF-related symptoms and QoL procedures in sufferers with intermediate-2 or high-risk MF, as described with the International Prognostic Credit scoring Program (IPSS) [6], in the stage III Managed MyeloFibrosis Research with Dental JAK Inhibitor Treatment (Convenience)-I and COMFORT-II research [7,8]. (biologyexperimentideas.net)
- Results of enzymatic assays revealed that against a panel of kinases, compound NSC13626 is a JAK2 inhibitor and has high selectivity toward the JAK2 and JAK3 isozymes. (frontiersin.org)
- Importantly, after comparing the proliferation, migration, and invasion of LUAD to the corresponding control groups treated in STAT3 inhibitor ADZ1480, we found that STEAP1 regulates EMT via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. (portlandpress.com)
- Baricitinib is a selective inhibitor Janus kinase 1 and 2. (medscape.com)
- Baricitinib is an orally administered inhibitor of janus kinase 1 and 2. (meduniwien.ac.at)
- TG 101348, is a potent inhibitor of Janus kinase 2 (JAK-2). (fiercebiotech.com)
- The binding mode was corroborated by solving the structure of the kinase-inhibitor complex. (aacrjournals.org)
- Ruxolitinib is a Janus kinases (JAK) 1/2 inhibitor, an enzyme-blocker that affects blood cell production. (eurekalert.org)
- The purpose of this study is to evaluate the percentage of spleen (largest lymph organ in the body) response and symptom response of 2 dose regimens of imetelstat in participants with intermediate-2 or high-risk myelofibrosis (MF) who are relapsed after or refractory to Janus Kinase (JAK) inhibitor treatment. (clinicaltrials.gov)
- This is a randomized (study medication assigned to participants by chance), multicenter (more than one hospital, medical school team or medical clinic work on a medical research study) study of 2 dosing regimens (treatment arms) of single-agent imetelstat in participants with intermediate-2 or high risk myelofibrosis (MF) whose disease is relapsed after or refractory to Janus Kinase (JAK) inhibitor treatment. (clinicaltrials.gov)
Mitogen-activa4
- In the present study, it was identified that dihydroartemisinin inhibited cell viability, promoted cell apoptosis, increased B‑cell lymphoma‑2‑associated X‑protein expression, increased caspase‑3/9 activities, decreased poly(ADP‑ribose) polymerase levels, decreased phosphorylation of extracellular‑signal‑regulated kinase, and increased phosphorylation of c‑Jun N‑terminal kinase and p38 mitogen‑activated protein kinase in colon cancer cells. (spandidos-publications.com)
- However, accumulation of activated extracellular signal-regulated kinase (ERK)1 and ERK2 were the only transducers measured in the study not affected by the 1% replacement pulse of growth hormone and were elevated 2- to 3-fold above normal when the pulse was renaturalized to 10% of physiological amplitude, suggesting the possible involvement of mitogen-activated protein kinase in episodic growth hormone regulation of CYP2C11. (aspetjournals.org)
- GH-stimulated activation of signal transducers and activators of transcription (STATs), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3' kinase (PI3K) cascades have been shown to regulate the transcription of GH-responsive genes. (biomedsearch.com)
- Mitogen-activated protein kinase plays an essential role in the erythropoietin-dependent proliferation of CTLL-2 cells. (biomedsearch.com)
JAK312
- The JAK proteins are a family of four cytosolic tyrosine kinases (JAK1, JAK2, JAK3, and TYK2). (aacrjournals.org)
- Structural and thermodynamic characterization of the TYK2 and JAK3 kinase domains in complex with CP-690550 and CMP-6. (guidetopharmacology.org)
- Janus kinases (JAKs) are a family of intracellular, non-receptor tyrosine kinases including four family members such as JAK1, JAK2, JAK3, and Tyk2. (biomedcentral.com)
- Tyrosine-protein kinase JAK3 is a tyrosine kinase enzyme that in humans is encoded by the JAK3 gene. (wikipedia.org)
- Functional reconstitution of kinase activity by recombinant Jak3 using Jak3-wt or villin/gelsolin-wt as substrate showed that Jak3 autophosphorylation was the rate-limiting step during interactions between Jak3 and cytoskeletal proteins. (wikipedia.org)
- while TNF-alpha levels in LPS + 50 mmol/L CORM-2 and LPS + 100 mmol/L CORM-2 groups decreased obviously as compared with that of LPS group [(5.7 +/- 1.4), (3.2 +/- 0.9) pg/mL, with t value respectively 2.104 and 2.363, P values all below 0.05], and it was the same with phosphorylation levels of JAK1, JAK3 in a dose -dependent manner. (bvsalud.org)
- while plasma levels of TNF-alpha and IL-1beta and the phosphorylation levels of JAK1, JAK3 in liver tissue decreased significantly in CLP + CORM-2 group (with t value respectively 2.115 and 2.398, and P values all below 0.05). (bvsalud.org)
- The four JAK family members are: Janus kinase 1 (JAK1) Janus kinase 2 (JAK2) Janus kinase 3 (JAK3) Tyrosine kinase 2 (TYK2) Transgenic mice that do not express JAK1 have defective responses to some cytokines, such as interferon-gamma. (wikipedia.org)
- Global Markets Direct's, 'Tyrosine Protein Kinase JAK3 (Janus Kinase 3 or Leukocyte Janus Kinase or JAK3 or EC 2.7.10.2) - Pipeline Review, H2 2016', provides in depth analysis on Tyrosine Protein Kinase JAK3 (Janus Kinase 3 or Leukocyte Janus Kinase or JAK3 or EC 2.7.10.2) targeted pipeline therapeutics. (globalmarketsdirect.com)
- The report provides comprehensive information on the Tyrosine Protein Kinase JAK3 (Janus Kinase 3 or Leukocyte Janus Kinase or JAK3 or EC 2.7.10.2), targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (globalmarketsdirect.com)
- Additionally, the report provides an overview of key players involved in Tyrosine Protein Kinase JAK3 (Janus Kinase 3 or Leukocyte Janus Kinase or JAK3 or EC 2.7.10.2) targeted therapeutics development and features dormant and discontinued projects. (globalmarketsdirect.com)
- Second, Jak3 is widely believed to be expressed only in cells of the lymphoid and myeloid lineages, while Jak1, Jak2, and tyrosine kinase 2 are ubiquitously expressed ( 2 , 4 , 5 ). (jimmunol.org)
Protein kinase6
- In the present study, we investigated a novel AG490 analogue, ( E )-3(6-bromopyridin-2-yl)-2-cyano- N -((S0-1-phenylethyl)acrylamide) (WP1066), whose solubility and protein kinase-inhibitory profile suggested that this compound might be a good candidate for clinical development. (aacrjournals.org)
- In addition, HG increases the de novo synthesis of the protein kinase C activator diacylglycerol ( 3 ). (diabetesjournals.org)
- Thus, a mechanism by which HG induces GMC production of TGF-β and extracellular matrix molecules may be through the chronic activation of one or more isoforms of protein kinase C ( 4 ). (diabetesjournals.org)
- Additionally, TM increased the expression of nuclear respiratory factor 2 (Nrf2), catalase, heme oxygenase 1, heme oxygenase 2, and manganese superoxide dismutase 2 and decreased the expression of protein kinase C alpha, phosphor-janus kinase 2, phosphor-signal transducer and activator of transcription 3, and phosphor-nuclear factor- κ B in the kidneys. (hindawi.com)
- However, greater activation of protein kinase C and loss of Akt and endothelial nitric oxide synthase phosphorylation occurred in the Akita/ACE2KO hearts. (ahajournals.org)
- Tyrosine-protein kinase Tec is an enzyme that in humans is encoded by the TEC gene . (wn.com)
V617F6
- The V617F mutation in the JAK-2 gene is associated with myeloproliferative disorders (MPDs). (5minuteconsult.com)
- The role of Janus Kinase 2 V617F mutation in extramedullary hematopoiesis of the spleen in neoplastic myeloid disorders. (cdc.gov)
- She had thrombocytosis in the peripheral blood, and a genetic test for thrombocytosis revealed the presence of the valine-to-phenylalanine (V617F) mutation of the Janus kinase 2 (JAK2) gene. (jkna.org)
- 야누스키나아제(janus kinase 2, JAK2)는 티로신인산화효소(tyrosine kinase)의 일종으로 조혈기능에 관여하는 유전자로, JAK2 유전자의 valine-to-phenylalanine (V617F) 돌연변이는 진성적혈구증가증, 본태혈소판증가증과 같은 골수증식성질환을 초래하고 혈전색전증의 위험을 높이는 것으로 알려져 있다[ 1 ]. (jkna.org)
- Jak2 +/VF mice have an inverted exon 14, carrying a valine to phenylalanine mutation (V617F), downstream of the endogenous exon 14 of the Janus kinase 2 ( Jak2 ) gene. (jax.org)
- The V617F mutation results in constitutive activation of JAK2 kinase signaling. (jax.org)
Inhibitors10
- A screen of 72 inhibitors against 456 human kinases. (guidetopharmacology.org)
- The discovery of an activating Janus kinase 2 (JAK2) activating mutation (JAK2V617F) that is present in almost all patients with PV and in about 50-60 % of patients with ET and PMF led to the initiation of several trials investigating the clinical effectiveness of various JAK2 (or JAK1/JAK2) inhibitors for the treatment of patients with ET, PV, and MF. (biomedcentral.com)
- However, for inhibitors that do not affect the actin cytoskeleton or induce cell death, we show that chemokine-induced cell migration is not dependent on activation of Janus kinase 2 or STAT3. (edu.au)
- The similarity between the ATP binding site of protein kinases has made development of specific inhibitors difficult. (frontiersin.org)
- It is thought that increasing selectivity of kinase inhibitors may reduce the side effects seen with current treatment options. (frontiersin.org)
- Molecular modeling-driven approach for identification of Janus kinase 1 inhibitors through 3D-QSAR, docking and molecular dynamics simulations. (nih.gov)
- We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib). (bmj.com)
- Paris, France - June 30, 2010 - Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today that it has signed an agreement for the acquisition of TargeGen Inc., ("TargeGen") a privately held US biopharmaceutical company developing small molecule kinase inhibitors for the treatment of certain forms of leukemia, lymphoma and other hematological malignancies and blood disorders. (fiercebiotech.com)
- TargeGen is a privately held US biopharmaceutical company based in San Diego, CA, USA, developing small molecule kinase inhibitors for the treatment of hematological malignancies and certain other disorders. (fiercebiotech.com)
- As Janus kinase inhibitors alter the immune response they increase the risk of serious infections. (nps.org.au)
Pathway27
- The driving force for the leukemia is the activated tyrosine kinase of Bcr-Abl, which stimulates several signal transduction pathways ( 1 ), including the Janus kinase (Jak) 2 pathway ( 2 ) and, separately, the signal transducer and activator of transcription 5 (STAT5) pathway ( 3 ). (aacrjournals.org)
- Using the Mono Mac 1 monocytic cell line, we show that monocyte chemotactic protein 1 (MCP-1) triggers activation of the Janus kinase 2 (JAK2)/STAT3 pathway and CCR2 receptor tyrosine phosphorylation. (uniprot.org)
- These results implicate the tyrosine kinase pathway in early chemokine signaling, suggesting a key role for this kinase in later events. (uniprot.org)
- Objective Angiotensin II (AngII) activates via angiotensin-II-type-I receptor (AT1R) Janus-kinase-2 (JAK2)/Arhgef1 pathway and subsequently RHOA/Rho-kinase (ROCK), which induces experimental and probably human liver fibrosis. (bmj.com)
- A considerable number of reports have indicated that episodic growth hormone effects are mediated by the activation of the Janus kinase 2 (Jak2)/signal transducer and activator of transcription (Stat)5B signal transduction pathway. (aspetjournals.org)
- Several studies have established a role for the Janus tyrosine kinase/signal transducer and activator of transcription (Jak/Stat) signal transduction pathway in mediating the actions of GH. (aspetjournals.org)
- Therefore, we investigated here the molecular mechanisms of CCL3-, CCL5- and CCL8-induced cells migration and investigated whether the Janus kinase/signal transducer and activator of transcription (STAT) signalling pathway is involved. (edu.au)
- To study the inhibitive effect of exogenous carbon monoxide -releasing molecules 2 (CORM-2) on the activation of Janus kinase /signal transducer and activator of transcription (JAK/STAT) pathway in sepsis . (bvsalud.org)
- Exogenous CORM-2 can obviously inhibit the phosphorylation of JAKs molecules and then inhibit the activation of JAK/STAT signal pathway in sepsis , and decrease the expression of downstream cytokines to effectively prevent cascade reaction in the inflammatory response after severe infection . (bvsalud.org)
- Non-coding RNA 886 promotes renal cell carcinoma growth and metastasis through the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. (bvsalud.org)
- Janus kinase ( JAK ) is a family of intracellular non-receptor tyrosine kinases , ranging from 120-140 kDa in size, that transduce cytokine -mediated signals via the JAK-STAT pathway . (wikidoc.org)
- Janus kinase 2, the downstream signal pathway of growth hormone receptor, was activated time-dependently by stimulating the BPC 157-treated tendon fibroblasts with growth hormone. (mdpi.com)
- We have recently shown that in vascular smooth muscle cells (VSMCs), exposure to HG results in the activation of the janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. (diabetesjournals.org)
- In addition, we have shown that the activation of JAK2 was essential for both the Ang II and platelet-derived growth factor-induced MAP kinase pathway activation and VSMC growth ( 8 ). (diabetesjournals.org)
- Although the explicit pathogenesis of SLE remains unclear, increasing evidence suggests that dysregulation of cytokine signals contributes to the progression of SLE through the Janus kinase/signal transducer and activator of transcription (STAT) signaling pathway. (frontiersin.org)
- Many cytokines can activate the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 1 (STAT1) signaling pathway. (frontiersin.org)
- JAK2 is a member of the Janus kinase (JAK) family and aberrant JAK2/STAT is involved with various diseases, making the pathway a therapeutic target. (frontiersin.org)
- Our results suggest that MAP kinase activation is, at least in part, an important component for mitotic signal from the EPOR, and CTLL-2 cells probably lack signaling molecule(s) in JAK2 and the Ras-MAP kinase pathway. (biomedsearch.com)
- Janus kinase (JAK) is a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. (wikipedia.org)
- It inhibits the intracellular signalling pathway of cytokines such as IL-2, IL-6, IL-10, interferon-γ, and granulocyte macrophage colony-stimulating factor. (medscape.com)
- The present study was designed to investigate the specific role of IL‑23 in myocardial I/R injury, and whether the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2‑STAT3) signaling pathway, one of the important downstream signaling pathways of IL‑23, and the IL‑17A downstream pro‑inflammatory cytokine, were involved. (spandidos-publications.com)
- The present study attempted to test the hypothesis that IL-23 aggravates myocardial I/R injury by promoting inflammatory responses and myocardial apoptosis, which may be associated with the high expression of IL-17A and upregulation of the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2-STAT3) signaling pathway. (spandidos-publications.com)
- Renal protein levels of Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway components were determined by western blot assay. (spandidos-publications.com)
- The Janus kinase 2 (JAK2)/STAT3 pathway is well known to be involved in the immune response of numerous cytokines, including TNF-α and IL-6 ( 6 ). (spandidos-publications.com)
- Frequent subversion of the PI3K (phosphoinositide 3-kinase) pathway during neoplastic transformation contributes to several hallmarks of cancer that result in a competitive advantage for cancer cells. (biochemsoctrans.org)
- Deregulation of this pathway can be the result of genomic alterations such as PIK3CA mutation, PTEN (phosphatase and tensin homologue deleted on chromosome 10) loss or the activation of upstream protein tyrosine kinases. (biochemsoctrans.org)
- There are two large subgroups of cytokine-receptor interactions that cause signal transduction via the Janus kinase-Signal Transducer and Activation of Transcription (JAK-STAT) pathway. (nps.org.au)
Proteins6
- We have shown that Bcr-Abl is associated with a cluster of signaling proteins, including Janus kinase (Jak) 2, growth factor receptor binding protein 2-associated binder (Gab) 2, Akt, and glycogen synthase kinase (GSK)-3β. (aacrjournals.org)
- Each LepRb tyrosine phosphorylation site recruits specific Src homology 2 (SH2) domain-containing effector proteins: Tyr 985 recruits Src homology phosphatase-2 (SHP-2) and suppressor of cytokine signaling 3 and attenuates LepRb signaling, but does not appear to play other roles in leptin action in vivo ( 13 - 15 ). (diabetesjournals.org)
- Upon binding to their cellular receptors, hematopoietic growth factors and cytokines activate Janus-activated kinase (JAK) proteins. (aacrjournals.org)
- The differential tyrosine phosphorylation of these proteins suggests involvement of a kinase other than Jak2 in Stat5A activation. (lu.se)
- Since members of the type I and type II cytokine receptor families possess no catalytic kinase activity, they rely on the JAK family of tyrosine kinases to phosphorylate and activate downstream proteins involved in their signal transduction pathways. (wikidoc.org)
- The encoded kinase phosphorylates STAT proteins (signal transducers and activators of transcription) and plays a key role in interferon-alpha/beta and interferon-gamma signal transduction. (nih.gov)
Phosphorylation10
- The activation step involves phosphorylation of critical Tyr 1007 ( 2 , 5 ). (aacrjournals.org)
- Leptin binding to LepRb initiates signaling by activating the associated Janus kinase 2 (Jak2) tyrosine kinase, which promotes the phosphorylation of tyrosine residues on the intracellular tail of LepRb. (diabetesjournals.org)
- The chemokine monocyte chemotactic protein 1 triggers Janus kinase 2 activation and tyrosine phosphorylation of the CCR2B receptor. (uniprot.org)
- Mashili F, Chibalin AV, Krook A, Zierath JR. Constitutive STAT3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. (umassmed.edu)
- Similar to its parent compound AG490, WP1066 inhibited the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein, thereby blocking its downstream signal transducer and activator of transcription (STAT) and phosphoinositide-3-kinase pathways. (aacrjournals.org)
- Conversely, the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was suppressed by dihydroartemisinin in colon cancer cells. (spandidos-publications.com)
- In vitro growth hormone (GH) stimulation of Janus kinase 2 (Jak2) tyrosine phosphorylation and activation has been detected in rat adipocytes where GH exerts both chronic diabetogenic and acute insulin-like effects but not in adipocytes where only chronic diabetogenic effects are exerted. (lu.se)
- The interaction of GH with GH receptors (GHR) on target cells promotes the association of the cellular tyrosine kinase JAK2 with the GHR, initiating tyrosine phosphorylation of GHR and JAK2, and activation of multiple signaling cascades. (biomedsearch.com)
- The kinase inhibitory region of SOCS1 targets the substrate binding groove of JAK1 and JAK2 with high specificity and thereby blocks any subsequent phosphorylation. (nih.gov)
- This is mediated by phosphorylation of latent cytoplasmic STAT3 on specific residues (Y705, Ser727) by a variety of tyrosine and serine kinases leading to its dimerization and nuclear translocation, where it acts as a transcription factor for a plethora of genes governing the malignant properties of the tumor cell. (mdpi.com)
Mutations7
- Janus kinase 2 mutations in Philadelphia negative chronic myeloproliferative disorders: clinical implications. (semanticscholar.org)
- This study aimed to evaluate the association of factor V Leiden (FVL), Janus kinase 2 (JAK2), prothrombin, and methylene tetrahydrofolate reductase (MTHFR) mutations with primary BCS. (cdc.gov)
- Mutations that abrogate Janus kinase 3 function cause an autosomal SCID (severe combined immunodeficiency disease), while activating Janus kinase 3 mutations lead to the development of leukemia. (wikipedia.org)
- Dysregulated Janus kinase (JAK)-sign transducer and activator of transcription (STAT) signaling, aswell as mutations in JAK2, are normal in Philadelphia chromosome-negative MPNs [3]. (biologyexperimentideas.net)
- Janus kinase 2 ( JAK2 ) mutations define polycythemia vera (PV). (bloodjournal.org)
- Fms-like tyrosine kinase 3 (Flt3), PI3K, and signal transducer and activator of transcription (Stat)] are dysregulated by these mutations in Cbl has helped to identify potential targets for therapy of myeloid neoplasms. (curehunter.com)
- MF is a chronic and progressive disorder in which there is a proliferation of certain cells of the bone marrow resulting in bone marrow fibrosis and is associated with activating mutations of JAK-2. (fiercebiotech.com)
TYK22
- Non-phosphorylated TYK2 kinase with CMP6. (guidetopharmacology.org)
- Other members of the Janus family include JAK1, JAK2 and TYK2. (wikipedia.org)
STAT33
- Additionally, tubulosine suppressed IL-6-induced Janus kinase 2 (JAK2)/STAT3 signaling, resulting in decreased viability and induction of apoptotic cell death in breast cancer cells. (bvsalud.org)
- Furthermore, whether nc886 exerts its function on RCC via Janus kinase 2 / signal transducer and activator of transcription 3 (JAK2/STAT3) signaling was investigated. (bvsalud.org)
- We recently found that exposure of cells to HG also activates the growth-promoting enzyme janus kinase 2 (JAK2) and its latent signal transducers and activators of transcription (STAT) transcription factors (STAT1, STAT3, and STAT5). (diabetesjournals.org)
Mice3
- Mice with hepatocyte -specific deletion of Janus kinase 2 (L-JAK2 KO mice ) develop spontaneous steatosis as early as 2 weeks of age. (bvs.br)
- Thirty-five male BALB/c mice were divided into normal control group , cecal ligation and puncture (CLP) group, CLP + iCORM-2 (8.0 mg/kg) group and CLP + CORM-2 group (8.0 mg/kg) according to the random number table. (bvsalud.org)
- Mice in CLP + CORM-2 group were treated the same as mice in CLP group except for administration of CORM-2 after CLP. (bvsalud.org)
Humans1
- In December 2019, the first known cases of the coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were identified in humans in Wuhan, China. (jmir.org)
Ruxolitinib1
- Ruxolitinib and baracitinib mainly inhibit Janus kinase 1 and 2. (nps.org.au)
JAKs5
- Janus kinases (JAKs) are relatively large kinases of approximately 1150 amino acids with apparent molecular weights of 120-130 kDa. (wikipedia.org)
- The JH3-JH4 domain of JAKs shares homology with Src-homology -2 (SH2) domains. (wikidoc.org)
- this domain is also found in the focal adhesion kinase (FAK) family and is involved in association of JAKs with cytokine receptors and/or other kinases [2] . (wikidoc.org)
- The name is taken from the two-faced Roman god of beginnings and endings, Janus, because the JAKs possess two near-identical phosphate-transferring domains. (wikipedia.org)
- JAKs range from 120-140 kDa in size and have seven defined regions of homology called Janus homology domains 1 to 7 (JH1-7). (wikipedia.org)
Pseudokinase domain3
- An interesting note is that only one of these carboxy-terminal JH domains retains full kinase function (JH1) while the other (JH2), previously thought to have no kinase functionality and accordingly termed a pseudokinase domain, has since been found to be catalytically active, albeit at only 10% that of the JH1 domain. (wikipedia.org)
- We review evidence that the pseudokinase STRAD controls the function of the tumour suppressor kinase LKB1 and that a single amino acid substitution within the pseudokinase domain of the tyrosine kinase JAK2 leads to several malignant myeloproliferative disorders. (nih.gov)
- JH2 is a pseudokinase domain , a domain structurally similar to a tyrosine kinase and is essential for a normal kinase activity yet lacks enzymatic activity. (wikidoc.org)
Intracellular2
- Signal transducers and activators of transcription (STATs), a protein family comprised of seven members (STAT1, −2, −3, −4, −5a, −5b and −6), generally transduce signals from activated receptors or intracellular kinases to the nucleus, thus activating and regulating gene transcription ( 5 ). (spandidos-publications.com)
- Tec family kinases are involved in the intracellular signaling mechanisms of cytokine receptors, lymphocyte surface antigens, heterotrimeric G-protein-coupled receptors, and integrin molecules. (wn.com)
Transducer and activator of transcription1
- Khabbazi S., Jacques R.O., Moyano Cardaba C. and Mueller A. (2013) Janus kinase 2 and signal transducer and activator of transcription 3 activation is not essential for CCL3-, CCL5- or CCL8-induced chemotaxis. (edu.au)
Downstream1
- The Jak2 VF targeting vector was designed to insert an inverted mutated exon 14 downstream of endogenous exon 14 of the Janus kinase 2 ( Jak2 ) gene. (jax.org)
Myeloproliferative disorders3
- Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS. (umassmed.edu)
- Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. (labcorp.com)
- The JAK2V617F tyrosine kinase mutation in myeloproliferative disorders: Status report and immediate implications for disease classification and diagnosis. (labcorp.com)
RECEPTORS9
- It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF receptor family (IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g. (wikipedia.org)
- Like other type I cytokine receptors ( 11 ), LepRb (which is required for physiologic leptin action) contains no intrinsic enzymatic activity, but associates with and activates the Janus kinase 2 (Jak2) tyrosine kinase to mediate leptin signaling. (diabetesjournals.org)
- They are cytosolic tyrosine kinases that are specifically associated with cytokine receptors. (wikipedia.org)
- Several distinct classes of cytokine receptors engage Jak kinases as primary effectors. (unh.edu)
- Among type 1 receptors, Janus-activated kinase (Jak) recruitment is mediated by membrane-proximal cytoplasmic domains, which typically contain conserved box motifs. (unh.edu)
- Tyrosine kinases of the Janus kinase (Jak) family transduce signals from the type I and type II cytokine receptors. (jimmunol.org)
- The type I receptor (cytokine/hematopoietic growth factor receptor) family and the type II receptor (IFNR) family use Janus kinase (Jak) 3 protein tyrosine kinases and STAT transcription factors to transduce signals from the receptors to the nucleus ( 1 , 2 , 3 , 4 , 5 , 6 ). (jimmunol.org)
- It appears to be essential for responsiveness of receptors that use this subunit, including the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. (jimmunol.org)
- The Janus kinase family of enzymes are associated with cytokine receptors on the surface of cells. (nps.org.au)
Interleukin5
- The box1 domain of the erythropoietin receptor specifies Janus kinase 2 activation and functions mitogenically within an interleukin 2 beta-receptor chimera. (unh.edu)
- It has been shown that the ectopic expression of EPOR confers EPO-dependent proliferation on an interleukin 3 (IL3)-dependent cell line, Ba/F3, whereas the IL2-dependent T cell line, CTLL-2 expressing the EPOR (T-ER), fails to proliferate in response to EPO. (biomedsearch.com)
- Myocardial I/R can induce local myocardial inflammation, including promoting the release of various cytokines, including interleukin (IL)-17A, tumor necrosis factor-α (TNF-α) and IL-6, and promoting the activation of inflammatory cells, including neutrophils, which is one of the crucial pathophysiological processes in myocardial I/R injury ( 2 - 4 ). (spandidos-publications.com)
- Increasing evidence has indicated that pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, have an important role in the pathological mechanisms of SAP and SAP-associated organ failure ( 2 - 4 ). (spandidos-publications.com)
- For example, the cytokine interleukin-2 stimulates the production of T cells. (nps.org.au)
Myelofibrosis2
- In 2005, a mutation located at exon 14 of the Janus Kinase gene on chromosome 9 was discovered in patients with Polycythaenia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF). (up.ac.za)
- TG 101348 has completed a multicenter clinical Phase 1/2 trial in patients with myelofibrosis. (fiercebiotech.com)
Pathways2
- JAK2 is a protein tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways and is misregulated or mutated in some myeloproliferative diseases and cancers. (jax.org)
- These mechanisms include the nonenzymatic modification of macromolecules to form advanced glycation end products, changes in sorbitol and myoinositol metabolism, increased oxidant formation, and activation of mitogen-activated protein (MAP) kinase pathways ( 5 , 6 ). (diabetesjournals.org)
Called Janus homology1
- these are called Janus homology domain 1-7 (JH1-7). (wikidoc.org)
Recombinant1
- Description: In an assay using the kinase domain of the recombinant human enzyme, a biotinylated peptide substrate, and [ 33 P]ATP. (guidetopharmacology.org)
Metabolism2
- TM promoted glucose metabolism by increasing the levels of pyruvate kinase and hepatic glycogen. (hindawi.com)
- Janus kinase 3 regulates renal 25-hydroxyvitamin D 1α-hydroxylase expression, calcitriol formation, and phosphate metabolism. (xenbase.org)
Receptor tyrosi4
- Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. (wikipedia.org)
- Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. (uniprot.org)
- Non-receptor tyrosine kinase involved in various processes such as cell cycle progression, apoptosis, mitotic recombination, genetic instability and histone modifications. (abcam.com)
- A receptor tyrosine kinase that is involved in HEMATOPOIESIS. (curehunter.com)
Panel of kinases1
- NVP-BSK805 displays more than 20-fold selectivity over the other JAK family members and more than 100-fold selectivity over a panel of kinases in vitro . (aacrjournals.org)
Another kinase1
- Initially discovered in a PCR-based screen of kinases [1] and named ironically as "just another kinase" 1 & 2 (since they were two of a large number of new kinases discovered in the screen) JAK1 and JAK2 were ultimately published as Janus kinase 1 and Janus kinase 2. (wikidoc.org)
Activates1
- Bcr-Abl activates the Jak2 tyrosine kinase ( 2 , 5 ), a member of the Jak family. (aacrjournals.org)
Expression3
- Pulse amplitudes that decline to ∼2% or less of normal become incapable of inducing CYP2C11 expression ( Agrawal and Shapiro, 2000 ). (aspetjournals.org)
- Fc receptor-mediated opsonization also enhances expression of costimulatory molecules such as CD40, B7-1 (CD80), and B7-2 (CD86) on the DC surface, promoting T cell activation. (nih.gov)
- Expression of Janus Kinase 1 in vitiligo & psoriasis before and after narrow band UVB: a case-control study. (nih.gov)
Enzyme3
- Angiotensin-converting enzyme-2 (ACE2) is a negative regulator of the renin-angiotensin system. (ahajournals.org)
- 8 - 11 Angiotensin-converting enzyme-2 (ACE2) is a carboxypeptidase that metabolizes angiotensin II (Ang II) to yield angiotensin 1 to 7 (Ang 1-7), essentially negatively regulating the RAS. (ahajournals.org)
- After a cytokine binds to its receptor, an enzyme called Janus kinase (JAK) contributes to the processes within the cell to produce an immune or inflammatory response. (nps.org.au)
Cytokines4
- Several cytokines and growth factors that stimulate the proliferation of acute myelogenous leukemia (AML) cells transduce their signals by activating the transcription factor Janus-activated kinase 2 (JAK2). (aacrjournals.org)
- Janus kinase 2 (JAK2) is associated with the embryonic development of normal individuals and is widely expressed in various types of cell, catalyzing the immune responses induced by cytokines ( 7 ). (spandidos-publications.com)
- Growth factors and cytokines produced by the cells of hematopoietic origin use Jak kinases for signal transduction in both immune and nonimmune cells. (wikipedia.org)
- These cytokines are secreted by activated T cells and macrophages that infiltrate the islets (referred to as the insulitis lesion) during the autoimmune reaction ( 2 ). (jimmunol.org)
Constitutive1
- Furthermore, chromosomal translocations that involve the JAK2 kinase, such as the t(9;12) TEL-JAK2 fusion in rare cases of T-cell acute lymphoblastic leukemia, can also cause constitutive kinase activation ( 13 ). (aacrjournals.org)
Glycogen3
- Up-Regulation of the Large-Conductance Ca2+-Activated K+ Channel by Glycogen Synthase Kinase GSK3β. (xenbase.org)
- by Lithium Sensitive Glycogen Synthase Kinase GSK3ß. (xenbase.org)
- SLC6A8) by Glycogen Synthase Kinase GSK3ß. (xenbase.org)
Regulates1
- One domain exhibits the kinase activity, while the other negatively regulates the kinase activity of the first. (wikipedia.org)
Extracellular2
- One of the basic underlying mechanisms of diabetic nephropathy seems to involve high glucose (HG)-induced production of transforming growth factor-β (TGF-β) and extracellular matrix molecules such as fibronectin ( 1 , 2 ). (diabetesjournals.org)
- Glomerular mesangial cells (GMCs) cultured under HG conditions produce TGF-β and extracellular matrix molecules at a significantly faster rate than those cultured under normal glucose (NG) conditions ( 1 , 2 ). (diabetesjournals.org)
Homology binding1
- Epo-R, Tpo-R, GH-R, PRL-R). The distinguishing feature between janus kinase 2 and other JAK kinases is the lack of Src homology binding domains (SH2/SH3) and the presence of up to seven JAK homology domains (JH1-JH7). (wikipedia.org)
Growth3
- OBJECTIVE: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity. (bireme.br)
- Janus kinase 2 influences growth hormone receptor metalloproteolysis. (semanticscholar.org)
- Janus kinase 2 enhances the stability of the mature growth hormone receptor. (semanticscholar.org)