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.
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.
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.
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.
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.
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.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A subclass of receptor-like protein tryosine phosphatases that contain a single cytosolic protein tyrosine phosphate domain and multiple extracellular fibronectin III-like domains.
Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.
A subclass of receptor-like protein tryosine phosphatases that contain short highly glycosylated extracellular domains and two active cytosolic protein tyrosine phosphatase domains.
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.
A subclass of receptor-like protein tryosine phosphatases that contain an extracellular fibronectin III-like domain along with a carbonic anhydrase-like domain.
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.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A 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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A 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.
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.
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.
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.
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)
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.
Established cell cultures that have the potential to propagate indefinitely.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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.
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.
A subclass of receptor-like protein tryosine phosphatases that contain an extracellular RDGS-adhesion recognition motif and a single cytosolic protein tyrosine phosphate domain.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Methods for determining interaction between PROTEINS.
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.
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.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
A 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.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
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.
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.
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.
An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC
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).
Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.
The rate dynamics in chemical or physical systems.
Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A 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.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Proteins prepared by recombinant DNA technology.
A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3.
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. The subtype was originally identified in a cell line derived from MEGAKARYOCYTES.
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.
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.
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.
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).)
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.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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.
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.
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.
Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)
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.
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.
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.
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 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.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
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.
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.
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.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Artificially produced membranes, such as semipermeable membranes used in artificial kidney dialysis (RENAL DIALYSIS), monomolecular and bimolecular membranes used as models to simulate biological CELL MEMBRANES. These membranes are also used in the process of GUIDED TISSUE REGENERATION.
Glycoproteins found on the membrane or surface of cells.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)
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.
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.
Techniques to partition various components of the cell into SUBCELLULAR FRACTIONS.
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.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
The sum of the weight of all the atoms in a molecule.
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)
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.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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.
An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC
Elements of limited time intervals, contributing to particular results or situations.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
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).
Adherence of cells to surfaces or to other cells.
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.
A cell line derived from cultured tumor cells.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
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.
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.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
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.
A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
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.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature.
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)
The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.
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.
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.
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).
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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.
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.
A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
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.
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.
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.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
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.
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
A 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)
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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.
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.
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.
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.
The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.
A 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).
A subfamily of Q-SNARE PROTEINS which occupy the same position as syntaxin 1A in the SNARE complex and which also are most similar to syntaxin 1A in their AMINO ACID SEQUENCE. This subfamily is also known as the syntaxins, although a few so called syntaxins are Qc-SNARES.
A fungal metabolite which is a macrocyclic lactone exhibiting a wide range of antibiotic activity.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
A superfamily of small proteins which are involved in the MEMBRANE FUSION events, intracellular protein trafficking and secretory processes. They share a homologous SNARE motif. The SNARE proteins are divided into subfamilies: QA-SNARES; QB-SNARES; QC-SNARES; and R-SNARES. The formation of a SNARE complex (composed of one each of the four different types SNARE domains (Qa, Qb, Qc, and R)) mediates MEMBRANE FUSION. Following membrane fusion SNARE complexes are dissociated by the NSFs (N-ETHYLMALEIMIDE-SENSITIVE FACTORS), in conjunction with SOLUBLE NSF ATTACHMENT PROTEIN, i.e., SNAPs (no relation to SNAP 25.)
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
A broad category of proteins involved in the formation, transport and dissolution of TRANSPORT VESICLES. They play a role in the intracellular transport of molecules contained within membrane vesicles. Vesicular transport proteins are distinguished from MEMBRANE TRANSPORT PROTEINS, which move molecules across membranes, by the mode in which the molecules are transported.
Inorganic or organic compounds that contain arsenic.
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.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.
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.
A contactin subtype that is predominantly expressed in the CEREBELLUM; HIPPOCAMPUS; NEOCORTEX; and HYPOTHALAMUS.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
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.
Antibodies produced by a single clone of cells.
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.
A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. EC 3.6.1.-.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
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)
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
A subclass of receptor-like protein tryosine phosphatases that contain heavily glycosylated and cysteine-rich extracellular regions that include fibronectin type III-like domains.
Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
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.
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.
A darkly stained mat-like EXTRACELLULAR MATRIX (ECM) that separates cell layers, such as EPITHELIUM from ENDOTHELIUM or a layer of CONNECTIVE TISSUE. The ECM layer that supports an overlying EPITHELIUM or ENDOTHELIUM is called basal lamina. Basement membrane (BM) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. BM, composed mainly of TYPE IV COLLAGEN; glycoprotein LAMININ; and PROTEOGLYCAN, provides barriers as well as channels between interacting cell layers.
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.
Proteins found in any species of bacterium.
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.
... to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs ... the bradykinin receptor B2 has been shown to interact directly with a protein tyrosine phosphatase. The presence of a tyrosine- ... However, in other types of receptors that have been studied, wherein ligands bind externally to the membrane, the ligands of ... transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors ( ...
Ostman A, Böhmer FD (June 2001). "Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatases". Trends in ... Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor ... Eph receptor family) RTK class X (AXL receptor family) RTK class XI (TIE receptor family) RTK class XII (RYK receptor family) ... Phosphorylation of these tyrosines then initiates intracellular signal transduction processes. Ephrin and Eph receptors are the ...
cAMP primarily acts as an intracellular second messenger whose major intracellular receptor is the cAMP-dependent protein ... 1999), "Inhibition of T cell signaling by MAP kinase-targeted hematopoietic tyrosine phosphatase (HePTP)", J. Biol. Chem., 274 ... that acts through the phosphorylation of target proteins. The signal transduction pathway begins with ligand-receptor ... PKA type I colocalizes with the T-cell and B-cell antigen receptors and causes inhibition of T- and B-cell activation. PKA has ...
"Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT)". Brain Research. 1116 (1 ... May 2007). "Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load- ... These proteins have extracellular domains that mediate homophilic interactions between adjacent cells, and C-terminal, ... "Entrez Gene: CDH2 cadherin 2, type 1, N-cadherin (neuronal)". Ramis-Conde I, Chaplain MA, Anderson AR, Drasdo D (March 2009). " ...
"Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT)". Brain Res. 1116 (1): 50- ... "A novel endothelial-specific membrane protein is a marker of cell-cell contacts". J. Cell Biol. 118 (6): 1511-22. doi:10.1083/ ... Cadherin 5, type 2 or VE-cadherin (vascular endothelial cadherin) also known as CD144 (Cluster of Differentiation 144), is a ... Shasby DM, Ries DR, Shasby SS, Winter MC (Jun 2002). "Histamine stimulates phosphorylation of adherens junction proteins and ...
Tyrosine-protein phosphatase non-receptor type 3 is an enzyme that in humans is encoded by the PTPN3 gene. The protein encoded ... Töpffer S, Müller-Schiffmann A, Matentzoglu K, Scheffner M, Steger G (2007). "Protein tyrosine phosphatase H1 is a target of ... "Subcellular localization of intracellular protein tyrosine phosphatases in T cells". Eur. J. Immunol. 30 (8): 2412-21. doi: ... "Isolation of a cDNA clone encoding a human protein-tyrosine phosphatase with homology to the cytoskeletal-associated proteins ...
... to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs ... the bradykinin receptor B2 has been shown to interact directly with a protein tyrosine phosphatase. The presence of a tyrosine- ... Receptor structureEdit. GPCRs are integral membrane proteins that possess seven membrane-spanning domains or transmembrane ... transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors ( ...
PD-1 is a type I membrane protein of 288 amino acids. PD-1 is a member of the extended CD28/CTLA-4 family of T cell regulators ... target the similar PD-L1 receptor. Drugs targeting PD-1 in combination with other negative immune checkpoint receptors, such as ... The intracellular tail contains two phosphorylation sites located in an immunoreceptor tyrosine-based inhibitory motif and an ... This is consistent with binding of SHP-1 and SHP-2 phosphatases to the cytoplasmic tail of PD-1 upon ligand binding. In ...
CD45 - a transmembrane protein whose intracellular tail functions as a tyrosine phosphatase that activates Src family kinases ... UMich Orientation of Proteins in Membranes protein/pdbid-2hac - Zeta-zeta dimer of T cell receptor ... or any other cell type (MHC class I) [11] High on-rate and off-rate is characteristic for TCR and peptide/MHC interaction at ... antigens despite the low affinity of TCR for its peptide/MHC and low numbers of specific peptide/MHC on the surface of target ...
... morphine through opioid receptors) or ligand-gated ion channels. Complement proteins can activate membrane receptors on mast ... The tyrosine kinase FYN phosphorylates Grb2-associated-binding protein 2 (Gab2), which binds to phosphoinositide 3-kinase, ... The MRGPRX receptor is a possible therapeutic target and can be pharmacologically activated using a 48/80 agonist to control ... Type 2 helper T cells,(Th2) and many other cell types lack the β chain, so signaling is mediated only by the γ chain. This is ...
"Multiple interactions between receptor protein-tyrosine phosphatase (RPTP) alpha and membrane-distal protein-tyrosine ... Receptor-type tyrosine-protein phosphatase delta is an enzyme that, in humans, is encoded by the PTPRD gene. The protein ... and intermolecular interactions between intracellular domains of receptor protein-tyrosine phosphatases". J. Biol. Chem. 277 ( ... a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins". J. Biol. Chem. 273 (25): 15611-20. doi: ...
HKs can act as cellular receptors for signaling molecules in a way analogous to tyrosine kinase receptors (RTK). ... whereas its two products are ADP and protein N-phospho-L-histidine. This type of enzyme is involved in signal transduction ... proteins of the transferase class of enzymes that play a role in signal transduction across the cellular membrane. The vast ... portions that span the cell membrane (transmembrane domain), and portions within the cell (intracellular domain) that contain ...
Examples of membrane receptors include G Protein-Coupled Receptors and Receptor Tyrosine Kinases. Intracellular receptors are ... Also important to the phosphorylation cascade are a group of proteins known as protein phosphatases. Protein phosphatases are ... move through cells or by diffusing through the air as a gas to reach their targets. There are three different types of basic ... Examples of membrane receptors include G Protein-Coupled Receptors and Receptor Tyrosine Kinases. Intracellular receptors are ...
Smad target gene protein tyrosine phosphatase receptor type kappa is required for TGF-{beta} function". Molecular and Cellular ... of adaptor proteins linking integrin and tyrosine kinase receptors to the c-Jun N-terminal kinase/stress-activated protein ... either by blocking EGFR binding sites on the extracellular domain of the receptor or by inhibiting intracellular tyrosine ... and a 36-kDa membrane-bound tyrosine phosphoprotein is implicated in ras activation in T cells". The Journal of Biological ...
Phosphorylation and dephosphorylation can be used on all types of substrates, such as structural proteins, enzymes, membrane ... Because protein dephosphorylation is a key process involved in cell signalling[citation needed], protein phosphatases are ... and tyrosine within specific target proteins is a fundamental part of the regulation of every physiologic process. ... "Regulation of AMP-activated protein kinase activity by G-protein coupled receptors: potential utility in treatment of diabetes ...
Mendrola JM, Shi F, Park JH, Lemmon MA (August 2013). "Receptor tyrosine kinases with intracellular pseudokinase domains". ... instead functioning as phosphate-binding proteins, integrators of signalling or subcellular traps. Examples of membrane- ... Protein Ser/Thr phosphatases were originally classified using biochemical assays as either, type 1 (PP1) or type 2 (PP2), and ... and non-receptor PTPs (b), which are strictly tyrosine-specific, and the DSPs (c) which target Ser/Thr as well as Tyr and are ...
"Adapter function of protein-tyrosine phosphatase 1D in insulin receptor/insulin receptor substrate-1 interaction". The Journal ... the activated protein binds to the PIP2 proteins embedded in the membrane. The activated IRS-1 acts as a secondary messenger ... 4548-G05 Insulin Insulin-like growth factor 1 Mecasermin The Insulin Receptor is a type of tyrosine kinase receptor, in which ... This indirectly activates a protein kinase, PKB (Akt), via phosphorylation. PKB then phosphorylates several target proteins, ...
Receptor-type tyrosine-protein phosphatase N2 (R-PTP-N2) also known as islet cell autoantigen-related protein (ICAAR) and ... Pietropaolo M, Hutton JC, Eisenbarth GS (February 1997). "Protein tyrosine phosphatase-like proteins: link with IDDM". Diabetes ... and a single intracellular catalytic domain, and thus represents a receptor-type PTP. The catalytic domain of this PTP is most ... cell signaling and membrane trafficking. The protein produced by PTPRN2 possesses an extracellular region, a single ...
Receptor tyrosine kinases (RTKs) are transmembrane proteins with an intracellular kinase domain and an extracellular domain ... "Differential binding of calmodulin-related proteins to their targets revealed through high-density Arabidopsis protein ... The prevalence of basement membranes in the tissues of Eumetazoans means that most cell types require attachment to survive. ... examples include tyrosine kinase and phosphatases. Often such enzymes are covalently linked to the receptor. Some of them ...
Protein Tyrosine Phosphatase; Rab11a: Member RAS Oncogene Family; RGS2: Regulator Of G-Protein Signaling 2; RyR1: Ryanodine ... Transient receptor potential canonical 1; TRPML3: Transient receptor potential Mucolipin-3. The Ca2+-selective channel proteins ... "Diverse calcium channel types are present in the human placental syncytiotrophoblast basal membrane". Placenta. 27 (11-12): ... The intracellular skirt portion of the TRPV6 protein is mainly made up of the ankyrin repeats. The TRP domain is oriented ...
The PI3K is activated by G protein-coupled receptors and tyrosine kinase receptors. Class I PI3Ks are heterodimeric molecules ... Many other proteins have been identified that are regulated by PtdIns(3,4,5)P3, including Bruton's tyrosine kinase (BTK), ... survival and intracellular trafficking. Many of these functions relate to the ability of class I PI3Ks to activate protein ... and mammalian target of rapamycin (mTOR). They are protein serine/threonine kinases. The various 3-phosphorylated ...
Once the tyrosine kinase is activated in insulin receptor, it triggers the activation of the docking proteins, also called IRS ... Brady MJ, Nairn AC, Saltiel AR (November 1997). "The regulation of glycogen synthase by protein phosphatase 1 in 3T3-L1 ... The activated GLUT4 will translocate to the cell membrane and promotes the transportation of glucose into the intracellular ... Non-L-Type Ca+2 channels (including R-Type) and the T-type Ca+2 channels. There are two phases of the insulin secretion, the ...
"DSD-1-Proteoglycan/Phosphacan and receptor protein tyrosine phosphatase-beta isoforms during development and regeneration of ... The mutated proteins carrying the duplications displayed a non-wild-type subcellular distribution, with a marked enrichment at ... PTEN acts as a phosphatase to dephosphorylate PIP3 back to PIP2. This removes the membrane-localization factor from the Akt ... June 2020). "Akt-targeted therapy as a promising strategy to overcome drug resistance in breast cancer - A comprehensive review ...
"Phosphorylation-dependent regulation of Kv2.1 Channel activity at tyrosine 124 by Src and by protein-tyrosine phosphatase ... this apoptotic regulation is dependent on cancer type, potassium channel type, expression levels, intracellular localization as ... This interaction between these intracellular regions is believed to be linked with membrane-spanning regions of S1 and S6, and ... These channels can also act as effectors in downstream signaling in G-protein coupled receptor transduction. KCNB1's regulation ...
Receptor-type tyrosine-protein phosphatase mu is an enzyme that in humans is encoded by the PTPRM gene. The protein encoded by ... in its intracellular domain, and thus represents an RPTP.Only the membrane proximal phosphatase domain, D1, is catalytically ... molecules of PTPmu that can not dephosphorylate their target proteins) in the developing retina, it was shown that PTPmu is ... "Multiple interactions between receptor protein-tyrosine phosphatase (RPTP) alpha and membrane-distal protein-tyrosine ...
KARs and KIRs can have tyrosine containing activatory or inhibitory motifs in the intracellular part of the receptor molecule ( ... On the other hand, CD94/NKG2C consists in a complex formed by the CD94 protein, which is a C-type lectin molecule bonded to the ... When an inhibitory receptor is stimulated by the binding of MHC class I, kinases and phosphatases are recruited to the receptor ... Killer Activation Receptors (KARs) are receptors expressed on the plasmatic membrane of Natural Killer cells (NK cells). KARs ...
This receptor is called the Fc-alpha/mu receptor (Fcα/μR) and is a type I transmembrane protein. With one Ig-like domain in its ... occurring twice in close succession in the intracellular tail of a receptor. When phosphate groups are added to the tyrosine (Y ... the low-affinity receptor FcεRII (CD23) is a C-type lectin. FcεRII has multiple functions as a membrane-bound or soluble ... The Fc receptor on NK cells recognize IgG that is bound to the surface of a pathogen-infected target cell and is called CD16 or ...
Smad target gene protein tyrosine phosphatase receptor type kappa is required for TGF-{beta} function". Mol Cell Biol. 25 (11 ... Skarnes WC, Moss JE, Hurtley SM, Beddington RS (1995). "Capturing genes encoding membrane and secreted proteins important for ... subunit and an intracellular phosphatase (P) subunit. In response to high cell density or calcium influx following ... The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. Protein tyrosine phosphatases ...
"Induction of neurite outgrowth through contactin and Nr-CAM by extracellular regions of glial receptor tyrosine phosphatase ... Nakayama M, Kikuno R, Ohara O (2003). "Protein-protein interactions between large proteins: two-hybrid screening using a ... This gene encodes a neuronal cell adhesion molecule with multiple immunoglobulin-like C2-type domains and fibronectin type-III ... 2002). "Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances ...
... be transported to the plasma membrane for secretion and it allows the Wnt protein to bind its receptor Frizzled Wnt proteins ... Examples include lipoprotein receptor-related protein (LRP)-5/6, receptor tyrosine kinase (RTK), and ROR2. Upon activation of ... This destruction complex includes the following proteins: Axin, adenomatosis polyposis coli (APC), protein phosphatase 2A (PP2A ... Other proteins that cause multiple cancer types in the absence of proper functioning include ROR1, ROR2, SFRP4, Wnt5A, WIF1 and ...
The NMDA receptor is ionotropic, meaning it is a protein which allows the passage of ions through the cell membrane.[4] The ... and the influx of Ca2+ triggers intracellular signaling pathways.[11][31] Allosteric receptor binding sites for zinc, proteins ... The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and kainate receptors. ... which contain residues that can be directly modified by a series of protein kinases and protein phosphatases, as well as ...
... parts of the protein that pass through the plasma membrane), proteins interacting with the subunit indicated that the N- ... glutamate receptor-interacting protein 1 (GRIP1) has been implicated in intracellular sequestration of AMPARs.[64] ... NMDA-type receptor, along with the kainate receptor. Its name is derived from its ability to be activated by the artificial ... Molecular target for epilepsy therapy[edit]. The noncompetitive AMPA receptor antagonists talampanel and perampanel have been ...
Protein: cell membrane proteins (other than Cell surface receptor, enzymes, and cytoskeleton) ... Activated protein kinase C inhibits the tyrosine kinase activity of epidermal growth factor receptor (EGFR), the rational ... Depending on the type of hemolysin and the microorganism that produces it, manifestation of symptoms and diseases may differ ... These monomers diffuse to the target cells and are attached to them by specific receivers. After this is done, they oligomerize ...
negative regulation of intracellular estrogen receptor signaling pathway. • protein autoubiquitination. • positive regulation ... Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 (/ˌbrækəˈwʌn/) gene.[5] ... The target tissue may have receptors for the pathogen, may become selectively exposed to an inflammatory process or to a ... BRCA1 interacts with the DNA mismatch repair protein MSH2.[39] MSH2, MSH6, PARP and some other proteins involved in single- ...
Tyrosine:. *protein tyrosine phosphatase: Receptor-like protein tyrosine phosphatase. *Sh2 domain-containing protein tyrosine ... Types of G protein signaling[edit]. G protein can refer to two distinct families of proteins. Heterotrimeric G proteins, ... that span the cell membrane.[2] Signaling molecules bind to a domain of the GPCR located outside the cell, and an intracellular ... It is estimated that about 30% of the modern drugs' cellular targets are GPCRs." [12] The human genome encodes roughly 800 [13] ...
This receptor is called the Fc-alpha/mu receptor (Fcα/μR) and is a type I transmembrane protein. With one Ig-like domain in its ... occurring twice in close succession in the intracellular tail of a receptor. When phosphate groups are added to the tyrosine (Y ... the low-affinity receptor FcεRII (CD23) is a C-type lectin. FcεRII has multiple functions as a membrane-bound or soluble ... The Fc receptor on NK cells recognize IgG that is bound to the surface of a pathogen-infected target cell and is called CD16 or ...
Tyrosine:. *protein tyrosine phosphatase: Receptor-like protein tyrosine phosphatase. *Sh2 domain-containing protein tyrosine ... G protein-coupled receptors (GPCRs) are a large family of integral membrane proteins that respond to a variety of extracellular ... a conformational change is induced in the receptor that is transmitted to an attached intracellular heterotrimeric G protein ... Bos JL (December 2006). "Epac proteins: multi-purpose cAMP targets". Trends Biochem. Sci. 31 (12): 680-6. doi:10.1016/j.tibs. ...
Kinases phosphorylate proteins and phosphatases dephosphorylate proteins. Many enzymes and receptors are switched "on" or "off ... Types of phosphorylation[edit]. Further information: Kinase. Within a protein, phosphorylation can occur on several amino acids ... since tyrosine phosphorylated proteins are relatively easy to purify using antibodies, tyrosine phosphorylation sites are ... These target proteins become substrates for particular E3 ubiquitin ligases only when they are phosphorylated. ...
positive regulation of protein localization to plasma membrane. • regulation of receptor activity. • positive regulation of ... IFNγ is the only Type II interferon and it is serologically distinct from Type I interferons; it is acid-labile, while the type ... positive regulation of tyrosine phosphorylation of STAT protein. • negative regulation of transcription, DNA-templated. • ... Interferon-γ has been shown to be a crucial player in the immune response against some intracellular pathogens, including that ...
PI3K binds to AMPA receptors in a conserved region to orient the receptors in the membrane, specifically at the GluR subunit.[4 ... protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is activated in approximately 30-40% of BC cases. In TNBC, ... Another advantage of simultaneously targeting PI3K and mTOR is the ensuing more robust inhibition of receptor tyrosine kinase- ... This is a type of trace conditioning which is a form of learning that requires association of a conditioned stimulus with an ...
1g4u: CRYSTAL STRUCTURE OF THE SALMONELLA TYROSINE PHOSPHATASE AND GTPASE ACTIVATING PROTEIN SPTP BOUND TO RAC1 ... intracellular signal transduction. • regulation of cell migration. • endocytosis. • ephrin receptor signaling pathway. • T cell ... plasma membrane. • actin filament. • cytoplasmic ribonucleoprotein granule. • endoplasmic reticulum membrane. • Golgi membrane ... of Rac1 are shown to play active roles in promoting mesenchymal-type of cell movement assisted by NEDD9 and DOCK3 protein ...
... the CagA protein is phosphorylated on tyrosine residues by a host cell membrane-associated tyrosine kinase (TK). CagA then ... pylori have been shown to activate the epidermal growth factor receptor (EGFR), a membrane protein with a TK domain. Activation ... The type-IV secretion apparatus also injects the cag PAI-encoded protein CagA into the stomach's epithelial cells, where it ... allosterically activates protein tyrosine phosphatase/protooncogene Shp2.[58] Pathogenic strains of H. ...
... activated tyrosine kinase. The receptor protein tyrosine phosphatase PTPmu (PTPRM) is capable of dephosphorylating PLCG1.[7] ... The SH2 domains bind phosphorylated tyrosine residues on target proteins via their FLVR sequence motifs, activating the ... intracellular. Biological process. • intracellular signal transduction. • Fc-gamma receptor signaling pathway involved in ... Non-receptor tyrosine kinases interact with PLCG1 in large complexes at the plasma membrane. For example, in T cells, Lck and ...
... receptor tyrosine kinases, Ras or Raf proteins. Although no MKK1/2 or ERK1/2 inhibitors were developed for clinical use, kinase ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ... some tyrosine phosphatases are also involved in inactivating MAP kinases (e.g. the phosphatases HePTP, STEP and PTPRR in ... happens at the cell membrane, where most of their activators are bound (note that small G-proteins are constitutively membrane- ...
"Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT)". Brain Research 1116 (1 ... "The inner nuclear membrane protein emerin regulates beta-catenin activity by restricting its accumulation in the nucleus". The ... "Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate ... Peifer M, Berg S, Reynolds AB (Mar 1994). "A repeating amino acid motif shared by proteins with diverse cellular roles". Cell ...
... the glucocorticoid receptor (GR) resides in the cytosol complexed with a variety of proteins including heat shock protein 90 ( ... Kino T, Pavlakis GN (2004). "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA Cell ... Membrane glucocorticoid receptor Familial/sporadic glucocorticoid resistance (Chrousos Syndrome) Selective glucocorticoid ... In the absence of activated GR, other transcription factors such as NF-κB or AP-1 themselves are able to transactivate target ...
Although the majority of protein substrates are ubiquitinated, there are examples of non-ubiquitinated proteins targeted to the ... "Epidermal growth factor receptor signaling intensity determines intracellular protein interactions, ubiquitination, and ... Few ubiquitin-like protein (FUB1), MUB (membrane-anchored UBL), ubiquitin fold-modifier-1 (UFM1) and ubiquitin-like protein-5 ( ... and modulating protein-protein interactions. These effects are mediated by different types of substrate ubiquitination, for ...
Liu F, Hill DE, Chernoff J (1996). "Direct binding of the proline-rich region of protein tyrosine phosphatase 1B to the Src ... NEDD9 is a difficult molecule to target. Because NEDD9 serves as a scaffolding molecule for other signaling proteins that play ... "T cell receptor-mediated tyrosine phosphorylation of Cas-L, a 105-kDa Crk-associated substrate-related protein, and its ... compared to wild type. In cancer cells, NEDD9 can drive mesenchymal-type movement by activating RAC1 GTPase and WAVE in complex ...
Protein p11 can also be presented on the cell surface as a receptor for tissue-type plasminogen activator (tPA) and plasminogen ... with cytosolic and peripheral membrane-associated proteins such as AHNAK in the development of the intracellular membrane. P11 ... phosphorylating target proteins, and facilitating endosomal activities. P11 is coexpressed with 5-HT4 mRNA and its protein in ... Protein Kinase A (PKA) reverses the effects of PKC by activating a phosphatase, which reactivates the complex through ...
The PDGFRB gene encodes a typical receptor tyrosine kinase, which belongs to the type III tyrosine kinase receptor (RTK) family ... An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1". J. Cell Biol. 152 (2): 325-34. doi:10.1083/jcb. ... The activated receptor phosphorylates itself and other proteins, and thereby engages intracellular signaling pathways that ... SH2 and SH3 domain-containing Nck protein is oncogenic and a common target for phosphorylation by different surface receptors ...
... which leads to unregulated proteolysis of both target and non-target proteins and consequent irreversible tissue damage. ... Additionally, phosphorylation by protein kinase A and dephosphorylation by alkaline phosphatase have been found to positively ... As the first calpain whose three-dimensional structure was determined, m-calpain is the type-protease for the C2 (calpain) ... This can lead to degradation of the cytoskeleton and plasma membrane. Calpain may also break down sodium channels that have ...
Therefore, there are four main transmembrane receptor types: G protein coupled receptors (GPCRs), tyrosine kinase receptors ( ... like transcription of genes and then the effect of newly formed proteins in a specific target. The target could be a protein or ... In the first one, first messenger cross through the cell membrane, binding and activating intracellular receptors localized at ... They are involved in regulation of kinases and phosphatases, G protein associated factors and transcriptional factors. Gaseous ...
As FGF1 treatment induces phosphorylation of intracellular proteins, we searched for phosphopeptides in our MS data. Although ... a membrane bound tyrosine phosphatase, is an important modulator of FGFR tyrosine kinase activity. We demonstrate that PTPRG ... It is known that PTPRG has other targets than FGFR1 (50), but it remains an interesting question if additional tyrosine ... fibroblast growth factor receptor. PTPRG. protein tyrosine phosphatase receptor type G. TIRF. total internal reflection ...
Accordingly, the whole cell-scattered PTEN translocated towards the cell membrane 20 minutes after stimulating with LPS. ... P3 located on the cell membrane and exerts its dephosphorylated function and subsequently depresses the activity of downstream ... The initial findings from ELISA demonstrate that PTEN influences TNF-,i,α,/i, secretion by its lipid phosphatase activity. ... PTEN functions as a lipid phosphatase and as a protein tyrosine phosphatase. As a lipid phosphatase, PTEN antagonizes PI3K ( ...
1995) Cell-surface-bound Yersinia translocate the protein tyrosine phosphatase YopH by a polarized mechanism into the target ... 1981) Cytoplasmic and membrane proteins of yersiniae cultivated under conditions simulating mammalian intracellular environment ... 1998) Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol. Mol. Biol. Rev. 62:379-433. ... Upon contact with the eukaryotic target cell, a sensor interacts with a receptor on the cell surface, which results in the ...
... a protein tyrosine phosphatase (PTP) that plays an overall positive role in insulin signaling, is linked to the pathogenesis of ... The relationship between PTP1B and human diseases exhibits PTP1B as the target to treat these diseases. In this article, small ... Finally, we report a novel inhibitor, Compound 13, that specifically inhibits PTP1B over the closely related phosphatase Src ... homology 2 (SH2) domain-containing phosphatase 2 (SHP-2) at 80 μΜ. Its IC50 values are reported in this paper as well. This ...
WP1130 of the molecules interacted with target cells by binding to two types of receptor-like protein tyrosine phosphatases ( ... Even though the high proteins creation WP1130 in the cytoplasm makes the purification from the soluble focus on protein ... residues at positions 14 and 18 in VacA diminishes VacA oligomerization vacuolating activity and anion-selective membrane ... biological activity conducting in vivo activity assays due to greater access of the targeted protein to the substrate higher ...
Homophilic binding of PTPμ, a receptor-type protein tyrosine phosphatase, can mediate cell-cell aggregation. J Cell Biol 1993; ... which releases the intracellular portion of PTPκ containing the active phosphatase domain from the membrane ( 23). The ... Experimental Therapeutics, Molecular Targets, and Chemical Biology Proteolytic Cleavage of Protein Tyrosine Phosphatase μ ... we biotinylated cell surface proteins and used avidin resin to enrich the pool of biotinylated cell surface proteins. Despite ...
Lee MS, Dirkx R Jr, Solimena M, Dannies PS: Stabilization of the receptor protein tyrosine phosphatase-like protein ICA512 in ... a protein-tyrosine phosphatase homologue localized to insulin secretory granule membranes. J Biol Chem271 :18161 -18170,1996. ... suggesting that the protein is a target for secretagogue-activated protein kinases (8,9). Both IA-2 and phogrin associate with ... Rabbit antibody to the α subunit of the insulin receptor (type A and B) was from Biogenesis (Poole, U.K.). Polyclonal guinea ...
... to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs ... the bradykinin receptor B2 has been shown to interact directly with a protein tyrosine phosphatase. The presence of a tyrosine- ... However, in other types of receptors that have been studied, wherein ligands bind externally to the membrane, the ligands of ... transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors ( ...
"Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT)". Brain Research. 1116 (1 ... May 2007). "Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load- ... These proteins have extracellular domains that mediate homophilic interactions between adjacent cells, and C-terminal, ... "Entrez Gene: CDH2 cadherin 2, type 1, N-cadherin (neuronal)". Ramis-Conde I, Chaplain MA, Anderson AR, Drasdo D (March 2009). " ...
... fail to recruit protein tyrosine phosphatases to the plasma membrane due to defects in phosphorylation of inhibitory receptors ... 1 d). Several tyrosine-phosphorylated proteins coprecipitated with phospho-SHP-1 in unstimulated Lynup/up B cells and to a ... the activation of which results in intracellular calcium flux (36). Minimal tyrosine-phosphorylated Syk was observed in ... A second pathway to autoimmunity in Lynup/up mice may lie in their elevated numbers of B1 cells; a cell type that is associated ...
Článek The Human Cytomegalovirus UL11 Protein Interacts with the Receptor Tyrosine Phosphatase CD45, Resulting in Functional ... None of the proteins resemble type I or type II viral fusion proteins by sequence so that determination of the 3-dimensional ... WolffeEJVijayaSMossB 1995 A myristylated membrane protein encoded by the vaccinia virus L1R open reading frame is the target of ... four proteins mediate cell attachment and twelve that are associated in a membrane complex and conserved in all poxviruses are ...
... which includes Receptor Protein Tyrosine Phosphatase RPTP) σ RPTP-δ and the Leukocyte Common Antigen Receptor (LAR), and two ... While these targeted approaches determined the involvement of these known proteins, a more global approach to identify proteins ... Our major hypothesis is that CSPGs interact with receptors to initiate an intracellular signaling cascade resulting in an ... Block the membrane in blocking buffer (5% milk in PBS-Tween) at room temperature for 1 h or overnight at 4°C on the shaker. ...
... which display the CD94/NKG2C-activating receptor. Evidence supporting that adaptive NKG2C+ NK cells may contribute to control ... an adaptive differentiation and expansion of a subset of mature NK cells which display the CD94/NKG2C activating receptor. ... may display alloreactive potential in case of mismatch between recipient inhibitory killer-cell immunoglobulin-like receptors ( ... may display alloreactive potential in case of mismatch between recipient inhibitory killer-cell immunoglobulin-like receptors ( ...
Proteins Tyrosine Phosphatase Receptor Type Kappa (PTPRK), among the 21 known receptor type PTPs, is certainly a transmembrane ... protein unc-5 homolog C-like), is a 518amino acid single-pass type III membrane protein that belongs to the unc-5 family. ... possess fallen lacking targets [3], [7]. Latest studies suggest an integral role of proteins tyrosine phosphatases (PTPs) ... The energetic type of Notch, the Notch intracellular domains, is produced by cleavage on the receptor juxtamembrane area with ...
Proteins Tyrosine Phosphatase Receptor Type Kappa (PTPRK), among the 21 known receptor type PTPs, is certainly a transmembrane ... protein unc-5 homolog C-like), is a 518amino acid single-pass type III membrane protein that belongs to the unc-5 family. ... possess fallen lacking targets [3], [7]. Latest studies suggest an integral role of proteins tyrosine phosphatases (PTPs) ... The intracellular area of PTPRK includes phosphatase domains with dephosphorylating activity and potential transcriptional ...
Proteins Tyrosine Phosphatase Receptor Type Kappa (PTPRK), among the 21 known receptor type PTPs, is certainly a transmembrane ... CUB\site\containing\proteins\1 (CDCP1) can be an essential membrane protein whose expression is. CUB\site\containing\proteins\1 ... possess fallen lacking targets [3], [7]. Latest studies suggest an integral role of proteins tyrosine phosphatases (PTPs) ... The intracellular area of PTPRK includes phosphatase domains with dephosphorylating activity and potential transcriptional ...
p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21 ... a major negative regulator of intracellular signaling, in this process. Wild-type SHIP and a phosphatase-deficient mutant SHIP ... domain in its carboxyl terminus that targets it to the plasma membrane by binding PI-3,4,5-P3 (47, 48). In Jurkat cells ... Furthermore, PMA-induced activation of LFA-1 on DA-ER cells overexpressing wild-type SHIP was dependent on protein kinase C but ...
... hyperfusion by DAPT treatment by causing the association of the phosphatase vascular endothelial-protein tyrosine phosphatase ... composed of the extracellular domain of the PDGF receptor-α and the intracellular domain of FGFR-1. Mutation of tyrosine 766 to ... To this end, proteins transiently up-regulated during vessel morphogenesis were screened for their potential as targets in ... It seems that the biology of the different VEGFR2 and VEGFR3 ligands overlaps quite extensively and that both receptor types ...
The protein-tyrosine phosphatase SHP-1 associates with the phosphorylated immunoreceptor tyrosine-based activation motif of Fc ... type of stimulus, subcellular compartment, and/or posttranslational modifications of the interacting proteins (34). ... 4 Upon receptor clustering by immune complexes, the tyrosines in the ITAM are phosphorylated by the membrane-associated Src ... and the Tec family tyrosine kinase Btk, involved in intracellular calcium mobilization (12). The Ras/extracellular signal- ...
... receptor protein tyrosine phosphatase; VDCC, voltage-dependent Ca2+-channel. Broken lines indicate putative intracellular ... Proteins were electrophoretically transferred to a nitrocellulose membrane (Invitrogen, Carlsbad, CA, USA) that was immersed ... The overexpression of PSA appears to be critical to this process because in the cerebellum of wild-type mice PSA is present, ... Do the alterations in PSA-NCAM expression following TBI present as possible targets of therapy? The ability of PSA to modulate ...
Notch receptors are transmembrane proteins containing both types of extracellular and intracellular domains [19]. When Notch ... EGFR is a transmembrane protein belonging to the ErbB family of receptors, which functions as a receptor tyrosine kinase (RTK ... proteins. One of the adaptor proteins, GRB2 recruits SOS to the membrane. SOS activates GDP/GTP exchange which recruits RAF to ... protein translation, growth and metabolism. Phosphatase and tensin homologue protein (PTEN), a tumor suppressor molecule, ...
We also summarize recent developments using PTPRs as prognostic or predictive biomarkers and/or direct targets. Increased ... Receptor-type protein tyrosine phosphatases (PTPRs) are a subgroup of PTPs that share a transmembrane domain with resulting ... and promoter methylation of PTPRs in cancer and consider the consequences of PTPR alterations in different types of cancers. ... play an important role in regulating cell signaling events in coordination with tyrosine kinases to control cell proliferation ...
Trafficking of proteins from the plasma membrane and within intracellular compartments is modulated by small GTPases, including ... Zhang X, Simons M. Receptor tyrosine kinases endocytosis in endothelium: biology and signaling. Arterioscler Thromb Vasc Biol. ... zirconium oxide bead type, 2.8-mm bead size). Protein precipitation was induced by acetonitrile/acetone (60:40 v/v), and ... leads to trafficking of activated VEGFR2/NRP1 away from RAB5-positive endosomes that contain a tyrosine phosphatase (thereby ...
Activation of Insulin Receptor Signaling Pathway Using Ligand Mic - Free download as PDF File (.pdf), Text File (.txt) or read ... cloning of target proteins for receptor tyrosine kinases. Cell, 65, 83-90. 111. Smith, G. D., Swenson, D. C., Dodson, E.J., ... Apparent translocation of intracellular transport systems to the plasma membrane. J. Biol. Chem., 255, 4758-4762. 22. Czech, M ... TCA (trichloroacetic acid) fixes proteins on cells and helps preserve cell structure. It inactivates tyrosine phosphatases ( ...
... or receptor tyrosine kinase-mediated and GEF-dependent RAS activation (such as by targeting the scaffolding phosphatase SHP2). ... Wild-type (WT) RAS proteins are guanosine triphosphate (GTP)-hydrolyzing proteins [guanosine triphosphatases (GTPases)] that ... Insight into additional aspects of RAS protein and pathway regulation reveals more ways to potentially target RAS. Biancucci et ... to stimulate intracellular signaling. RAS is inactivated by the hydrolysis of bound GTP by GTPase-activating proteins (GAPs; ...
In a time-dependent manner, leptolide (0.1 µM) augmented insulin-stimulated phosphorylation of protein kinase B (PKB) by two- ... Type 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. Current antidiabetic ... resulting in tyrosine phosphorylation of insulin receptor substrate (IRS) proteins [29]. In the liver, IRS2 is important for ... Past and current perspective on new therapeutic targets for Type-II diabetes. Drug Des. Devel. Ther. 2017, 11, 1567-1583. [ ...
We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their ... InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in ... Dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins) ...
... to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs ... the bradykinin receptor B2 has been shown to interact directly with a protein tyrosine phosphatase. The presence of a tyrosine- ... Receptor structureEdit. GPCRs are integral membrane proteins that possess seven membrane-spanning domains or transmembrane ... transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors ( ...
... is an intracellular kinase - Market research report and industry analysis - 10246183 ... Protein threonine/tyrosine kinase activity. Protein-tyrosine kinase activity. Receptor activity. Receptor binding. Receptor ... The mammalian target of rapamycin (mTOR) is an intracellular kinase that controls the production of proteins through its ... Mitochondrial membrane. Mitochondrion. Nuclear membrane. Nucleolus. Nucleus. Perinuclear region. Peroxisome. Plasma membrane. ...
CD45 - a transmembrane protein whose intracellular tail functions as a tyrosine phosphatase that activates Src family kinases ... UMich Orientation of Proteins in Membranes protein/pdbid-2hac - Zeta-zeta dimer of T cell receptor ... or any other cell type (MHC class I) [11] High on-rate and off-rate is characteristic for TCR and peptide/MHC interaction at ... antigens despite the low affinity of TCR for its peptide/MHC and low numbers of specific peptide/MHC on the surface of target ...
  • The ErbB protein family or epidermal growth factor receptor (EGFR) family is a family of four structurally related receptor tyrosine kinases. (
  • In this review, we will focus on the mitogen-activated protein kinase (MAPK) cascades downstream of the epidermal growth factor receptor (EGFR), Notch, PI3K/AKT pathway, transforming growth factor-β (TGF-β), and Wnt signaling pathways. (
  • In metastatic breast cancer cells, increased cell adhesion and migration upon stimulation of epidermal growth factor receptor are also dependent on PI3K ( 17 ). (
  • Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is under clinical testing and use in cancer patients, including glioma. (
  • We continue our long-standing interest in the regulation of the Epidermal Growth Factor Receptor (EGFR) family of receptor tyrosine kinases (RTKs), and also expand our study to several other families of RTKs. (
  • GBM has been genetically characterized, yet the nature of signaling pathways downstream of key oncogenic mutations, such as epidermal growth factor receptor activating mutation (EGFRvIII) and phosphatase and tensin homolog (PTEN) tumor suppressor gene loss associated with receptor tyrosine kinase (RTK)/PI3K signaling, are incompletely understood ( 13 - 15 ). (
  • Here, we present a brief survey of the use of aptamers in signaling pathways, in particular of polypeptide growth factors, starting with the published as well as potential applications of aptamers targeting Epidermal Growth Factor Receptor signaling. (
  • To date, epidermal growth factor receptor (EGFR) has been one of the best-studied receptors in regard to the connection between its trafficking and signaling. (
  • Also reported to dephosphorylate integrin, epidermal growth factor receptor, JAK2 and TYK2, regulating cell growth control and the cellular response to interferon. (
  • As a transmembrane adhesion receptor, PTPμ has the ability to sense an extracellular signal via its extracellular segment and transduce this signal intracellularly via its phosphatase activity ( 12 - 14 ). (
  • The PTPμ extracellular domain is composed of a MAM (meprin/A5-protein/PTPμ) domain, an immunoglobulin-like (Ig) domain, and four fibronectin type III (FNIII) repeats ( 12 , 15 , 16 ). (
  • PTPμ is expressed as a 200-kDa protein that is proteolytically cleaved in the fourth FNIII repeat, resulting in a 100-kDa extracellular fragment (E-subunit) that remains associated with the 100-kDa transmembrane and intracellular portion (P-subunit) through a noncovalent interaction ( 11 , 21 , 22 ). (
  • The extracellular ADAM cleaves the P-subunit adjacent to the membrane to generate PΔE and shed the ectodomain ( 23 ). (
  • Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). (
  • Seven years later, the crystallization of β2-adrenergic receptor (β2AR) with a diffusible ligand brought surprising results because it revealed quite a different shape of the receptor extracellular side than that of rhodopsin. (
  • moreover, ligand binding to the extracellular domain induces formation of receptor dimers. (
  • Each monomer has a single hydrophobic transmembrane-spanning domain composed of 25 to 38 amino acids, an extracellular N terminal region, and an intracellular C terminal region. (
  • Phosphate ATP Tyrosine Phosphotyrosine When a growth factor binds to the extracellular domain of a RTK, its dimerization is triggered with other adjacent RTKs. (
  • Through diverse means, extracellular ligand binding will typically cause or stabilize receptor dimerization. (
  • The extracellular area includes a MAM area, an immunoglobulin like-domain and four fibronectin type III domains, comparable to homophilic cell adhesion substances, needed for cell-cell adhesions [8]. (
  • PTPRs consist of a transmembrane domain, unequal number of extracellular domains, and intracellular catalytic domains. (
  • Immunoglobulin-like domains and fibronectin type III-like domains comprise the extracellular domain of many PTPRs. (
  • RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). (
  • The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail . (
  • These acronyms stand for Killer cell Immunoglobulin (Ig)-like Receptor (KIR), with extracellular part containing 3 Ig Domains (3D), and cytoplasmic tails being either long (L) or short (S). CD158e1 comprises 3 C-type extracellular Ig domains, and two characteristic ITIM motifs (Immunoreceptor Tyrosine-based Inhibition Motif) in the intracellular portion. (
  • The process by which extracellular signals are relayed from the plasma membrane to specific intracellular sites is an essential facet of cellular regulation. (
  • An extracellular signal input drives autophosphorylation of the receptor and leads to the recruitment of cytoplasmic proteins that contain various protein modules. (
  • The extracellular parts of the receptor can be glycosylated . (
  • These extracellular loops also contain two highly-conserved cysteine residues that form disulfide bonds to stabilize the receptor structure. (
  • Hog1 regulates intracellular osmolarity in response to extracellular osmolarity and citric acid stress, Mpk1 regulates cell integrity and budding in response to mechanical changes at the cell wall/plasma membrane (with undefined input by Mpl1) and Smk1 regulates sporulation, being expressed only after meiosis has been initiated in response to carbon and nitrogen deprivation. (
  • By interacting with the ECM, integrins transfer signals from the extracellular environment to intracellular compartments and control many cellular functions, such as proliferation, migration, differentiation, and gene expression ( 12 - 14 ). (
  • This C-terminus localization is ubiquitous as the majority of proteins containing odd numbers of helices, such as those in the large 1TM and 7TM groups, have intracellular C-termini with N-termini in the extracellular environment, and protein groups with even helical numbers have a greater amount of both termini located intracellularly. (
  • 12 In the AT 2 receptor, IC3 is also important for its function involving reduction of SHP-1 activity and inhibition of extracellular signal regulated kinase (ERK) activity, and AT 2 receptor-induced apoptosis. (
  • HMGB1 was later discovered to express on cell surface membranes, cytosol, and mitochondria and release into the extracellular space. (
  • A subset of the oncogenically activated EGFR mutations that have been identified from patient samples lie in the extracellular region of the receptor. (
  • To address this we are investigating, in collaboration with Mark Lemmon, how the extracellular and intracellular regions of EGFR are coupled. (
  • Alternative splicing generates several integral-membrane LepR isoforms that possess identical extracellular, transmembrane, and membrane-proximal intracellular domains. (
  • The different structural domains of Cx43, including extracellular loops, transmembrane domains, and an intracellular carboxyl terminal, have distinct functions in the invasion and proliferation of gliomas. (
  • A) At the plasma membrane, functional hemichannels are composed of 6 connexin subunits to allow mass exchange between the cell and the extracellular environment. (
  • Transmembrane and intracellular signal transduction mechanisms are the focus of our group, especially understanding how extracellular stimuli control cell growth and division, cell morphology, and gene expression at the biochemical level. (
  • Receptors of this type are ubiquitous and transduce binding of a wide variety of extracellular ligands (peptide hormones, neurotransmitters and other bioactive compounds) into a physiological signal. (
  • Defined signaling pathways where aberrant regulation of phosphorylation contributes to oncogenesis include receptor tyrosine kinases/PI 3-kinase/Akt/mTOR, receptor tyrosine kinases/Ras/Raf/MEK/ERK, MEKK/MKK/JNK, and JAK/STAT. All of these signaling cascades, where phosphorylation occurs at nearly each step, have profound control in cell growth, survival, apoptosis, or responses to various extracellular signals. (
  • It participates in signaling events downstream of receptors for growth factors, cytokines, hormones, antigens and extracellular matrices in the control of cell growth, differentiation, migration, and death. (
  • Each module has homologues in other extracellular mosaic proteins such as Von Willebrand factor, slit, thrombospondins, fibrillar collagens, IGF-binding proteins and mucins. (
  • Although the majority of VWA-containing proteins are extracellular, the most ancient ones present in all eukaryotes are all intracellular proteins involved in functions such as transcription, DNA repair, ribosomal and membrane transport and the proteasome. (
  • A pig sperm protein that binds to the extracellular matrix of the egg in a species-specific manner was recently identified and named zonadhesin (Hardy, D. M., and Garbers, D. L. (1995) J. Biol. (
  • Extracellular matrix proteins and cell adhesion receptors (integrins) play essential roles in the regulation of cell adhesion and migration. (
  • Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. (
  • a and a ß subunit, with a long extracellular domain binding to the ECM, a transmembrane domain, and a short cytoplasmic domain that associates with the actin cytoskeleton and adaptor proteins (3). (
  • Type I transmembrane protein with an N-terminal signal peptide of 26aa, followed by a 156-aa extracellular region, a 23-aa transmembrane domain, and a short 30-aa cytoplasmic region. (
  • As a balance, there is suppression of B cell stimulation from Lyn-dependent phosphorylation of tyrosine residues within immunoreceptor tyrosine-based inhibitory motifs in proteins such as CD22, PIR-B, and FcγRIIb1, with the concomitant recruitment to the plasma membrane of phosphatases such as SHP-1 and SHIP-1 ( 15 - 21 ). (
  • Lyn-deficient B cells fail to recruit protein tyrosine phosphatases to the plasma membrane due to defects in phosphorylation of inhibitory receptors ( 16 - 19 , 22 ). (
  • For many viruses, one or two proteins allow cell attachment and entry, which occurs through the plasma membrane or following endocytosis at low pH. (
  • This allows a tyrosine in the cytoplasmic portion of each receptor monomer to be trans-phosphorylated by its partner receptor, propagating a signal through the plasma membrane. (
  • The study of cell surface receptors and their associated signaling pathways on the plasma membrane are vital in understanding cellular responses. (
  • A number of putative fusion proteins have recently been identified in the plasma membrane of various types of fusing cells from different species, many of which belong to the immunoglobulin superfamily of proteins (see reference 5 for a review). (
  • Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. (
  • The latter catalyzes the 3′-phosphorylation of phosphatidylinositol (PI) in the plasma membrane glycolipids, thereby converting PI4,5-bisphosphate to PI3,4,5-triphosphate and PI4-phosphate to PI3,4 biphosphate. (
  • The effect of insulin is brought about by the translocation of a large intracellular pool of GLUTs (associated with low density microsomes) to the plasma membrane [1,2,84,92]. (
  • The MAPKKKK or MAPKKK can be linked to the plasma membrane - for example, through association with a small GTPase or lipid (e.g. (
  • Signal bound to plasma membrane of signaling cell. (
  • Alpha-synuclein interacts with plasma membrane phospholipids. (
  • In particular, it can bind to phospholipids of the plasma membrane and to synaptobrevin-2 via its C-terminus domain to influence synaptic activity. (
  • Six connexins oligomerize into a connexon to form functional hemichannels at the plasma membrane. (
  • We also showed that the scaffold protein Ste5 helps ensure signaling fidelity in pheromone response by binding the appropriate MAPK (Fus3), MEK (Ste7), and upstream activating kinase or MEKK (Ste11) and by shuttling from the nucleus to the plasma membrane, thereby delivering the MAPK module to its most proximal activator- a fourth plasma membrane-associated protein kinase (Ste20). (
  • We have shown that Ypk1, a member of the AGC class of protein kinases conserved from yeast to humans, is the essential target of and activated via phosphorylation by the plasma membrane-associated TORC2 complex. (
  • It is now generally accepted that receptor tyrosine kinase signaling occurs intracellularly and on the plasma membrane, although many important details remain to be worked out. (
  • Although traditionally RTKs are thought to signal from the plasma membrane, recent studies have demonstrated that several critical signaling events occur in the cytoplasm, after RTK endocytosis, which bring them into close proximity with either downstream signaling targets or phosphatases. (
  • 5 In addition to plasma membrane signaling, much of EGFR signaling output occurs from various endocytic compartments because its uptake and intracellular trafficking brings EGFR into association with a series of adaptor proteins involved in various signaling cascade. (
  • These characteristics include retraction of pseudopods with the consequent reduction of cellular volume and rounding of the cell, nuclear volume reduction (pyknosis) and fragmentation (karyorrhexis), structural modification of organelles followed by the formation of vesicles due to blebbing of the plasma membrane [ 3 , 4 ]. (
  • Studies by others have found that Gab1 can be recruited to the plasma membrane via increased PIPS levels. (
  • There are two principal signal transduction pathways involving the G protein-coupled receptors: the cAMP signal pathway and the phosphatidylinositol signal pathway. (
  • Phosphorylation and activation of these two proteins on receptor binding lead to the initiation of signal transduction pathways. (
  • These adaptor proteins link RTK activation to downstream signal transduction pathways, such as the MAP kinase signalling cascade. (
  • An example of a vital signal transduction pathway involves the tyrosine kinase receptor, c-met, which is required for the survival and proliferation of migrating myoblasts during myogenesis. (
  • As RTK receptors phosphorylate multiple tyrosine residues, they can activate multiple signal transduction pathways. (
  • The SH2-containing inositol phosphatase (SHIP) 3 plays a major role as a negative regulator of intracellular signal transduction ( 11 ). (
  • G protein-coupled receptors ( GPCRs ), also known as seven-(pass)-transmembrane domain receptors , 7TM receptors , heptahelical receptors , serpentine receptor , and G protein-linked receptors ( GPLR ), constitute a large protein family of receptors that detect molecules outside the cell and activate internal signal transduction pathways and, ultimately, cellular responses. (
  • When the TCR engages with antigenic peptide and MHC (peptide/MHC), the T lymphocyte is activated through signal transduction, that is, a series of biochemical events mediated by associated enzymes, co-receptors, specialized adaptor molecules, and activated or released transcription factors. (
  • Mutation of these specific tyrosines severely impairs the ability of insulin to stimulate glycogen synthesis, establishing the important role of IRS-1 in insulin signal transduction [12,84 - 88]. (
  • Activation of the insulin signal transduction system in insulin target tissues leads to the stimulation of glucose transport. (
  • The role of scaffold, anchoring, and adaptor proteins that contribute to the specificity of signal transduction events by recruiting active enzymes into signaling networks or by placing enzymes close to their substrates is discussed. (
  • In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. (
  • The signal transduction pathways involved in T-cell activation are initiated by the activation of phospholipase C-γ by specific tyrosine kinases at the lipid rafts resulting in the hydrolysis of the phosphatidylinositol 4,5 bisphosphate and the generation of inositol (1,4,5) triphosphate and diacylglycerol. (
  • These hemichannels are normally closed, but they can open under pathological conditions and thus participate in the development of many diseases.10-12 Signaling molecules and metabolic products (ATP, NAD+, glutamate, glutathione, prostaglandin-E2, and glucose13) can pass through these hemichannels to influence the signal transduction and metabolic status of cells in an autocrine or paracrine manner. (
  • This platform helps provide a comprehensive picture of altered signal transduction networks in tumor cells and provides insight into the effect of targeted therapies on protein signaling networks. (
  • We used the SCBC to study signal transduction in glioblastoma multiforme (GBM), a primary malignant brain tumor ( 12 ). (
  • We propose that peptide aptamers can provide a very useful and new alternative for interfering with protein-protein interactions in intracellular signal transduction cascades, including those emanating from activated receptors for growth factors. (
  • The ability of phosphoproteins to recruit other proteins is critical for signal transduction, in which downstream effector proteins are recruited to phosphorylated signaling proteins. (
  • There is a similar problem in Ph CML, where imatinib-resistant patients do not reach molecular remission even when second-or third-line BCR-ABL1 tyrosine kinase inhibitors (TKIs) are applied, particularly in patients exhibiting the BCR-ABL1 T315I mutant.3 During disease progression, additional signal transduction pathways become activated in neoplastic cells. (
  • Focal adhesion kinase (FAK) becomes tyrosine-phosphorylated during integrin-mediated cell adhesion and is believed to play important roles in integrin signal transduction (7,8). (
  • We have also shown that NO targets the IGF1 receptor, inducing receptor tyrosine dephosphorylation and interrupting IGFl-induced signal transduction in cultured cells. (
  • Lyn's role in activation is mediated by the phosphorylation of tyrosine residues within immunoreceptor tyrosine-based activation motifs of proteins such as Igα, Igβ, and CD19, and the subsequent recruitment of enzymes such as Syk, phospholipase Cγ2 (PLCγ2), and phosphatidyl inositol-3 kinase ( 14 ). (
  • The activated receptor as a result then becomes autophosphorylated on multiple specific intracellular tyrosine residues. (
  • The phosphorylation of specific tyrosine residues within the activated receptor creates binding sites for Src homology 2 (SH2) domain- and phosphotyrosine binding (PTB) domain-containing proteins. (
  • Furthermore, new insights have come from the growing appreciation that neither all RAS proteins (HRAS, NRAS, and KRAS4A/KRAS4B) nor all oncogenic RAS mutations (such as at residues Gly 12 , Gly 13 , and Gln 61 ) have the same impact on RAS signaling and function. (
  • The activating single missense mutations that have been found in human cancers occur primarily at codons encoding glycines at residues 12 (Gly 12 , commonly referred to clinically and per nomenclature as G12) and 13 (G13) or glutamine at residue 61 (Q61). (
  • Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. (
  • Phosphorylated on tyrosine residues in response to stimulation with EGF, growth hormone, insulin and PDGF. (
  • It serves by dephosphorylation of particular phosphotyrosine (pTyr) residues over the insulin receptor and insulin receptor substrate protein [7]. (
  • The insulin receptor is a glycoprotein consisting of two α subunits and two β subunits linked by disulfide bonds and expresses insulin-stimulated kinase activity directed towards its own tyrosine residues [12,84-87]. (
  • In muscle, the phosphorylated tyrosine residues on IRS-1 mediate an association between the SH2 domain of the 85-kDa regulatory subunit of PI3K, leading to activation of the enzyme (Figure 14.14). (
  • Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. (
  • Many signaling pathways do so by altering the phosphorylation state of tyrosine, serine, or threonine residues of target proteins. (
  • For example, src homology 2 (SH2) domains bind specific phosphotyrosyl residues on activated receptors (Fig. 2 A), and src homology 3 (SH3) domains bind to polyproline motifs on a separate set of target proteins (Fig. 2 D) ( 2 ). (
  • Residues 150 to 183 are responsible for binding to RAGE, whereas residues 89 to 108 and residues 7 to 74 are responsible for binding to Toll-like receptor 4 (TLR4) and p53 transactivation domain, respectively. (
  • Leptin binding to LepRb initiates signaling by activating the associated Janus kinase 2 (Jak2) tyrosine kinase, which promotes the phosphorylation of tyrosine residues on the intracellular tail of LepRb. (
  • Leptin stimulation promotes the autophosphorylation and activation of LepRb-associated Jak2, which phosphorylates three LepRb tyrosine residues (Tyr 985 , Tyr 1077 , and Tyr 1138 ). (
  • Activation of the IRs leads to transphosphorylation of tyrosine residues in the IR activation loop, which in turn leads to the enhanced ability of the IRs to phosphorylate target proteins, such as insulin receptor substrates (IRSs). (
  • Reversible protein phosphorylation, principally on serine, threonine or tyrosine residues, is one of the most important and well-studied post-translational modifications. (
  • By virtue of neutralizing surface charges on lysine residues, acetylation can regulate protein function or its association with other proteins. (
  • Negatively regulates insulin signaling by dephosphorylating the phosphotyrosine residues of insulin receptor. (
  • PTPs constitute a large, structurally diverse family of receptor-like and cytoplasmic enzymes expressed in all eukaryotes. (
  • Cytoplasmic protein tyrosine phosphatases such as SHP-1 also modulate BCR signaling ( 9 ) as exemplified by the severe B cell lymphopenia and autoantibody production of motheaten mice ( 10 ) that carry a debilitating mutation in SHP-1 ( 11 , 12 ). (
  • Dimerization leads to a rapid activation of the protein's cytoplasmic kinase domains, the first substrate for these domains being the receptor itself. (
  • The Constant region is proximal to the cell membrane, followed by a transmembrane region and a short cytoplasmic tail, while the Variable region binds to the peptide/MHC complex. (
  • For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. (
  • The assembly of signaling proteins into biochemical pathways or networks is typified by the association of autophosphorylated receptor tyrosine kinases with cytoplasmic proteins that contain specialized protein modules that mediate formation of signaling complexes (Fig. 2 ) ( 1 ). (
  • We provide evidence that β 1C -mediated up-regulation of IGF-II levels increases adhesion to Laminin-1, a basement membrane protein down-regulated in prostate cancer, and that the β 1C cytoplasmic domain contains the structural motif sufficient to increase cell adhesion to Laminin-1. (
  • This autocrine mechanism that locally supports cell adhesion to Laminin-1 via IGF-II is selectively regulated by the β 1 cytoplasmic domain via activation of the growth factor receptor binding protein 2-associated binder-1/SH2-containing protein-tyrosine phosphatase 2/phosphatidylinositol 3-kinase pathway. (
  • For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. (
  • We found that CAPE inhibited NF-κB-dependent transcriptional activity without affecting the degradation of the cytoplasmic NF-κB inhibitory protein, IκBα. (
  • Latent cytoplasmic STAT3 becomes activated through phosphorylation of Y705 by cytoplasmic nonreceptor tyrosine kinases including Janus-activated kinase (JAK) and Src ( 10 ). (
  • We describe a microchip designed to quantify the levels of a dozen cytoplasmic and membrane proteins from single cells. (
  • The smooth identification and low-cost production of highly specific agents that interfere with signaling cascades by targeting an active domain in surface receptors, cytoplasmic and nuclear effector proteins, remain important challenges in biomedical research. (
  • Finally, we have shown that NO decreases cytoplasmic Ca and attenuates IGFl-induced hydrogen peroxide generation and that this effect is mimicked by independent lowering of intracellular Ca by a Ca chelator. (
  • The Lyn tyrosine kinase is involved in both positive and inhibitory signaling pathways in B lymphocytes ( 13 ). (
  • Having noted the effects of the absence of Lyn activity ( 24 ), we now ask what immunological consequences flow from the constitutive engagement of both stimulatory and inhibitory signaling pathways using a targeted gain-of-function Lyn tyrosine kinase mutant (Lyn up/up mice). (
  • It is estimated that GPCRs are targets for about 50% of drugs currently on the market, mainly due to their involvement in signaling pathways related to many diseases i.e. mental, metabolic including endocrinological disorders, immunological including viral infections, cardiovascular, inflammatory, senses disorders, and cancer. (
  • Latest genomic profiling research have indeed proven overactivation of receptor tyrosine kinase pathways via tyrosine phosphorylation buy 198481-33-3 as the utmost commonly changed phenomena in glioma, with an increase of than 80% of glioma exhibiting epidermal growth aspect receptor (EGFR) constitutive TP and following buy 198481-33-3 tyrosine kinase burst [5], [6]. (
  • These results suggest that SHIP may regulate two distinct inside-out signaling pathways and that the phosphatase activity of SHIP is essential for both of them. (
  • Accordingly, numerous efforts have been carried out to target the signaling pathways to develop novel therapeutic approaches. (
  • Signaling pathways are coordinately controlled by a balance between activators, such as protein tyrosine kinases (TKIs), and inactivators, including protein tyrosine phosphatases (PTPs). (
  • Studies of Endogenous G-Protein-Mediated Pathways in Neurons by Whole-Cell Electrophysiology. (
  • Mitogen-activated protein kinase (MAPK) pathways regulate diverse processes ranging from proliferation and differentiation to apoptosis. (
  • As a consequence of an increase of intracellular Ca 2+ levels, several signaling pathways are activated ( Lewis, 2001 ). (
  • For example, an AT 1 /AT 2 chimeric receptor-study showed that substitution of IC3 in the AT 1 receptor failed to induce AT 1 receptor function via Gq protein coupling, 11 and also revealed that IC3 is a critical determinant of the mutually antagonistic AT 1 and AT 2 receptor signaling pathways. (
  • We showed that one device used by the cell for discrimination between parallel MAPK pathways is a specific docking interaction between a MAPK and the N-terminus of its cognate upstream protein kinase (MEK). (
  • A different scaffold protein, Ste50, is required for signal propagation in the invasive growth and hyperosmotic stress response pathways and is also under study. (
  • We are investigating pathways that regulate the activity, localization, and stability of this enzyme, and other bud-neck associated protein kinases (Gin4, Kcc4 and Hsl1), including their recruitment to septin filaments, which assemble at the presumptive site of cell division. (
  • Protein-protein interactions within signaling pathways are often elucidated by assessing the levels of relevant pathway proteins in model and tumor-derived cell lines and with various genetic and molecular perturbations. (
  • The reliance of neoplastic but not normal cells on such pathways for survival is the basis for targeted cancer therapy. (
  • This could be because of different endocytosis pathways or intracellular trafficking routes that these receptors take ( Figure 1 ). (
  • General receptor tyrosine kinase (RTK) endocytosis and recycling pathways. (
  • These findings suggest that alternative transcripts of protein kinases and phosphatases are produced that encode different domain structures, and that these variants are likely to play important roles in phosphorylation-dependent signaling pathways. (
  • Apoptotic cell death can be triggered through different intracellular signaling pathways that lead to morphological changes and eventually cell death. (
  • Paradoxically, these same pathways are utilized during infection by distinct intracellular microorganisms in order to evade recognition by the immune system, inhibit apoptosis, and therefore survive, reproduce, and develop inside cells. (
  • IA-2 and phogrin are tyrosine phosphatase-like proteins that may mediate interactions between secretory granules and cytoskeleton in islets and neuroendocrine tissues. (
  • four proteins mediate cell attachment and twelve that are associated in a membrane complex and conserved in all poxviruses are dedicated to entry. (
  • One or two glycoproteins that provide cell binding and membrane fusion are sufficient to mediate entry of many enveloped viruses [2] . (
  • Natural killer cells constitute an innate lymphoid lineage involved in early defense against certain intracellular pathogens and tumors, which mediate cytotoxicity and pro-inflammatory cytokine production upon interaction with pathological cells ( 1 - 3 ). (
  • As immunoglobulin proteins do not contain a fusion peptide or α-helical spring, these cannot be the universal tools that mediate membrane fusion. (
  • 5-HT receptors, including 5-HT1B/1D and 5-HT2A receptors mediate 5-HT-induced PA contraction of pulmonary vessels. (
  • Integrins are transmembrane αβ heterodimeric receptors that mediate cell adhesion to the ECM ( 12 ). (
  • Because Jak2-autonomous LepRb signals fail to mediate most leptin action, however, signals from other LepRb intracellular sequences predominate. (
  • Like other type I cytokine receptors ( 11 ), LepRb (which is required for physiologic leptin action) contains no intrinsic enzymatic activity, but associates with and activates the Janus kinase 2 (Jak2) tyrosine kinase to mediate leptin signaling. (
  • GP is necessary and sufficient to mediate viral entry into target cells. (
  • Left panel: Protein kinases mediate phosphorylation at serine, threonine and tyrosine side chains, and phosphatases reverse protein phosphorylation by hydrolyzing the phosphate group. (
  • Reversible protein tyrosine phosphorylation catalyzed by the coordinated actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) is of paramount importance in the regulation of the signaling events that underlie such fundamental processes as growth and proliferation, differentiation and survival or apoptosis, as well as adhesion and motility [ 1 ]. (
  • And PTPs have been shown to be negative regulators of the insulin receptor. (
  • Inhibition of PTPs may be an effective method in the treatment of type 2 diabetes [ 4 ]. (
  • Protein tyrosine phosphatase 1B (PTP1B), an intercellular non-receptor PTPs, is a key element in the negative regulation of the insulin signaling pathway and a valid potential drug target for the treatment of type 2 diabetes and other associated metabolic syndromes [ 5 , 6 ]. (
  • PTPμ is the prototype of the type IIb subfamily of receptor PTPs (RPTP). (
  • Proteins Tyrosine Phosphatase Receptor Type Kappa (PTPRK), among the 21 known receptor type PTPs, is certainly a transmembrane proteins that regulates cell-cell get in touch with. (
  • Protein tyrosine phosphatases (PTPs) play an important role in regulating cell signaling events in coordination with tyrosine kinases to control cell proliferation, apoptosis, survival, migration, and invasion. (
  • Receptor-type protein tyrosine phosphatases (PTPRs) are a subgroup of PTPs that share a transmembrane domain with resulting similarities in function and target specificity. (
  • Inhibition of PTPs could be an effective technique in the treating type 2 diabetes [4]. (
  • Proteins tyrosine phosphatase 1B (PTP1B), an intercellular non-receptor PTPs, is normally a key aspect in the detrimental regulation from the insulin signaling pathway and a valid potential medication target for the treating type 2 diabetes and various other linked metabolic syndromes [5,6]. (
  • The id of particular small-molecular-weight inhibitors of tyrosine phosphatases is normally a challenging undertaking, because the foot of the catalytic cleft, the personal CTS-1027 motif, is extremely conserved among all PTPs [11]. (
  • Protein phosphatases are classified according to their substrate specificity and sensitivity to inhibitory or activator agents, into two families of protein phosphatases: serine/threonine phosphatases and tyrosine phosphatases (PTPs). (
  • PTPs can be divided into 3 groups: t (mais) yrosine specific phosphatases, dual and low molecular weight phosphatases. (
  • A screen for protein tyrosine phosphatases (PTPs) expressed in the chick inner ear yielded a high proportion of clones encoding an avian ortholog of protein tyrosine phosphatase receptor Q (Ptprq), a receptor-like PTP. (
  • Recent studies have shown that TLR4 signaling can be regulated at multiple levels by many regulators which target different key molecules in the TLR4 signaling [ 5 - 8 ]. (
  • Three molecules possess been recognized as the primary cellular factors required for binding and access of human T-cell leukemia virus type 1 (HTLV-1): glucose transporter 1 (GLUT1), heparan sulfate (HS), and neuropilin 1 (NRP-1). (
  • G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. (
  • The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters, and vary in size from small molecules to peptides to large proteins. (
  • Beyond the pivotal role of alloantigen-specific T cells and antibodies in the pathogenesis of rejection, natural killer (NK) cells may display alloreactive potential in case of mismatch between recipient inhibitory killer-cell immunoglobulin-like receptors (KIRs) and graft HLA class I molecules. (
  • Inhibitory killer-cell immunoglobulin-like receptors (KIRs) and CD94/NKG2A complement each other, scanning potential target cells for altered surface expression of HLA class I (HLA-I) molecules. (
  • With the first small molecules that directly target one oncogenic RAS mutant (G12C) undergoing clinical evaluation, there have been substantial advances in finding anti-RAS therapeutic strategies. (
  • The T-cell receptor complex with TCR-α and TCR-β chains, CD3 and ζ-chain accessory molecules. (
  • The T-cell receptor , or TCR , is a molecule found on the surface of T cells , or T lymphocytes, [1] that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. (
  • The TCR is a disulfide-linked membrane-anchored heterodimeric protein normally consisting of the highly variable alpha (α) and beta (β) chains expressed as part of a complex with the invariant CD3 chain molecules. (
  • The fusion of viruses with cells, in particular influenza virus and human immunodeficiency virus (HIV), provided strong evidence that fusion is mediated both by viral proteins and host cell surface molecules that function as viral receptors ( 3 ). (
  • In an effort to validate new targets in neuroinflammatory conditions, our strategy has been to identify molecules whose levels of expression are highly regulated in the brain in different pathologies with overt neuroinflammation 8 . (
  • The CD158e1 and CD158e2 molecules (also known as p70 molecules) are monomeric integral membrane glycoproteins of 70 kDa. (
  • These proteins belong to the family of NK receptors for MHC class I molecules and show a high degree of homology with p58 and p140 receptors. (
  • CD158e1/e2 function as inhibitory receptors for HLA-B molecules of the Bw4 supertype. (
  • A ) Assembly of modular signaling molecules on an activated receptor tyrosine kinase. (
  • In this review, we compare and contrast the protein modules, adaptor molecules, targeting subunits, and anchoring proteins that coordinate signaling networks. (
  • Initially, inositol lipids were believed to recruit signaling molecules to specific membrane compartments, but many of the domains clearly do not possess high enough affinity to act alone as localisation signals. (
  • led to the current notion that production of specific inositol lipids in well-defined membrane compartments upon stimulation helps recruit signaling molecules to membranes and hence contributes to the organization of signaling complexes. (
  • Intriguingly, proteins involved in transport are more than double the 15 % of transporters in the entire human membrane proteome, which might suggest that the 4TM topological architecture is more favored for transporting molecules over other functions. (
  • The present report will not concentrate on these therapeutic Abs that have been described in recent comprehensive reviews (for example [ 1 , 2 ]), but will rather focus on fusion proteins, peptides and small molecules that represent excellent alternative tools for immune intervention in lupus. (
  • Sphingolipids are structural components of membranes, sphingolipid metabolites serve as signaling molecules. (
  • These auto-reactive cells, upon recognizing target molecules on normal cells have the potential to induce tissue destruction leading to toxic autoimmunity. (
  • A limiting factor in PTM research is that technologies to screen vast numbers of molecules for a particular type of modification are often not available, although recent developments of specific probes and multiplexed platforms may now make broader scale PTM surveying feasible ( 1 - 6 ). (
  • The macrophage scavenger receptors were discovered by Brown and Goldstein and functionally described for their ability to bind modified low-density lipoproteins (LDLs), such as acetylated LDL (AcLDL) and oxidized LDL (OxLDL), but not native LDL molecules. (
  • These proteins are connected to intracellular proteins that include diverse signaling molecules recruited to sites of focal adhesion, and are also linked to the actin cytoskeleton (2). (
  • Cyclic GMP affects the activity of effector molecules, specifically cGMP-dependent protein kinases (PKG), cGMP-regulated phosphodiesterases (PDEs), and cGMP-regulated cation channels. (
  • Resumo em inglês Protein phosphorylation-dephosphorylation catalyzed by the opposing and dynamic action of protein kinases and phosphatases probably, is the most crucial chemical reaction taking place in living organisms. (
  • YopH is a tyrosine phosphatase that causes dephosphorylation of the adaptor protein SKAP2, among other targets in neutrophils. (
  • Moreover, CAPE inhibited both the DNA-binding and transcriptional activity of NFAT, a result that correlated with its ability to inhibit phorbol 12-myristate 13-acetate plus ionomycin-induced NFAT1 dephosphorylation. (
  • At inhibitory synapses, postsynaptic LPA signaling resulted in dephosphorylation, and internalization from the GABAA2 subunit through the LPA1/G12/13-proteins/RhoA/Rho kinase/calcineurin pathway. (
  • May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET (By similarity). (
  • This PTP has been shown to interact with glutamate receptor delta 2 and epsilon subunits, and is thought to play a role in signalling downstream of the glutamate receptors through tyrosine dephosphorylation. (
  • These novel and exciting findings describe for the first time a mechanistic link between NO and tyrosine kinase receptor dephosphorylation involving a protein tyrosine phosphatase. (
  • Targeting different domains of gap junction protein to control malignant glioma Wang, Jun;Yang, Ze-Yu;Guo, Yu-Feng;Kuang, Jing-Ya;Bian, Xiu-Wu;Yu, Shi-Cang 2017-11-02 00:00:00 Abstract A rational treatment strategy for glioma, the most common primary central nervous system tumor, should focus on early invasive growth and resistance to current therapeutics. (
  • GAG chains are attached to the serine of a core protein through a linkage region of Xyl-Gly-Gly. (
  • PtdIn3,4,5P 3 , the lipid product of PtdIns3-kinase, is an important second messenger that is necessary for the activation of pleckstrin homology domain-containing enzymes such as the serine/threonine kinase Akt, the guanine nucleotide exchange factor Vav, and the Tec family tyrosine kinase Btk, involved in intracellular calcium mobilization ( 12 ). (
  • This permits simultaneous association of a single protein containing both SH2 and SH3 domains with two or more binding partners, and hence, the assembly of complexes of signaling proteins around an activated cell-surface receptor (Fig. 1 A). Similarly, subcellular organization of serine-threonine kinases and phosphatases occurs through interactions with the targeting subunits or anchoring proteins that localize these enzymes ( 3 ). (
  • MAPKs are attenuated by dual specificity MAPK phosphatases (MKPs), tyrosine phosphatases and serine/threonine phosphatases ( Keyse, 2000 ). (
  • Akt (also known as protein kinase B alpha) is a 60 kD serine/threonine specific kinase containing a pleckstrin domain. (
  • Yeast Orm1 and Orm2 belong to a conserved family of ER membrane proteins that regulate serine palmitoyltransferase, catalyzing the first and rate-limiting step in sphingolipid synthesis. (
  • While phosphorylation is a prevalent post-translational modification (PTM) for regulating protein function, it only occurs at the side chains of three amino acids, serine, threonine and tyrosine, in eukaryotic cells. (
  • Considering the heterogeneity of secondary injury processes, it can be appreciated that the levels and functional capacity of receptors and other proteins and their respective ligands and downstream signaling cascades may be adversely affected. (
  • Last, the development of agents that target downstream effectors of RAS signaling has advanced substantially. (
  • In the GTP-bound state, RAS engages downstream effectors through its dynamic conformation switch regions (SWI and SWII) to stimulate intracellular signaling. (
  • Shp2 acts downstream of many receptor tyrosine kinases such as Met, fibroblast growth factor (FGF), epidermal growth factor (EGF), and insulin receptors ( 10 ). (
  • Downstream of the hepatocyte growth factor/scatter factor (HGF/SF) receptor Met, Shp2 is activated by association with Gab1 and is both essential and sufficient for Met function ( 18 , 19 ). (
  • This is defined as the transfer of phosphoryl groups [(PO3)2-] from one molecule to another, and serves as a transfer of energy that results in the activation, or deactivation of downstream proteins. (
  • The role played by downstream of tyrosine kinase 2 (Dok2) phosphorylation in mediating the effects of CD200R activation was evaluated by siRNA knockdown of Dok2. (
  • As described here, microscopic analysis of null mutants have revealed that the class I phosphoinositide 3-kinases, PIK1 and PIK2, and the downstream effector protein kinase B (PKB/Akt) are important in regulating completion of macropinocytosis. (
  • Other proteins that interact with the activated receptor act as adaptor proteins and have no intrinsic enzymatic activity of their own. (
  • In addition, kinase binding proteins such as 14-3-3 proteins serve as adaptor proteins for signaling networks, whereas proteins such as Sterile 5 (Ste 5) and AKAP79 maintain signaling scaffolds of several kinases or phosphatases (Fig. 1 B) ( 4 ). (
  • This autoinhibition is relieved by binding of the SH2 domains to specific phosphotyrosine sites on receptors or receptor-associated adaptor proteins ( 10 ). (
  • Finally, we report a novel inhibitor, Compound 13 , that specifically inhibits PTP1B over the closely related phosphatase Src homology 2 (SH2) domain-containing phosphatase 2 (SHP-2) at 80 μM. (
  • The intracellular domain of PTPμ contains a juxtamembrane sequence with homology to cadherins and two phosphatase domains of which only the membrane proximal is catalytically active ( 17 , 18 ). (
  • The phosphorylated ITAMs serve as docking sites for Src homology 2 domain-containing cytosolic proteins, including the tyrosine kinase Syk, the Ras adapter Shc, and the p85 subunit of phosphatidylinositol (PtdIns) 3-kinase. (
  • Phosphatidylinositol 3-kinase (PI3K) signaling, a major insulin receptor signaling pathway, phosphorylates the 3-position hydroxyl group of the inositol ring of phosphatidylinositol-4,5-biphosphate, resulting in phosphatidylinositol-3,4,5-triphosphate (PIP3) that acts by recruiting specific pleckstrin homology (PH) domain containing proteins to cell membranes. (
  • Src homology 2 (SH2) domain-containing phosphatase 2 (SHP-2), another non-receptor PTP, provides two Src homology 2 (SH2) domains and a catalytic domains [9,10]. (
  • Innovative inhibitors from the tyrosine phosphatase PTP1B, could involve some kind of influence on the carefully related phosphatase SHP-2 using the same connections due to the homology in the concentrating on sites between PTP1B and SHP-2 [12]. (
  • In muscle, IRS-1 serves as the major docking protein that interacts with the insulin receptor tyrosine kinase and undergoes tyrosine phosphorylation in regions containing amino acid sequence motifs (YXXM or YMXM) that, when phosphorylated, serve as recognition sites for proteins containing src-homology 2 (SH2) domains. (
  • Shp2 is a nonreceptor PTP that harbors a classical tyrosine phosphatase domain and two N-terminal Src homology 2 (SH2) domains ( 7 , 8 ). (
  • Each LepRb tyrosine phosphorylation site recruits specific Src homology 2 (SH2) domain-containing effector proteins: Tyr 985 recruits Src homology phosphatase-2 (SHP-2) and suppressor of cytokine signaling 3 and attenuates LepRb signaling, but does not appear to play other roles in leptin action in vivo ( 13 - 15 ). (
  • The Src family of proteins contain a Src homology (SH) 2 domain and SH3 domain, a catalytic domain, and a C-terminal tail. (
  • The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs, Gαi/o, Gαq/11, Gα12/13). (
  • The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [ PMID: 15078142 ], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [ PMID: 15320712 ]. (
  • Laminin-1 (composed of α 1 β 1 γ 1 subunits) is found in normal human prostate glands ( 5 - 7 ) and in adult mouse prostate ( 8 ), but its expression is lost in basement membrane surrounding primary carcinoma and metastatic lymph node lesions ( 7 ). (
  • The GP precursor is post-translationally cleaved by the pro-protein convertase furin within the Golgi compartment of virus-producer cells, yielding two disulfide-linked subunits, GP1 and GP2 [ 13 ]. (
  • Genetic ablation of the Lyn tyrosine kinase has revealed unique inhibitory roles in B lymphocyte signaling. (
  • For example, mice with altered dosages of genes encoding B cell inhibitory and costimulatory receptors such as CD22, PD-1, FcγRIIb1, and CD19, all of which play key roles in modulating the strength of the B cell antigen receptor (BCR) * signal, are predisposed to autoimmune disease ( 2 - 8 ). (
  • This results in defective inhibitory signaling and as a consequence, Lyn-deficient B cells are hyperresponsive to BCR stimulation and show enhanced proliferation, calcium flux, and activation of the mitogen-activated protein kinase pathway ( 15 - 19 , 23 ). (
  • NK cells are controlled by an array of germ line-encoded inhibitory and activating/co-stimulatory receptors (NKR), as well as by different cytokines (e.g. (
  • These motifs are involved in the transduction of an inhibitory signal through the activation of the protein tyrosine phosphatases SHP-1 and/or SHP-2. (
  • To further characterize the inhibitory mechanisms of CAPE at the transcriptional level, we examined the DNA binding and transcriptional activities of nuclear factor (NF)-κB, nuclear factor of activated cells (NFAT), and activator protein-1 (AP-1) transcription factors in Jurkat cells. (
  • whole-cell patch-clamp research of 38 BNST neurons, we reported that neurons from the anterolateral BNST exhibited a variety of replies to exogenous 5-HT program, including an inhibitory membrane hyperpolarization, an excitatory membrane depolarization, or a biphasic response of hyperpolarization accompanied by depolarization. (
  • Nevertheless, in those neurons that do react to 5-HT, the response was often along with a reduction in membrane insight level of resistance (range: 23 C 40%), recommending that both inhibitory- as well as the excitatory response had been mediated with the starting of ion stations. (
  • At the single-cell level, inhibitory and activating protein-protein relationships, as well as stochastic (single-cell) fluctuations, are revealed. (
  • This is a proposal to investigate the role of protein tyrosine phosphatase PTPIB as mediator of the inhibitory effects of nitric oxide (NO) in vascular smooth muscle and in vascular remodeling. (
  • In the GDP-bound state, they are unable to engage effector proteins and are considered inactive. (
  • by Lamyaa Shaban, Giang T. Nguyen, Benjamin D. Mecsas-Faxon, Kenneth D. Swanson, Shumin Tan, Joan Mecsas Yersinia suppress neutrophil responses by using a type 3 secretion system (T3SS) to inject 6-7 Yersinia effector proteins (Yops) effectors into their cytoplasm. (
  • MyD88-dependent pathway is responsible for proinflammatory cytokine expression while the other one mediates the induction of Type 1 interferons and interferon-inducible genes. (
  • Thus, a receptor-ligand interaction mediates the binding of viruses to the membrane of the host cell. (
  • In liver, IRS-2 serves as the primary docking protein that undergoes tyrosine phosphorylation and mediates the effect of insulin on hepatic glucose production, gluconeogenesis, and glycogen formation. (
  • Although inositol (1,4,5) triphosphate mobilizes Ca 2+ from intracellular stores, diacylglycerol mediates activation of protein kinase C family members ( Baier, 2003 ). (
  • Pellino proteins contain a cryptic FHA domain that mediates interaction with phosphorylated IRAK1. (
  • Even renin has now been identified to have a "life on its own" and mediates profibrotic effects via binding to specific receptors. (
  • Considerable evidence has suggested that the experience from the bed nucleus from the stria terminalis (BNST) mediates many types of anxiety-like behavior in individual and nonhuman pets. (
  • Over expressing in PTPN1 (encoding Protein tyrosine phosphatase 1B, PTP1B), a protein tyrosine phosphatase (PTP) that plays an overall positive role in insulin signaling, is linked to the pathogenesis of diabetes and obesity. (
  • The relationship between PTP1B and human diseases exhibits PTP1B as the target to treat these diseases. (
  • Over expressing in (encoding Proteins tyrosine phosphatase 1B, PTP1B), a proteins tyrosine phosphatase (PTP) that has a standard positive function in insulin signaling, is from the pathogenesis of diabetes and weight problems. (
  • Zinker reported that PTP1B antisense oligonucleotides (ASOs) could decrease PTP1B protein appearance and could be utilized as potential therapeutics in the treating type 2 diabetes and weight problems [8]. (
  • As a result, the analysis of particular PTP1B inhibitors as medications plays a part in the boost of the precise affinity for PTP1B and prevents the mixture with proteins SHP-2 so far as feasible. (
  • The binding types of Substances 13, 15 and 20 with PTP1B and SHP-2 are forecasted and analyzed utilizing a molecular dynamics (MD) simulation by the end of this content. (
  • We have identified the phenylhydrazonopyrazolone sulfonate PHPS1 as a potent and cell-permeable inhibitor, which is specific for Shp2 over the closely related tyrosine phosphatases Shp1 and PTP1B. (
  • Liver-specific PTP1B deletion also protects against high-fat diet-induced endoplasmic reticulum stress response in vivo, as evidenced by decreased phosphorylation of p38MAPK, JNK, PERK, and eIF2α and lower expression of the transcription factors C/EBP homologous protein and spliced X box-binding protein 1. (
  • PTP1B: a non-receptor phospho-tyrosine protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. (
  • PTP1B knockout mice show resistance to dietary weight gain and enhanced insulin sensitivity, suggesting a possible role in treatment of obesity as well as type 2 diabetes. (
  • Moreover, we have found that PDGF and FGF increase PTP1B protein levels in cultured cells and that vascular injury similarly induces increased PTP1B protein levels in injured rat carotid artery. (
  • Determine whether PDGF, FGF or NO induce upregulation of PTP1B protein or activity levels in vascular injury. (
  • Determine whether PTP1B plays a role in attenuating IGF receptor activation in vivo. (
  • Reconstitution of wild-type PTPRK in malignant glioma cell lines suppressed cell development and migration by inhibiting EGFR and -catenin signaling and improved the result of standard therapies for glioma. (
  • EGFR is a transmembrane protein belonging to the ErbB family of receptors, which functions as a receptor tyrosine kinase (RTK). (
  • Pathway analysis of glioblastoma tissue after preoperative treatment with the EGFR tyrosine kinase inhibitor gefitinib--a phase II trial. (
  • EGFR is an important and clinically validated cancer target. (
  • We have also shown that nanobodies or VHH domains, the smallest natural antigen-binding modules (from heavy chain only camelid antibodies), can inhibit EGFR either by mimicking existing antibodies or through unique mechanisms - emphasizing the power of nanobodies as possible 'designer inhibitors' and as tools for asking mechanistic questions about their binding targets. (
  • We interrogated 11 proteins directly or potentially associated with PI3K signaling (see SI Appendix, Methods I ) through three isogenic GBM cell lines: U87 (expressing wild-type p53, mutant PTEN, and low levels of wild-type EGFR, no EGFRvIII) ( 16 , 17 ), U87 EGFRvIII (U87 cells stably expressing EGFRvIII deletion mutant), and U87 EGFRvIII PTEN (U87 cells coexpressing EGFRvIII and PTEN) ( 18 ). (
  • Endocytosis of EGFR, as well as of other receptors, is regulated by the Rab family proteins. (
  • The initial findings from ELISA demonstrate that PTEN influences TNF- α secretion by its lipid phosphatase activity. (
  • PTEN functions as a lipid phosphatase and as a protein tyrosine phosphatase. (
  • As a lipid phosphatase, PTEN antagonizes PI3K (phosphatidylinositol-3-kinase)/Akt signaling by dephosphorylating phosphatidylInositol (3,4,5)-trisphosphate (PIP3) at position 3 and is involved in various cellular processes including survival, proliferation, energy metabolism, and cellular architecture [ 10 ]. (
  • In addition, a potent neutralizing L1 monoclonal antibody blocked entry at a post-membrane lipid-mixing step. (
  • Entry of enveloped viruses into cells can be divided into three steps: (i) close apposition of viral and cellular membranes, (ii) lipid mixing of the outer membrane leaflets leading to formation of a hemifusion intermediate, and (iii) formation and expansion of a fusion pore allowing entry of the viral nucleoprotein or core into the cytoplasm [1] . (
  • Most viral fusion proteins contain a stretch of hydrophobic amino acids, known as a fusion peptide, which penetrates host cells like a sword, destabilizing the lipid bilayer of the host cell. (
  • Inositol lipids have emerged as universal lipid regulators of protein signaling complexes in defined membrane compartments. (
  • Another important notion is that some (and probably most) of these protein modules also have protein binding partners, and their protein- and lipid-binding activities might influence one another through allosteric mechanisms. (
  • Comparison of the structural features of these domains not only reveals a high degree of conservation of their lipid interaction sites but also highlights their evolutionary link to protein modules known for protein-protein interactions. (
  • Protein-protein interactions involving lipid-binding domains could serve as the basis for phosphoinositide-induced conformational regulation of target proteins at biological membranes. (
  • Moreover, recruitment of multiple proteins containing PH domains binding to the same inositol lipid would create a large degree of information `spreading' and it is hard to see how cells could maintain signaling specificity if this were the case. (
  • Here, I focus on the structural and functional similarities between these modules, emphasising their proven or potential protein-protein interactions in combination with their lipid-binding properties. (
  • Conversely, the calcium- and calcineurin-dependent pathway signals ER stress response upon lipid dysregulation in the absence of the Orm proteins to restore ER homeostasis. (
  • The myotubularin-related genes define a large family of eukaryotic proteins, most of them initially characterized by the presence of a ten-amino acid consensus sequence related to the active sites of tyrosine phosphatases, dual-specificity protein phosphatases and the lipid phosphatase PTEN. (
  • Although myotubularin was thought to be a dual-specificity protein phosphatase, recent results indicate that it is primarily a lipid phosphatase, acting on phosphatidylinositol 3-monophosphate, and might be involved in the regulation of phosphatidylinositol 3-kinase (PI 3-kinase) pathway and membrane trafficking. (
  • Phosphatidylinositol 3-kinases are a family of dual specificity lipid/protein kinases. (
  • Lipid kinases and their phosphorylated products are important regulators of many cellular processes, including intracellular membrane traffic. (
  • In cultured 5-day-old rat islets, IA-2 protein and mRNA was increased by glucose and agents that potentiate insulin secretion by the cAMP pathway. (
  • Addition of insulin increased IA-2 protein levels and insulin biosynthesis without affecting IA-2 mRNA. (
  • Blocking insulin secretion with diazoxide or insulin action with insulin receptor antibodies inhibited glucose-induced increases in IA-2 protein, but not those of mRNA. (
  • Thus, IA-2 is regulated at the mRNA level by glucose and elevated cAMP, whereas locally secreted insulin modulates IA-2 protein levels by stimulating biosynthesis. (
  • These results demonstrate differential regulation of two closely related secretory granule components and identify IA-2 as a granule membrane protein subject to autocrine regulation by insulin. (
  • Evidence is emerging that glucose-regulated transcription of other β-cell proteins, such as glucokinase, may also be mediated in part by insulin signaling ( 3 ). (
  • Defective insulin action on pancreatic β -cells has been suggested to contribute to impaired insulin secretion and may have relevance to insulin deficiency in type 2 diabetes ( 4 ). (
  • Understanding the influence of insulin on pancreatic β-cell function requires identification of proteins relevant to the secretory process whose expression or activity is regulated by insulin. (
  • Glucose stimulates biosynthesis of a number of β-cell proteins, many of which localize to insulin secretory granules and are therefore likely to participate in insulin storage or secretion ( 5 ). (
  • The identities of these glucose-response proteins and the contribution of insulin signaling to their increased synthesis are largely unknown. (
  • Phogrin is phosphorylated in intact β-cells on stimulation of insulin secretion, suggesting that the protein is a target for secretagogue-activated protein kinases ( 8 , 9 ). (
  • The insulin receptor is a tyrosine kinase that is activated in response to insulin microbeads presented to three mammalian cell lines: CHO, NIH-3T3 and COS-7. (
  • Immunofluorescence staining (IF) and western blots confirmed insulin receptor and phosphotyrosine activity in cells. (
  • The activated insulin receptor complex was captured and isolated by insulin coated microbeads on the surface of cells. (
  • Type 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. (
  • In a time-dependent manner, leptolide (0.1 µM) augmented insulin-stimulated phosphorylation of protein kinase B (PKB) by two-fold above vehicle-treated HepG2 cells. (
  • Insulin resistance is one of the hallmarks of type 2 diabetes (T2DM) and obesity. (
  • Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. (
  • Insulin receptor phosphorylation of the α subunit, with subsequent activation of insulin receptor tyrosine kinase, represents the first step in the action of insulin on glucose metabolism. (
  • Insulin receptors devoid of tyrosine activity are completely ineffective in mediating insulin stimulation of cellular metabolism. (
  • Mutagenesis of any of the three major phosphorylation sites (at residue 1158, 1163, and 1162) impairs the insulin receptor kinase activity, and this is associated with a marked decreased in the acute metabolic and growth-promoting effects of insulin [12,86-88]. (
  • After activation, insulin receptor tyrosine kinase phosphorylates specific intracellular proteins, of which at least nine have been identified (Figure 14.14). (
  • In adipocytes, Cb1 is phosphorylated after its interaction with the insulin receptor tyrosine kinase and is required for stimulation of GLUT4 translocation [2]. (
  • The effect of insulin is mediated via the PI3K pathway, which inactivates phosphatases, particularly PP-1. (
  • The precise steps that link insulin receptor tyrosine kinase/PI3K activation to stimulation of PP-1 have yet to be defined. (
  • Using gene expression analysis, we show here that the β 1C variant, an inhibitor of cell proliferation, which is down-regulated in prostate cancer, up-regulates insulin-like growth factor-II (IGF-II) mRNA and protein levels. (
  • This protein kinase is activated by insulin and various growth and survival factors to function in a wortmannin-sensitive pathway involving PI 3-kinase. (
  • The events after insulin binds to its receptor are highly regulated and specific. (
  • Defining the key steps that lead to the specificity in insulin signaling presents a major challenge to biochemical research, but the outcome should offer new therapeutic approaches for treatment of patients suffering from insulin-resistant states, including type 2 diabetes. (
  • Insulin action is mediated by insulin receptors (IRs) on the plasma membranes of responsive cells ( 4 ). (
  • Readily-available high calorie foods and sedentary lifestyles are major factors for obesity which contribute to insulin resistance and type 2 diabetes. (
  • Insulin resistance is defined as defective insulin signalling and decreased insulin efficiency to induce glucose transport from the blood into key target cells. (
  • Considerable research has focused on the molecular mechanism of LPS-induced sepsis, especially the cellular signaling of activation of toll-like receptor 4 (TLR4) in the past few years. (
  • The aim of the present study was to determine the roles of cellular and viral proteins in initial stages of entry, specifically fusion of the membranes of the mature virion and cell. (
  • Taken together, these results suggested a 2-step entry model and implicated an unprecedented number of viral proteins and cellular components involved in signaling and actin rearrangement for initiation of virus-cell membrane fusion during poxvirus entry. (
  • Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. (
  • Rabbit polyclonal to ZU5.Proteins containing the death domain (DD) are involved in a wide range of cellular processes,and play an important role in apoptotic and inflammatory processes. (
  • With regards to the cellular framework, Notch signaling is normally decreased or potentiated by Fringe protein, a course of glycosyltransferases that adjust the receptor (21). (
  • Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. (
  • Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [ PMID: 12368087 ]. (
  • Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. (
  • Host proteins that interact with TRPs are involved in cellular processes, including cell signaling, vesicle trafficking and intracellular transport, transcriptional regulation, metabolism, protein posttranslational modification, and apoptosis. (
  • These findings emphasize the critical need for an understanding of the cell biology of postsynaptic receptor trafficking under healthy physiological conditions and how such cellular processes go awry in the early stages of AD. (
  • Association of LAR-like Receptor Protein Tyrosine Phosphatases with an Enabled Homolog in Hirudo Medicinalis Molecular and Cellular Neurosciences. (
  • Protein misfolding in the endoplasmic reticulum (ER) is accompanied by adaptive cellular responses to promote cell survival. (
  • PTP-PEST: Dephosphorylates cellular tyrosine kinases, including PTK2B/PYK2, and thereby regulates signaling via PTK2B/PYK2. (
  • The dual nature of Lyn's role in the regulation of B cell signaling makes it a potentially critical target in analyzing the development of B cell dysfunction. (
  • Accordingly, recent advances in this area demonstrated that phagocytosis is a highly regulated process involving negative regulation by protein tyrosine phosphatases as well as inositol phosphatases ( 2 , 3 , 4 , 5 , 6 ). (
  • Tyrosine phosphorylation has a crucial role in the regulation of physiological processes such as cell proliferation, differentiation, adhesion, and migration, which are closely relevant to human diseases, especially cancer. (
  • The mammalian target of rapamycin (mTOR) is an intracellular kinase that controls the production of proteins through its regulation of translational machinery. (
  • Expression and Characterization of Rat Brain Phospholipase D. G-Protein-Coupled Receptor Regulation of Phospholipase D. Analysis and Quantitation of Ceramide. (
  • a-synuclein may be involved in the regulation of dopamine release and transport and also may function to induce fibrillization of microtubule-associated protein tau. (
  • These emerging concepts of regulation of Ang II receptors and a new insight into future drug discovery are discussed in this review. (
  • Recently, several GIPs have been reported to have unique roles in the regulation of AT 1 and AT 2 receptors via interaction with the C terminus of their receptors. (
  • Orm protein phosphorylation mediating feedback regulation of SPT activity occurs in response to multiple sphingolipid intermediates, including long chain base and complex sphingolipids. (
  • For a large subset of proteins, phosphorylation is tightly associated with protein activity and is a key point of protein function regulation. (
  • Receptor tyrosine kinases are involved in regulation of key processes in endothelial biology, including proliferation, migration, and angiogenesis. (
  • The regulation of protein phosphorylation requires a balance in the activity of protein kinases and protein phosphatases. (
  • Src induces up-regulation of ERK activity and its target transcription factors, CREB and ERα, through attenuation of PP2A activity. (
  • In general, changes in protein phosphorylation require coordinate regulation of protein kinases and protein phosphatases. (
  • Recently, two types of signaling by integrins have been extensively discussed: transmission of signals into the cell following binding of ligands or counter-receptors to the integrins (outside-in signaling), and regulation of the avidity and conformation of integrins by signals generated by other receptors within the cell (inside-out signaling) (5). (
  • Dual specificity protein kinases (e.g. (
  • Determination of Strength and Specificity of Membrane-Bound G Protein-Phospholipase C Association Using Fluorescence Spectroscopy. (
  • Pathway specificity is regulated at several levels, including kinase-kinase and kinase-substrate interactions, colocalization of kinases by scaffold proteins, and inhibition of cross-talk/output by the MAPKs themselves. (
  • and, various classes of phosphotyrosine-directed, phosphoserine- / phosphothreonine-directed, and dual-specificity phosphoprotein phosphatases that can act to dephosphorylate activated MAPKs. (
  • By their targeting of short, linear motif type of interactions, peptide aptamers have joined nucleic acid aptamers for use in signaling studies because of their ease of production, their stability, their high specificity and affinity for individual target proteins, and their use in high-throughput screening protocols. (
  • 2 ]. indicated that large numbers of PTP genes were encoded within the human genome, including trans-membrane, receptor-like, and intracellular, non receptor-like enzymes. (
  • Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. (
  • The protein kinase complement of the human genome. (
  • An early study based on available DNA sequence suggested that the human genome encodes roughly 750 G protein-coupled receptors, [17] about 350 of which detect hormones, growth factors, and other endogenous ligands. (
  • The human genome encodes thousands of G protein-coupled receptors, [ 10 ] about 350 of which detect hormones, growth factors, and other endogenous ligands. (
  • phase III trial by Human Genome Sciences, Rickville, IN, USA) that targets B-lymphocyte stimulator, and epratuzumab, a humanized antibody (Ab) that targets the CD22 receptor on B cells (phase IIb trial by UCB Pharma, Colombes, Belgium). (
  • Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. (
  • Nevertheless, PTPRK mutations abrogated tumor suppressive ramifications of wild-type PTPRK and modified level of sensitivity of glioma cells to chemotherapy. (
  • Activating mutations in RAS proteins are found in ~24% of all cancers [as reported in the Catalog of Somatic Mutated in Cancer (COSMIC) database, v89] and are commonly associated with resistance to frontline therapies ( 1 ). (
  • Despite the similar functional consequences of these mutations, they are found at disparate frequencies among cancer types and among RAS genes. (
  • These findings suggest that the different RAS isoforms, as well as individual mutations within one RAS protein, have distinct properties despite their high sequence similarity and conserved function. (
  • All included targets have been cross-referenced for the presence of mutations associated with human cancer. (
  • To date 126 out of the 127 studied drug targets so far have been recorded with somatic mutations. (
  • The software application lets you narrow in on these mutations and links out to the mutational analysis for each of the drug targets for detailed information. (
  • All targets are cross-referenced with the Catalogue of Somatic Mutations in Cancer (COSMIC). (
  • To date 126 out of the 127 studied drug targets so far have been recorded with somatic mutations and the software application lets you narrow in on these mutations and links out to the mutational analysis for each of the drug targets for detailed information. (
  • We apply MiSL to 12 different cancers and predict 145,891 SL partners for 3,120 mutations, including known mutation-specific SL partners. (
  • Gain-of-function mutations in several types of leukemia define Shp2 as a bona fide oncogene. (
  • We currently have no molecular understanding of how these mutations activate of the receptor. (
  • New structures complemented with biochemical investigations uncovered mechanisms of action of molecular switches which modulate the structure of the receptor leading to activation states for agonists or to complete or partial inactivation states for inverse agonists. (
  • Note: Reduce the methanol concentration in transfer buffer to 10 % instead of 20%, to facilitate transfer of high molecular weight proteins such as CSPGs). (
  • It is obvious that TBI continues to be a significant worldwide problem demanding effective therapy that affects high yield molecular targets to decrease morbidity and mortality-a demand that has, to this point, not been met. (
  • Studies aimed at identifying molecular targets that may improve survivability and decrease disability following TBI are manifold. (
  • Analyzing the molecular events leading to PTEN influence on LPS/Toll-like receptor 4 (TLR4) signaling, we found that LPS-induced activation of mitogen-activated protein kinases is suppressed in PTEN −/− cells. (
  • All drugs targets are further categorized on in the software application by 38 classifications of molecular function and with pathway referrals to BioCarta, KEGG, NCI-Nature and NetPath. (
  • These studies provide important molecular evidence that such processes are key targets of Aβ. (
  • Importantly, they go far beyond this observation and provide evidence for an Aβ-dependent molecular cascade that involves the α7 nicotinic receptor, protein phosphatase 2B, and tyrosine phosphatase, ultimately culminating in enhanced endocytosis of the NMDA receptor. (
  • Identifying novel molecular targets therefore remains an important issue in the treatment of lupus. (
  • Molecular targeted therapies have created an encouraging trend in the treatment of lupus. (
  • Immunological and molecular polymorphisms of OspC, an immunodominant major outer surface protein of Borrelia burgdorferi. (
  • We are interested in understanding molecular mechanisms that regulate receptor signaling at and across membranes. (
  • These effects are achieved by modification of key molecular targets, either by reversible phosphorylation or by alteration of gene expression. (
  • This study examined the molecular mechanisms by which Src activates ERK cascade through protein phosphatases following cerebral ischemia. (
  • The term apoptosis was coined since 1972 by Kerr, to define a type of programmed cell death with morphological and molecular characteristics different from other types of cell death. (
  • Akt (protein kinase B) containing PH domain gets activated, binds to PIP3 and localizes to the site of receptor activation. (
  • For example, the HIV surface ligand gp120 binds to its receptor (CD4) on T lymphocytes and macrophages, and the hemagglutinin protein of influenza binds to its receptor (sialic acid) on epithelial cells. (
  • 1 Ang II binds 2 major receptors: the Ang II type-1 (AT 1 ) receptor and type-2 (AT 2 ) receptor. (
  • AngII then binds to specific receptors in adrenal cortex, resulting in release of aldosterone. (
  • LIF binds to its receptor complex composed of LIFR and gp130 to activate the LIF signaling pathway. (
  • When cGMP is elevated in these cells, it is not only broken down at the catalytic site of PDE5, but it also binds to cGMP-selective sites on several types of proteins, including cGMP-dependent protein kinase (PKG), cGMP-gated cation channels, and allosteric sites on PDE5. (
  • Lyn up/up B cells are characterized by the constitutive phosphorylation of negative regulators of B cell antigen receptor (BCR) signaling including CD22, SHP-1, and SHIP-1, and display attributes of lymphocytes rendered tolerant by constitutive engagement of the antigen receptor. (
  • There have been at least seven other Nobel Prizes awarded for some aspect of G protein-mediated signaling. (
  • Excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. (
  • Moreover, our recent research has shown that CSPG signaling is dependent on 4-sulfation of GalNAc, especially at the non-reducing end (the furthest from the protein core). (
  • Notch signaling impacts cell destiny during embryogenesis and subsequently affects cell proliferation, differentiation, and apoptosis (12). (
  • Signaling takes place between apposing cells that exhibit Notch receptors and DSL ligands. (
  • Here we examined the role of the SH2-containing inositol phosphatase (SHIP), a major negative regulator of intracellular signaling, in this process. (
  • This activation of LFA-1 by "inside-out signaling" does not require increased expression of LFA-1 on the cell surface or de novo protein synthesis ( 5 , 6 ). (
  • Evolution of protein kinase signaling from yeast to man. (
  • Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies. (
  • May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). (
  • From the physiologic standpoint, it makes sense that activation of glucose transport and glycogen synthase should be linked to the same signaling mechanisms to provide a coordinated and efficient stimulation of intracellular glucose metabolism. (
  • Protein modules for the assembly of signaling complexes. (
  • The receptor-mediated activation of the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5) P 2 ] with the resultant production of inositol 1,4,5-trisphosphate (InsP 3 ) and diacylglycerol (DAG), the two second messengers linked to Ca 2+ signaling and protein-kinase-C-mediated phosphorylations, respectively, had become textbook knowledge by the early 90s. (
  • The protein tyrosine phosphatase Shp2 is a positive regulator of growth factor signaling. (
  • What are four signaling types in animal cells? (
  • The role of tyrosine phosphorylation in mitogenic signaling is well documented, and one would predict that vanadate, pervanadate and other oxidant agents (protein tyrosine phosphatase inhibitors) may act as a growth stimulator. (
  • Recent accumulating evidence has suggested that the AT 2 receptor not only opposes the AT 1 receptor but also has unique effects beyond an interaction with AT 1 receptor signaling. (
  • however, the third intracellular loop (IC3) of these receptors plays a pivotal role in signaling activation by both receptors. (
  • 14 These proteins mainly associate with the carboxyl (C) terminus of GPCRs and regulate their functions by trafficking, fine-tuning, and signaling modification. (
  • Local control of phosphatidylinositol 4-phosphate signaling in the Golgi apparatus by Vps74 and Sac1 phosphoinositide phosphatase. (
  • Finally, drugs that are used to block the RAAS, such as ACE inhibitors or certain AngII type 1 receptor antagonists, may have properties on cells independent of AngII (ACE inhibitor-mediated outside-inside signaling and peroxisome proliferator-activated receptor-γ stimulatory effects of certain sartanes). (
  • We now show that activation of mitochondrial respiration is a critical component of an adaptive ER stress response, requiring the unfolded protein response (UPR) sensor Ire1, and also calcium signaling via calcineurin. (
  • Sphingolipids are structural components of cell membranes that have signaling roles to regulate many activities, including mitochondrial function and cell death. (
  • We now show that sphingolipid synthesis via Orm1 is a target of TOR signaling which regulates cell growth in response to nutritional signals. (
  • We use the platform to assess protein-protein interactions associated with the EGF-receptor-mediated PI3K signaling pathway. (
  • Such interactions, and the implied signaling networks, may also be elucidated via quantitative measurements of multiple pathway-related proteins within single cells ( 6 ). (
  • We describe quantitative, multiplex assays of intracellular signaling proteins from single cancer cells using a platform called the single-cell barcode chip (SCBC). (
  • Phosphorylation regulates protein function and cell signaling by causing conformational changes in the phosphorylated protein. (
  • Endocytosis and subsequent intracellular trafficking spatiotemporally regulate receptor tyrosine kinase signaling, whereas signaling endosomes provide a platform for the compartmentalization of signaling events. (
  • This review summarizes recent advances in our understanding of endothelial receptor tyrosine kinase endocytosis and signaling using vascular endothelial growth factor receptor-2 as a paradigm. (
  • 4 Interestingly, the extent to which a specific RTK's signaling is affected by endocytosis is different for different receptors. (
  • The diverse realm of posttranslational modification (PTM) 1 of proteins encompasses many of the critical signaling events occurring during neoplastic transformation. (
  • In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. (
  • FAK, a non-receptor tyrosine kinase, interacts with a pool of intracellular signaling proteins, including c-Src, phosphatidylinositol 3-kinase (PI3-K), Rho GTPase family members, Grb2, and p130 CAS (6). (
  • Yet, these observations still support the idea that receptor-ligand interactions are universally required for fusion. (
  • Assays of G Protein/cGMP-Phosphodiesterase Interactions. (
  • Assaying G Protein-Phosphodiesterase Interactions in Sensory Systems. (
  • This study confirms that the majority of host proteins known to interact with TRP effectors influence infection and further extends the current knowledge that E. chaffeensis TRPs participate in a complex array of host protein interactions in order to reprogram the host cell and promote intracellular survival. (
  • Fus3 is activated by the MAPKK Ste7 on the Ste5 scaffold through localizing interactions involving a heterotrimeric G protein and Cdc42 GTPase, which guide the MAPKKK Ste11 to the MAPKKKK Ste20. (
  • Detailed knowledge of the host-virus interactions that accompany filovirus entry into cells is expected to identify determinants of viral virulence and host range, and to yield targets for the development of antiviral therapeutics. (
  • The measured protein abundances are consistent with previous work, and single-cell analysis uniquely reveals single-cell heterogeneity, and different types and strengths of protein-protein interactions. (
  • These are domains comprised of about 160 amino acids that are present in transmembrane proteins such as the meprins and receptor protein-tyrosine phosphatases, where they appear to function in cell/cell interactions. (
  • This area is important because it is responsible for the ligand binding and is targeted by many drugs. (
  • In the other receptors crystallized shortly afterwards the binding side was even more easily accessible to the ligand. (
  • After ligand binding, a cascade of proteolytic cleavages from the Notch receptor ensues (15). (
  • Moreover, ligand-independent receptor activation systems such as mechanical stretch for the AT 1 receptor have also been revealed. (
  • One of the most-studied ligand-receptor pairs is CD200-CD200 receptor (CD200R). (
  • Integrin clusters in macromolecular complexes, ligand occupancy, and tyrosine phosphorylation are the key events that result in diverse processes such as cell migration and differentiation, tissue remodelling, cell proliferation, angiogenesis, and tumor cell invasion and metastasis (3,6). (
  • 1. Drexler HG Expression of FLT3 receptor and response to FLT3 ligand by leukemic cells. (
  • There are two main cell types that regulate neuroinflammation, namely astrocytes and microglia, the resident macrophages in the brain. (
  • First, conformational changes regulate the catalytic activity of the protein. (
  • Accordingly, the whole cell-scattered PTEN translocated towards the cell membrane 20 minutes after stimulating with LPS. (
  • Furthermore, the protein phosphatase activity of PTEN influences cell motility, invasion, and migration [ 11 ]. (
  • By this mechanism, sometimes referred to as "type III," extracellularly located bacteria that are in close contact with a eukaryotic cell deliver toxic bacterial proteins into the cytosol of this cell. (
  • Intro Human being T-cell leukemia computer virus type 1 (HTLV-1) is usually the causative agent of adult T-cell leukemia (16, 49) and HTLV-1-connected myelopathy, also known as tropical spastic paraparesis (10, 24, 45). (
  • In this scholarly study, we looked into the susceptibilities of numerous WP1130 human being cell lines to cell-free HTLV-1 contamination using extremely contagious vesicular stomatitis computer virus (VSV) pseudotypes harboring the Env proteins of HTLV-1. (
  • GBM tumor cells disperse extensively throughout the brain parenchyma, and the need for tumor-specific drug targets and pharmacologic agents to inhibit cell migration and dispersal is great. (
  • The receptor protein tyrosine phosphatase μ (PTPμ) is a homophilic cell adhesion molecule. (
  • These neoplasms are categorized by their putative cell of origin based on morphologic similarities to various types of normal glia ( 2 , 3 ). (
  • We recently showed that the receptor protein tyrosine phosphatase μ (PTPμ) negatively regulates GBM cell migration, and full-length PTPμ protein is lost in human GBM tumors in comparison with low-grade astrocytomas ( 8 ). (
  • Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. (
  • Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. (
  • Among the often changed regulatory indicators in glioma is certainly constitutive proteins tyrosine phosphorylation (TP) that drives cell development and migration [4], [5]. (
  • Follicles are made up of three MCM2 cells types: oocytes, encircling granulosa cells, and an exterior thecal cell level. (
  • Wild-type SHIP and a phosphatase-deficient mutant SHIP were overexpressed in the murine myeloid cell line, DA-ER, and the effects on LFA-1-mediated cell adhesion to ICAM-1 (CD54) were tested. (
  • Overexpression of wild-type SHIP significantly enhanced cell adhesion to immobilized ICAM-1, and PMA, IL-3, or erythropoietin further augmented this adhesion. (
  • In this study, we examined the role of SHIP in the activation of LFA-1 by testing the effects of overexpressing wild-type (WT) and phosphatase dead SHIP in a hemopoietic cell line on LFA-1-mediated cell adhesion to ICAM-1. (
  • Confocal microscopy confirmed Akt-PH recruitment to the cell membrane. (
  • mTOR-activated proteins promote several hallmarks of cancer such as cell growth and proliferation, angiogenesis, and bioenergetics. (
  • SYK is a positive effector of B-cell antigen receptor (BCR) stimulated responses [ PMID: 19670961 , PMID: 19592646 ]. (
  • A new study now reveals an unexpected role for the receptor, dendritic cell-specific transmembrane protein (DC-STAMP), in this process. (
  • Most of the viral proteins that are responsible for the binding of the virus to the host cell also play a role in fusion. (
  • For example, the attachment of HIV to its target cell via gp120 leads to a conformational change that exposes the associated fusion protein gp41 (gp120 and gp41 are derived from a single protein, gp160, that is posttranslationally cleaved). (
  • The fusion protein then undergoes a conformational change, forming a hairpin-like α-helical bundle, which acts like a spring to propel the viral membrane close enough to the cell membrane to trigger fusion. (
  • Another type of fusion occurs between distinct membranes within a cell, such as during intracellular trafficking between the endoplasmic reticulum and the Golgi apparatus. (
  • As thus far no two cell types share the same putative fusion protein, it seems plausible that alternative mechanisms for fusion might have evolved for each cell type, with fusion being cell type-specific and depending on different proteins in different species ( 5 ). (
  • Immunoglobulin-like cell surface receptor for CD47. (
  • E. chaffeensis TRPs are type 1 secreted effectors that interact with a functionally diverse group of host cell targets associated with various biological processes. (
  • Selected host targets were examined by immunofluorescent microscopy during infection and were found to localize with the morulae, or in the host cell cytoplasm adjacent to morulae. (
  • SHP-2 is known as to be always a component of many intracellular indication transduction systems involved with embryonic advancement that modulate cell department, differentiation, and migration, including that mediated by epidermal development elements [3,10]. (
  • Functioning as a classic cadherin by imparting to cells the ability to adhere in a homophilic manner, the protein may play an important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions. (
  • Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. (
  • Recently, it has become apparent that regulatory mechanisms exist to influence where and when protein kinases and phosphatases are activated in the cell. (
  • Yet, understanding the mechanisms that allow intracellular signals to be relayed from the cell membrane to specific intracellular targets still remains a daunting challenge. (
  • Hence, the cell uses related mechanisms for controlling the subcellular organization of tyrosine and Ser-Thr phosphorylation events. (
  • 13. The method of claim 12 wherein the quantitative immunoassay comprises an enzyme-linked immunosorbent assay (ELISA), specific analyte labeling and recapture assay (SALRA), liquid chromatography, mass spectrometry, fluorescence-activated cell sorting, or a combination thereof. (
  • Laminin-1 is an important component of the basement membrane and is involved in epithelial cell adhesion and polarization ( 9 ). (
  • Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. (
  • The tyrosine phosphorylation is assumed to play roles in spermatogenesis because this process is important for cell proliferations, divisions, and differentiations. (
  • We previously identified a C-type lectin in Aedes aegypti , designated as mosquito galactose specific C-type lectin-1 ( mosGCTL-1 ), facilitating the attachment of West Nile virus (WNV) on the cell membrane. (
  • Akt promotes cell survival by inhibiting apoptosis through phosphorylation and by inactivation of several targets, including Bad, forkhead transcription factor, c-Raf and caspase-9. (
  • We report here the cloning and embryonic expression of Lena, the leech homolog of Enabled, a cytosolic protein implicated in actin-based cell motility. (
  • Since T-cells play a key role in the onset of several inflammatory diseases, we have evaluated the immunosuppressive activity of CAPE in human T-cells, discovering that this phenolic compound is a potent inhibitor of early and late events in T-cell receptor-mediated T-cell activation. (
  • Inside the cell, HMGB1 is a highly conserved chromosomal protein acting as a DNA chaperone. (
  • Mitochondrial membrane permeabilization in cell death. (
  • Moreover, in a yeast genetic screen, three mitochondrial proteins Mrx9, Mrm1, and Aim19 that increase mitochondrial biogenesis were identified as high copy suppressors of ER stress-mediated cell death. (
  • It has been reported that LIF activates the AKT pathway in several different cell types, including human embryonic kidney 293T, liver Hep3B, and oligodendrocytes [7, 27]. (
  • The Wee1 class of protein-tyrosine kinase has an important role in cell cycle control. (
  • A considerable effort is underway to understand the roles of other classes of protein kinases and additional post-translational modifications in septin complex assembly, formation of different septin-based supramolecular ensembles, disassembly of septin-containing structures, and the function of septin organization in the events required for cell division and membrane septation during cytokinesis. (
  • Phosphorylation is the most common mechanism of regulating protein function and transmitting signals throughout the cell. (
  • These two families of enzymes facilitate the dynamic nature of phosphorylated proteins in a cell. (
  • Indeed, the size of the phosphoproteome in a given cell is dependent upon the temporal and spatial balance of kinase and phosphatase concentrations in the cell and the catalytic efficiency of a particular phosphorylation site. (
  • Prominent examples of this type of vaccine based on undefined antigen are intact cells, cell lysate, total (amplified) RNA vaccines and heat-shock proteins. (
  • The tau hypothesis (Boutajangout & Wisniewski, 2014) proposes that hyperphosphorylated tau proteins form neurofibrillary tangles inside the nerve cell bodies, causing microtubules to disintegrate, collapsing the neuron's transport system. (
  • Species diversity in the structure of zonadhesin, a sperm-specific membrane protein containing multiple cell adhesion molecule-like domains. (
  • Although actin-rich membrane protrusions form in these cell lines, they recede without forming macropinosomes. (
  • Downregulation of SCRIB expression in a macrophage cell line, RAW 264.7, significantly impaired phorbol 12-myristate 13-acetate (PMA)-induced generation of ROS. (
  • 7. Matthews W,Jordan CT,Wiegand GW,Pardoll D,Lemischka IR A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations. (
  • Its most likely mechanism of action is activation of intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface. (
  • 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. (
  • Notch genes encode conserved transmembrane receptors, as well as the DSL ligands may also be membrane destined. (
  • The three human RAS genes encode four highly identical proteins (83 to 85% identity): HRAS, NRAS, and KRAS4A and KRAS4B, with KRAS encoding splice variants due to alternative exon 4 utilization. (
  • 2]. indicated that many PTP genes had been encoded inside the individual genome, including trans-membrane, receptor-like, and intracellular, non receptor-like enzymes. (
  • Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion (By similarity). (
  • Overall, we estimate that 58 % of the dataset has a known association to disease conditions with 19 % of the genes possibly involved in different types of cancer. (
  • Estas interações proteína-proteína são fundamentais para transmitir o sinal do receptor em direção ao efeito celular final, tais como translocação de vesículas contendo transportadores de glicose (GLUT4) do pool intracelular para a membrana plasmática, ativação da síntese de glicogênio e de proteínas, e transcrição de genes específicos. (
  • We show that, at drug concentrations routinely achieved clinically in human plasma, atovaquone inhibits STAT3 phosphorylation, the expression of STAT3 target genes, and the viability of STAT3-dependent hematological cancer cells. (
  • A family of growth regulators (originally called cef10, connective tissue growth factor, fisp-12, cyr61, or, alternatively, beta IG-M1 and beta IG-M2), all belong to immediate-early genes expressed after induction by growth factors or certain oncogenes. (
  • Many protein kinases and protein phosphatases have relatively broad substrate specificities and may be used in varying combinations to achieve distinct biological responses. (
  • Alternative transcripts of protein kinases and protein phosphatases are known to encode peptides with altered substrate affinities, subcellular localizations, and activities. (
  • Caspase-8-mediated cleavage of Bid and protein phosphatase 2A-mediated activation of Bax are necessary for Verotoxin-1-induced apoptosis in Burkitt's lymphoma cells. (
  • Apoptosis is a biological process carried out during maturation, remodeling, growth, and developmental processes in tissues, and also represents an important defense mechanism of cells against intracellular microorganisms. (
  • In counterpart, diverse intracellular pathogens have developed a wide array of strategies to evade apoptosis and persist inside cells. (
  • We now report the consequences of sustained activation of Lyn in vivo using a targeted gain-of-function mutation (Lyn up/up mice). (
  • They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. (
  • Furthermore, PMA-induced activation of LFA-1 on DA-ER cells overexpressing wild-type SHIP was dependent on protein kinase C but independent of mitogen-activated protein kinase activation, whereas cytokine-induced activation was independent of protein kinase C and mitogen-activated protein kinase activation but required phosphatidylinositol-3 kinase activation. (
  • The results show that overexpression of a phosphatase active, but not inactive, SHIP enhances the activation of LFA-1 in both resting and stimulated cells. (
  • Furthermore, PMA-induced activation of LFA-1 on cells overexpressing SHIP is regulated by protein kinase C (PKC), whereas erythropoietin (Epo)- or IL-3-induced activation of LFA-1 involves a phosphatidylinositol-3 kinase (PI-3K) regulated pathway. (
  • Previous reports indicated that LPS-induced mitogen-activated protein kinase activation is down-regulated by phosphatidylinositol 3-kinase through the activation of Akt. (
  • FcγRI and IIIa are activating receptors, and are associated with low m.w. γ-subunit homodimers, which contain an immunoreceptor tyrosine-based activation motif (ITAM). (
  • The role of the nonmutated, wild-type RAS proteins in the context of mutant RAS is increasingly considered to be targetable, with reports of strategies that directly disrupt either the RAS interaction with activating guanine nucleotide exchange factors (GEFs) or receptor tyrosine kinase-mediated and GEF-dependent RAS activation (such as by targeting the scaffolding phosphatase SHP2). (
  • Nonisotopic Methods for Detecting Activation of Small G Proteins. (
  • Activation of PI3K by phosphorylated IRS-1 also stimulates glycogen synthase, via a process that involves activation of protein kinases B/Akt and subsequent inhibition of kinase such as GSK3 and activation of protein phosphatase-1 [89]. (
  • Continuous basal repression of MAPKs by phosphatases occurs and may poise a pathway for activation above a particular threshold. (
  • Genetic experiments in Drosophila ( 11 ) and Caenorhabditis elegans ( 12 ) and biochemical experiments in vertebrates ( 10 ) have shown that Shp2 acts upstream of the Ras/MAP kinase pathway to promote its activation. (
  • In mast cells, activation of PI3K by tyrosine kinase receptors, like platelet-derived growth factor receptor, increases the affinity of α 5 β 1 ( 16 ). (
  • This kinase is ubiquitously expressed and translocates to the membrane upon activation. (
  • Recently, new evidence has accumulated showing the existence of several novel receptor interacting proteins and various angiotensin II receptor activation mechanisms beyond the classical actions of receptors for Ang II. (
  • Receptor dimerization of Ang II receptors such as homodimer, heterodimer, and complex formation with other G protein-coupled receptors has also been focused on as a new mechanism of their activation or inactivation. (
  • In collaboration with Mark Lemmon, we are trying to understand the relationship between oligomerization of Tie receptors and receptor activation state. (
  • Abnormal Ras activation in csg2Δ cells is associated with impaired Snf1/AMPK protein kinase, a key regulator of energy homeostasis. (
  • Activation of the receptor-coupled G protein initiates a four-tiered cascade of protein kinases, ultimately resulting in stimulation of a messenger-activated protein kinase or MAPK (Fus3) that translocates into the nucleus. (
  • There is evidence of increased activation under resting and stimulated conditions in microglia prepared from CD200-deficient mice compared with wild-type mice, whereas activation of the receptor by CD200 fusion protein (CD200Fc) ameliorates inflammatory changes which are evident in the central nervous system (CNS) of the mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) and also in the hippocampus of aged rats. (
  • Another neuroprotective protein induced by ERK activation is cyclic AMP response element-binding protein (CREB). (
  • Anti-phospho-mitogen-activated protein kinase (MAPK) Abs were obtained from New England Biolabs (Mississauga, Ontario, Canada), anti-Erk-1-CT Abs were obtained from Upstate Biotechnology (Lake Placid, NY), and anti-Raf-1 Abs were obtained from Santa Cruz Biotechnology (Santa Cruz, CA). The generation of the N-terminal-specific anti-SHIP Ab was described ( 19 ). (
  • Second, whereas potent and selective inhibitors of the RAF-MEK-ERK mitogen-activated protein kinase (MAPK) cascade have been developed to block this key RAS effector pathway, the development and efficacy of MEK inhibitors have been limited by resistance caused by the relief of ERK-mediated feedback inhibition, leading to compensatory reactivation of ERK. (
  • Some seven-transmembrane helix proteins ( channelrhodopsin ) that resemble GPCRs may contain ion channels, within their protein. (
  • When compared to the well-characterized seven-transmembrane containing proteins (7TM), other TM groups are less explored and in particular the 4TM group. (
  • Containing adeath domain and a ZU5 domain, ZUD plays a role in the inhibition of NFB-dependenttranscription by inhibiting the binding of NFB to its target, interacting specifically with NFBsubunits p65 and p50. (
  • Inhibition of phosphorylation of these targets has proven their crucial role in disease-evolution in both malignancies. (
  • [0003] The use of single-domain antibodies (sdAbs) as single antigen-binding proteins or as an antigen-binding domain in larger protein or polypeptide offers a number of significant advantages over the use of conventional antibodies or antibody fragments. (
  • Kinase enzymes that specifically phosphorylate tyrosine amino acids are termed tyrosine kinases. (
  • In addition, the other identified mosGCTLs interacted with the DENV-2 E protein, indicating that DENV may employ multiple mosGCTLs as ligands to promote the infection of vectors. (
  • Nucleic acid aptamers are short, single-stranded RNAs and DNAs that represent high-affinity and highly selective ligands for different targets, ranging from large proteins to peptides, nucleotides, drugs and small compounds, and even metal ions. (
  • The human alpha-synuclein protein is made of 140 amino acids, encoded by the SNCA gene. (
  • The most common form of the protein, is the full 140 amino acid-long transcript. (
  • Resumo em inglês The amino acids composition of the muscle tissue of pintado (Pseudoplatystoma corruscans) was determined with basis on the ideal protein concept. (
  • LepR intracellular domains diverge beyond the first 29 intracellular amino acids, however, with the so-called "short" isoforms (e.g. (
  • LepRa) containing an additional 3-10 amino acids, and the single "long" isoforms (LepRb) containing a 300-amino acid intracellular tail ( 10 ). (
  • the amino and carboxyl terminal domains are intracellular. (
  • Now, Greengard, Gouras, and colleagues reveal that β-amyloid-the toxic peptide which accumulates in AD-exerts an unexpected influence over the abundance of both primary types of neurotransmitter at excitatory synapses: the AMPA- and NMDA-type glutamate receptors. (
  • study demonstrates a specific loss of surface NMDA glutamate receptors in cortical neurons exposed to Aβ. (
  • In one project, we are analyzing the roles of membrane-proximal fibronectin type III (FNIII) domains (found in 23/58 RTKs, including Tie2). (
  • Both IA-2 and phogrin associate with the cytoskeleton, and direct interaction with the cytoskeletal-associated proteins βIV spectrin and β2-syntrophin has been demonstrated for IA-2 ( 10 , 11 ). (
  • May act at junctions between the membrane and the cytoskeleton. (
  • Incubate the membrane with HRP-conjugated goat anti-mouse IgM secondary antibody at room temperature for 35 min. (
  • E. chaffeensis TRPs are major immunoreactive proteins that elicit strong host antibody responses during infection. (
  • The anti-KIR/p70 antibody Z27 restores the ability of p70+ NK clones to lyse HLA-Bw4 targets. (
  • The cells are lysed on-chip, and the levels of released proteins are assayed using the antibody arrays. (
  • The SCBC is simple in concept: A single or defined number of cells is isolated within an approximately 2 nL volume microchamber that contains an antibody array ( 10 ) for the capture and detection of a panel of proteins. (
  • An antibody to the intracellular domain of Ptprq, anti-Ptprq, stains hair bundles in mice and chicks. (
  • If you cannot find the target and/or product is not available in our catalog, please click here to contact us and request the product or submit your request for custom elisa kit production , custom recombinant protein production or custom antibody production . (
  • PI(3,4,5)P3 and PI(3,4)P2 lead to the stimulation of glucose transport [12,84-88]. (
  • The majority of well-known Ang II actions are mediated via AT 1 receptor stimulation, and angiotensin converting enzyme inhibitors (ACEI) and AT 1 receptor blockers (ARBs) have been widely used as antihypertensive drugs, with the expectation of cardiovascular protective effects. (
  • AT 2 receptor stimulation by unbound Ang II could also be expected during treatment with ARBs. (
  • Clinically important could be that AngII can bind to AngII type 2 (AT 2 ) receptors and AngIV to AT 4 receptors that are not antagonized by sartanes, inducing proinflammatory and profibrotic effects ( e.g. , induction of chemokines, stimulation of plasminogen activator inhibitor-1). (
  • Both PMA and lipopolysaccharide (LPS) induced ROS in wild-type cells and in SCRIB ishRNA cells in the absence of Dox stimulation. (
  • Proteolysis of PTPμ generates a series of proteolytic fragments, including a soluble catalytic intracellular domain fragment that translocates to the nucleus. (
  • The intracellular C terminal region displays the highest level of conservation and comprises catalytic domains responsible for the kinase activity of these receptors, which catalyses receptor autophosphorylation and tyrosine phosphorylation of RTK substrates. (
  • Twelve of the 21 PTPRs have two catalytic domains arranged in tandem. (
  • The catalytic activity mainly resides in the membrane-proximal domain (D1) for many PTPRs with the exception of PTPRA, whose membrane-distal domain (D2) also has some activities[ 5 ]. (
  • The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. (
  • Expression, Purification, and Assay of Cytosolic (Catalytic) Domains of Membrane-Bound Mammalian Adenylyl Cyclases. (
  • Active MAPKs frequently translocate from the cytoplasm to the nucleus to phosphorylate nuclear targets, and MAPKKs can shuttle in and out of the nucleus carrying the MAPK as a passenger and anchor them in the cytoplasm. (
  • Although the kinases that phosphorylate the Y705 residue of STAT3 are well defined in epithelial and hematopoietic cells, the phosphatases that specifically dephosphorylate pY705 have received little attention. (
  • Protein phosphorylation is a reversible PTM that is mediated by kinases and phosphatases, which phosphorylate and dephosphorylate substrates, respectively. (
  • PTEN (phosphatase and tensin homolog deleted on chromosome ten) was cloned as a tumor suppressor for gliomas in 1997 [ 9 ] and has been identified to be involved in most tumorigenesis. (
  • In this study, we have examined the role of the inositol 3-phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in FcγR-induced macrophage function. (
  • However, PTEN did not seem to influence tyrosine phosphorylation events induced by FcγR clustering. (
  • Liberated Notch intracellular buy Meisoindigo domains translocates in to the nucleus where it associates using the transcriptional regulator C-promoter binding aspect 1/suppressor of hairless/Lag-1 (CSL) to market Notch focus on gene transcription (13). (
  • The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. (
  • PTPN4 (Protein Tyrosine Phosphatase, Non-Receptor Type 4) is a Protein Coding gene. (
  • GO annotations related to this gene include phosphatase activity and cytoskeletal protein binding . (
  • 6. Mackarehtschian K,Hardin JD,Moore KA,Boast S,Goff SP,Lemischka IR Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors. (
  • Assays and Characterization of Mammalian Phosphatidylinositol 4,5-Bisphosphate-Sensitive Phospholipase D. Characterization and Purification of Phosphatidylinositol Trisphosphate 5-Phosphatase from Rat Brain Tissues. (
  • This cleavage is mediated by a furin-like protease in the endoplasmic reticulum during intracellular trafficking ( 21 ). (
  • The protein tyrosine phosphatase (PTP) Shp2 (PTPN11) is mutated in human disease. (
  • The presence of activated or up-regulated Shp2 protein ( 5 ) in human cancers and other disease makes Shp2 an excellent target for generating interfering substances ( 6 ). (
  • Several direct targets of Shp2 have been identified, including the platelet-derived growth factor receptors [PDGFR ( 13 )/Torso ( 14 )], the multiadaptor protein Gab1 ( 15 ), Csk-binding protein [Cbp/PAG ( 16 )], and paxillin ( 17 ). (
  • Also known as Tyrosine-protein phosphatase non-receptor type 11 (Protein-tyrosine phosphatase 1D) (PTP-1D) (Protein-tyrosine phosphatase 2C) (PTP-2C) (SH-PTP2) (SHP-2) (Shp2) (SH-PTP3). (
  • We determined that inhibitors of tyrosine protein kinases, dynamin GTPase and actin dynamics had little effect on binding of virions to cells but impaired membrane fusion, whereas partial cholesterol depletion and inhibitors of endosomal acidification and membrane blebbing had a severe effect at the later stage of core entry. (
  • The monoclonal anti-phosphotyrosine (clone 4G10) was used to probe tyrosine phosphorylated proteins and also to examine the expression of such proteins using immuno-Western blotting in rat testis. (
  • study, cultured primary neurons from the well-studied Tg2576 AD mouse model were used to demonstrate both presynaptic (reduced synaptophysin protein levels) and postsynaptic (reduced AMPA glutamate receptor subunit and PSD-95 protein levels, general reduction in dendritic spines) deficits. (
  • Targeted disruption of the β 1 integrin subunit, lethal to embryonic development, has indicated a requirement for this receptor in the proper assembly and subsequent function of embryonic basement membrane ( 20 ). (
  • Given that the mTOR pathway is deregulated in a number of cancers, it is anticipated that mTOR inhibitors will have broad therapeutic application across many tumor types. (
  • The previously elusive PDK2, responsible for phosphorylation of Akt at Ser473, has been identified as a mammalian target of rapamycin (mTOR) in a rapamycin-insensitive complex with rictor and Sin1. (
  • It is currently unclear whether LIF activates the AKT-mTOR pathway to promote tumorigenesis and metastasis in other types of cancers. (