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.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.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.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.Receptor-Like Protein Tyrosine Phosphatases, Class 2: A subclass of receptor-like protein tryosine phosphatases that contain multiple extracellular immunoglobulin G-like domains and fibronectin type III-like domains. An additional memprin-A5-mu domain is found on some members of this subclass.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 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.Receptor-Like Protein Tyrosine Phosphatases, Class 3: A subclass of receptor-like protein tryosine phosphatases that contain a single cytosolic protein tyrosine phosphate domain and multiple extracellular fibronectin III-like domains.Receptor-Like Protein Tyrosine Phosphatases, Class 4: A subclass of receptor-like protein tryosine phosphatases that contain short highly glycosylated extracellular domains and two active cytosolic protein tyrosine phosphatase domains.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.Receptor-Like Protein Tyrosine Phosphatases, Class 5: A subclass of receptor-like protein tryosine phosphatases that contain an extracellular fibronectin III-like domain along with a carbonic anhydrase-like domain.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.Receptor-Like Protein Tyrosine Phosphatases: A subcategory of protein tyrosine phosphatases that are bound to the cell membrane. They contain cytoplasmic tyrosine phosphatase domains and extracellular protein domains that may play a role in cell-cell interactions by interacting with EXTRACELLULAR MATRIX components. They are considered receptor-like proteins in that they appear to lack specific ligands.Protein Tyrosine Phosphatase, Non-Receptor Type 12: A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of a N-terminal catalytic domain and a large C-terminal domain that is enriched in PROLINE, GLUTAMIC ACID, SERINE, and THREONINE residues (PEST sequences). The phosphatase subtype is ubiquitously expressed and implicated in the regulation of a variety of biological processes such as CELL MOVEMENT; CYTOKINESIS; focal adhesion disassembly; and LYMPHOCYTE ACTIVATION.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.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.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.Protein Tyrosine Phosphatase, Non-Receptor Type 13: A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an amino-terminal FERM domain, an intervening region containing five different PDZ domains, and a carboxyl-terminal phosphatase domain. In addition to playing a role as a regulator of the FAS RECEPTOR activity this subtype interacts via its PDZ and FERM domains with a variety of INTRACELLULAR SIGNALING PROTEINS and CYTOSKELETAL PROTEINS.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.Receptor-Like Protein Tyrosine Phosphatases, Class 7: A subclass of receptor-like protein tryosine phosphatases that contain a short extracellular domain, a cytosolic kinase-interaction domain, and single protein tyrosine kinase domain.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.Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)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.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.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Protein Tyrosine Phosphatase, Non-Receptor Type 22: A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an N-terminal catalytic domain and a C-terminal PROLINE-rich domain. The phosphatase subtype is predominantly expressed in LYMPHOCYTES and plays a key role in the inhibition of downstream T-LYMPHOCYTE activation. Polymorphisms in the gene that encodes this phosphatase subtype are associated with a variety of AUTOIMMUNE DISEASES.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Receptor-Like Protein Tyrosine Phosphatases, Class 8: A subclass of receptor-like protein tryosine phosphatases that contain an extracellular RDGS-adhesion recognition motif and a single cytosolic protein tyrosine phosphate domain.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 enzymesProtein Tyrosine Phosphatase, Non-Receptor Type 3: A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an amino-terminal FERM domain, an intervening region containing one or more PDZ domains, and a carboxyl-terminal phosphatase domain. Expression of this phosphatase subtype has been observed in BONE MARROW; fetal LIVER; LYMPH NODES; and T LYMPHOCYTES.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.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.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.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.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.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.PhosphoproteinsEnzyme 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.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.Antigens, CD45: High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Lymphocyte Specific Protein Tyrosine Kinase p56(lck): This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.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.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.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.Transfection: 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.Immunoreceptor Tyrosine-Based Activation Motif: A conserved AMINO ACID SEQUENCE located in the intracellular domains of a family of transmembrane proteins involved in various IMMUNE RESPONSES. The CONSENSUS SEQUENCE of this motif is YXXL(or I)X(6-8)YXXL(or I) (where X denotes any amino acid). When phosphorylated ITAM motifs provide docking sites for PROTEIN TYROSINE KINASES of the Syk family thus forming signaling complexes which lead to activation of immune responses.Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 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.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.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.Tyrosine 3-Monooxygenase: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.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).Adaptor Proteins, Vesicular Transport: A class of proteins involved in the transport of molecules via TRANSPORT VESICLES. They perform functions such as binding to the cell membrane, capturing cargo molecules and promoting the assembly of CLATHRIN. The majority of adaptor proteins exist as multi-subunit complexes, however monomeric varieties have also been found.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Genistein: An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.Kinetics: The rate dynamics in chemical or physical systems.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Protein Tyrosine Phosphatase, Non-Receptor Type 4: A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an amino-terminal FERM domain, an intervening region containing one or more PDZ domains, and a carboxyl-terminal phosphatase domain. The subtype was originally identified in a cell line derived from MEGAKARYOCYTES.Proto-Oncogene Proteins pp60(c-src): Membrane-associated tyrosine-specific kinases encoded by the c-src genes. They have an important role in cellular growth control. Truncation of carboxy-terminal residues in pp60(c-src) leads to PP60(V-SRC) which has the ability to transform cells. This kinase pp60 c-src should not be confused with csk, also known as c-src kinase.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).)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.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.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.Receptors, IgG: Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).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.Proto-Oncogene Proteins c-fyn: Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Receptors, Antigen, B-Cell: IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.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.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.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Receptors, Antigen, T-Cell: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Mice, Inbred C57BLPhospholipase 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.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.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.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.Cell Adhesion: Adherence of cells to surfaces or to other cells.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).3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.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.Dual-Specificity Phosphatases: A sub-class of protein tyrosine phosphatases that contain an additional phosphatase activity which cleaves phosphate ester bonds on SERINE or THREONINE residues that are located on the same protein.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Receptor, Epidermal Growth Factor: A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.PhosphopeptidesIsoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Cell Line, Tumor: A cell line derived from cultured tumor cells.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Receptor Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Paxillin: Paxillin is a signal transducing adaptor protein that localizes to FOCAL ADHESIONS via its four LIM domains. It undergoes PHOSPHORYLATION in response to integrin-mediated CELL ADHESION, and interacts with a variety of proteins including VINCULIN; FOCAL ADHESION KINASE; PROTO-ONCOGENE PROTEIN PP60(C-SRC); and PROTO-ONCOGENE PROTEIN C-CRK.Tyrphostins: A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.Nerve Tissue ProteinsReceptors, IgE: Specific molecular sites on the surface of B- and T-lymphocytes which combine with IgEs. Two subclasses exist: low affinity receptors (Fc epsilon RII) and high affinity receptors (Fc epsilon RI).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.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.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)Receptor, Insulin: A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.ZAP-70 Protein-Tyrosine Kinase: A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.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.Focal Adhesion Kinase 1: A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Molecular Weight: The sum of the weight of all the atoms in a molecule.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.Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Glucose-6-Phosphatase: An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Adaptor Protein Complex 2: An adaptor protein complex primarily involved in the formation of clathrin-related endocytotic vesicles (ENDOSOMES) at the CELL MEMBRANE.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Crk-Associated Substrate Protein: Crk-associated substrate was originally identified as a highly phosphorylated 130 kDa protein that associates with ONCOGENE PROTEIN CRK and ONCOGENE PROTEIN SRC. It is a signal transducing adaptor protein that undergoes tyrosine PHOSPHORYLATION in signaling pathways that regulate CELL MIGRATION and CELL PROLIFERATION.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.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.cdc25 Phosphatases: A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.Okadaic Acid: A specific inhibitor of phosphoserine/threonine protein phosphatase 1 and 2a. It is also a potent tumor promoter. (Thromb Res 1992;67(4):345-54 & Cancer Res 1993;53(2):239-41)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.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.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.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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Benzoquinones: Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Lectins, C-Type: A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.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.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.Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.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.Lactams, Macrocyclic: LACTAMS forming compounds with a ring size of approximately 1-3 dozen atoms.Adaptor Protein Complex 1: A clathrin adaptor protein complex primarily involved in clathrin-related transport at the TRANS-GOLGI NETWORK.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Janus Kinase 1: A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.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.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.Antigens, Differentiation: Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.Mice, Inbred BALB CCercopithecus 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.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.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.Arsenicals: Inorganic or organic compounds that contain arsenic.Antigens, CD79: A component of the B-cell antigen receptor that is involved in B-cell antigen receptor heavy chain transport to the PLASMA MEMBRANE. It is expressed almost exclusively in B-LYMPHOCYTES and serves as a useful marker for B-cell NEOPLASMS.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Membrane Microdomains: Detergent-insoluble CELL MEMBRANE components. They are enriched in SPHINGOLIPIDS and CHOLESTEROL and clustered with glycosyl-phosphatidylinositol (GPI)-anchored proteins.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.Contactin 1: A contactin subtype that is predominantly expressed in the CEREBELLUM; HIPPOCAMPUS; NEOCORTEX; and HYPOTHALAMUS.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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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)Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Immunoreceptor Tyrosine-Based Inhibition Motif: A conserved AMINO ACID SEQUENCE located in the intracellular domains of a family of transmembrane proteins that negatively regulate the signal transduction processes emanating from transmembrane proteins containing IMMUNORECEPTOR TYROSINE-BASED ACTIVATION MOTIFS. The CONSENSUS SEQUENCE of this motif is I(or V)LXYXXL(or V) (where X denotes any amino acid). Also known as ITIM motifs.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Receptor-Like Protein Tyrosine Phosphatases, Class 1: A subclass of receptor-like protein tryosine phosphatases that contain heavily glycosylated and cysteine-rich extracellular regions that include fibronectin type III-like domains.Dual Specificity Phosphatase 3: A dual specificity phosphatase subtype that plays a role in intracellular signal transduction by inactivating MITOGEN-ACTIVATED PROTEIN KINASES. It has specificity for EXTRACELLULAR SIGNAL-REGULATED MAP KINASES.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Then, Killer Inhibitory Receptors (KIRs) examine the surface of the tumor cell in order to determine the levels of MHC class I ... or with an adaptor protein, which can be either DAP10 or DAP12. All of these signaling molecules contain immunoreceptor ... When an inhibitory receptor is stimulated by the binding of MHC class I, kinases and phosphatases are recruited to the receptor ... a common feature of such receptors is the presence of noncovalently linked subunits that contain immunoreceptor tyrosine-based ...
Ligand binding enables interaction between receptor and ITAM-bearing adaptor protein DAP12 (ITAM, Immunoreceptor tyrosine-based ... CD94/NKG2 is a family of C-type lectin receptors which are expressed predominantly on the surface of NK cells and a subset of ... Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 ... probably Src family kinase phosphorylates tyrosine residue, and this allows recruitment of the tyrosine phosphatase SHP-1, SHP- ...
"FcεR1-mediated tyrosine phosphorylation of multiple proteins, including phospholipase Cγ1 and the receptor βγ2 complex, in RBL- ... Surface markers: cell surface markers of mast cells were discussed in detail by Heneberg, claiming that mast cells may be ... Mast cells are very similar to basophil granulocytes (a class of white blood cells) in blood. Both are granulated cells that ... An important adaptor protein activated by the Syk phosphorylation step is the linker for activation of T cells (LAT). LAT can ...
An Fc receptor is a protein found on the surface of certain cells - including, among others, B lymphocytes, follicular ... gamma receptors generate signals within their cells through an important activation motif known as an Immunoreceptor tyrosine- ... Another FcR is expressed on multiple cell types and is similar in structure to MHC class I. This receptor also binds IgG and is ... This adaptor protein is called the Fcγ subunit and, like FcγRIIA, contains the two YXXL sequences that are characteristic of an ...
In kidney cells, the bradykinin receptor B2 has been shown to interact directly with a protein tyrosine phosphatase. The ... G protein-coupled receptors database List of MeSH codes (D12.776) Metabotropic receptor Orphan receptor Pepducins, a class of ... the extracellular signal molecule binds with the G-protein receptor (Gq) on the cell surface and activates phospholipase C, ... presence of a tyrosine-phosphorylated ITIM (immunoreceptor tyrosine-based inhibitory motif) sequence in the B2 receptor is ...
In kidney cells, the bradykinin receptor B2 has been shown to interact directly with a protein tyrosine phosphatase. The ... Class A (Rhodopsin-like), Class B (Secretin-like), Class C (Glutamate Receptor-like), Others (Adhesion (33), Frizzled (11), ... the extracellular signal molecule binds with the G-protein receptor (Gq) on the cell surface and activates phospholipase C, ... presence of a tyrosine-phosphorylated ITIM (immunoreceptor tyrosine-based inhibitory motif) sequence in the B2 receptor is ...
When inhibitory KIR receptors bind to a ligand, their ITIMs are tyrosine phosphorylated and protein tyrosine phosphatases, ... KIR3DS1 NK cell receptors bind directly to the MHC class I molecules on the surface of target cells. Human killer cell ... an adaptor molecule containing a negatively charged residue as well as immunoreceptor tyrosine-based activation motifs (ITAM). ... receptors expressed on the surface of NK cells are each expressed on a subset of NK cells in such a way that not all classes of ...
Therefore, there are four main transmembrane receptor types: G protein coupled receptors (GPCRs), tyrosine kinase receptors ( ... some adaptor proteins are phosphorylated, like BLNK (B cells) and LAT (T cells). These proteins after phosphorylation become ... immunoreceptor tyrosine-based activation motif) and resulting in different signal pathways. The antigen receptor and signal ... a transmembrane glycoprotein receptor that establishes contact with another cadherin present in the surface of a neighbour cell ...
CD45 - a transmembrane protein whose intracellular tail functions as a tyrosine phosphatase that activates Src family kinases ... The T-cell receptor, or TCR, is a molecule found on the surface of T cells, or T lymphocytes,[1] that is responsible for ... On helper T cells and regulatory T cells, this co-receptor is CD4 that is specific for MHC class II. ... to bind to the ITAM and activated ZAP-70 phosphorylates tyrosines on the adaptor protein LAT, which then attracts PLC-γ. Other ...
Then, Killer Inhibitory Receptors (KIRs) examine the surface of the tumor cell in order to determine the levels of MHC class I ... or with an adaptor protein, which can be either DAP10 or DAP12. All of these signaling molecules contain immunoreceptor ... When an inhibitory receptor is stimulated by the binding of MHC class I, kinases and phosphatases are recruited to the receptor ... a common feature of such receptors is the presence of noncovalently linked subunits that contain immunoreceptor tyrosine-based ...
Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature. 1998; 391: 703-707. ... Cytotoxicity of T cells can be triggered by signals derived from the T-cell receptor. Alternatively, MHC class I-recognizing ... Cell-surface phenotypes of the clonal T-cell cultures were confirmed by flow cytometry. Clones expressed the T-cell markers, ... Phosphorylated ITIMs serve as recruitment points for cytosolic protein tyrosine phosphatases, which dephosphorylate substrates ...
Ligand binding enables interaction between receptor and ITAM-bearing adaptor protein DAP12 (ITAM, Immunoreceptor tyrosine-based ... CD94/NKG2 is a family of C-type lectin receptors which are expressed predominantly on the surface of NK cells and a subset of ... Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 ... probably Src family kinase phosphorylates tyrosine residue, and this allows recruitment of the tyrosine phosphatase SHP-1, SHP- ...
In natural killer (NK) and T cells, DAP10 was identified as a cell surface adaptor protein in an activating receptor complex ... immunoreceptor tyrosine-based inhibition motifs in their cytoplasmic domains that recruit cytoplasmic tyrosine phosphatases, ... class I, including Ly49 and the killer cell immunoglobulin-like receptor (KIR) (1). These receptors have ... NK cells, α/β− and γ/δ−T cell receptor+ T cells, and U937 (myeloid cell), but not substantially in other tissues or JY (B ...
Identification of the tyrosine phosphatase PTP1C as a B cell antigen receptor-associated protein involved in the regulation of ... Anti-MHC class I Abs were used as a negative control because they bind to the T cell surface, but do not initiate signals that ... the SH2-containing inositol phosphatase or the SH2-containing protein tyrosine phosphatase is regulated by the adaptor protein ... CD22 associates with protein tyrosine phosphatase 1C, Syk, and phospholipase C-γ(1) upon B cell activation. J. Exp. Med. 183: ...
NK cells express several activating and inhibitory receptors that recognize the altered expression of proteins on target cells ... NK cells express several activating and inhibitory receptors that recognize the altered expression of proteins on target cells ... cells that show strong cytolytic function against physiologically stressed cells such as tumor cells and virus-infected cells. ... cells that show strong cytolytic function against physiologically stressed cells such as tumor cells and virus-infected cells. ...
Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn ... of component peptides with MHC class II molecules that are routed to the cells surface for priming of helper T cell precursors ... A novel adapter protein orchestrates receptor patterning and cytoskeletal polarity in T cell contacts. Cell. 1998;94(5):667-677 ... Actin-dependent immunoreceptor microclusters operate in part through a principle of receptor tyrosine phosphatase exclusion and ...
Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the ... However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs) and genotoxically altered cells, while ... However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs) and genotoxically altered cells, while ... Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the ...
... phosphorylates the immunoreceptor tyrosine-based activation motifs (ITAMs) in FcεRI and activates the protein tyrosine kinase ... cells, a process that may be enhanced by engagement of Notch at the surface of T cells with Jagged on dendritic cells). TH2 ... immunoreceptor tyrosine-based inhibitory motif) and the recruitment of the inositol phosphatase SHIP1 (which catalyses the ... class II molecules to naive T cells. In the presence of early interleukin 4 (IL-4) (potentially derived from a range of cells ...
PIR-B associates with the protein tyrosine kinase Lyn and depends on the protein tyrosine phosphatase SHP-1, and possibly SHP-2 ... Peripheral B cell activation is inhibited by a variety of cell surface receptors including CD22, FcγRII, CD72, and PIR-B (49). ... B cell receptor; Bis I, bisindolylmaleimide I; EST, expressed sequence tag; HL, Hodgkin lymphoma; ITIM, immunoreceptor tyrosine ... including modulating surface antigen expression and Ig class switching (22, 23). The IL-4Rα chain is a component of IL-13 ...
... in the case of tyrosine kinase receptors, adaptors, scaffolding proteins, and enzymes are recruited to the cytoplasmic side of ... "Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface," Cell ... activation of other enzymes and adaptors, and rearrangement of the cytoskeleton that culminates in the release of three classes ... the signaling complex is protected from other proteins, such as membrane phosphatases, localized in the disordered region of ...
DAP12 contains an immunoreceptor tyrosine-based activation motif that functions as docking site for the protein tyrosine ... is an immunoglobulin-like cell surface receptor associated with DAP12/KARAP that activates monocyte-derived dendritic cells ( ... The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function. Immunol. Today. 21:611-614. ... OCs were stained in 24-well plates for tartrate-resistant acid phosphatase (TRAP) activity (Acid Phosphatase Kit; Sigma-Aldrich ...
In kidney cells, the bradykinin receptor B2 has been shown to interact directly with a protein tyrosine phosphatase. The ... the extracellular signal molecule binds with the G-protein receptor (Gq) on the cell surface and activates phospholipase C, ... presence of a tyrosine-phosphorylated ITIM (immunoreceptor tyrosine-based inhibitory motif) sequence in the B2 receptor is ... this phosphorylation results in the switching of the coupling from the Gs class of G-protein to the Gi class. [23] cAMP- ...
F. Kiefer, J. Brumell, N. Al-Alawi et al., "The Syk protein tyrosine kinase is essential for Fcγ/receptor signaling in ... In fact, most phagocytic receptors are short molecules that extend only around 5 nm from the surface of the cell (Figure 4(a)) ... The tyrosine phosphatase CD45 must be taken away from sites of FcγR engagement to allow full activation of Src tyrosine kinases ... or by adaptor proteins such as Gab2 [89] (Figure 1). These dramatic changes in membrane lipid composition during Fcγ receptor- ...
Ly49 proteins are type II membrane glycoproteins of the C-type lectin-like family, expressed on the cell surface as disulfide- ... Two classes of SH2-containing inhibitory signaling effector molecules have been identified: the tyrosine phosphatase SHP-1 and ... Arrest of proliferation in B cells is also dependent on the ITIM pathway, through the activation of the adaptor protein Dok and ... The significance of these receptors is further evidenced by the conservation of immunoreceptor tyrosine-based inhibitory motifs ...
This receptor complex serves to link CD36 to the adaptor FcRγ, which bears an immunoreceptor tyrosine activation motif. By ... a highly glycosylated transmembrane protein belonging to the class B scavenger receptor family, is expressed by several cell ... Cells were treated with 1 μg/mL DiI-labeled oxidized LDL for 20 min. Non-internalized oxLDL was stripped off the cell surface ... SHIP1, an SH2 domain containing polyinositol-5-phosphatase, regulates migration through two critical tyrosine residues and ...
She is a widely expressed adapter protein that plays an important role in signaling via a variety of cell surface receptors and ... Protein tyrosine phosphatases (PTPs) constitute a family of receptor-like and cytoplasmic signal transducing enzymes that ... In mast cells, Syk specifically associates with doubly phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) ... non-catalytic region of the non-receptor class of tyrosine kinases. In addition, the structure of p47gag-crk has striking ...
1996) Recruitment of tyrosine phosphatase HCP by the killer cell inhibitor. receptor. Immunity 4: 77-85.. 15. Dustin ML, ... adaptor protein orchestrates receptor patterning and cytoskeletal polarity in Tcell. contacts. Cell 94: 667-677.. 16. Grakoui A ... of the activating immunoreceptor NKG2D and its MHC class I-like ligand. MICA. Nat Immunol 2: 443-451.. 36. Staunton DE, Dustin ... 2B4, the natural killer and T cell immunoglobulin superfamily surface protein, is. a ligand for CD48. J Exp Med 188: 2083-2090. ...
... receptor class and it interacts with intracellular protein tyrosine kinases as well as a number of adaptor proteins that relay ... IMMUNE CELL SURFACE RECEPTORS AND THEIR FUNCTIONS LECTURE: 07 Title: IMMUNE CELL SURFACE RECEPTORS AND THEIR FUNCTIONS LEARNING ... sets of target proteins. Some receptors are protein tyrosine phosphatases (PTPs) able to dephosphorylate tyrosine residues ... This means that alterations in the phosphorylation of each immunoreceptor tyrosine-based activation motif (ITAM) in the course ...
... of Natural Killer Cells Definition Morphology Origin and Tissue Distribution Mechanisms of Natural Killer Cell Functions Cell- ... Mediated Cytotoxicity Production of Cytokines Physiologic Roles of Natural Killer Cells Natural Resistance Regulation of… ... CHAPTER 85 FUNCTIONS OF NATURAL KILLER CELLS Williams Hematology CHAPTER 85 FUNCTIONS OF NATURAL KILLER CELLS GIORGIO ... cell receptors for the grafted parental cells.24 The KIR molecules and the CD94/NKG2A receptor have an immunoreceptor tyrosine- ...
Regulation of many aspects of cell behaviour occurs through the interaction of cytokines with specific cell surface receptors, ... immunoreceptor tyrosine-based activation motif), suggesting that STAM acts as an adaptor molecule involved in signal ... These proteins fall into five classes based on the protein motifs found N-terminal of the SOCS box. In addition to four new ... The negative regulation of cytokine signaling, with the exception of the tyrosine phosphatases, is not widely understood. We ...
... and TREM-Like Receptors (Treml). The TREM were discovered through screens for proteins capable of facilitating the cell surface ... Treml-1 and Treml-6 have more substantial cytoplasmic tails that include canonical immunoreceptor tyrosine-based inhibitory ... Our work has defined a key adaptor protein, Linker for Activated B cells (LAB), in TREM2 signaling in macrophages. Moreover, we ... function approach to understanding the basis of the interactions of these receptors with HLA Class I proteins. By dissecting ...
In kidney cells, the bradykinin receptor B2 has been shown to interact directly with a protein tyrosine phosphatase. The ... Membrane proteins, receptors: cell surface receptors. G protein-coupled receptor. Class A. *Eicosanoid receptor (Prostaglandin ... presence of a tyrosine-phosphorylated ITIM (immunoreceptor tyrosine-based inhibitory motif) sequence in the B2 receptor is ... "The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis". Proc. Natl. Acad. ...
... family is a family of adaptor proteins recruited by a wide variety of receptor tyrosine kinases (RTKs) such as EGFR, HGFR, ... Background: Integrins are α/β heterodimeric cell surface receptors that play a pivotal role in cell adhesion and migration, as ... Phosphorylation of Tyr627 and Tyr659 is required for Gab1 binding to and activation of the protein tyrosine phosphatase SHP2 (6 ... An immunoreceptor tyrosine-based activation motif (ITAM) found in the CD79A intracellular region appears to be important for ...
In some cell types, can also activate STAT1 and STAT3. May also activate LYN tyrosine kinase (By similarity). ... Receptor for erythropoietin. Mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO ... The tyrosine-phosphorylated form interacts with several SH2 domain-containing proteins including LYN, the adapter protein APS, ... appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor ...
  • Cumulative expression of CD158j and DAP12 endowed cytolytic competence on CD4 + CD28 null T cells, allowing them to kill in the absence of T-cell receptor triggering. (
  • Recently, it has been shown that genetic defects of human DAP12/KARAP and TREM-2 result in a rare syndrome characterized by bone cysts and presenile dementia called Nasu-Hakola disease. (
  • Triggering receptors expressed on myeloid cells (TREM) are members of the immunoglobulin superfamily that promote myeloid cell activation by associating with the transmembrane adaptor protein DAP12/KARAP ( 1 - 4 ). (
  • Rare TREM-2- and DAP12-deficient individuals have been recently identified ( 7 , 8 ). (
  • This observation suggests that the TREM-2-DAP12 complex may regulate the function of an unexpectedly vast array of myeloid cells, including not only DCs, but also osteoclasts (OCs) and microglial cells, which are critical for bone modeling and brain function, respectively. (
  • Gels were blotted onto nitrocellulose membranes and incubated with anti-TREM-2 antibodies (clones 21E10 and 20G3) or rabbit anti-DAP12 antiserum as previously described ( 2 ). (
  • One of the best-characterized myeloid DAP12-coupled receptor systems are the triggering receptors expressed on myeloid cells (TREM) and TREM-Like Receptors (Treml). (
  • The TREM were discovered through screens for proteins capable of facilitating the cell surface expression of DAP12. (
  • Five of the eight proteins (TREM-1, 2, 3, PDC-TREM, and Treml-4) have a transmembrane domain with a single charged residue that mediates their physical and functional association with DAP12, followed by short cytoplasmic domains. (
  • Background: DNAX-activating protein 12 (DAP12, TYROBP) is a signaling adaptor for several pathogen receptors expressed by cells of the innate immune system (1). (
  • T cells modified to express a KIR-CAR and DAP12 exhibit superior antitumor activity compared with standard first- and second-generation CD3ζ-based CARs in a xenograft model of mesothelioma highly resistant to immunotherapy. (
  • 13 genes encoded within the leukocyte receptor complex (LRC) on chromosome 19q13.4 14-16 and are expressed on NK cells and infrequently on CD8 + T cells. (
  • CD94/NKG2 family includes seven members: NKG2A, B, C, D, E, F and H. Genes encoding these receptors are clustered in the natural killer complex (NKC) on human chromosome 12 and mouse chromosome 6 together with Clr (C-lectin related) genes. (
  • HACS1 is an adaptor protein identified in our transcriptional study of genes expressed in multiple myeloma ( 1 ). (
  • The exact size of the GPCR superfamily is unknown, but at least 831 different human genes (or ~ 4% of the entire protein-coding genome ) have been predicted to code for them from genome sequence analysis . (
  • The largest class by far is class A, which accounts for nearly 85% of the GPCR genes. (
  • In contrast, antigen receptors on B and T lymphocytes diversify enormously in each individual: genes for these receptors composed of multiple various parts are assembled randomly through gene recombination during development of these cells throughout the life of the individuals. (
  • It is miraculous that only a few genes generate a repertoire of receptors that match essentially all of the molecular structures existing on earth including even newly generated chemical compounds, the mechanisms for which have mostly been clarified to date as briefly mentioned below. (
  • These other cells are almost to the generic swimming of domain genes, but correspond designated to determine such Substrates in additional glycoprotein gene( Javitt 2002). (
  • Some genes have boost-invariant, responsible, viral aminopropyl-transferases of the Finnish proteins with additional e0 of binding transcription and G1 S15( Frishberg et al. (
  • Each multidomain thrombopoiesis is a breast of 7 transcriptional co-chaperone genes in two proteins, the city and neuronal cells. (
  • HBV is ready not only to feed the blood-testis hurdle and enter the male germ cells but also integrate to their genomes C.The prior work WHI-P97 has confirmed that human sperm cells could serve as possible vectors for vertical transmission of HBV genes. (
  • After getting introduced in to the embryo via the WHI-P97 sperm, HBV genes had been replicated and expressed in the embryonic cells C. (
  • Tcra, Tcrb, Tcrg and Tcrd each have constant and variable regions which are assembled through this site specific recombination mediated by recombination activating genes, RAG-1/2. (
  • The HLA class I genes map within the MHC at 6p21.3, and the KIR genes map within the leukocyte receptor complex (LRC) at 19q13.4. (
  • When introduced into CD4 T cells, this construct mimics the activity of endogenous PD-1 in terms of its ability to suppress T cell expansion and cytokine production. (
  • In contrast, mutation of the ITSM abrogated the ability of PD-1 to block cytokine synthesis and to limit T cell expansion. (
  • TREM-2 suppresses cytokine production by TLR-stimulated BMMØ and both Trem2-/- and Tyrobp-/- DC are hyper-responsive to TLR stimulation in vitro. (
  • Chen D, Heath V, O'Garra A, Johnston J, McMahon M (1999) Sustained activation of the raf-MEK-ERK pathway elicits cytokine unresponsiveness in T cells. (
  • The cytokine is used to stimulate the mononuclear cells to develop in the direction of NK cells, and the corresponding cell culture medium is used to make the NK cells proliferate in a large amount. (
  • Reciprocally, acute cytokine stimulation restored reactivity of hyporesponsive NK cells through mTOR activation. (
  • These results demonstrate that mTOR acts as a molecular rheostat of NK cell reactivity controlled by educating receptors and uncover how cytokine stimulation overcomes NK cell education. (
  • As the subgingival biofilm is majorly composed of Gram -ve bacteria, endotoxins produced by them leads to the induction of cytokine production by host cells, which causes inflammatory changes, like increased vascular permeability and engorgement of blood vessels. (
  • Superantigen - A class of antigens that cause non-specific activation of T-cells, resulting in polyclonal T-cell activation and massive cytokine release. (
  • These findings stimulated research into strategies to induce anti-tumor responses and led to immunotherapies such as cytokine therapy, peptide vaccine, dendritic-cell vaccine, and adoptive T-cell therapy. (
  • The protein encoded by this gene is essential for T-cell proliferation and survival, cytokine production, and T-helper type-2 development. (
  • H-60 and Rae1 are structurally similar to MHC glycoproteins class I and their expression is increased in tumor cells. (
  • Natural killer (NK) cells are innate immune cells that show strong cytolytic function against physiologically stressed cells such as tumor cells and virus-infected cells. (
  • NK cells have been used in several clinical trials to control tumor growth. (
  • Increasing evidence suggests that tumor microenvironment regulate the phenotype and function of NK cells. (
  • In this review, we discussed the NK cell phenotypes and its effector function and impact of the tumor microenvironment on effector and cytolytic function of NK cells. (
  • Natural killer (NK) cells are a group of innate immune cells that show spontaneous cytolytic activity against cells under stress such as tumor cells and virus-infected cells. (
  • After activation, NK cells also secrete several cytokines such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF), and chemokines (CCL1, CCL2, CCL3, CCL4, CCL5, and CXCL8) that can modulate the function of other innate and adaptive immune cells. (
  • Natural killer (NK) cells, which express PKCθ, play a prominent role in this process, mainly by elimination of tumor cells with reduced or absent major histocompatibility complex class-I (MHC-I) expression. (
  • This justifies the increased interest of the use of activated NK cells in anti-tumor immunotherapy in the clinic. (
  • Cell surface proteins major histocompatibility complex (MHC) class I-related chain A (MICA) and UL16-binding proteins (ULBP) 1, 2, and 3 are up-regulated upon infection or tumor transformation and can activate human natural killer (NK) cells. (
  • NKG2D is a C-type lectin-activating receptor that recognizes cell surface MHC class I-like proteins up-regulated upon cell stress, including viral or bacterial infection and tumor transformation (for review see references 1 , 2 ). (
  • Our laboratory further demonstrated in mouse models that PIRB regulated functional development of myeloid-derived suppressor cell and the formation of a tumor-permissive microenvironment. (
  • We are currently pursuing new mass spectrometry approaches to identify peptides arrayed on individual types of antigen-presenting cells, and defining at a molecular level the extent of T cell recognition of individual immunodominant epitopes as well as non-immunodominant epitopes.In the next year, we expect to apply these tools and approaches for characterizing human immune recognition to the area of tumor immunology. (
  • Research studies have demonstrated that DAF/CD55 is overexpressed in a variety of solid and liquid tumors, which functions to protect tumor cells from complement-mediated attack (3,4). (
  • Given its ability to disable the complement cascade and facilitate immune evasion by tumor cells, DAF/CD55 has received attention as a potential therapeutic target for the treatment of human malignancies. (
  • NK cells play a major role in host rejection of tumor and virus-infected cells. (
  • trophoblast cells (human tumor cells, i.e., human leukemia K562 cells) are cells that do not divide or proliferate but remain metabolically active. (
  • My group develops and applies genomic biomarkers of tumor cells, whether detected through biopsy of the primary neoplasm, or noninvasively through monitoring of the bodily fluids including blood. (
  • We are also interested in better molecular understanding of normal tissue stem cells and their malignant tumor-initiating counterparts (cancer stem cells), toward identification of the underlying mechanisms relevant to specific cancers of the hematopoietic system. (
  • They make up the bulk of the innate defense against viral infections and the surveillance of tumor cells. (
  • Progress in understanding the complex molecular mechanisms that regulate T cell activation, migration to tumor site and effector functions within tumors has led to the identification of several mechanisms that prevent immune-mediated tumor rejection in most patients. (
  • The dysregulated cellular processes in cancer cells are in tandem with accumulation of variable genetic alterations and consequent expression of tumor neoantigens which are not present in normal cells [ 2 ]. (
  • Firstly, dissemination of cancer neoantigens to tumor microenvironment (TME) occurs following cancer cell death (step 1). (
  • Following the priming and activation, the activated effector T cells then migrate to the tumor site via blood vessels (step 4). (
  • When the activated effector T cells arrive in the vicinity of the tumor site, they pass through endothelial cells and infiltrate the tumor microenvironment (step 5). (
  • Targeting the tumor-restricted, glycosylation-dependent Siglec-9 axis may unleash this intratumoral T-cell subset, while confining T-cell activation to the tumor microenvironment. (
  • Altered tumor cell-surface glycosylation is common and has been extensively exploited for diagnostic purposes ( 9 ), such as the detection of cancer antigen (CA) 15-3, CA 19-9, and CA 125, yet evidence also suggests a role for glycosylation in cancer immunity ( 10, 11 ). (
  • While early immunotherapies focused on accelerating T-cell activity, current immune-checkpoint inhibitors take the brakes off the anti-tumor immune responses. (
  • Several companies are currently conducting phase 3 trials for different tumor types, including renal-cell cancer (RCC), bladder cancer, head and neck cancer, ovarian cancer, and brain cancer. (
  • While most cancer immunotherapies accelerate T-cell activity, immune-checkpoint inhibitors release the immune system's brakes to unleash anti-tumor immune responses. (
  • Mast cells are effector cells of allergic and anaphylactic reactions and play a role in many physiological and pathological processes [ 7 , 8 ]. (
  • They are also known as the central effector cell in IgE-mediated allergic and inflammatory disorders. (
  • T Cells from Tolerized αβ T Cell Receptor (TCR)-deficient Mice Inhibit Contact Sensitivity-effector T Cells in Vivo, and Their Interferon-γ Production in Vitro," The Journal of Experimental Medicine, Dec. 1, 1996, vol. 184, pp. 2129-2139. (
  • In this chapter, emphasis has been placed on the core mechanisms underlying the broad categories of hypersensitivity responses distinguished on the basis of the Gell and Coombs classification and based on differences in the immune reactants (antibodies or cells), the form of the presented antigen, and the effector mechanisms involved. (
  • In addition, Rap proteins share a similar effector region as Ras, but have different flanking amino acids. (
  • The absence of PD-1 induced proliferation of effector T cells in the adenovirus-infected liver and resulted in rapid clearance of the virus. (
  • These results indicate that PD-1 plays an important role in T cell tolerance at the effector phase and the blockade of the PD-1 pathway can augment antiviral immunity. (
  • When naive T cells differentiate into effector cells, they change their activation requirement. (
  • Effector T cells are much less dependent on costimulation than naive T cells. (
  • Effector T cells, unlike naive T cells, can be activated by TCR signal alone ( 2 , 3 ). (
  • A more perplexing and less easily understandable observation is that effector T cells can be activated by costimulatory signal in the absence of TCR signal ( 4 , 5 ). (
  • As effector T cells can be easily activated, their negative regulatory system should play vital roles in the maintenance of peripheral tolerance. (
  • Nevertheless, little is known about the mechanism that prevents undesirable or excessive activation of effector T cells in the periphery. (
  • However, resistance to immunotherapy due to loss of T-cell effector function remains a significant barrier, especially in solid malignancies. (
  • The following step is priming and activation of effector T cell against the cancer neoantigens (step 3). (
  • Oftentimes, cancer cells or immunosuppressive cells in the TME provide immune inhibitory signals lest effector T cells function properly. (
  • In the context of the cancer-immunity cycle, checkpoint inhibitors aim to reset or reinstate dysfunctional effector T cells. (
  • In contrast, human T cells, a major anticancer effector cell, only rarely express Siglecs. (
  • We identified Siglec-9 + CD8 + T cells as a subset of effector memory cells with high functional capacity and signatures of clonal expansion. (
  • Clinical responses have been achieved by immune-checkpoint therapies targeting inhibitory receptors on CD8 + T cells in order to exploit their antitumor effector functions ( 1-4 ). (
  • Inasmuch as the mast cell is the key effector cell of the biologic response in allergic rhinitis, urticaria, anaphylaxis, and systemic mastocytosis, its developmental biology, activation pathway, product profile, and target tissues will be considered in the introduction to these clinical disorders. (
  • Signaling through the T cell costimulatory receptor CD28 is essential for the full activation of naïve T cells and their differentiation into effector cells. (
  • Mast cell activation is initiated by the binding of oligomeric antigens to receptor-bound IgE, which crosslinks Fc ε RI and results in its aggregation. (
  • Another surprise is that such diverse receptors in an individual do not react with any structures contained in the self body (self-antigens) in principle, which is called self-tolerance. (
  • Cherukuri A, Cheng PC, Pierce SK (2001a) The role of the CD19/CD21 complex in B-cell processing and presentation of complement-tagged antigens. (
  • In ideal state, immune cells recognize these new antigens and kill the cancer cells. (
  • Cells of the immune system detect and respond to the presence of foreign antigens by signaling through an array of receptors, which include the multichain immune recognition receptor (MIRR) family. (
  • Immune cells express a variety of receptors to detect foreign antigens and respond in a selective manner to clear pathogens and infected cells from the body. (
  • In immunology , antigens (Ag) are structures (aka substances) specifically bound by antibodies (Ab) or a cell surface version of Ab ~ B cell antigen receptor (BCR). (
  • Antigens are usually proteins , peptides (amino acid chains) and polysaccharides (chains of monosaccharides/simple sugars) but lipids and nucleic acids become antigens only when combined with proteins and polysaccharides. (
  • The immune system is supposed to identify and attack "non-self" invaders from the outside world or modified/harmful substances present in the body and usually does not react to self-antigens under normal homeostatic conditions due to negative selection of T cells in the thymus . (
  • The expression of cell surface B-lineage-restricted antigens such as CD20 makes it an attractive target for antibody therapy. (
  • Antibody responses against extracellular bacteria are directed against cell wall antigens and secreted and cell-associated toxins, which may be polysaccharides or proteins. (
  • The appearance of clinically detectable tumors may be the result of the proliferation of cells that have developed sophisticated strategies to escape the immune response. (
  • Knock down of HACS1 in a human B lymphoma cell line by small interfering ribonucleic acid did not significantly change IL-4-stimulated B cell proliferation. (
  • Small GTPases, adhesion, cell cycle control and proliferation. (
  • 3BP2 −/− B cells demonstrated a proliferation defect in response to antigen receptor cross-linking and a heightened sensitivity to B-cell receptor-induced death via a caspase-3-dependent apoptotic pathway. (
  • 3BP2 −/− B cells demonstrate diminished proliferation and cell survival following cross-linking of the B-cell receptor (BCR). (
  • Title: Gp78 involvement in cellular proliferation: Can act as a promising modulator for cell cycle regulatory proteins? (
  • Liver nonparenchymal cells including sinusoidal endothelial cells and Kupffer cells constitutively expressed PD-L1 and inhibited proliferation and cell division of activated T cells expressing PD-1. (
  • Human mast cells and basophils express Fc epsilon RI that consists of three subunits -alpha,beta, gamma, and formes tetramer (AlphaBetaGamma2). (
  • However, the Fc epsilon RI on the surface of human monocytes consist of alpha and gamma subunits and form a trimeric (AlphaGamma2) complex. (
  • The Alpha-chain binding with IgE and the others subunits are essential for downstream signaling [2] . (
  • Such receptors have a broad binding specificity and, therefore, are able to broadcast opposite signals. (
  • Multiple factors such as cell-intrinsic signals (transcription factors) and external signals (cytokines and growth factors) govern the development of NK cells. (
  • Linkage of microclusters through myosin II ensures that T cells respond to multiple coincident MHC-peptide signals. (
  • Our study demonstrates that HACS1 is up-regulated by B cell activation signals and is a participant in B cell activation and differentiation. (
  • NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. (
  • The lamina is from the de novo one in that the episodic phenotypes angiotensin-(1-9 for each serum underlie activated by complex signals been with the biological part CRY, down by affected receptors of a carboxy-terminal scientific catalytic heat. (
  • Target cell recognition and NK cell activation are controlled by the balance between positive and negative signals arising from the engagement of an array of NK activating receptors (NKar) and NK inhibitory receptors (NKir). (
  • For proper T cell activation, two separate signals are required (Fig. 1 ) [ 8 ]. (
  • These studies also shed a new light on the signals regulating the maintenance of the normal mature murine B‐cell pool. (
  • This maintenance is dependent on signals from the BAFF receptor since blocking of BAFF-BAFF‐R interaction results in decreased numbers of Syk‐deficient B cells. (
  • Full activation of T cells requires two distinct but synergistic signals. (
  • In the absence of costimulatory signals, T cells may undergo unresponsiveness (anergy) or programmed cell death (apoptosis) upon antigen stimulation. (
  • Extracellular signals are recognized by additional cell surface receptors like CD28 or LFA-1 and further regulate cellular response. (
  • Background: Valosin-containing protein (VCP) is a highly conserved and abundant 97 kDa protein that belongs to the AAA (ATPase associated with a variety of cellular activities) family of proteins. (
  • VCP homo-hexamers associate with a variety of protein cofactors to form many distinct protein complexes, which act as chaperones to unfold proteins and transport them to specific cellular compartments or to the proteosome (4). (
  • These protein complexes participate in many cellular functions, including vesicle transport and fusion, fragmentation and reassembly of the golgi stacks during mitosis, nuclear envelope formation and spindle disassembly following mitosis, cell cycle regulation, DNA damage repair, apoptosis, B- and T-cell activation, NF-κB-mediated transcriptional regulation, endoplasmic reticulum (ER)-associated degradation and protein degradation (4). (
  • As a result of its cellular distribution, this receptor plays a major role in controlling allergic responses . (
  • Tracking temporal and positional p-Tyr changes across the cellular proteome, i.e . tyrosine phosphoproteomics, is therefore tremendously valuable. (
  • Availability permitting, a virtually unlimited number of Abs, each recognizing a specific cellular protein, may be arrayed on a chip, incubated with total cell or tissue extracts or with biological fluids, and then probed with a fluorescently labeled p-Tyr-specific monoclonal Ab, PY-KD1, specifically generated for this assay as part of the current study. (
  • Mass spectrometry, already the standard method to identify proteins ( 13 ), has also gained popularity for phosphoproteome analysis, as practiced either with or without prior gel fractionation of the cellular proteome or subsets thereof ( 14 - 20 ). (
  • Protein interactions are essential for most cellular functions. (
  • Selective protein-protein interactions are important for many cellular functions and are often mediated by short regions, but such regions are difficult to identify because of their short lengths and degenerate sequences. (
  • In addition to its participation as the only cell capable of reabsorbing the calcified bone matrix, the osteoclast is one of the cellular elements effective in the immune system, a function still little-known but expected, given its belonging to the monocyte-macrophage lineage. (
  • A better understanding of PDZ protein-protein interaction networks and regulatory mechanisms will improve our knowledge of many cellular and biological processes. (
  • Mast cells are the primary cellular mediators of allergic reactions and also function in innate immunity and defense against helminths (1). (
  • that may become a SUMO (little ubiquitin-like modifier proteins) E3 ligase to modify a broader selection of cellular procedures including autophagy. (
  • Other exotoxins interfere with normal cellular functions without killing cells, and yet other exotoxins stimulate the production of cytokines that cause disease. (
  • Fc receptor for IgE, designated FcϵRI, also stabilizes the cellular expression of the receptor. (
  • 16. Enzymatic ADP-ribosylation of proteins and regulation of cellular activity. (
  • PE- and FITC-labeled (Fab′) 2 isotype-specific goat anti-mouse antibodies (Southern Biotechnology Associates, Inc.) were used as second step antibodies. (
  • Fc receptors bind to antibodies that are attached to infected cells or invading pathogens . (
  • Finally, we show that CD300a is expressed at the surface of primary macrophages and anti-CD300a polyclonal antibodies partially inhibited DENV infection of these cells. (
  • Mechanisms, to the extent that they are currently understood, of other types of "hypersensitivity" reactions or intolerances, some mediated by antibodies other than IgE, and others by cells, are also discussed. (
  • Bello C, Sotomayor E M. Monoclonal antibodies for B-cell lymphomas: Rituximab and beyond. (
  • Phagocytes (neutrophils and macrophages) use surface receptors, including mannose receptors and scavenger receptors, to recognize extracellular bacteria, and they use Fc receptors and complement receptors to recognize bacteria opsonized with antibodies and complement proteins, respectively. (
  • Antibodies that specifically block PD-1 were approved for melanoma in 2014 and for non-small-cell lung cancer (NSCLC) in 2015 in the United States, European Union, and Japan. (
  • Other experts in this issue extensively describe the biochemical and functional aspects of PKCθ regulation in T cells. (
  • Despite this information, the gene regulation and function of the HACS1 protein remains unknown. (
  • The expression of representative members of each class of proteins differs markedly, as does the regulation of expression by cytokines. (
  • Dr. McVicar's laboratory studies the regulation of innate immune cell metabolism and function in cancer. (
  • We provide evidence that this occurs via Casitas B‐lymphoma (Cbl)‐b E3 ubiquitin ligase up‐regulation in CD8 T cells. (
  • Kim-Schulze S, Seki T, Vlad G, Scotto L, Fan J, Colombo PC, Liu J, Cortesini R, Suciu-Foca N (2006) Regulation of ILT3 gene expression by processing of precursor transcripts in human endothelial cells. (
  • Regulation of thymocyte trafficking by Tagap, a GAP domain protein linked to human autoimmunity. (
  • Dynamic anticipation by Cdk2/Cyclin A-bound p27 mediates signal integration in cell cycle regulation. (
  • Multiple functions of p27 in cell cycle, apoptosis, epigenetic modification and transcriptional regulation for the control of cell growth: A double-edged sword protein. (
  • These parts are been by axonemes whom appear shared towards velocity of massive obstacles of epidermis, water, gift, inactivation, flux of expression, example pro-IL1B - CO2, Regulation, and cell interphase. (
  • However, advances which have been made in recent years have changed this concept drastically, and we now know that this multinuclear cell is subject to complex biological regulation, necessary for it to exert a multifunctional role of unknown dimensions. (
  • As in the case of the CD4 antigen, the CD8 antigen appears to serve as a receptor for nonpolymorphic regions of products of the major histocompatibility complex and has been implicated in the regulation of T-cell growth. (
  • Regulation of natural killer (NK) cytolytic activity is a function of engagement of one or more NK surface receptors that may be activating or inhibitory. (
  • Recently, however, a number of PI4P-dependent processes have been characterized, in particular its role in the regulation of protein trafficking. (
  • These findings provide insight into the mechanism of NK cell licensing and signalling generated by the Ly49: MHC I interaction. (
  • This degron overlaps a PCNA interaction protein (PIP) box and is recognised by the CRL4 Cdt2 ubiquitin ligase in a PCNA- and chromatin-dependent manner. (
  • This degron, occurring in non-Vertebrates, overlaps a PCNA interaction protein (PIP) box and is recognised by the CRL4 Cdt2 ubiquitin ligase in a PCNA- and chromatin-dependent manner. (
  • This interaction represents a potential mechanism by which T-cell growth may be regulated and offers a model by which other members of the src family (products of c-src, c-yes, c-fgr, etc.) may interact with mammalian growth factor receptors. (
  • Abundant ∼500-bp DAP10 transcripts were detected in human peripheral blood leukocytes, spleen, thymus, NK cells, α/β− and γ/δ−T cell receptor + T cells, and U937 (myeloid cell), but not substantially in other tissues or JY (B lymphoblastoid cell), 293T (epithelial cell), or primary fibroblasts ( Fig. 2 A) ( 6 ). (
  • A ) Northern blot analysis of DAP10 in human tissues and a T leukemia cell (Jurkat), a B lymphoblastoid cell (JY), an NK leukemia cell (YT), an NK cell line (NKL), a myeloid cell (U937), and an epithelial cell (293T) ( 14 ). (
  • This observation suggests that TREM-2 may function in myeloid cells other than DCs, most probably osteoclasts (OCs) and microglial cells, which are involved in bone modeling and brain function. (
  • These results demonstrate a critical role for TREM-2 in the differentiation of mononuclear myeloid precursors into functional multinucleated OCs. (
  • CD36, a highly glycosylated transmembrane protein belonging to the class B scavenger receptor family, is expressed by several cell types such as adipocytes, erythrocytes, platelets, as well as endothelial and myeloid cells. (
  • The Triggering Receptors Expressed on Myeloid Cells (TREM) and TREM-Like Receptors. (
  • The leukocyte immunoglobulin-like receptor (LILR) family comprises a set of paired immunomodulatory receptors expressed among human myeloid and lymphocyte cell populations. (
  • This review presents the evidence supporting a role of LILRs as myeloid cell regulators and ongoing efforts to understand the functional immunology surrounding this family. (
  • Accumulating data support that their functions are dysregulated in lymphoid neoplasms, including plasma cell myeloma, myelodysplastic syndrome, and acute myeloid leukemia. (
  • It is highly specific to the hematopoietic compartment and is expressed on monocytes, activated T cells, granulocytes, myeloid progenitors, and mast cells. (
  • The discovery of phosphatase micro-exclusion from signaling elements in immunological synapses and innate phagocytic synapses define a common functional unit at a common sub-micron scale across synapse types. (
  • Similarly, the immune response is a relay race against the pathogen in which the baton is passed from innate to adaptive immune cells (Figure 2 ). (
  • Besides the roles in pathological conditions, the biological functions of mast cells include roles in innate immunity, involvement in host defense mechanisms against parasites, immunomodulation of the immune system, tissue repair, and angiogenesis. (
  • Receptors on innate immune cells that recognize pathogens, such as Toll-like receptors, have been diversified and selected through evolution. (
  • Mast cells are important innate immune cells that can amplify the adaptive immune response ( 1 ). (
  • In turn, many viruses mount defenses against the attack from their host by encoding proteins that actively subvert innate and adaptive immune responses. (
  • 9. Hoglund P, Glas R, Ohlen C, Ljunggren HG, Karre K (1991) Alteration of the natural killer repertoire in H-2 transgenic mice: specificity of rapid lymphoma cell clearance determined by the H-2 phenotype of the target. (
  • It was discovered and named in 1975 for its morphological specificity and was developed from common lymphoid precursor cells in the bone marrow. (
  • The first signal, delivered through the T-cell antigen receptor, is provided by antigen and MHC complex on APCs and is responsible for the specificity of the immune response. (
  • Some seven transmembrane helix proteins (such as channelrhodopsin ) that resemble GPCRs may contain different functional groups, such as entire ion channels, within their protein. (
  • Additionally, investigators have found that mutations in the CD79A (MB1) gene are associated with abnormally low levels of functional B cell receptors in some cases of chronic B cell lymphocytic leukemia (9). (
  • This trend is more evident in those protein functional groups that are frequently reported to interact with specific domains. (
  • The correlation between SLiM conservation with disorder prediction demonstrates that functional SLiMs recognized by each domain occur more often in disordered as compared to structured regions of proteins. (
  • MIM:230400), an energy-related genetic T of propionyl-CoA direction consisting in variations that responses encode, receptors and functional bicarbonate( Bosch 2006). (
  • In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. (
  • Functional profiling of the tyrosine phosphoproteome during liver transplantation is therefore of great biological significance and is likely to lead to the identification of novel targets for drug discovery and provide a basis for novel therapeutic strategies. (
  • Microbes produce disease by directly killing the host cells they infect, or by liberating toxins that can cause tissue damage and functional derangements in neighboring or distant cells and tissues that are not infected. (
  • Functional Protein Dynamics Laboratory Judit Fidy. (
  • Anti-CD40 and goat F(ab′)2 anti-human or mouse IgM were from Southern Biotechnology Associates, Inc. Anti-HACS1 is a rabbit polyclonal antibody raised against a glutathione S -transferase fusion containing the SAM domain and COOH-terminal region of the human HACS1 protein. (
  • 2. The method according to claim 1 wherein said antibody is the 9E18.2 antibody. (
  • Some viruses such as flaviviruses use Fc receptors to help them infect cells, by a mechanism known as antibody-dependent enhancement of infection . (
  • There are several different types of Fc receptors (abbreviated FcR), which are classified based on the type of antibody that they recognize. (
  • For example, those that bind the most common class of antibody, IgG , are called Fc-gamma receptors (FcγR), those that bind IgA are called Fc-alpha receptors (FcαR) and those that bind IgE are called Fc-epsilon receptors (FcεR). (
  • Another receptor can also bind IgA, although it has higher affinity for another antibody called IgM . (
  • 3) HBs monoclonal antibody (MAb) and N-Acetylcysteine (NAC) decreased the amount of ROS-positive sperm cells. (
  • Applications Tested: This HI100 antibody has been pre-titrated and tested by flow cytometric analysis of normal human peripheral blood cells. (
  • A test is defined as the amount (µg) of antibody that will stain a cell sample in a final volume of 100 µL. (
  • Antibody therapy of non-Hodgkin's B-cell lymphoma. (
  • PRRSV contamination can induce significant and specific antibody and B-cell responses to a variety of PRRSV protein , . (
  • Here, we show that mouse NK cell education is associated with a higher basal activity of the mTOR/Akt pathway, commensurate to the number of educating receptors. (
  • In lymphoid neoplasms, aberrations in 9p24.1 ( PD-L1 , PD-L2 , and JAK2 locus ), latent Epstein-Barr virus infection, PD-L1 3′-untranslated region disruption, and constitutive JAK-STAT pathway are known mechanisms to induce PD-L1 expression in lymphoma cells. (
  • Peptidoglycans in the cell walls of Gram-positive bacteria and LPS in Gram-negative bacteria activate complement by the alternative pathway. (
  • However, it remains unknown how these interactions change the natural killer cells, or how these changes control their killing activity. (
  • Diverse biological activities are regulated through the dynamic interactions of modular protein domains (e.g. (
  • Proteomic methods, such as large scale protein arrays [ 28 - 30 ] and peptide libraries [ 31 - 44 ], have also been used to understand the binding properties of PDZ protein-protein interactions at a genome-wide level, which may provide clues about novel functions of proteins of interest in various cells. (
  • NKG2D, which doesn't bind to CD94, is a homodimeric lectin-like receptor. (
  • The domains are frequently found as repeats in a single protein sequence and will then often bind both mono- and di-phosphorylated substrates. (
  • Thus, ELMs and SLiMs are both identified as sequence patterns in multiple proteins that bind to a common target, with the SLiM-containing set likely to be entirely non-homologous but with no such restriction on the ELM-containing set. (
  • Abacavir changes the shape of the HLA antigen-binding cleft producing an alteration in the repertoire of self-peptides that bind HLA-B*57:01 and a T cell response to self-proteins. (
  • These GTP-binding proteins cycle between an inactive GDP-bound form or an active GTP-bound form which can bind downstream effectors. (
  • The specific subset of NK cell is reported to control the development at the fetal-maternal interface during the first trimester of the pregnancy, and it constitutes about 50-90% of total lymphoid cells in the uterus ( 2 , 3 ). (
  • Similar to T and B cells, NK cells also develop from common lymphoid progenitor cells ( 5 ). (
  • Most are short-lived, with life spans calculated to be from a few days to a few weeks.7,8 Natural killer cells derive from the common lymphoid progenitor cell that gives rise to T, B, and NK cells. (
  • Owing to higher density of antigen presenting cells in lymphoid organs, the second and third steps mostly occur in peripheral lymphoid organs. (
  • CD33 is useful for distinguishing myelogenous leukemia cells from lymphoid or erythroid leukemias. (
  • cell of a language earlier than 37 chips tyrosine consists in a spliceosome of mobilization and Initiation for phosphorylates. (
  • Volz A, Wende H, Laun K, Ziegler A (2001) Genesis of the ILT/LIR/MIR clusters within the human leukocyte receptor complex. (