Protein Tyrosine Phosphatase, Non-Receptor Type 11: A subtype of non-receptor protein tyrosine phosphatases that contain two SRC HOMOLOGY DOMAINS. Mutations in the gene for protein tyrosine phosphatase, non-receptor type 11 are associated with NOONAN SYNDROME.LEOPARD Syndrome: An autosomal dominant disorder with an acronym of its seven features (LENTIGO; ELECTROCARDIOGRAM abnormalities; ocular HYPERTELORISM; PULMONARY STENOSIS; abnormal genitalia; retardation of growth; and DEAFNESS or SENSORINEURAL HEARING LOSS). This syndrome is caused by mutations of PTPN11 gene encoding the non-receptor PROTEIN TYROSINE PHOSPHATASE, type 11, and is an allelic to NOONAN SYNDROME. Features of LEOPARD syndrome overlap with those of NEUROFIBROMATOSIS 1 which is caused by mutations in the NEUROFIBROMATOSIS 1 GENES.Protein Tyrosine Phosphatase, Non-Receptor Type 6: A Src-homology domain-containing protein tyrosine phosphatase found in the CYTOSOL of hematopoietic cells. It plays a role in signal transduction by dephosphorylating signaling proteins that are activated or inactivated by PROTEIN-TYROSINE KINASES.Protein Tyrosine Phosphatases: An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.Noonan Syndrome: A genetically heterogeneous, multifaceted disorder characterized by short stature, webbed neck, ptosis, skeletal malformations, hypertelorism, hormonal imbalance, CRYPTORCHIDISM, multiple cardiac abnormalities (most commonly including PULMONARY VALVE STENOSIS), and some degree of INTELLECTUAL DISABILITY. The phenotype bears similarities to that of TURNER SYNDROME that occurs only in females and has its basis in a 45, X karyotype abnormality. Noonan syndrome occurs in both males and females with a normal karyotype (46,XX and 46,XY). Mutations in a several genes (PTPN11, KRAS, SOS1, NF1 and RAF1) have been associated the the NS phenotype. Mutations in PTPN11 are the most common. LEOPARD SYNDROME, a disorder that has clinical features overlapping those of Noonan Syndrome, is also due to mutations in PTPN11. In addition, there is overlap with the syndrome called neurofibromatosis-Noonan syndrome due to mutations in NF1.Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.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.SH2 Domain-Containing Protein Tyrosine Phosphatases: A subcategory of protein tyrosine phosphatases that contain SH2 type SRC HOMOLOGY DOMAINS. Many of the proteins in this class are recruited to specific cellular targets such as a cell surface receptor complexes via their SH2 domain.Steroid 12-alpha-Hydroxylase: A liver microsomal cytochrome P450 enzyme that catalyzes the 12-alpha-hydroxylation of a broad spectrum of sterols in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP8B1gene, converts 7-alpha-hydroxy-4-cholesten-3-one to 7-alpha-12-alpha-dihydroxy-4-cholesten-3-one and is required in the synthesis of BILE ACIDS from cholesterol.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.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.Cholesterol 7-alpha-Hydroxylase: A membrane-bound cytochrome P450 enzyme that catalyzes the 7-alpha-hydroxylation of CHOLESTEROL in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP7, converts cholesterol to 7-alpha-hydroxycholesterol which is the first and rate-limiting step in the synthesis of BILE ACIDS.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.GRB2 Adaptor Protein: A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).Chlorpropamide: A sulfonylurea hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. (From Martindale, The Extra Pharmacopoeia, 30th ed, p277)Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Adaptor Protein Complex 4: An adaptor protein complex involved in transport of molecules between the TRANS-GOLGI NETWORK and the endosomal-lysosomal system.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.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 enzymesPhosphoproteinsCytokine Receptor gp130: A cytokine receptor that acts through the formation of oligomeric complexes of itself with a variety of CYTOKINE RECEPTORS.Adamantane: A tricyclo bridged hydrocarbon.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.DAX-1 Orphan Nuclear Receptor: An orphan nuclear receptor that is implicated in regulation of steroidogenic pathways. It is unlike most orphan nuclear receptors in that it appears to lack an essential DNA-binding domain and instead acts as a transcriptional co-repressor. Mutations in the gene Dax-1 cause congenital adrenal hypoplasia.Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.Megakaryocyte Progenitor Cells: The parent cells that give rise to cells in the MEGAKARYOCYTE lineage, and ultimately BLOOD PLATELETS.Pyrazolones: Compounds with a five-membered heterocyclic ring with two nitrogens and a keto OXYGEN. Some are inhibitors of TNF-ALPHA production.CinnamatesCholic Acid: A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Hepatocyte Nuclear Factor 4: A subfamily of nuclear receptors that regulate GENETIC TRANSCRIPTION of a diverse group of GENES involved in the synthesis of BLOOD COAGULATION FACTORS; and in GLUCOSE; CHOLESTEROL; and FATTY ACIDS metabolism.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.Elafin: A secretory proteinase inhibitory protein that was initially purified from human SKIN. It is found in a variety mucosal secretions and is present at high levels in SPUTUM. Elafin may play a role in the innate immunity (IMMUNITY, INNATE) response of the LUNG.STAT3 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.Son of Sevenless Protein, Drosophila: A guanine nucleotide exchange factor from DROSOPHILA. Sevenless refers to genetic mutations in DROSOPHILA that cause loss of the R7 photoreceptor which is required to see UV light.Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones.Head Injuries, Penetrating: Head injuries which feature compromise of the skull and dura mater. These may result from gunshot wounds (WOUNDS, GUNSHOT), stab wounds (WOUNDS, STAB), and other forms of trauma.Phosphoenolpyruvate Carboxykinase (ATP): An enzyme of the lyase class that catalyzes the conversion of ATP and oxaloacetate to ADP, phosphoenolpyruvate, and carbon dioxide. The enzyme is found in some bacteria, yeast, and Trypanosoma, and is important for the photosynthetic assimilation of carbon dioxide in some plants. EC 22.214.171.124.Leukemia, Myelomonocytic, Juvenile: A leukemia affecting young children characterized by SPLENOMEGALY, enlarged lymph nodes, rashes, and hemorrhages. Traditionally classed as a myeloproliferative disease, it is now considered a mixed myeloproliferative-mylelodysplastic disorder.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Mice, Inbred C57BLTransfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Hemeproteins: Proteins that contain an iron-porphyrin, or heme, prosthetic group resembling that of hemoglobin. (From Lehninger, Principles of Biochemistry, 1982, p480)Monocyte-Macrophage Precursor Cells: Parent cells in the lineage that gives rise to MONOCYTES and MACROPHAGES.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Cell Line, Tumor: A cell line derived from cultured tumor cells.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.Protein Phosphatase 2: A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.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.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.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.Fibroblast Growth Factors: A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.Trauma, Nervous System: Traumatic injuries to the brain, cranial nerves, spinal cord, autonomic nervous system, or neuromuscular system, including iatrogenic injuries induced by surgical procedures.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Suppressor of Cytokine Signaling Proteins: A family of structurally related proteins that are induced by CYTOKINES and negatively regulate cytokine-mediated SIGNAL TRANSDUCTION PATHWAYS. SOCS proteins contain a central SH2 DOMAIN and a C-terminal region of homology known as the SOCS box.Protein Tyrosine Phosphatase, Non-Receptor Type 1: A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM.Hep G2 Cells: A human liver tumor cell line used to study a variety of liver-specific metabolic functions.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Epidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Proto-Oncogene Proteins c-fyn: Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.Mitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 126.96.36.199.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Hydrazones: Compounds of the general formula R:N.NR2, as resulting from the action of hydrazines with aldehydes or ketones. (Grant & Hackh's Chemical Dictionary, 5th ed)Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Sulfonic Acids: Inorganic or organic oxy acids of sulfur which contain the RSO2(OH) radical.Myeloid Progenitor Cells: Stem cells derived from HEMATOPOIETIC STEM CELLS. Derived from these myeloid progenitor cells are the MEGAKARYOCYTES; ERYTHROID CELLS; MYELOID CELLS; and some DENDRITIC CELLS.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Class Ia Phosphatidylinositol 3-Kinase: A phosphatidylinositol 3-kinase subclass that includes enzymes formed through the heterodimerization of a p110 catalytic and a p85, p55, or p50 regulatory subunit. This subclass of enzymes is a downstream target of TYROSINE KINASE RECEPTORS and G PROTEIN-COUPLED RECEPTORS.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.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.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).Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Thrombopoiesis: The process of generating thrombocytes (BLOOD PLATELETS) from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW via the MEGAKARYOCYTES. The humoral factor with thrombopoiesis-stimulating activity is designated THROMBOPOIETIN.Janus Kinase 1: A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.Proto-Oncogene Proteins c-yes: Members of the src-family tyrosine kinases that are activated during the transition from G2 PHASE to M PHASE of the CELL CYCLE. It is highly homologous to PROTO-ONCOGENE PROTEIN PP60(C-SRC).Glucose-6-Phosphatase: An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC 188.8.131.52.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.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Gluconeogenesis: Biosynthesis of GLUCOSE from nonhexose or non-carbohydrate precursors, such as LACTATE; PYRUVATE; ALANINE; and GLYCEROL.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.Neuregulin-1: A peptide factor originally identified by its ability to stimulate the phosphorylation the erbB-2 receptor (RECEPTOR, ERBB-2). It is a ligand for the erbB-3 receptor (RECEPTOR, ERBB-3) and the erbB-4 receptor. Variant forms of NEUREGULIN-1 occur through alternative splicing of its mRNA.Ependymoglial Cells: The macroglial cells of EPENDYMA. They are characterized by bipolar cell body shape and processes that contact BASAL LAMINA around blood vessels and/or the PIA MATER and the CEREBRAL VENTRICLES.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Streptococcus pyogenes: A species of gram-positive, coccoid bacteria isolated from skin lesions, blood, inflammatory exudates, and the upper respiratory tract of humans. It is a group A hemolytic Streptococcus that can cause SCARLET FEVER and RHEUMATIC FEVER.Protein Tyrosine Phosphatase, Non-Receptor Type 2: A subtype of non-receptor protein tyrosine phosphatase that is closely-related to PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 1. Alternative splicing of the mRNA for this phosphatase results in the production at two gene products, one of which includes a C-terminal nuclear localization domain that may be involved in the transport of the protein to the CELL NUCLEUS. Although initially referred to as T-cell protein tyrosine phosphatase the expression of this subtype occurs widely.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.Benzenesulfonates: Organic salts and esters of benzenesulfonic acid.Myelopoiesis: Formation of MYELOID CELLS from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW via MYELOID STEM CELLS. Myelopoiesis generally refers to the production of leukocytes in blood, such as MONOCYTES and GRANULOCYTES. This process also produces precursor cells for MACROPHAGE and DENDRITIC CELLS found in the lymphoid tissue.Sialic Acid Binding Immunoglobulin-like Lectins: A family of SIALIC ACID binding proteins found in vertebrate species. They are transmembrane proteins which act as cell surface receptors for a variety of sialylated GLYCOCONJUGATES. While a subset of siglec protein subtypes are evolutionarily conserved between mammalian species, there are many others that are species specific.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.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.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.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Protein Interaction Domains and Motifs: Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Interleukin-3: A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells.Tobacco Products: Substances and products derived from NICOTIANA TABACUM.Oncogene Protein p21(ras): Transforming protein encoded by ras oncogenes. Point mutations in the cellular ras gene (c-ras) can also result in a mutant p21 protein that can transform mammalian cells. Oncogene protein p21(ras) has been directly implicated in human neoplasms, perhaps accounting for as much as 15-20% of all human tumors. This enzyme was formerly listed as EC 184.108.40.206.Fatty Acid Synthase, Type I: Animal form of fatty acid synthase which is encoded by a single gene and consists of seven catalytic domains and is functional as a homodimer. It is overexpressed in some NEOPLASMS and is a target in humans of some ANTINEOPLASTIC AGENTS and some ANTI-OBESITY AGENTS.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Gastrulation: A process of complicated morphogenetic cell movements that reorganizes a bilayer embryo into one with three GERM LAYERS and specific orientation (dorsal/ventral; anterior/posterior). Gastrulation describes the germ layer development of a non-mammalian BLASTULA or that of a mammalian BLASTOCYST.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Mitogen-Activated Protein Kinase 7: A 110-kDa extracellular signal-regulated MAP kinase that is activated in response to cellular stress and by GROWTH FACTOR RECEPTORS-mediated pathways.Hemin: Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen.Single-Cell Analysis: Assaying the products of or monitoring various biochemical processes and reactions in an individual cell.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.ras GTPase-Activating Proteins: PROTEINS that specifically activate the GTP-phosphohydrolase activity of RAS PROTEINS.Protein Phosphatase 1: A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions.Hepatocyte Nuclear Factor 6: A onecut transcription factor that regulates expression of GENES involved in EMBRYONIC DEVELOPMENT of the PANCREAS and LIVER.Helminth Proteins: Proteins found in any species of helminth.rhoA GTP-Binding Protein: A RHO GTP-BINDING PROTEIN involved in regulating signal transduction pathways that control assembly of focal adhesions and actin stress fibers. This enzyme was formerly listed as EC 220.127.116.11.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)Luciferases, Firefly: Luciferases from FIREFLIES, usually Photinus, that oxidizes FIREFLY LUCIFERIN to cause emission of PHOTONS.STAT1 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to INTERFERONS. Stat1 interacts with P53 TUMOR SUPPRESSOR PROTEIN and regulates expression of GENES involved in growth control and APOPTOSIS.Leukemia: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.Phospholipase C gamma: A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Leukemia Inhibitory Factor Receptor alpha Subunit: A receptor subunit that combines with CYTOKINE RECEPTOR GP130 to form the dual specificity receptor for LEUKEMIA INHIBITORY FACTOR and ONCOSTATIN M. The subunit is also a component of the CILIARY NEUROTROPHIC FACTOR RECEPTOR. Both membrane-bound and secreted isoforms of the receptor subunit exist due to ALTERNATIVE SPLICING of its mRNA. The secreted isoform is believed to act as an inhibitory receptor, while the membrane-bound form is a signaling receptor.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.Interleukin-6: A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.Protein Tyrosine Phosphatases, Non-Receptor: A subcategory of protein tyrosine phosphatases that occur in the CYTOPLASM. Many of the proteins in this category play a role in intracellular signal transduction.Cardiomegaly: Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.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.Vanadates: Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects.Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is PROTO-ONCOGENE PROTEINS C-MET.Orphan Nuclear Receptors: A broad category of receptor-like proteins that may play a role in transcriptional-regulation in the CELL NUCLEUS. Many of these proteins are similar in structure to known NUCLEAR RECEPTORS but appear to lack a functional ligand-binding domain, while in other cases the specific ligands have yet to be identified.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Feedback, Physiological: A mechanism of communication with a physiological system for homeostasis, adaptation, etc. Physiological feedback is mediated through extensive feedback mechanisms that use physiological cues as feedback loop signals to control other systems.QuinolinesGene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Annexin A2: A member of the annexin family that is a substrate for a tyrosine kinase, ONCOGENE PROTEIN PP60(V-SRC). Annexin A2 occurs as a 36-KDa monomer and in a 90-KDa complex containing two subunits of annexin A2 and two subunits of S100 FAMILY PROTEIN P11. The monomeric form of annexin A2 was formerly referred to as calpactin I heavy chain.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Genes, Reporter: Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.Basic Helix-Loop-Helix Leucine Zipper Transcription Factors: A family of transcription factors that contain regions rich in basic residues, LEUCINE ZIPPER domains, and HELIX-LOOP-HELIX MOTIFS.Myoblasts: Embryonic (precursor) cells of the myogenic lineage that develop from the MESODERM. They undergo proliferation, migrate to their various sites, and then differentiate into the appropriate form of myocytes (MYOCYTES, SKELETAL; MYOCYTES, CARDIAC; MYOCYTES, SMOOTH MUSCLE).Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Receptors, Immunologic: Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.MADS Domain Proteins: A superfamily of proteins that share a highly conserved MADS domain sequence motif. The term MADS refers to the first four members which were MCM1 PROTEIN; AGAMOUS 1 PROTEIN; DEFICIENS PROTEIN; and SERUM RESPONSE FACTOR. Many MADS domain proteins have been found in species from all eukaryotic kingdoms. They play an important role in development, especially in plants where they have an important role in flower development.Adenoma, Liver Cell: A benign epithelial tumor of the LIVER.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Quorum Sensing: A phenomenon where microorganisms communicate and coordinate their behavior by the accumulation of signaling molecules. A reaction occurs when a substance accumulates to a sufficient concentration. This is most commonly seen in bacteria.Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Benzene DerivativesGene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Receptors, Retinoic Acid: Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.Histone Deacetylase 1: A histone deacetylase subtype that is found along with HISTONE DEACETYLASE 2; RETINOBLASTOMA-BINDING PROTEIN 4; and RETINOBLASTOMA-BINDING PROTEIN 7 as core components of histone deacetylase complexes.Blood-Air Barrier: The barrier between capillary blood and alveolar air comprising the alveolar EPITHELIUM and capillary ENDOTHELIUM with their adherent BASEMENT MEMBRANE and EPITHELIAL CELL cytoplasm. PULMONARY GAS EXCHANGE occurs across this membrane.Cholestyramine Resin: A strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium Cl(-) anion.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Interleukin Receptor Common gamma Subunit: An interleukin receptor subunit that was originally discovered as a component of the INTERLEUKIN 2 RECEPTOR. It was subsequently found to be a component of several other receptors including the INTERLEUKIN 4 RECEPTOR, the INTERLEUKIN 7 RECEPTOR, the INTERLEUKIN-9 RECEPTOR, the INTERLEUKIN-15 RECEPTOR, and the INTERLEUKIN-21 RECEPTOR. Mutations in the gene for the interleukin receptor common gamma chain have been associated with X-LINKED COMBINED IMMUNODEFICIENCY DISEASES.Carcinoma, Hepatocellular: A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.Leukemia Inhibitory Factor: An INTERLEUKIN-6 related cytokine that exhibits pleiotrophic effects on many physiological systems that involve cell proliferation, differentiation, and survival. Leukemia inhibitory factor binds to and acts through the lif receptor.Adherens Junctions: Anchoring points where the CYTOSKELETON of neighboring cells are connected to each other. They are composed of specialized areas of the plasma membrane where bundles of the ACTIN CYTOSKELETON attach to the membrane through the transmembrane linkers, CADHERINS, which in turn attach through their extracellular domains to cadherins in the neighboring cell membranes. In sheets of cells, they form into adhesion belts (zonula adherens) that go all the way around a cell.Granulocyte Precursor Cells: The cells in the granulocytic series that give rise to mature granulocytes (NEUTROPHILS; EOSINOPHILS; and BASOPHILS). These precursor cells include myeloblasts, promyelocytes, myelocytes and metamyelocytes.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Neural Cell Adhesion Molecule L1: A member of the immunoglobulin superfamily of neuronal cell adhesion molecules that is required for proper nervous system development. Neural cell adhesion molecule L1 consists of six Ig domains, five fibronectin domains, a transmembrane region and an intracellular domain. Two splicing variants are known: a neuronal form that contains a four-amino acid RSLE sequence in the cytoplasmic domain, and a non-neuronal form that lacks the RSLE sequence. Mutations in the L1 gene result in L1 disease. Neural cell adhesion molecule L1 is predominantly expressed during development in neurons and Schwann cells; involved in cell adhesion, neuronal migration, axonal growth and pathfinding, and myelination.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Isoxazoles: Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.Focal Adhesion Kinase 2: A non-receptor protein-tyrosine kinase that is expressed primarily in the BRAIN; OSTEOBLASTS; and LYMPHOID CELLS. In the CENTRAL NERVOUS SYSTEM focal adhesion kinase 2 modulates ION CHANNEL function and MITOGEN-ACTIVATED PROTEIN KINASES activity.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Precursor Cells, B-Lymphoid: Lymphocyte progenitor cells that are restricted in their differentiation potential to the B lymphocyte lineage. The pro-B cell stage of B lymphocyte development precedes the pre-B cell stage.Nuclear Receptor Coactivators: Proteins that enhance gene expression when associated with ligand bound activated NUCLEAR RECEPTORS. The coactivators may act through an enzymatic process that affects the rate of transcription or the structure of chromatin. Alternatively nuclear receptor coactivators can function as adaptor proteins that bring nuclear receptors into close proximity with transcriptional complexes.Shc Signaling Adaptor Proteins: A family of signaling adaptor proteins that contain SRC HOMOLOGY DOMAINS. Many members of this family are involved in transmitting signals from CELL SURFACE RECEPTORS to MITOGEN-ACTIVATED PROTEIN KINASES.U937 Cells: A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Megakaryocytes: Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.
"Visualization of SHP-1-target interaction". Journal of Cell Science. 117 (Pt 21): 5165-78. doi:10.1242/jcs.01397. PMID 15456853 ... Cell. 131 (6): 1190-203. doi:10.1016/j.cell.2007.11.025. PMID 18083107. Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, ... Cell. 131 (6): 1190-203. doi:10.1016/j.cell.2007.11.025. PMID 18083107. Bergethon K, Shaw AT, Ou SH, Katayama R, Lovly CM, ... modulates cell morphology, and induces cell transformation". Molecular and Cellular Biology. 20 (24): 9212-24. doi:10.1128/MCB. ...
Cell. Endocrinol. 166 (2): 89-99. doi:10.1016/S0303-7207(00)00277-X. PMID 10996427. Zhu M, John S, Berg M, Leonard WJ (January ... Potential role of SHP-2 in STAT5 regulation". J. Biol. Chem. 275 (1): 599-604. doi:10.1074/jbc.275.1.599. PMID 10617656. ... Cell Biol. 42 (2): 186-92. doi:10.1016/j.biocel.2009.11.001. PMC 2818495 . PMID 19914392. Pestell, Richard G.; Nevalainen, ... This protein is activated by, and mediates the responses of many cell ligands, such as IL2, IL3, IL7 GM-CSF, erythropoietin, ...
In various hematopoietic cells, Lyn has emerged as a key enzyme involved in the regulation of cell activation. In these cells, ... Lyn-CD22-SHP-1 pathway GRCh38: Ensembl release 89: ENSG00000254087 - Ensembl, May 2017 GRCm38: Ensembl release 89: ... attenuate cell activation and can mediate tolerance. In B cells, Lyn sets the threshold of cell signaling and maintains the ... the Juxtamembrane Region of c-Kit and Is Activated by Stem Cell Factor in Hematopoietic Cell Lines and Normal Progenitor Cells ...
Cell. Biol. 19 (12): 8314-25. PMC 84915 . PMID 10567556. Berg KL, Siminovitch KA, Stanley ER (1999). "SHP-1 regulation of p62( ... Vuica M, Desiderio S, Schneck JP (1997). "Differential effects of B cell receptor and B cell receptor-FcgammaRIIB1 engagement ... induced by cell adhesion and insulin: possible role in cell migration". EMBO J. 18 (7): 1748-60. doi:10.1093/emboj/18.7.1748. ... "Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells". ...
SHP-1 negatively regulates pathways related to the actions of IFN-γ and insulin. LAM may regulate SHP-1 by multiple mechanisms ... In addition to serving as a major cell wall component, it is thought to serve as a modulin with immunoregulatory and anti- ... Once activated, SHP-1 translocates from the cytosol to the membrane. By activating a phosphatase, LAM can inhibit LPS and IFN-γ ... LAM's activation of SHP-1 also works to deactivate IL-12. IL-12 is important for innate resistance to M. tuberculosis ...
In addition the expression of SHP-1 is low in epithelial cells and high in hemopoetic cells. SHP-1 level in epithelial cells ... SHP-1 gene has two promoters: P-1, active in epithelial cells, and P-2, active in hemopoietic cells. ... SHP-1) association with Jak2 in UT-7/Epo cells". Blood Cells Mol. Dis. 26 (1): 15-24. doi:10.1006/bcmd.2000.0273. PMID 10772872 ... An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1". J. Cell Biol. 152 (2): 325-34. doi:10.1083/jcb. ...
In resting T cells, Lck is constitutively inhibited by Csk phosphorylation on tyrosine 505. Lck is also inhibited by SHP-1 ... It associates with the cytoplasmic tails of the CD4 and CD8 co-receptors on T helper cells and cytotoxic T cells, respectively ... to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen ... "CD45-associated kinase activity requires lck but not T cell receptor expression in the Jurkat T cell line". The Journal of ...
University of Texas Medical Branch
"Cell Biology Graduate Program". University of Texas Medical Branch. Retrieved 26 July 2013. "Department of Pathology Home Page ... "SHP Departments and Programs". University of Texas Medical Branch. Retrieved 23 September 2017. "ITS - Institute for ... The graduate school has 11 degree-granting programs: Biochemistry and Molecular Biology, Cell Biology, Cellular Physiology and ... the Sealy Center for Cancer Cell Biology, the Sealy Center for Environmental Health and Medicine, the World Health Organization ...
An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1". J. Cell Biol. 152 (2): 325-34. doi:10.1083/jcb. ... In vitro studies using cultured cells indicate that endothelial cells secrete PDGF, which recruits PDGFRβ-expressing pericytes ... Olson LE, Soriano P (2011). "PDGFRβ signaling regulates mural cell plasticity and inhibits fat development". Developmental Cell ... Cell. Biol. 12 (12): 5824-33. doi:10.1128/MCB.12.12.5824. PMC 360522 . PMID 1333047. Chen M, She H, Davis EM, Spicer CM, Kim L ...
Lam IP, Lee LT, Choi HS, Chow BK (2006). "Localization of small heterodimer partner (SHP) and secretin in mouse duodenal cells ... It is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands. In humans, the ... Secretin helps regulate the pH of the duodenum by (1) inhibiting the secretion of gastric acid from the parietal cells of the ... Secretin is synthesized in cytoplasmic secretory granules of S-cells, which are found mainly in the mucosa of the duodenum, and ...
Estrogen receptor beta
Cell. Endocrinol. 138 (1-2): 199-203. doi:10.1016/S0303-7207(98)00050-1. PMID 9685228. Seol W, Hanstein B, Brown M, Moore DD ( ... 1998). "Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner)". Mol. Endocrinol. 12 (10 ... Lung Cell Mol. Physiol. 293 (2): L272-8. doi:10.1152/ajplung.00174.2007. PMID 17575008. Stettner M, Kaulfuss S, Burfeind P, ... ERβ also plays a role in regulating APOE, a risk factor for AD that redistributes lipids across cells. APOE expression in the ...
Janus kinase 1
Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and ... Yin T, Shen R, Feng GS, Yang YC (1997). "Molecular characterization of specific interactions between SHP-2 phosphatase and JAK ... Cell. 93 (3): 373-83. doi:10.1016/S0092-8674(00)81166-6. PMID 9590172. Christian Nordqvist. "Protein JAK Makes Cancer Cells ... activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells". Cell Growth Differ. 13 (1): 13-8. PMID 11801527. ...
Small heterodimer partner
"Nuclear translocation of SHP and visualization of interaction with HNF-4alpha in living cells". Biochemical and Biophysical ... SHP is a member of the nuclear receptor family of intracellular transcription factors. SHP is unusual for a nuclear receptor in ... The small heterodimer partner (SHP) also known as NR0B2 (nuclear receptor subfamily 0, group B, member 2) is a protein that in ... Seol W, Hanstein B, Brown M, Moore DD (Oct 1998). "Inhibition of estrogen receptor action by the orphan receptor SHP (short ...
Actinin alpha 4
2001). "Association of tyrosine phosphatase SHP-2 with F-actin at low cell densities". J. Biol. Chem. 276 (31): 29479-84. doi: ... Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal ... 1998). "Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion". J. Cell Biol. 140 (6): ... 2002). "Raver1, a dual compartment protein, is a ligand for PTB/hnRNPI and microfilament attachment proteins". J. Cell Biol. ...
"Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling". Science. 272 (5265): 1173-6. doi:10.1126/science. ... is a protein normally expressed near the surface membrane of T cells and natural killer cells. It is part of the T cell ... The final outcome of T cell activation is the transcription of several gene products which allow the T cells to differentiate, ... dendritic cells and B cells) via the MHC. Upon this activation, the TCR co-receptor CD4 or CD8 binds to the MHC, activating the ...
French submarine Mariotte
Lymphocyte cytosolic protein 2
Mizuno K, Katagiri T, Hasegawa K, Ogimoto M, Yakura H (August 1996). "Hematopoietic cell phosphatase, SHP-1, is constitutively ... Mizuno K, Katagiri T, Hasegawa K, Ogimoto M, Yakura H (1996). "Hematopoietic cell phosphatase, SHP-1, is constitutively ... SLP-76 might serve as an integration point for signals by activating NK cell receptors. In NK cells, SLP-76 can be ... "SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors". J. Biol. Chem. 273 (42): 27518-23. doi: ...
... and miR-136 however, are only maternally expressed in the somatic cells and thus play a role in antisense regulation of ... Song G, Wang L (October 2008). "Transcriptional mechanism for the paired miR-433 and miR-127 genes by nuclear receptors SHP and ... Ectopic expression of miR-127 resulted in a reduction in Rtl1 expression in Human Hela cell and mouse Heppa-1. Experiments ... Upregulation of miR-127 caused a downregulation of B-cell lymphoma 6 protein, a proto-oncogene which is usually hypermutated in ...
"Activation of PKC-δ and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy". Nature Medicine. 15 ( ... The resulting withdrawal of this signaling leads to the programmed cell death (apoptosis) of the cells in this experimental ... which recruit inflammatory cells; and advanced dysfunction and degeneration of the neurons and glial cells of the retina. An ... The light from the mask stops rod cells in the retina from dark adapting, which is thought to reduce their oxygen requirement, ...
"Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility". Molecular and ... LNCaP prostate cancer cells increase cell adhesion and diminish cell motility via IGF-1 independent mechanism, when IRS-1 is ... Overexpression of PTEN in MCF-7 epithelial breast cancer cells inhibits cell growth by inhibiting MAPK pathway. ERK ... Decreased anchorage- dependent/independent cell growth and initiation of cell death under low growth factor and estrogen ...
Janus kinase 2
SHP-1) association with Jak2 in UT-7/Epo cells". Blood Cells, Molecules & Diseases. 26 (1): 15-24. doi:10.1006/bcmd.2000.0273. ... This mutation (V617F), a change of valine to phenylalanine at the 617 position, appears to render hematopoietic cells more ... Yin T, Shen R, Feng GS, Yang YC (January 1997). "Molecular characterization of specific interactions between SHP-2 phosphatase ... Cell. 74 (2): 227-36. doi:10.1016/0092-8674(93)90414-L. PMID 8343951. Sayeski PP, Ali MS, Safavi A, Lyles M, Kim SO, Frank SJ, ...
Insulin-like growth factor 1 receptor
"Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility". Mol. Cell. Biol. 19 ... This event triggers a cascade of intracellular signaling that, while cell type-specific, often promotes cell survival and cell ... sensitizes small cell lung cancer cell lines to the effects of chemotherapy". Clin. Cancer Res. 11 (4): 1563-71. doi:10.1158/ ... in tongue squamous cell carcinoma cells". Biochemical Journal. 432 (1): 199-205. doi:10.1042/BJ20100859. PMC 3130335 . PMID ...
"Constitutive association of SHP-1 with leukocyte-associated Ig-like receptor-1 in human T cells". J. Immunol. 166 (3): 1763-70 ... including NK cells, T cells, and B cells. Inhibitory receptors regulate the immune response to prevent lysis of cells ... "Constitutive association of SHP-1 with leukocyte-associated Ig-like receptor-1 in human T cells". J. Immunol. 166 (3): 1763-70 ... is differentially expressed during human B cell differentiation and inhibits B cell receptor-mediated signaling". Eur. J. ...
It is used in cell-cell contacts, binding to sialylated glycans on target cells leading to inhibition of NK cell-dependent ... Once bound to their ligands, Siglecs recruit inhibitory proteins such as SHP phosphatases via their ITIM domains. The tyrosine ... Mammalian cells contain high levels of sialic acid and so when NK cells bind so called "self-cells", they are not activated and ... Examples of negative signalling: CD22 is found on B cells. B cells become active when the B-cell receptor (BCR) binds to its ...
"CD22 regulates B cell receptor-mediated signals via two domains that independently recruit Grb2 and SHP-1". The Journal of ... It is found on the surface of mature B cells and to a lesser extent on some immature B cells. Generally speaking, CD22 is a ... CD22 functions as an inhibitory receptor for B cell receptor (BCR) signaling. It is also involved in the B cell trafficking to ... "SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates ...
Liver receptor homolog-1
SHP-1, and LRH-1 represses bile acid biosynthesis". Molecular Cell. 6 (3): 517-26. doi:10.1016/S1097-2765(00)00051-4. PMID ... LRH-1 is important for maintaining pluripotence of stem cells during embryonic development. Liver receptor homolog-1 has been ... Privalsky ML (Jul 2003). "Activation incarnate". Developmental Cell. 5 (1): 1-2. doi:10.1016/S1534-5807(03)00196-5. PMID ... Trends in Cell Biology. 14 (5): 250-60. doi:10.1016/j.tcb.2004.03.008. PMID 15130581. Luo Y, Liang CP, Tall AR (Jul 2001). "The ...
SHP-2, and Cbl in hematopoietic cells". Biochemical and Biophysical Research Communications. 239 (2): 412-7. doi:10.1006/bbrc. ... "BLNK is associated with the CD72/SHP-1/Grb2 complex in the WEHI231 cell line after membrane IgM cross-linking". European ... "Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and their association with Grb2 and Shc in Baf3/Flt3 cells". ... "CD22 regulates B cell receptor-mediated signals via two domains that independently recruit Grb2 and SHP-1". The Journal of ...
Signal-regulatory protein alpha
... that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion". Mol. Cell. ... Recruitment of SHP phosphatases to the membrane leads to the inhibition of myosin accumulation at the cell surface and results ... "CD47: A Cell Surface Glycoprotein Which Regulates Multiple Functions of Hematopoietic Cells in Health and Disease". ISRN ... This interaction negatively controls effector function of innate immune cells such as host cell phagocytosis. SIRPα diffuses ...
"Reconstitution of B Cell Antigen Receptor-induced Signaling Events in a Nonlymphoid Cell Line by Expressing the Syk Protein- ... "ST6Gal-I restrains CD22-dependent antigen receptor endocytosis and Shp-1 recruitment in normal and pathogenic immune signaling ... Cell. 123: 1307-1321. doi:10.1016/j.cell.2005.09.041. PMID 16377570. Chui, D.; Sellakumar, G.; Green, R.; Sutton-Smith, M.; ... "Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting". Science. 265: 103-6. doi: ...
Control of cell signaling via SHP-1 is thought to occur through a balance between PILRalpha-mediated inhibition and PILRbeta- ... SHP-1-mediated dephosphorylation of protein tyrosine residues is central to the regulation of several cell signaling pathways. ... 2004). "The SH3-SAM Adaptor HACS1 is Up-regulated in B Cell Activation Signaling Cascades". J. Exp. Med. 200 (6): 737-47. doi: ... Cell signaling pathways rely on a dynamic interaction between activating and inhibiting processes. ...
cell nucleus. Biological process. • anterior/posterior pattern specification. • multicellular organism development. • anterior/ ... Scott MP (Dec 1992). "Vertebrate homeobox gene nomenclature". Cell. 71 (4): 551-3. doi:10.1016/0092-8674(92)90588-4. PMID ... and HOXD8 homeobox gene expression in human neuroblastoma cells following chemical induction of differentiation". Tumour Biol. ...
FOXP2 - 维基百科，自由的百科全书
podfamilija 4 NUR (NGFIB, NOR1, NURR1) • podfamilija 5 (LRH-1, SF1) • podfamilija 6 (GCNF) • podfamilija 0 (DAX1, SHP) ... Cell Genet. 57 (2-3): 109-11. PMID 1914517. doi:10.1159/000133124. CS1 održavanje: Eksplicitna upotreba et al. (link) ... Dang CV, O'donnell KA, Juopperi T (2005). "The great MYC escape in tumorigenesis". Cancer Cell 8 (3): 177-8. PMID 16169462. doi ... Nilsson JA, Cleveland JL (2004). "Myc pathways provoking cell suicide and cancer". Oncogene 22 (56): 9007-21. PMID 14663479. ...
List of oldest trees
"Differentiation of insulin-producing cells from human neural progenitor cells". PLoS Med. 2 (4): e103. doi:10.1371/journal.pmed ... Cell. Biol. 18 (7): 4245-51. PMC 109008 . PMID 9632808.. *. Hromas R, Moore J, Johnston T, et al. (1993). "Drosophila forkhead ... Cell Mol. Biol. 38 (6): 750-8. doi:10.1165/rcmb.2007-0350OC. PMC 2396252 . PMID 18239190.. ... cell nucleus. Biological process. • cellular glucose homeostasis. • regulation of transcription from RNA polymerase II promoter ...
RAR-srodni orfan receptor beta
Sterol regulatory element-binding protein
In cells with low levels of sterols, SREBPs are cleaved to a water-soluble N-terminal domain that is translocated to the ... Animal cells maintain proper levels of intracellular lipids (fats and oils) under widely varying circumstances (lipid ... Conversely, when there is enough cholesterol around, the cell stops making those mRNAs and the level of the enzymes falls. As a ... Gasic GP (Apr 1994). "Basic-helix-loop-helix transcription factor and sterol sensor in a single membrane-bound molecule". Cell ...
Farnesoid X receptor
cell-cell junction assembly. • toll-like receptor 9 signaling pathway. • negative regulation of monocyte chemotactic protein-1 ... Rather, FXR induces expression of small heterodimer partner (SHP), which then functions to inhibit transcription of the CYP7A1 ... cell nucleus. Biological process. • Notch signaling pathway. • cellular triglyceride homeostasis. • cellular response to ... Similar to other nuclear receptors, when activated, FXR translocates to the cell nucleus, forms a dimer (in this case a ...
Transkripcioni faktor - Википедија, слободна енциклопедија
potfamilija 4 NUR (NGFIB, NOR1, NURR1) • potfamilija 5 (LRH-1, SF1) • potfamilija 6 (GCNF) • potfamilija 0 (DAX1, SHP) ... Mitchell PJ, Tjian R (1989). „Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins". Science ... Essential cell biology. New York: Garland Science. стр. 896 pages. ISBN 0-8153-3480-X.. ... Cell Biol. 29 (12): 1305-12. PMID 9570129. doi:10.1016/S1357-2725(97)00085-X.. ...
cell-cell signaling. • embryonic hemopoiesis. • cell development. • positive regulation of erythrocyte differentiation. • ... particularly red blood cells and platelets but also eosinophils, basophils, mast cells, and dendritic cells. The knock-out mice ... myeloid cell differentiation. • negative regulation of apoptotic process. • homeostasis of number of cells within a tissue. • ... Its critical roles in red blood cell formation include promoting the maturation of precursor cells, e.g. erythroblasts, to red ...
positive regulation of T-helper cell differentiation. • transcription from RNA polymerase II promoter. • mitotic cell cycle. • ... positive regulation of smooth muscle cell proliferation. • positive regulation of glial cell proliferation. • cellular response ... positive regulation of hepatic stellate cell proliferation. • positive regulation of hepatic stellate cell activation. • ... Cell. Biol. 18 (2): 989-1002. PMC 108811 . PMID 9447996.. *. Hedge SP, Kumar A, Kurschner C, Shapiro LH (1998). "c-Maf ...
cell junction. • cell nucleus. Biological process. • dopaminergic neuron differentiation. • regulation of insulin secretion ... positive regulation of cell-cell adhesion mediated by cadherin. • anatomical structure morphogenesis. • chromatin organization ... and cell survival". Stem Cells. 28 (3): 501-12. doi:10.1002/stem.294. PMID 20049900.. ... cell fate specification. • adult locomotory behavior. • negative regulation of sequence-specific DNA binding transcription ...
G protein-coupled receptor
... interaction between a G protein-coupled receptor and the phosphatase SHP-2 is involved in bradykinin-induced inhibition of cell ... "Cell. 172 (1-2): 41-54.e19. doi:10.1016/j.cell.2017.11.033. PMC 5766829. PMID 29249361.. ... "Cell. 166 (4): 907-19. doi:10.1016/j.cell.2016.07.004. PMC 5418658. PMID 27499021.. ... Protein kinase A is an important enzyme in cell metabolism due to its ability to regulate cell metabolism by phosphorylating ...
"Visualization of SHP-1-target interaction" (PDF). Journal of Cell Science. 117 (Pt 21): 5165-78. doi:10.1242/jcs.01397. PMID ... cell membrane. • cell surface. • perinuclear region of cytoplasm. • cytoplasm. • integral component of plasma membrane. • ... columnar/cuboidal epithelial cell development. • regulation of cell growth. • negative regulation of signal transduction. • ... doi:10.1016/j.cell.2007.11.025. PMID 18083107.. *^ a b c Bergethon K, Shaw AT, Ou SH, Katayama R, Lovly CM, McDonald NT, ...
neural crest cell development. • cell proliferation involved in outflow tract morphogenesis. • adult heart development. • ... cell differentiation. • mesenchymal cell proliferation. • determination of heart left/right asymmetry. • regulation of ... cardiac neural crest cell migration involved in outflow tract morphogenesis. • negative regulation of DNA binding. • coronary ... cardiac neural crest cell development involved in outflow tract morphogenesis. • positive regulation of transcription, DNA- ...
CEBPA - Вікіпедія
regulation of cell proliferation. • brown fat cell differentiation. • lipid homeostasis. • white fat cell differentiation. • ... negative regulation of cell cycle. • negative regulation of transcription from RNA polymerase II promoter. • cell maturation. • ... myeloid cell differentiation. • regulation of transcription, DNA-templated. • cellular response to lithium ion. • glucose ... negative regulation of cell proliferation. • transcription from RNA polymerase II promoter. • cellular response to tumor ...
epidermal cell fate specification. • positive regulation of cell proliferation. • Clara cell differentiation. • interleukin-4 ... auditory receptor cell fate commitment. • B cell differentiation. • regulation of gene expression. • Notch signaling pathway. • ... somatic stem cell population maintenance. • endocardium development. • cell fate commitment. • DNA recombination. • ... myeloid dendritic cell differentiation. • blood vessel remodeling. • secondary heart field specification. • regulation of cell ...
"Cell. 154 (2): 452-64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.. ... Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9-13. doi:10.1016/j.cell.2006.12.018. PMID ... cell nucleus. Biological process. • regulation of transcription, DNA-templated. • transcription, DNA-templated. • regulation of ... Yan W, Burns KH, Ma L, Matzuk MM (Oct 2002). "Identification of Zfp393, a germ cell-specific gene encoding a novel zinc finger ...
Sterol regulatory element-binding protein
"Cell Metabolism. 14 (1): 21-32. doi:10.1016/j.cmet.2011.06.002. PMC 3652544. PMID 21723501.. ... In cells with low levels of sterols, SREBPs are cleaved to a water-soluble N-terminal domain that is translocated to the ... Animal cells maintain proper levels of intracellular lipids (fats and oils) under widely varying circumstances (lipid ... Conversely, when there is enough cholesterol around, the cell stops making those mRNAs and the level of the enzymes falls. As a ...
Langerhans cells Phagocytosis. Degranulation (eosinophils) FcγRIIB1 (CD32) IgG Low (Kd , 10−7 M) B Cells. Mast cells No ... Huang ZY, Hunter S, Kim MK, Indik ZK, Schreiber AD (June 2003). "The effect of phosphatases SHP-1 and SHIP-1 on signaling by ... Mast cells. Follicular dendritic cells Induction of microbe killing FcεRI IgE High (Kd ~ 10−10 M) Mast cells. Eosinophils. ... On NK cellsEdit. The Fc receptor on NK cells recognize IgG that is bound to the surface of a pathogen-infected target cell and ...
Growth hormone receptor
Secretina, a enciclopedia libre
Lam IP, Lee LT, Choi HS, Chow BK (2006). "Localization of small heterodimer partner (SHP) and secretin in mouse duodenal cells ... Lee LT, Tan-Un KC, Chow BK (2006). "Retinoic acid-induced human secretin gene expression in neuronal cells is mediated by ... transcriptional events controlling the terminal differentiation of intestinal endocrine cells". Aliment. Pharmacol. Ther. 14 ... Cell. Biol. 27 (7): 2499-2511. PMC 1899889. PMID 17283064. doi:10.1128/MCB.01088-06.. ...
The cell types that Osr1 expressing cells will differentiate into are determined by the timing of loss of expression - cells ... it induces cell cycle arrest and induces apoptosis in gastric cancer cell. OSR1 is methylated in above 85% of squamous cell ... stem cell differentiation. • odontogenesis. • mesonephros development. • cell proliferation involved in kidney development. • ... Osr1 expressing cells will become mesangial cells, pericytes, ureteric smooth muscle and the kidney capsule. ...
CD114, a enciclopedia libre
Ward AC, Monkhouse JL, Hamilton JA, Csar XF (1998). "Direct binding of Shc, Grb2, SHP-2 and p40 to the murine granulocyte ... Kimura A, Sultana TA (2005). "Granulocyte colony-stimulating factor receptors on CD34++ cells in patients with myelodysplastic ... and characterization of receptors for granulocyte colony-stimulating factor on human placenta and trophoblastic cells.". Proc. ...
GATA5 - Вікіпедія
cell development. • anatomical structure formation involved in morphogenesis. • digestive tract development. • cardiac muscle ... Cell. Cardiol. 53: 277 - 281. PubMed DOI:10.1016/j.yjmcc.2012.05.009 ... intestinal epithelial cell differentiation. • transcription from RNA polymerase II promoter. • positive regulation of ...
cell development. • cell maturation. • Peyer's patch development. • embryonic digestive tract morphogenesis. • positive ... negative regulation of B cell differentiation. • positive regulation of fat cell differentiation. • positive regulation of ... negative regulation of neural precursor cell proliferation. • neuron differentiation. • regulation of cell cycle. ... cell nucleus. • cytosol. • cytoplasm. • macromolecular complex. Biological process. • regulation of G1/S transition of mitotic ...
"J. Cell. Mol. Med. 11 (2): 299-306. doi:10.1111/j.1582-4934.2007.00020.x. PMC 3822828. PMID 17488478.. ... cell nucleus. • nucleoplasm. • cytosol. Biological process. • multicellular organism development. • embryonic skeletal joint ... Scott MP (Dec 1992). "Vertebrate homeobox gene nomenclature". Cell. 71 (4): 551-553. doi:10.1016/0092-8674(92)90588-4. PMID ... all-trans retinoic acid dependent expression of HOXB and HOXC homeogenes in human embryonal and small-cell lung carcinoma cell ...
The protein tyrosine phosphatase SHP-2 is required for EGFRvIII oncogenic transformation in human glioblastoma cells. - PubMed...
Exp Cell Res. 2009 Aug 15;315(14):2343-57. doi: 10.1016/j.yexcr.2009.05.001. Epub 2009 May 8. Research Support, N.I.H., ... and the deleted SHP-2 (lower band) . (B) 2500 MEF shp-2+/+ (a, d), shp-2+/− (b, e) and shp-2−/− (c, f) cells with vector (a, ... A) Shp-2 +/+. Shp-2 +/− and Shp-2 −/− MEF cells were transfected with EGFRvIII and clones were selected. Equal amounts of ... shp-2 wild-type (b, e) and shp-2 C459S (c, f) were cultured on coverslips in 10% serum. After cells were attached, cells were ...
CD5 negatively regulates the T-cell antigen receptor signal transduction pathway: involvement of SH2-containing phosphotyrosine...
Mol Cell Biol. 1999 Apr;19(4):2903-12. Research Support, Non-U.S. Govt ... Tyrosine phosphorylation pattern of chimeric mCD6-hCD5 proteins expressed in Jurkat cells: SHP-1 coprecipitation with different ... Indo 1-loaded wild-type Jurkat cells (A and B) or CD5-fl (C and D) or CD5-F378 (E and F) stably transfected cells were ... Mol Cell Biol. 1999 Apr;19(4):2903-12.. CD5 negatively regulates the T-cell antigen receptor signal transduction pathway: ...
Correction: SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-β signaling | JEM
POD-1/TCF21 Reduces SHP Expression, Affecting LRH-1 Regulation and Cell Cycle Balance in Adrenocortical and Hepatocarcinoma...
POD-1/TCF21 Reduces SHP Expression, Affecting LRH-1 Regulation and Cell Cycle Balance in Adrenocortical and Hepatocarcinoma ... TCF21 Reduces SHP Expression, Affecting LRH-1 Regulation and Cell Cycle Balance in Adrenocortical and Hepatocarcinoma Tumor ... Tumor Cells. Monica Malheiros França,1 Bruno Ferraz-de-Souza,2 Antonio Marcondes Lerario,3 Maria Candida Barisson Villares ... Cells," BioMed Research International, vol. 2015, Article ID 841784, 9 pages, 2015. doi:10.1155/2015/841784 ...
Repression of SHP-1 expression by p53 leads to trkA tyrosine phosphorylation and suppression of breast cancer cell...
... the tumour suppressor p53 and the phosphatase SHP-1 are critical in cell proliferation and differentiation. SHP-1 is a trkA ... Repression of SHP-1 expression by p53 leads to trkA tyrosine phosphorylation and suppression of breast cancer cell ... BrdU-incorporation experiments reveal lack of incorporation in cells expressing wt-trkA and wtp53, or wt-trkA and SHP-1-siRNA. ... In cell lines (but not in normal breast epithelia) trkA is functional and can be NGF-stimulated to promote cell proliferation. ...
Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and chest deformity, and calvarial defects in mice ...
Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and chest deformity, and calvarial defects in mice ... Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and chest deformity, and calvarial defects in mice ... Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and chest deformity, and calvarial defects in mice ... Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and chest deformity, and calvarial defects in mice ...
SHP-1 Acts as a Key Regulator of Alloresponses by Modulating LFA-1-Mediated Adhesion in Primary Murine T Cells | Molecular and...
GST-SHP-1 and GST-SHP-2 fusion proteins were used to confirm the specificity of our SHP-1 and SHP-2 antibodies by Western ... Thus, we cotransfected a plasmid with wild-type SHP-2 or a catalytically inactive form of SHP-2 (SHP-2 C/S) instead of SHP-1 ( ... SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels. Immunol Rev 228:342-359. doi:10.1111/j.1600-065X. ... pJ3omega-SHP-1 WT and pJ3omega-SHP-1 C/S (gifts from Ben Neel, Toronto, ON, Canada), pRc/CMV-SHP-2 and pRc/CMV-SHP-2 C/S (gifts ...
Role of the cytoplasmic tyrosine phosphatase SHP-2 in haemopoietic cells following IL-3 stimulation | Biochemical Society...
Role of the cytoplasmic tyrosine phosphatase SHP-2 in haemopoietic cells following IL-3 stimulation. H. Wheadon, M.J. Welham ... Role of the cytoplasmic tyrosine phosphatase SHP-2 in haemopoietic cells following IL-3 stimulation ... Role of the cytoplasmic tyrosine phosphatase SHP-2 in haemopoietic cells following IL-3 stimulation ... Role of the cytoplasmic tyrosine phosphatase SHP-2 in haemopoietic cells following IL-3 stimulation ...
Hematopoietic cell phosphatase, SHP-1, is constitutively associated with the SH2 domain-containing leukocyte protein, SLP-76,...
... we studied proteins that interact with SHP-1 in B cells. Both anti-SHP-1 antibody and the two SH2 domains of SHP-1 expressed as ... Constitutive association of SHP-1 with SLP-76 could also be detected in normal splenic B cells. Collectively, these results ... More recently, SHP-1 has been shown to negatively regulate B cell antigen receptor (BCR)-initiated signaling. To elucidate ... Hematopoietic cell phosphatase, SHP-1, is constitutively associated with the SH2 domain-containing leukocyte protein, SLP-76, ...
Novel mesenchymal and haematopoietic cell isoforms of the SHP-2 docking receptor, PZR: identification, molecular cloning and...
... and all three isoforms occur in erythroid precursor cell lines. Importantly, using SHP-2 mutant (Delta 46-110) and SHP-2 rescue ... dependent migration of cells expressing a competent SHP-2 molecule. These observations will be instrumental in determining the ... endothelial and mesenchymal cells. Both PZR and PZRb are present in CD133(+) precursors and endothelial cells, PZRb ... In the present study, we describe a unique monoclonal antibody, WM78, which interacts with PZR, a SHP-2 binding partner. ...
The Role of SHP-2 in Cell Signalling and Human Disease | Bentham Science
The Role of SHP-2 in Cell Signalling and Human Disease. Author(s): Hanna Mannell, Florian Krotz. Cardiology, Medical Policlinic ... SHP-2 directly interacts with several growth factors, cell surface adhesion molecules and different adaptor molecules such as ... SHP-2 directly interacts with several growth factors, cell surface adhesion molecules and different adaptor molecules such as ... Hanna Mannell and Florian Krotz, " The Role of SHP-2 in Cell Signalling and Human Disease", Current Enzyme Inhibition (2007) 3 ...
Knockdown of SHP-1 Enhances Endothelial Cell Retention for Vascular Regeneration | ASME 2010 First Global Congress on...
Knockdown of SHP-1 Enhances Endothelial Cell Retention for Vascular Regeneration Brandon J. Tefft, Adrian M. Kopacz, Wing Kam ... Knockdown of SHP-1 Enhances Endothelial Cell Retention for Vascular Regeneration. ASME. Global Congress on NanoEngineering for ... Live Cell Detection of Specific Messenger RNA for Molecular Analysis of Plaque Formation ... Effect of Simvastatin on the Apoptosis and Permeability of Endothelial Cell Monolayers ...
Enhancement of Endothelial Cell Retention on ePTFE Vascular Constructs by siRNA-Mediated SHP-1 or SHP-2 Gene Silencing<...
Enhancement of Endothelial Cell Retention on ePTFE Vascular Constructs by siRNA-Mediated SHP-1 or SHP-2 Gene Silencing. In: ... Enhancement of Endothelial Cell Retention on ePTFE Vascular Constructs by siRNA-Mediated SHP-1 or SHP-2 Gene Silencing. / Tefft ... Enhancement of Endothelial Cell Retention on ePTFE Vascular Constructs by siRNA-Mediated SHP-1 or SHP-2 Gene Silencing. ... Enhancement of Endothelial Cell Retention on ePTFE Vascular Constructs by siRNA-Mediated SHP-1 or SHP-2 Gene Silencing. ...
Redox-Sensitive Signaling by Angiotensin II Involves Oxidative Inactivation and Blunted Phosphorylation of Protein Tyrosine...
Exact functions of vascular SHP-2 await elucidation.40 In stable cell lines overexpressing wild-type SHP-2, SHP-2 ... of SHP-2 was observed in SHR cells compared to WKY cells (Figure 3A). Ang II increased SHP-2 phosphorylation in WKY (P,0.001) ... Ang II regulates SHP-2 by increasing its phosphorylation in both WKY and SHR cells with a blunted effect in SHR cells. To ... We treated cells with Ang II and analyzed the activation of downstream signaling pathways after downregulating SHP-2 with SHP-2 ...
Gab1 and SHP-2 promote Ras/MAPK regulation of epidermal growth and differentiation | JCB
Immunoblots of cell extracts prepared from cells expressing wild-type or mutant Gab1 and SHP-2 using antibodies to the ... Effect of Gab1 and SHP-2 on levels of active Ras and MAPK in epidermal cells. (a) The SHP-2 binding-deficient dominant-negative ... In keratinocytes, both Gab1 and SHP-2 localize to the cell perimeter in response to EGF (Fig. 2). SHP-2 redistribution is ... Shp-2 tyrosine phosphatase: signaling one cell or many. Exp. Cell Res. 253:47-54. ...
Frontiers | Levodopa/Benserazide Loaded Microspheres Alleviate L-dopa Induced Dyskinesia through Preventing the Over-Expression...
Moreover, CDS induced no change of membrane D1R expression or phosphorylation of Shp-2, Src, DARPP-32 and ERK1/2 in the 6-OHDA- ... The critical protein changes in the D1R/Shp-2/ERK1/2 signaling pathway were compared between the two groups through Western ... The critical protein changes in the D1R/Shp-2/ERK1/2 signaling pathway were compared between the two groups through Western ... CDS effectively prevented the overexpression of D1R/Shp-2/ ERK1/2 signaling pathway, resulting in the reduction of LID in 6- ...
A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP
... Academic Article ... Thus, CD22 is a molecular switch for SHP that may bias mlg signaling to anatomic sites rich in T cells. ... Ligation of CD22 to prevent its coaggregation with mlg lowers the threshold at which mlg activates the B cell by a factor of ... CD22 is a membrane immunoglobulin (mlg)-associated protein of B cells. CD22 is tyrosine-phosphorylated when mlg is ligated. ...
SHP-2 acts via ROCK to regulate the cardiac actin cytoskeleton | Development
SHP-2N308D regulates actin deposition. (A-I) Cells were transfected with HA-SHP-2FL (A-C), HA-SHP-2N308D (D-F) or HA-SHP-2N308D ... K-R) Inhibition of ROCK activity rescues SHP-2N308D cell rounding phenotype. SHP-2N308D-transfected cells (blue; L,N,P,R) ... SHP-2FL and SHP-2E76A were kindly provided by Nikola Pavletich (Georgescu et al., 2000). SHP-2N308D and SHP-2N308D-PTP were ... However, we found that neither decreasing nor increasing the amount of any of the SHP-2 variants (SHP-2FL, SHP-2E76A or SHP-2 ...
PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine...
B cell receptor;. PLCγ2,. phospholipase C-γ2;. SH2,. src homology 2;. SHP,. SH2-domain-containing protein tyrosine phosphatase; ... Recruitment and phosphorylation of SHP-2 to tyrosine-phosphorylated FcPD. (A) IIA1.6 cells expressing FcPD, FcγRIIB, and FcKIR ... SHP-2 but neither SHP-1 nor SHIP was coimmunoprecipitated with FcPD when BCR and FcPD were coligated (Fig. 4A). Control ... 3 and data not shown). It is not known why the N-terminal tyrosine of PD-1 does not associate with either SHP-1 or SHP-2. A ...
Co-expression of ILT4/HLA-G in human non-small cell lung cancer correlates with poor prognosis and ILT4-HLA-G interaction...
Non-small cell lung cancer (NSCLC) is the most common malignant tumor in the world, of which prognosis is generally poor due to ... SHP. Protein tyrosine phosphatase. VEGF-C. Vascular endothelial growth factor-C. ANGPTLs. Angiopoietin-like proteins ... Clinical relevance and functional implications for human leucocyte antigen-g expression in non-small-cell lung cancer. J Cell ... Non-small cell lung cancer (NSCLC) is the most common malignant tumor in the world, of which prognosis is generally poor due to ...
SHP-2 phosphatase is required for hematopoietic cell transformation by Bcr-Abl<...
Treatment with proteasome inhibitors or reintroduction of SHP-2 restored p210 level in Bcr-Abl-transduced SHP-2 Δ/Δ cells. ... Treatment with proteasome inhibitors or reintroduction of SHP-2 restored p210 level in Bcr-Abl-transduced SHP-2 Δ/Δ cells. ... Treatment with proteasome inhibitors or reintroduction of SHP-2 restored p210 level in Bcr-Abl-transduced SHP-2 Δ/Δ cells. ... Treatment with proteasome inhibitors or reintroduction of SHP-2 restored p210 level in Bcr-Abl-transduced SHP-2 Δ/Δ cells. ...
Divergent roles of SHP-2 in ERK activation by leptin receptors
To directly investigate the role of SHP-2, we employed dominant negative strategies in transfected cells. We show that a ... The protein tyrosine phosphatase SHP-2 has been proposed to serve as a regulator of leptin signaling, but its specific roles ... To directly investigate the role of SHP-2, we employed dominant negative strategies in transfected cells. We show that a ... SHP-2, lacking two C-terminal tyrosine residues, partially inhibits ERK phosphorylation. We find similar effects of the SHP-2 ...
Orphan nuclear receptor SHP - Sus scrofa (Pig)
p>This section provides information on the location and the topology of the mature protein in the cell.,p>,a href=/help/ ... Orphan nuclear receptor SHPImported. Automatic assertion inferred from database entriesi ... tr,A0MNM4,A0MNM4_PIG Orphan nuclear receptor SHP (Fragment) OS=Sus scrofa OX=9823 PE=4 SV=1 ...
Topical Remetinostat Gel as Neoadjuvant Therapy in Patients With Squamous Cell Carcinoma (SCC) - Full Text View -...
SHP-141;. *and 4-[[8-(hydroxyamino)-1,8-dioxooctyl]oxy]-benzoic acid methyl ester ... Topical Remetinostat Gel as Neoadjuvant Therapy in Patients With Squamous Cell Carcinoma (SCC). The safety and scientific ... Carcinoma, Squamous Cell. Neoplasms, Glandular and Epithelial. Neoplasms by Histologic Type. Neoplasms. Neoplasms, Squamous ... purpose of this study is to determine if 8 weeks of topical remetinostat applied three times daily will suppress Squamous Cell ...
Inhibitory Receptors and Their Mode of Action: Key Insights from NK Cells | The Journal of Immunology
A role for SHP-1 was subsequently confirmed in vivo using NK cells from viable motheathen mice, a mouse strain with reduced SHP ... Target cells lacking MHC class I molecules were found to be susceptible to NK cell-mediated cytolysis, whereas cells expressing ... the absence of target cell MHC class I expression relieves NK cells from inhibition, thus allowing NK cells to become activated ... A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP. Science 269: 242-244. ...
Tumoral Prostate Shows Different Expression Pattern of Somatostatin Receptor 2 (SSTR2) and Phosphotyrosine Phosphatase SHP-1 ...
Many studies on SHP-1 revealed that the expression of this protein was diminished or abolished in several of the cancer cell ... Also, SSTR2 is expressed in stromal cells. In malignant prostate tissue, SHP-1 was diminished in 28/45 cases or absent in 12/45 ... However, it is necessary to confront the cell lines data with real situation in cancer cases. Our studies have shown that ... in normal and benign hyperplasia are localized in the luminal side of duct and acinar cells. ...
ROS1 - Wikipedia
"Visualization of SHP-1-target interaction". Journal of Cell Science. 117 (Pt 21): 5165-78. doi:10.1242/jcs.01397. PMID 15456853 ... Cell. 131 (6): 1190-203. doi:10.1016/j.cell.2007.11.025. PMID 18083107. Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, ... Cell. 131 (6): 1190-203. doi:10.1016/j.cell.2007.11.025. PMID 18083107. Bergethon K, Shaw AT, Ou SH, Katayama R, Lovly CM, ... modulates cell morphology, and induces cell transformation". Molecular and Cellular Biology. 20 (24): 9212-24. doi:10.1128/MCB. ...
STAT5A - Wikipedia
Cell. Endocrinol. 166 (2): 89-99. doi:10.1016/S0303-7207(00)00277-X. PMID 10996427. Zhu M, John S, Berg M, Leonard WJ (January ... Potential role of SHP-2 in STAT5 regulation". J. Biol. Chem. 275 (1): 599-604. doi:10.1074/jbc.275.1.599. PMID 10617656. ... Cell Biol. 42 (2): 186-92. doi:10.1016/j.biocel.2009.11.001. PMC 2818495 . PMID 19914392. Pestell, Richard G.; Nevalainen, ... This protein is activated by, and mediates the responses of many cell ligands, such as IL2, IL3, IL7 GM-CSF, erythropoietin, ...
Phosphatase activityInhibitionRegulatesApoptosisReceptorsHomologyKnockdownSiRNAInhibitorAntigenRegulationExpressionPtpn11VivoHematopoietic StemAntibodyMutantMolecularStimulationVitroInducesDownstreamMigrationMutationsEndogenousInteractionInhibitsInhibitRegulatorGeneMechanismsMesenchymalAbstractShp2ExtracellularTyrosine phosphatasesMAPKEpithelialPhospholipasePTP1CActivityMice
- Inhibition of SHP-2 expression by Shp-2 siRNA inhibited cell growth, transformation and altered morphology of these EGFRvIII transformed GBM cells. (nih.gov)
- Inhibition of EGFRvIII-induced cell growth and transformation by SHP-2 C459S or shp-2 siRNA was mediated by its ability to block cell cycle progression at different phases in these GBM cells. (nih.gov)
- Hanna Mannell and Florian Krotz, " The Role of SHP-2 in Cell Signalling and Human Disease", Current Enzyme Inhibition (2007) 3: 264. (eurekaselect.com)
- We show that these defects can be rescued in culture and in embryos through the inhibition of the Rho-associated, coiled-coil-containing protein kinase 1 (ROCK), thus demonstrating a direct relationship between SHP-2 N308D and ROCK activation in the developing heart. (biologists.org)
- Inhibition of SHP-2 enzymatic activity by overexpression of catalytically inactive SHP-2 mutant did not destabilize p210 but enhanced serum starvation-induced apoptosis, suggesting that SHP-2 also plays an important role in downstream signaling of p210 kinase. (elsevier.com)
- During the time when attention was focused on how immune cells could be stimulated and costimulated, a small group of immunologists was preoccupied with the question of whether inhibition was a key feature of the regulation of NK cell function. (jimmunol.org)
- One interpretation of these findings was that MHC class I expressed on target cells inhibits NK cells (receptor inhibition). (jimmunol.org)
- If so, the absence of target cell MHC class I expression relieves NK cells from inhibition, thus allowing NK cells to become activated. (jimmunol.org)
- The receptor inhibition model became widely accepted following the molecular identification of an NK cell receptor that prevented the lysis of target cells expressing certain MHC class I alleles ( 3 ). (jimmunol.org)
- According to the receptor inhibition model, lysis occurs when inhibitory receptors fail to interact with MHC class I on target cells. (jimmunol.org)
- Furthermore, inhibition of SHP-2 by shRNAs or pharmacological inhibitors disrupted the interaction of PI3K with PDGFRα, suppressed downstream AKT/mTOR activation, and impaired tumorigenesis of Ink4a/Arf-null cells, whereas expression of an activated PI3K mutant rescued the effect of SHP-2 inhibition on tumorigenicity. (jci.org)
- Since that discovery, multiple studies have demonstrated an incidence of approximately 1% in lung cancers, demonstrated oncogenicity, and showed that inhibition of tumor cells bearing ROS1 gene fusions by crizotinib or other ROS1 tyrosine kinase inhibitors was effective in vitro. (wikipedia.org)
- Dovitinib, a multiple kinase inhibitor, induces apoptosis and overcomes sorafenib resistance in hepatocellular carcinoma through SHP-1-mediated inhibition of STAT3. (aacrjournals.org)
- In conclusion, dovitinib induces significant apoptosis in HCC cells and sorafenib-resistant cells via SHP-1-mediated inhibition of STAT3. (aacrjournals.org)
- Death of tumor cells after intracellular acidification is dependent on stress-activated protein kinases (SAPK/JNK) pathway activation and cannot be inhibited by Bcl-2 expression or interleukin 1beta-converting enzyme inhibition. (semanticscholar.org)
- Stat5a/b is persistently active in prostate cancer cells and inhibition of STAT5a/b has resulted in large scale apoptotic death, although the specific role of STAT5a and distribution of activity remains largely unknown. (wikipedia.org)
- Inhibition of STAT5a alone would not effect colorectal cancer cells, but when combined with chemotherapies such as cisplatin, it could increase the chemosensitivity of the cancer cells to the drugs. (wikipedia.org)
- The inhibition of VEGFR2 and PDGFR-β activity was associated with increased SHP-1 expression. (diabetesjournals.org)
- ACA is a novel drug candidate for the inhibition of tumor metastasis through interference with the SHP-1/STAT3/MMPs signaling pathway. (sigmaaldrich.com)
- Moreover, knockdown of SHP-1 by small interfering RNA suppressed the induction of SHP-1 and reversed the inhibition of STAT3 activation, thereby indicating the critical role of SHP-1 in the action of this triterpene. (aacrjournals.org)
- SHP-1 inhibition during MDDC differentiation in the presence of TSP-1 mimics restored pSTAT-6 levels and CD1a(+)MDDC immunogenicity. (sigmaaldrich.com)
- To determine the cellular and molecular mechanisms by which SHP-2 regulates heart development and, thus, understand how Noonan-associated mutations affect cardiogenesis, we introduced SHP-2 encoding the most prevalent Noonan syndrome and JMML mutations into Xenopus embryos. (biologists.org)
- In vitro studies have revealed that the tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 (SHP-1) regulates signal transduction from receptors on T cells including the TCR, helping set the activation threshold, and therefore may shape responses of mature CD8 T cells in vivo. (fredhutch.org)
- Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. (ku.dk)
- Incubation of dovitinib with pure SHP-1 protein enhanced its phosphatase activity, indicating that dovitinib up-regulates the activity of SHP-1 via direct interactions. (aacrjournals.org)
- These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. (uni-muenchen.de)
- Our current studies are examining how CD72 regulates the balance between B cell tolerance and autoimmunity in several model systems. (stanford.edu)
- Finally, the lab is examining the biochemistry of signaling through CD72 to determine the molecular mechanisms by which CD72 regulates B cell responsiveness. (stanford.edu)
- Furthermore, Shp2 regulates cell fate decisions, by promoting neurogenesis while suppressing astrogliogenesis, through reciprocal regulation of the Erk and Stat3 signaling pathways. (asm.org)
- Shp2, an Src-homology 2 domain (SH2)-containing tyrosine phosphatase, is a widely expressed intracellular enzyme that regulates signaling events downstream of several growth factor/cytokine receptors in various cell types ( 8 , 18 ). (asm.org)
- In spite of its central positioning, the mechanisms of zinc function in immune responses and, in particular, how zinc regulates T cells are unknown. (pubmedcentralcanada.ca)
- SHP-1 inhibitor reversed down-regulation of p-STAT3 and apoptosis induced by dovitinib, and silencing of SHP-1 by RNA-interference abolished the effects of dovitinib on p-STAT3, indicating that SHP-1, a protein tyrosine phosphatase, mediates the effects of dovitinib. (aacrjournals.org)
- Interdependent regulation of intracellular acidification and SHP-1 in apoptosis. (semanticscholar.org)
- Protodynamic intracellular acidification by cis-urocanic acid promotes apoptosis of melanoma cells in vitro and in vivo. (semanticscholar.org)
- Induction of wild-type p53, Bax, and acidic endonuclease during somatostatin-signaled apoptosis in MCF-7 human breast cancer cells. (semanticscholar.org)
- This pathway is involved in several important cell functions, including the growth and division of cells (proliferation), the process by which cells mature to carry out specific functions (differentiation), cell movement (migration), and the self-destruction of cells (apoptosis). (medlineplus.gov)
- Finally, ursolic acid inhibited proliferation and induced apoptosis and the accumulation of cells in G 1 -G 0 phase of cell cycle. (aacrjournals.org)
- GAC 17:1 down-regulated the expression of STAT3 regulated gene products and induced apoptosis of tumor cells. (mdpi.com)
- The non-transmembrane protein tyrosine phosphatase SHP-2 (Src homology 2 domain containing tyrosine phosphatase 2) has been shown to be involved in several signalling pathways initiated by different growth factors, cytokines, hormones and extracellular matrix receptors. (eurekaselect.com)
- SHP-2 is thus a positive regulator of ERK by leptin receptors, and both the adaptor function and the phosphatase activity of SHP-2 are critical for this regulation. (nih.gov)
- An alternative explanation was that MHC class I expression masks target cell Ags that are recognized by activating NK cell receptors (target interference). (jimmunol.org)
- Gene transfer experiments and transgenic mice demonstrated that single receptors of either type conferred both the specificity for MHC class I molecules and the capacity to prevent target cell lysis ( 8 , 9 ). (jimmunol.org)
- IL-10R and TGF-β receptors) can result in DC-mediated regulatory T cell responses ( 6 ). (jimmunol.org)
- These CD2(hi)CD5(+)CD81(+) cells express classical pDC markers, as well as the toll-like receptors that enable conventional pDCs to respond to viral infection. (stanford.edu)
- Peptide-MHC (pMHC) multimers have become the "gold standard" for the detection and isolation of antigen-specific T-cells but recent evidence shows that normal use of these reagents can miss fully functional T-cells that bear T-cell receptors (TCRs) with low affinity for cognate antigen. (frontiersin.org)
- This issue is particularly pronounced for anticancer and autoimmune T-cells as self-reactive T-cell populations are enriched for low-affinity TCRs due to the removal of cells with higher affinity receptors by immune tolerance mechanisms. (frontiersin.org)
- T cell migration is directed by several mediators, including chemokine receptors and G protein-coupled receptors (GPCR), which are supported by guiding stromal structures and by TECs, including cortical TECs and medullary TECs (mTEC). (spandidos-publications.com)
- pancreatic centroacinar cells have secretin receptors in their plasma membrane. (wikipedia.org)
- CD5 was found associated with the Src homology 2 (SH2) domain containing hematopoietic phosphotyrosine phosphatase SHP-1 in both Jurkat cells and normal phytohemagglutinin-expanded T lymphoblasts. (nih.gov)
- SHP-2 (Src homology phosphatase type-2) is essential for haematopoietic skeletal and vascular development. (ox.ac.uk)
- This tyrosine was phosphorylated and recruited src homology 2-domain-containing tyrosine phosphatase 2 (SHP-2) on coligation of PD-1 with BCR. (pnas.org)
- More importantly, ACA treatment led to significant up-regulation of Src homology region 2 domain-containing phosphatase 1 (SHP-1), and the ACA-induced depression of cancer cell migration and STAT3 signaling could be apparently reversed by blockade of SHP-1. (sigmaaldrich.com)
- The importance of these differential activation properties was further indicated by small interfering RNA (siRNA) knockdown of SHP-1 in syngeneically and allogeneically stimulated T cells. (asm.org)
- Tefft BJ, Kopacz AM, Liu W, Liu SQ. Knockdown of SHP-1 Enhances Endothelial Cell Retention for Vascular Regeneration. (asme.org)
- By employing siRNA to knockdown the expression of SHP-1 or SHP-2, we observed a significant improvement in cell retention following 6 h of pulsatile fluid shear stress. (northwestern.edu)
- Two stable cell clones (#1 and #2) with different efficiencies of P16INK4A knockdown were used. (jci.org)
- (A) U87MG.EGFRvIII and LN229.EGFRvIII cells were transiently transfected with 20 picomoles of scrambled or shp-2 siRNA for 6 hour and cultured in DMEM plus 10% FBS for 72 h. (nih.gov)
- (B) 20 picomoles of scrambled shp-2 siRNA and shp-2 siRNA were transfected to U87MG.EGFRvIII and LN229.EGFRvIII cells for 6 h and cell number was then counted at the indicated time points. (nih.gov)
- A release from suppression is observed when these cells are transiently transfected with wt-SHP-1 and grown at 32 degrees C. Suppression is also detected when, as control, wt-trkA-expressing cells are transiently transfected with SHP-1-siRNA, but not when a dominant-negative (DN) mutant trkA is used to abolish wt-trkA activity. (uniprot.org)
- BrdU-incorporation experiments reveal lack of incorporation in cells expressing wt-trkA and wtp53, or wt-trkA and SHP-1-siRNA. (uniprot.org)
- At an average fluid shear stress of 15 dyn/cm 2 , cell retention was improved from approximately 30% for control groups to approximately 70 and 85% for cells treated with SHP-1 and SHP-2 specific siRNA, respectively (n = 8 for all groups). (northwestern.edu)
- We also observed that treatment with SHP-1 or SHP-2 specific siRNA caused a modest increase in focal contact density and did not cause a significant effect on the expression of the endothelial cell markers VEGFR-2, VE-cadherin, and PECAM-1. (northwestern.edu)
- SHP-2 and Nox1 were downregulated by siRNA. (ahajournals.org)
- Ang II-induced SHP-2 effects were inhibited by valsartan (AT 1 R blocker), apocynin (NAD(P)H oxidase inhibitor), and Nox1 siRNA. (ahajournals.org)
- Application of a recently introduced allosteric Shp-2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. (ku.dk)
- PTP Inhibitor I is a cell-permeable, protein tyrosine phosphatase (PTP) inhibitor with Ki values of 43 and 42 μM for SHP-1(ΔSH2) and PTP1B, respectively. (selleckchem.com)
- PTP Inhibitor I binds to PTPs with the highest affinity, having Ki values of 43 and 42 μM and Kinact values of 0.40 and 0.57/min for SHP-1(△SH2) and PTP1B, respectively. (selleckchem.com)
- It has lower affinity to wild-type SHP-1 than its catalytic domain (K= 530 vs 43 μM), likely due to the fact that the SH2 domains can directly bind to the PTP active site and interfere with substrate/inhibitor binding . (selleckchem.com)
- After incubation with varying concentrations of PTP Inhibitor I for 3 min, the cells are lysed, and the cellular proteins are separated on an SDS-PAGE gel, followed by western blot analysis. (selleckchem.com)
- Here, we stained a wide variety of self-reactive human T-cells using regular pMHC staining and an optimized technique that included: (i) protein kinase inhibitor (PKI), to prevent TCR triggering and internalization, and (ii) anti-fluorochrome antibody, to reduce reagent dissociation during washing steps. (frontiersin.org)
- SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). (uni-muenchen.de)
- Integrin-mediated adhesion between alloreactive T cells and antigen-presenting cells is essential for allorejection. (asm.org)
- Recipient-derived antigen-presenting cells (APCs) are pivotal for the induction of alloresponses ( 1 ). (asm.org)
- PD-1-deficient mice exhibit splenomegaly, selective augmentation of IgG3 Ab response to a T-independent type II antigen, and enhanced proliferative responses of B cells and myeloid cells by anti-IgM and granulocyte colony-stimulating factor stimulation, respectively (ref. 7 and unpublished data). (pnas.org)
- Because PD-L1, a ligand of PD-1, is highly expressed on heart ( 10 ), and the antigen recognized by the autoantibody is strictly restricted to heart, we assume that the direct interaction between the heart tissue and B cells by means of PD-1/PD-L1 is responsible for the prevention of this deadly disease. (pnas.org)
- To explore the molecular pathogenesis of NSCLC, the co-expression of immunoglobulin-like transcript 4 (ILT4) and its ligand human leukocyte antigen G (HLA-G) in NSCLC tissues and cells were investigated. (springer.com)
- BM-derived DC (BMDC) are powerful antigen-presenting cells. (stanford.edu)
- Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1/CD66a/Bgp) is a member of the immunoglobulin (Ig) superfamily. (biologists.org)
- Increased pSHP-1, decreased antigen processing, and depressed T cell stimulation characterized Pt Dysf DC. (sigmaaldrich.com)
- Here, we identified a novel role of the protein tyrosine phosphatase SHP-1 in the regulation of murine LFA-1-mediated adhesion in an allograft setting. (asm.org)
- This novel key role of SHP-1 in the regulation of LFA-1-mediated adhesion may provide a new insight into T cell-mediated alloresponses and may pave the way to the development of new immunosuppressive pharmaceutical agents. (asm.org)
- Negative regulation of IFN-γ responses by TGF-β1 in CD4⁺ T cells: involvement of protein tyrosine phosphatase SHP-1 and MAPK ERK. (dartmouth.edu)
- It is important to determine the molecular mechanisms underlying the thymic regulation of T cell development and of the proteins involved in T cell recognition. (spandidos-publications.com)
- T reg cells in the thymus are vital for the negative regulation of immune-mediated inflammation, which features prominently in autoimmune and autoinflammatory disorders, acute allergies, cancer, chronic infections and commensal microbiota. (spandidos-publications.com)
- Ectopic expression of a PTPase-inactive form of SHP-2, SHP-2 C459S, but not its wild-type SHP-2 or either of two SH2 domain mutants, abrogated transformation of EGFRvIII-expressing glioblastomas in soft agar and in nude mice. (nih.gov)
- TrkA protein expression is higher in breast-cancer cell lines than in normal breast epithelia. (uniprot.org)
- SHP-2 expression and activity were evaluated by immunoblotting and by a PTP activity assay, respectively. (ahajournals.org)
- The sequence, expression pattern and function of SHP-2 are highly conserved throughout evolution. (biologists.org)
- In NSCLC cell lines, HLA-G expression increased/decreased accordingly when ILT4 was up-/down-regulated, and ILT4 expression increased in a concentration-dependent manner via the stimulation of HLA-G fusion protein. (springer.com)
- Blockade of SHP-2 expression in p210-expressing cells by antisense or small-interfering RNA approaches decreased p210 level, causing cell death. (elsevier.com)
- Many studies on SHP-1 revealed that the expression of this protein was diminished or abolished in several of the cancer cell lines and tissues examined. (hindawi.com)
- The key experiment to demonstrate the relevance of SHP-1 was the expression of a catalytically inactive form of SHP-1 in NK cell clones. (jimmunol.org)
- Using FlnA-deficient melanoma and HT1080 cell lines as expression systems we showed that FlnA mutations reduce cell spreading and migration capacities. (chemweb.com)
- PDGFRα and PDGF-A are co-expressed in clinical glioblastoma specimens, and such co-expression is linked with activation of SHP-2/AKT/mTOR signaling. (jci.org)
- Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H⁺ extrusion, cell migration and survival. (semanticscholar.org)
- IL-6-treatment increased the expression of c-Met making cells HGF responsive, and IL-6 was dependent on c-Met signaling in activating both Ras and p44/42 MAPK by a mechanism involving the tyrosine phosphatase Shp2. (wiley.com)
- The mouse counterpart of this gene is found to induce the expression of BCL2L1/BCL-X(L), which suggests the antiapoptotic function of this gene in cells. (wikipedia.org)
- Unphosphorylated or inactive STAT5a may suppress tumor growth in colorectal cancer and active STAT5a expression in premalignant and tumor lesions has shown potential as a prognostic marker in oral squamous cell carcinoma. (wikipedia.org)
- Experiments to improve angiogenesis and vascular cell survival by local infusion of vascular endothelial growth factor (VEGF) or angiopoietin by increasing its expression have also been reported in nondiabetic animal models ( 6 , 7 ). (diabetesjournals.org)
- Our findings revealed, in both mice and humans, that upon exposure to IgG-IC, BMDC internalized the IC, increased costimulatory molecule expression, and stimulated autologous T cells. (stanford.edu)
- Based on cell physiological assays a strong decrease in the motility of breast cancer cells exogeneously expressing FGFR4 Gly388 was observed, whereas FGFR4 Arg388 expression slightly increased cell motility. (tum.de)
- CD72 is a B lymphocyte surface protein expressed from early stages of B cell development through to the mature B cell stage, but its expression is turned off as B cells differentiate into plasma cells. (stanford.edu)
- Indeed, we found that ursolic acid induced the expression of tyrosine phosphatase SHP-1 protein and mRNA. (aacrjournals.org)
- We also demonstrate that GAC 17:1 can induce the substantial expression of PTEN and SHP-1 at both protein and mRNA level. (mdpi.com)
- Recently, SHP-2 has become clinically relevant as germ-line missense mutations in the gene encoding SHP-2 (Ptpn11) have been found to cause the developmental disorders Noonan syndrome and the Leopard syndrome. (eurekaselect.com)
- SHP-2/PTPN11 Monoclonal antibody specifically detects SHP-2/PTPN11 in Human samples. (fishersci.com)
- The PTPN11 gene provides instructions for making a protein called SHP-2. (medlineplus.gov)
- Most of the PTPN11 gene mutations replace single amino acids used to make the SHP-2 protein. (medlineplus.gov)
- All known PTPN11 gene changes that cause Noonan syndrome with multiple lentigines are believed to disrupt the SHP-2 protein's normal function. (medlineplus.gov)
- We demonstrate for the first time in vitro and in vivo that SHP-1 activity is significantly reduced upon alloactivation, resulting in an increase in the allogeneic activation of T cells and their adhesion to major histocompatibility complex (MHC)-mismatched APCs. (asm.org)
- A role for SHP-1 was subsequently confirmed in vivo using NK cells from viable motheathen mice, a mouse strain with reduced SHP-1 activity ( 13 ). (jimmunol.org)
- Administration of SHP-1-inhibited DCs in vivo induced expansion of Ag-specific cytotoxic T cells and inhibited Foxp3 + regulatory T cell induction, resulting in an enhanced immune response against pre-established mouse melanoma and prostate tumors. (jimmunol.org)
- The release of cytokines by T cells defines a significant part of their functional activity in vivo, and their ability to produce multiple cytokines has been associated with beneficial immune responses. (pnas.org)
- Here, we used serial, time-dependent, single-cell analysis of primary human T cells to resolve the temporal dynamics of cytokine secretion from individual cells after activation ex vivo. (pnas.org)
- Indeed, the production of both IL-2 and IFN-γ by CD4 + T cells in vivo has been shown to begin within hours of stimulation and wane after 16-18 h ( 13 , 14 ). (pnas.org)
- In tumor metastasis model, ACA potently inhibited the human breast cancer cell-induced osteolysis, and had little apparent in vivo toxicity at the test concentrations. (sigmaaldrich.com)
- We also showed that anti-fluorochrome antibody-conjugated magnetic beads enhanced staining of self-reactive T-cells that could not be stained using standard protocols, thus enabling rapid ex vivo isolation of autoimmune T-cells. (frontiersin.org)
- We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. (uni-muenchen.de)
- Epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) have been shown to induce neural fate specification in embryonic stem cells (ESCs) and potently stimulate the self-renewal capacity of NSCs in vivo and in vitro ( 12 , 35 , 37 ). (asm.org)
- Both anti-SHP-1 antibody and the two SH2 domains of SHP-1 expressed as glutathione S-transferase fusion proteins precipitated at least three phosphoproteins of approximately 75, 110, and 150 kD upon anti-immunoglobulin M stimulation of the WEHI-231 immature B cell line. (rupress.org)
- In the present study, we describe a unique monoclonal antibody, WM78, which interacts with PZR, a SHP-2 binding partner. (ox.ac.uk)
- Using the WM78 monoclonal antibody, which recognizes the common extracellular domain of the PZR isoforms, we demonstrate that the PZR molecules are expressed on mesenchymal and haematopoietic cells, being present on the majority of CD34(+)CD38(+) and early clonogenic progenitors, and at lower levels on CD34(+)CD38(-) cells and the hierarchically more primitive pre-colony forming units. (ox.ac.uk)
- Optimized procedures stained an average of 40.5-fold ( p = 0.01, range between 1.4 and 198) more cells than could be detected without the inclusion of PKI and cross-linking anti-fluorochrome antibody. (frontiersin.org)
- Importantly, suppression is not seen with control trkA-negative breast-cancer cells (expressing wtp53, wt-SHP-1 and undetectable trkA), transfected with Y674F/Y675F mutant-trkA. (uniprot.org)
- Importantly, using SHP-2 mutant (Delta 46-110) and SHP-2 rescue of embryonic fibroblasts stably expressing the PZR isoforms, we demonstrate for the first time that PZR, but not PZRa or PZRb, facilitates fibronectin- dependent migration of cells expressing a competent SHP-2 molecule. (ox.ac.uk)
- These methods are adaptable to any cell culture signaling system in which isogenic wild type and mutant cells have been or can be derived using any available phosphopeptide enrichment strategy. (mcponline.org)
- Shp2-deficient erythroid, myeloid, or lymphoid progenitor cells are barely detectable in fetal liver, bone marrow, thymus, or spleen in the chimeric animals derived from aggregation of homozygous Shp2 mutant ESCs and wild-type embryos. (asm.org)
- These findings indicate that molecular modulation may be an effective strategy for improving the retention of endothelial cells within tissue engineered vascular grafts, which may in turn improve their clinical performance. (northwestern.edu)
- Thus, CD22 is a molecular switch for SHP that may bias mlg signaling to anatomic sites rich in T cells. (uab.edu)
- Tumors were harvested 28 days after treatment and assayed for molecular events by western blotting and for SHP-1 activity. (biomedcentral.com)
- Immunologists and microbiologists from the University of Melbourne's Bio21 Molecular Science and Biotechnology Institute and the Peter Doherty Institute for Infection and Immunity - a joint venture between the University of Melbourne and Royal Melbourne Hospital - have led a study that defined a new cell type responsible for turning the attack back on the bacteria. (news-medical.net)
- The present review addresses the signaling and transcriptional functions of the thymus, including the molecular mechanisms underlying the regulatory functions of T cells and their role in the immune system. (spandidos-publications.com)
- In: Gastroenteropancreatic neuroendocrine tumor disease: Molecular and cell biological aspects, pp. 170 - 178 (Eds. (mpg.de)
- Since the action of the protease may be long-lived (or irreversible), this would provide a molecular memory of previous Ca2+ signalling within the cell. (cardiff.ac.uk)
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1843(6), pp. 1182-1187. (cardiff.ac.uk)
- Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. (mdpi.com)
- The F378 point mutation ablated both SHP-1 binding and the down-regulating activity of CD5 during TCR-CD3 stimulation. (nih.gov)
- We find similar effects of the SHP-2 mutants after examining stimulation of an ERK-dependent egr-1 promoter-construct by leptin. (nih.gov)
- In the absence of dendritic cell (DC) stimulation, such antibodies provide little benefit, but in a stimulatory context they can initiate potent antitumor immunity. (stanford.edu)
- In vitro biological effects of Bcr-Abl transduction were diminished in SHP-2 Δ/Δ hematopoietic cells, and the leukemic potential of Bcr-Abl-transduced SHP-2 Δ/Δ cells in recipient animals was compromised. (elsevier.com)
- It has previously been shown by us and others HGF can act as a growth factor to myeloma cells in vitro although these effects have been moderate. (wiley.com)
- In vitro cultured mouse ES cells can be differentiated into any cell of the mouse body when placed back into blastocysts ( Beddington and Robertson, 1989 ) and, therefore, ES cells are named pluripotent. (rupress.org)
- Downstream of TLR4, SHP-1 showed increased interaction with several proteins including IL-1R-associated kinase-4, and modulated LPS signaling by inhibiting NF-κB, AP-1, ERK, and JNK activity, while enhancing p38 activity. (jimmunol.org)
- From a large-scale survey of tyrosine kinase activity in non-small cell lung cancer (NSCLC), and identified more than 50 distinct tyrosine kinases and over 2500 downstream substrates, with the goal of identifying candidate oncogenes. (wikipedia.org)
- In this context, T cell function depends on integrin-mediated adhesion and migration. (asm.org)
- Inhibiting SHP-1 in DCs enhanced proinflammatory cytokines, IL-6, IL-12, and IL-1β production, promoted survival, and increased DC migration to draining lymph nodes. (jimmunol.org)
- Myeloma cell lines and primary samples were tested for the combined effects of IL-6 and HGF in inducing DNA synthesis and migration. (wiley.com)
- The chavicol preferentially suppressed cancer cell migration and invasion, and this activity was superior to its cytotoxic effects. (sigmaaldrich.com)
- Noonan syndrome is one of the most common causes of human congenital heart disease and is frequently associated with missense mutations in the protein phosphatase SHP-2. (biologists.org)
- Interestingly, patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), juvenile myelomonocytic leukemia (JMML) and LEOPARD syndrome frequently carry a second, somatically introduced subset of missense mutations in SHP-2. (biologists.org)
- embryos expressing Noonan SHP-2 mutations exhibit morphologically abnormal hearts, whereas those expressing an SHP-2 JMML-associated mutation do not. (biologists.org)
- Our studies indicate that the cardiac defects associated with the introduction of the Noonan-associated SHP-2 mutations are coupled with a delay or arrest of the cardiac cell cycle in M-phase and a failure of cardiomyocyte progenitors to incorporate into the developing heart. (biologists.org)
- Our results revealed a direct relationship between Noonan mutations and the ability of SHP-2 to cause heart defects in Xenopus . (biologists.org)
- Gene mutations can be acquired during a person's lifetime and are present only in certain cells. (medlineplus.gov)
- These mutations cause the SHP-2 protein to be continuously active. (medlineplus.gov)
- Following the initial adhesive interaction between potentially alloreactive T cells and allogeneic APCs such as dendritic cells (DCs), LFA-1 facilitates the stable formation of the "immunological synapse," which enhances T cell activation and subsequent effector functions ( 4 , 5 ). (asm.org)
- Signal tranduction studies revealed an interaction of FGFR4 with the protein tyrosine phosphatase SHP-2 and the phospholipase PLC-gamma. (tum.de)
- Visualization of SHP-1-target interaction. (mpg.de)
- Here, we identified the protein tyrosine phosphatase (PTP) SHP-1 as a key regulator of LFA-1-mediated adhesion in primary murine T cells, with particular involvement in alloactivation. (asm.org)
- The protein tyrosine phosphatase SHP-2 has been proposed to serve as a regulator of leptin signaling, but its specific roles are not fully examined. (nih.gov)
- Taken together, these data demonstrate that SHP-1 is an intrinsic global regulator of DC function, controlling many facets of T cell-mediated immune responses. (jimmunol.org)
- We found the tyrosine phosphatase Shp-2 to be the master regulator of Pdgfr pTyr signaling. (ku.dk)
- Recent data have demonstrated that the gene encoding SHP-1 is mutated in motheaten (mc) and viable motheaten (mc') mice resulting in autoimmune disease. (rupress.org)
- This study utilized a gene silencing strategy to enhance the adhesion strength of vascular endothelial cells to fibronectin-coated expanded polytetrafluoroethylene, a common vascular graft material. (northwestern.edu)
- Gene rearrangements involving the ROS1 gene were first detected in glioblastoma tumors and cell lines. (wikipedia.org)
- Activation of this protein in myeloma and lymphoma associated with a TEL/JAK2 gene fusion is independent of cell stimulus and has been shown to be essential for the tumorigenesis. (wikipedia.org)
- Collectively, these results suggest possible mechanisms by which SHP-1 may modulate signals delivered by BCR engagement. (rupress.org)
- Angiotensin II (Ang II) signaling in vascular smooth muscle cells (VSMCs) involves reactive oxygen species (ROS) through unknown mechanisms. (ahajournals.org)
- Here, we summarise the current knowledge of the mechanisms controlling endothelial cell-cell adhesion in the developing and mature blood vasculature. (portlandpress.com)
- Interestingly, we show by reverse transcriptase-PCR that the PZR isoforms are differentially expressed in haematopoietic, endothelial and mesenchymal cells. (ox.ac.uk)
- Both PZR and PZRb are present in CD133(+) precursors and endothelial cells, PZRb predominates in mesenchymal and committed myelomonocytic progenitor cells, and all three isoforms occur in erythroid precursor cell lines. (ox.ac.uk)
- Each subcompartment contains numerous subtypes of thymic epithelial cells (TECs), in addition to dendritic cells, mesenchymal cells and endothelial cells ( 1 - 3 ). (spandidos-publications.com)
- In malignant prostate tissue, SHP-1 was diminished in 28/45 cases or absent in 12/45 cases, whereas SSTR2 epithelial was diminished in 38/45 cases or lost in only 2/45 cases. (hindawi.com)
- STAT5a is involved in the maintenance of integrated prostate epithelial structure and has been shown to be critical for cell viability and tumor growth. (wikipedia.org)
- Upon alloactivation, SHP-1 activity is reduced, resulting in an increase in LFA-1 adhesion compared to that for syngeneically activated T cells. (asm.org)
- The role of SHP-2 in the stability of p210 is independent of its catalytic activity. (elsevier.com)
- Right, the activity of SHP-1 in MDA-MB-468 tumors. (biomedcentral.com)
- Dovitinib showed significant antitumor activity in HCC cell lines PLC5, Hep3B, Sk-Hep1 and Huh-7. (aacrjournals.org)
- Notably, dovitinib increased SHP-1 activity in HCC cells. (aacrjournals.org)
- Analysis of CD8 T cells from motheaten mice, which are globally deficient in SHP-1, proved problematic due to cell-extrinsic effects of SHP-1 deficiency in non-T cells on CD8 T cells. (fredhutch.org)
- By combining two treatment strategies, both aimed at boosting the immune system's killer T cells, Johns Hopkins researchers report they lengthened the lives of mice with skin cancer more than by using either strategy on its own. (news-medical.net)