GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.rac GTP-Binding Proteins: A sub-family of RHO GTP-BINDING PROTEINS that is involved in regulating the organization of cytoskeletal filaments. This enzyme was formerly listed as EC 3.6.1.47.GTP Phosphohydrolases: Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.rac1 GTP-Binding Protein: A rac GTP-binding protein involved in regulating actin filaments at the plasma membrane. It controls the development of filopodia and lamellipodia in cells and thereby influences cellular motility and adhesion. It is also involved in activation of NADPH OXIDASE. This enzyme was formerly listed as EC 3.6.1.47.Guanosine Diphosphate: A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Monomeric GTP-Binding Proteins: A class of monomeric, low molecular weight (20-25 kDa) GTP-binding proteins that regulate a variety of intracellular processes. The GTP bound form of the protein is active and limited by its inherent GTPase activity, which is controlled by an array of GTPase activators, GDP dissociation inhibitors, and guanine nucleotide exchange factors. This enzyme was formerly listed as EC 3.6.1.47Guanosine 5'-O-(3-Thiotriphosphate): Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.rab GTP-Binding Proteins: A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. EC 3.6.1.-.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.ADP-Ribosylation Factors: MONOMERIC GTP-BINDING PROTEINS that were initially recognized as allosteric activators of the MONO(ADP-RIBOSE) TRANSFERASE of the CHOLERA TOXIN catalytic subunit. They are involved in vesicle trafficking and activation of PHOSPHOLIPASE D. This enzyme was formerly listed as EC 3.6.1.47Pertussis Toxin: One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.rho GTP-Binding Proteins: A large family of MONOMERIC GTP-BINDING PROTEINS that are involved in regulation of actin organization, gene expression and cell cycle progression. This enzyme was formerly listed as EC 3.6.1.47.Virulence Factors, Bordetella: A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.ADP Ribose Transferases: Enzymes that transfer the ADP-RIBOSE group of NAD or NADP to proteins or other small molecules. Transfer of ADP-ribose to water (i.e., hydrolysis) is catalyzed by the NADASES. The mono(ADP-ribose)transferases transfer a single ADP-ribose. POLY(ADP-RIBOSE) POLYMERASES transfer multiple units of ADP-ribose to protein targets, building POLY ADENOSINE DIPHOSPHATE RIBOSE in linear or branched chains.Botulinum Toxins: Toxic proteins produced from the species CLOSTRIDIUM BOTULINUM. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon ENDOCYTOSIS into PRESYNAPTIC NERVE ENDINGS. Once inside the cell the botulinum toxin light chain cleaves specific SNARE proteins which are essential for secretion of ACETYLCHOLINE by SYNAPTIC VESICLES. This inhibition of acetylcholine release results in muscular PARALYSIS.Adenosine Diphosphate Ribose: An ester formed between the aldehydic carbon of RIBOSE and the terminal phosphate of ADENOSINE DIPHOSPHATE. It is produced by the hydrolysis of nicotinamide-adenine dinucleotide (NAD) by a variety of enzymes, some of which transfer an ADP-ribosyl group to target proteins.Thionucleotides: Nucleotides in which the base moiety is substituted with one or more sulfur atoms.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Guanine Nucleotide Exchange Factors: Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.GTPase-Activating Proteins: Proteins that activate the GTPase of specific GTP-BINDING PROTEINS.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.rhoA GTP-Binding Protein: A RHO GTP-BINDING PROTEIN involved in regulating signal transduction pathways that control assembly of focal adhesions and actin stress fibers. This enzyme was formerly listed as EC 3.6.1.47.ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Poly(A)-Binding Proteins: Proteins that bind to the 3' polyadenylated region of MRNA. When complexed with RNA the proteins serve an array of functions such as stabilizing the 3' end of RNA, promoting poly(A) synthesis and stimulating mRNA translation.NADPH Dehydrogenase: A flavoprotein that reversibly oxidizes NADPH to NADP and a reduced acceptor. EC 1.6.99.1.Kinetics: The rate dynamics in chemical or physical systems.p21-Activated Kinases: A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.NADPH Oxidase: A flavoprotein enzyme that catalyzes the univalent reduction of OXYGEN using NADPH as an electron donor to create SUPEROXIDE ANION. The enzyme is dependent on a variety of CYTOCHROMES. Defects in the production of superoxide ions by enzymes such as NADPH oxidase result in GRANULOMATOUS DISEASE, CHRONIC.Cattle: 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.GTP Cyclohydrolase: (GTP cyclohydrolase I) or GTP 7,8-8,9-dihydrolase (pyrophosphate-forming) (GTP cyclohydrolase II). An enzyme group that hydrolyzes the imidazole ring of GTP, releasing carbon-8 as formate. Two C-N bonds are hydrolyzed and the pentase unit is isomerized. This is the first step in the synthesis of folic acid from GTP. EC 3.5.4.16 (GTP cyclohydrolase I) and EC 3.5.4.25 (GTP cyclohydrolase II).Tacrolimus Binding Proteins: A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS. EC 5.2.1.-Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Guanine NucleotidesHydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Poly(A)-Binding Protein I: A poly(A) binding protein that has a variety of functions such as mRNA stabilization and protection of RNA from nuclease activity. Although poly(A) binding protein I is considered a major cytoplasmic RNA-binding protein it is also found in the CELL NUCLEUS and may be involved in transport of mRNP particles.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Guanylyl Imidodiphosphate: A non-hydrolyzable analog of GTP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It binds tightly to G-protein in the presence of Mg2+. The nucleotide is a potent stimulator of ADENYLYL CYCLASES.Insulin-Like Growth Factor Binding Proteins: A family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (Int J Gynaecol Obstet 1992;39(1):3-9)Recombinant Proteins: Proteins prepared by recombinant DNA technology.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Cell Line: Established cell cultures that have the potential to propagate indefinitely.RNA-Binding Proteins: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.Escherichia coli: 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.cdc42 GTP-Binding Protein: A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions including cytoskeletal changes, filopodia formation and transport through the GOLGI APPARATUS. This enzyme was formerly listed as EC 3.6.1.47.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Fatty Acid-Binding Proteins: Intracellular proteins that reversibly bind hydrophobic ligands including: saturated and unsaturated FATTY ACIDS; EICOSANOIDS; and RETINOIDS. They are considered a highly conserved and ubiquitously expressed family of proteins that may play a role in the metabolism of LIPIDS.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Guanosine Monophosphate: A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.Peptide Elongation Factor Tu: A protein found in bacteria and eukaryotic mitochondria which delivers aminoacyl-tRNA's to the A site of the ribosome. The aminoacyl-tRNA is first bound to a complex of elongation factor Tu containing a molecule of bound GTP. The resulting complex is then bound to the 70S initiation complex. Simultaneously the GTP is hydrolyzed and a Tu-GDP complex is released from the 70S ribosome. The Tu-GTP complex is regenerated from the Tu-GDP complex by the Ts elongation factor and GTP.Transglutaminases: Transglutaminases catalyze cross-linking of proteins at a GLUTAMINE in one chain with LYSINE in another chain. They include keratinocyte transglutaminase (TGM1 or TGK), tissue transglutaminase (TGM2 or TGC), plasma transglutaminase involved with coagulation (FACTOR XIII and FACTOR XIIIa), hair follicle transglutaminase, and prostate transglutaminase. Although structures differ, they share an active site (YGQCW) and strict CALCIUM dependence.Transducin: A heterotrimeric GTP-binding protein that mediates the light activation signal from photolyzed rhodopsin to cyclic GMP phosphodiesterase and is pivotal in the visual excitation process. Activation of rhodopsin on the outer membrane of rod and cone cells causes GTP to bind to transducin followed by dissociation of the alpha subunit-GTP complex from the beta/gamma subunits of transducin. The alpha subunit-GTP complex activates the cyclic GMP phosphodiesterase which catalyzes the hydrolysis of cyclic GMP to 5'-GMP. This leads to closure of the sodium and calcium channels and therefore hyperpolarization of the rod cells. EC 3.6.1.-.Bacterial Proteins: Proteins found in any species of bacterium.Poly(A)-Binding Protein II: A poly(A) binding protein that is involved in promoting the extension of the poly A tails of MRNA. The protein requires a minimum of ten ADENOSINE nucleotides in order for binding to mRNA. Once bound it works in conjunction with CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR to stimulate the rate of poly A synthesis by POLY A POLYMERASE. Once poly-A tails reach around 250 nucleotides in length poly(A) binding protein II no longer stimulates POLYADENYLATION. Mutations within a GCG repeat region in the gene for poly(A) binding protein II have been shown to cause the disease MUSCULAR DYSTROPHY, OCULOPHARYNGEAL.ADP-Ribosylation Factor 1: ADP-RIBOSYLATION FACTOR 1 is involved in regulating intracellular transport by modulating the interaction of coat proteins with organelle membranes in the early secretory pathway. It is a component of COAT PROTEIN COMPLEX I. This enzyme was formerly listed as EC 3.6.1.47.Peptide Elongation Factor G: Peptide Elongation Factor G catalyzes the translocation of peptidyl-tRNA from the A to the P site of bacterial ribosomes by a process linked to hydrolysis of GTP to GDP.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.GTP Phosphohydrolase-Linked Elongation Factors: Factors that utilize energy from the hydrolysis of GTP to GDP for peptide chain elongation. EC 3.6.1.-.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Dynamins: A family of high molecular weight GTP phosphohydrolases that play a direct role in vesicle transport. They associate with microtubule bundles (MICROTUBULES) and are believed to produce mechanical force via a process linked to GTP hydrolysis. This enzyme was formerly listed as EC 3.6.1.50.Proto-Oncogene Proteins p21(ras): Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC 3.6.1.47.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Insulin-Like Growth Factor Binding Protein 3: One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Molecular Weight: The sum of the weight of all the atoms in a molecule.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.Periplasmic Binding Proteins: Periplasmic proteins that scavenge or sense diverse nutrients. In the bacterial environment they usually couple to transporters or chemotaxis receptors on the inner bacterial membrane.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Adenylosuccinate Synthase: A carbon-nitrogen ligase. During purine ribonucleotide biosynthesis, this enzyme catalyzes the synthesis of adenylosuccinate from GTP; IMP; and aspartate with the formation of orthophosphate and GDP. EC 6.3.4.4.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Peptide Elongation Factors: Protein factors uniquely required during the elongation phase of protein synthesis.Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.rab5 GTP-Binding Proteins: A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in transport from the cell membrane to early endosomes. This enzyme was formerly listed as EC 3.6.1.47.Tacrolimus Binding Protein 1A: A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Ribosomes: Multicomponent ribonucleoprotein structures found in the CYTOPLASM of all cells, and in MITOCHONDRIA, and PLASTIDS. They function in PROTEIN BIOSYNTHESIS via GENETIC TRANSLATION.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Latent TGF-beta Binding Proteins: A family of secreted multidomain proteins that were originally identified by their association with the latent form of TRANSFORMING GROWTH FACTORS. They interact with a variety of EXTRACELLULAR MATRIX PROTEINS and may play a role in the regulation of TGB-beta bioavailability.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Oncogene Protein p21(ras): Transforming protein encoded by ras oncogenes. Point mutations in the cellular ras gene (c-ras) can also result in a mutant p21 protein that can transform mammalian cells. Oncogene protein p21(ras) has been directly implicated in human neoplasms, perhaps accounting for as much as 15-20% of all human tumors. This enzyme was formerly listed as EC 3.6.1.47.rab2 GTP-Binding Protein: A protein involved in transport between the ENDOPLASMIC RETICULUM and the GOLGI APPARATUS. This enzyme was formerly listed as EC 3.6.1.47.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Affinity Labels: Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Insulin-Like Growth Factor Binding Protein 2: One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Septins: A family of GTP-binding proteins that were initially identified in YEASTS where they were shown to initiate the process of septation and bud formation. Septins form into hetero-oligomeric complexes that are comprised of several distinct septin subunits. These complexes can act as cytoskeletal elements that play important roles in CYTOKINESIS, cytoskeletal reorganization, BIOLOGICAL TRANSPORT, and membrane dynamics.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.TATA-Box Binding Protein: A general transcription factor that plays a major role in the activation of eukaryotic genes transcribed by RNA POLYMERASES. It binds specifically to the TATA BOX promoter element, which lies close to the position of transcription initiation in RNA transcribed by RNA POLYMERASE II. Although considered a principal component of TRANSCRIPTION FACTOR TFIID it also takes part in general transcription factor complexes involved in RNA POLYMERASE I and RNA POLYMERASE III transcription.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Saccharomyces cerevisiae Proteins: 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.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Insulin-Like Growth Factor Binding Protein 1: One of the six homologous proteins that specifically bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions. The function of this protein is not completely defined. However, several studies demonstrate that it inhibits IGF binding to cell surface receptors and thereby inhibits IGF-mediated mitogenic and cell metabolic actions. (Proc Soc Exp Biol Med 1993;204(1):4-29)Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Cyclic AMP Response Element-Binding Protein: A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.Actins: 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.rab3 GTP-Binding Proteins: A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in calcium-dependent EXOCYTOSIS. This enzyme was formerly listed as EC 3.6.1.47.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Retinol-Binding Proteins: Proteins which bind with RETINOL. The retinol-binding protein found in plasma has an alpha-1 mobility on electrophoresis and a molecular weight of about 21 kDa. The retinol-protein complex (MW=80-90 kDa) circulates in plasma in the form of a protein-protein complex with prealbumin. The retinol-binding protein found in tissue has a molecular weight of 14 kDa and carries retinol as a non-covalently-bound ligand.CREB-Binding Protein: A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.S100 Calcium Binding Protein G: A calbindin protein found in many mammalian tissues, including the UTERUS, PLACENTA, BONE, PITUITARY GLAND, and KIDNEYS. In intestinal ENTEROCYTES it mediates intracellular calcium transport from apical to basolateral membranes via calcium binding at two EF-HAND MOTIFS. Expression is regulated in some tissues by VITAMIN D.Cholera Toxin: An ENTEROTOXIN from VIBRIO CHOLERAE. It consists of two major protomers, the heavy (H) or A subunit and the B protomer which consists of 5 light (L) or B subunits. The catalytic A subunit is proteolytically cleaved into fragments A1 and A2. The A1 fragment is a MONO(ADP-RIBOSE) TRANSFERASE. The B protomer binds cholera toxin to intestinal epithelial cells, and facilitates the uptake of the A1 fragment. The A1 catalyzed transfer of ADP-RIBOSE to the alpha subunits of heterotrimeric G PROTEINS activates the production of CYCLIC AMP. Increased levels of cyclic AMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.PhosphoproteinsCytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.CCAAT-Enhancer-Binding Proteins: A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.Cross-Linking Reagents: Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Peptide Termination Factors: Proteins that are involved in the peptide chain termination reaction (PEPTIDE CHAIN TERMINATION, TRANSLATIONAL) on RIBOSOMES. They include codon-specific class-I release factors, which recognize stop signals (TERMINATOR CODON) in the MESSENGER RNA; and codon-nonspecific class-II release factors.Vitamin D-Binding Protein: An alpha-globulin found in the plasma of man and other vertebrates. It is apparently synthesized in the liver and carries vitamin D and its metabolites through the circulation and mediates the response of tissue. It is also known as group-specific component (Gc). Gc subtypes are used to determine specific phenotypes and gene frequencies. These data are employed in the classification of population groups, paternity investigations, and in forensic medicine.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.Polypyrimidine Tract-Binding Protein: A RNA-binding protein that binds to polypyriminidine rich regions in the INTRONS of messenger RNAs. Polypyrimidine tract-binding protein may be involved in regulating the ALTERNATIVE SPLICING of mRNAs since its presence on an intronic RNA region that is upstream of an EXON inhibits the splicing of the exon into the final mRNA product.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.ran GTP-Binding Protein: A monomeric GTP-binding protein involved in nucleocytoplasmic transport of proteins into the nucleus and RNA into the cytoplasm. This enzyme was formerly listed as EC 3.6.1.47.Fungal Proteins: Proteins found in any species of fungus.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Biological Transport: 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.Insulin-Like Growth Factor Binding Protein 4: One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.Insulin-Like Growth Factor Binding Protein 5: One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Nucleotides: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)Protein Structure, Secondary: 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.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Sterol Regulatory Element Binding Protein 1: A sterol regulatory element binding protein that regulates expression of GENES involved in FATTY ACIDS metabolism and LIPOGENESIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.Rabbits: 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.Dynamin I: A subtype of dynamin found primarily in the NEURONS of the brain.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Peptide Elongation Factor 2: Peptide Elongation Factor 2 catalyzes the translocation of peptidyl-tRNA from the A site to the P site of eukaryotic ribosomes by a process linked to the hydrolysis of GTP to GDP.Subcellular Fractions: 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)Protein Prenylation: A post-translational modification of proteins by the attachment of an isoprenoid to the C-terminal cysteine residue. The isoprenoids used, farnesyl diphosphate or geranylgeranyl diphosphate, are derived from the same biochemical pathway that produces cholesterol.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Endoplasmic Reticulum: 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)GTP-Binding Protein alpha Subunits, Gi-Go: A family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.RGS Proteins: A large family of evolutionarily conserved proteins that function as negative regulators of HETEROTRIMERIC GTP-BINDING PROTEINS. RGS PROTEINS act by increasing the GTPase activity of the G alpha subunit of a heterotrimeric GTP-binding protein, causing it to revert to its inactive (GDP-bound) form.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Insulin-Like Growth Factor I: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.Nerve Tissue ProteinsGTP-Binding Protein alpha Subunits: The GTPase-containing subunits of heterotrimeric GTP-binding proteins. When dissociated from the heterotrimeric complex these subunits interact with a variety of second messenger systems. Hydrolysis of GTP by the inherent GTPase activity of the subunit causes it to revert to its inactive (heterotrimeric) form. The GTP-Binding protein alpha subunits are grouped into families according to the type of action they have on second messenger systems.Maltose-Binding Proteins: Periplasmic proteins that bind MALTOSE and maltodextrin. They take part in the maltose transport system of BACTERIA.Heterogeneous-Nuclear Ribonucleoproteins: A family of ribonucleoproteins that were originally found as proteins bound to nascent RNA transcripts in the form of ribonucleoprotein particles. Although considered ribonucleoproteins they are primarily classified by their protein component. They are involved in a variety of processes such as packaging of RNA and RNA TRANSPORT within the nucleus. A subset of heterogeneous-nuclear ribonucleoproteins are involved in additional functions such as nucleocytoplasmic transport (ACTIVE TRANSPORT, CELL NUCLEUS) of RNA and mRNA stability in the CYTOPLASM.Cell Fractionation: Techniques to partition various components of the cell into SUBCELLULAR FRACTIONS.Spectrometry, Fluorescence: Measurement of the intensity and quality of fluorescence.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Photoreceptor Cells: Specialized cells that detect and transduce light. They are classified into two types based on their light reception structure, the ciliary photoreceptors and the rhabdomeric photoreceptors with MICROVILLI. Ciliary photoreceptor cells use OPSINS that activate a PHOSPHODIESTERASE phosphodiesterase cascade. Rhabdomeric photoreceptor cells use opsins that activate a PHOSPHOLIPASE C cascade.Signal Recognition Particle: A cytosolic ribonucleoprotein complex that acts to induce elongation arrest of nascent presecretory and membrane proteins until the ribosome becomes associated with the rough endoplasmic reticulum. It consists of a 7S RNA and at least six polypeptide subunits (relative molecular masses 9, 14, 19, 54, 68, and 72K).Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Trypsin: A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Somatomedins: Insulin-like polypeptides made by the liver and some fibroblasts and released into the blood when stimulated by SOMATOTROPIN. They cause sulfate incorporation into collagen, RNA, and DNA synthesis, which are prerequisites to cell division and growth of the organism.Ribonucleoproteins: Complexes of RNA-binding proteins with ribonucleic acids (RNA).Retinol-Binding Proteins, Cellular: A subclass of retinol-binding proteins that take part in the intracellular storage and transport of RETINOL. They are both functionally and structurally distinct from PLASMA RETINOL-BINDING PROTEINS.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Receptors, Muscarinic: One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.Phosphoenolpyruvate Carboxykinase (GTP): An enzyme of the lyase class that catalyzes the conversion of GTP and oxaloacetate to GDP, phosphoenolpyruvate, and carbon dioxide. This reaction is part of gluconeogenesis in the liver. The enzyme occurs in both the mitochondria and cytosol of mammalian liver. (From Dorland, 27th ed) EC 4.1.1.32.GTP-Binding Protein alpha Subunits, Gs: A family of heterotrimeric GTP-binding protein alpha subunits that activate ADENYLYL CYCLASES.Myelin P2 Protein: A positively charged protein found in peripheral nervous system MYELIN. Sensitive immunological techniques have demonstrated that P2 is expressed in small amounts of central nervous system myelin sheaths of some species. It is an antigen for experimental allergic neuritis (NEURITIS, EXPERIMENTAL ALLERGIC), the peripheral nervous system counterpart of experimental allergic encephalomyelitis. (From Siegel et al., Basic Neurochemistry, 5th ed, p133)RNA, Transfer: The small RNA molecules, 73-80 nucleotides long, that function during translation (TRANSLATION, GENETIC) to align AMINO ACIDS at the RIBOSOMES in a sequence determined by the mRNA (RNA, MESSENGER). There are about 30 different transfer RNAs. Each recognizes a specific CODON set on the mRNA through its own ANTICODON and as aminoacyl tRNAs (RNA, TRANSFER, AMINO ACYL), each carries a specific amino acid to the ribosome to add to the elongating peptide chains.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes

*Rac3

... (Ras-related C3 botulinum toxin substrate 3) is a small (~21 kDa) monomeric GTP-binding protein G protein and is an ... It is a member of the Rac subfamily of the Rho family of small G proteins and is encoded by the gene RAC3. Courjal F, Chuchana ... RAC3 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH). ...

*RhoG

Other proteins known to bind RhoG in its GTP-bound state include the microtubule-associated protein kinectin, Phospholipase D1 ... RhoG (Ras homology Growth-related) (or ARGH) is a small (~21 kDa) monomeric GTP-binding protein (G protein), and is an ... is sufficient to promote GTP-loading of Rac. RhoG-mediated Rac signalling has been shown to promote neurite outgrowth and cell ... Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG". The Journal of ...

*List of MeSH codes (D08)

... rac gtp-binding proteins MeSH D08.811.277.040.330.300.400.700.100.500 --- rac1 gtp-binding protein MeSH D08.811.277.040.330.300 ... monomeric gtp-binding proteins MeSH D08.811.277.040.330.300.400.100 --- adp-ribosylation factors MeSH D08.811.277.040.330.300. ... ran gtp-binding protein MeSH D08.811.277.040.330.300.400.475 --- rap gtp-binding proteins MeSH D08.811.277.040.330.300.400.475. ... rab1 gtp-binding proteins MeSH D08.811.277.040.330.300.400.400.050 --- rab2 gtp-binding protein MeSH D08.811.277.040.330.300. ...

*Guanine nucleotide exchange factor

eIF-2b regenerates the GTP-bound form of eIF-2 for an additional cycle in protein synthesis initiation, i.e., its binding to ... Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the ... There are 11 identified DOCK family members divided into subfamilies based on their activation of Rac and Cdc42. DOCK family ... GTP generally binds in its place, as the cytosolic ratio of GTP is much higher than GDP at 10:1. The binding of GTP to the ...

*Rho family of GTPases

Bustelo XR, Sauzeau V, Berenjeno IM (2007). "GTP-binding proteins of the Rho/Rac family: regulation, effectors and functions in ... If tagged with monomeric-enhanced green fluorescent protein, one can see that the activation of Cdc42 is limited to just the ... This protein cannot be inactivated normally, through GTP hydrolysis, and is thus "stuck on". When a Rho protein activated in ... Because Rho proteins are G-proteins and plasma membrane bound, their location can be easily controlled. In each situation, ...

*List of MeSH codes (D12.644)

... rac gtp-binding proteins MeSH D12.644.360.525.700.100.100 --- rac1 gtp-binding protein MeSH D12.644.360.525.700.200 --- rhoa ... mitogen-activated protein kinase 14 MeSH D12.644.360.525 --- monomeric gtp-binding proteins MeSH D12.644.360.525.100 --- adp- ... ral gtp-binding proteins MeSH D12.644.360.525.462 --- ran gtp-binding protein MeSH D12.644.360.525.475 --- rap gtp-binding ... rab1 gtp-binding proteins MeSH D12.644.360.525.400.050 --- rab2 gtp-binding protein MeSH D12.644.360.525.400.100 --- rab3 gtp- ...

*Cofilin 1

Davidson MM, Haslam RJ (1994). "Dephosphorylation of cofilin in stimulated platelets: roles for a GTP-binding protein and Ca2+ ... Saito Y, Doi K, Yamagishi N, Ishihara K, Hatayama T (Feb 2004). "Screening of Hsp105alpha-binding proteins using yeast and ... actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin ... "Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization". Nature. 393 (6687): 809-12. doi: ...
Looking for online definition of ras-related GTP-binding protein 4b in the Medical Dictionary? ras-related GTP-binding protein 4b explanation free. What is ras-related GTP-binding protein 4b? Meaning of ras-related GTP-binding protein 4b medical term. What does ras-related GTP-binding protein 4b mean?
Looking for online definition of guanine nucleotide binding protein (G protein), beta polypeptide 4 in the Medical Dictionary? guanine nucleotide binding protein (G protein), beta polypeptide 4 explanation free. What is guanine nucleotide binding protein (G protein), beta polypeptide 4? Meaning of guanine nucleotide binding protein (G protein), beta polypeptide 4 medical term. What does guanine nucleotide binding protein (G protein), beta polypeptide 4 mean?
TY - JOUR. T1 - Signal transduction by guanine nucleotide binding proteins. AU - Spiegel, Allen M.. PY - 1987/1. Y1 - 1987/1. N2 - High affinity binding of guanine nucleotides and the ability to hydrolyze bound GTP to GDP are characteristics of an extended family of intracellular proteins. Subsets of this family include cytosolic initiation and elongation factors involved in protein synthesis, and cytoskeletal proteins such as tubulin (Hughes S.M. (1981) FEBS Lett. 164, 1-8). A distinct subset of guanine nucleotide binding proteins is membrane-associated; members of this subset include the ras gene products (Ellis R.W. et al. (1981) Nature 292, 506-511) and the heterotrimeric G-proteins (also termed N-proteins) (Gilman A.G. ...
Author: Praefcke, G. J. K. et al.; Genre: Other; Published in Print: 2000; Title: Identification of regions in human guanylate binding protein 1 (hGBP1) responsible for oligomerization and GTPase activity
Ras-homologous GTPases constitute a large family of signal transducers that alternate between an activated, GTP-binding state and an inactivated, GDP-binding state. These proteins represent cellular switches that are operated by GTP-exchange factors and factors that stimulate their intrinsic GTPase activity. All GTPases of the Ras superfamily have in common the presence of six conserved motifs involved in GTP/GDP binding, three of which are phosphate-/magnesium-binding sites (PM1-PM3) and three of which are guanine nucleotide-binding sites (G1-G3). Transcript variants encoding distinct isoforms have been identified. ...
Itsui, Y., Sakamoto, N., Kakinuma, S., Nakagawa, M., Sekine-Osajima, Y., Tasaka-Fujita, M., Nishimura-Sakurai, Y., Suda, G., Karakama, Y., Mishima, K., Yamamoto, M., Watanabe, T., Ueyama, M., Funaoka, Y., Azuma, S. and Watanabe, M. (2009), Antiviral effects of the interferon-induced protein guanylate binding protein 1 and its interaction with the hepatitis C virus NS5B protein. Hepatology, 50: 1727-1737. doi: 10.1002/hep.23195 ...
LOW-molecular-weight GTP-binding proteins are strong candidates for regulators of membrane traffic1-3. In yeast, mutations in the sec4 or ypt1 genes encoding small GTP-binding proteins inhibit constitutive membrane flow at the plasma membrane or Golgi complex, respectively4-6. It has been suggested that membrane fusion-fission events are regulated by cycling of small GTP-binding proteins between a membrane-bound and free state7, but although most of these small proteins are found in both soluble and tightly membrane-bound forms, there is no direct evidence to support such cycling. In rat brain a small GTP-binding protein, rab3A, is exclusively associated ...
The Rac proteins, Rac1 and Rac2, are essential components of the NADPH oxidase system of phagocytes and regulate the actin assembly associated with membrane ruffling. These functions are controlled by the GTP-bound form of Rac. The biochemical interaction between Rac and its only known GDP-dissociation stimulator (termed smgGDS) was characterized. SmgGDS was able to stimulate the incorporation of guanosine 5′-[gamma-thio]-triphosphate GTP[gamma S] into the RhoA, Rac2, Rac1, Rap1A and CDC42Hs GTP-binding proteins, but the activity was greatest toward RhoA and Rac2. Isoprenoid modification of these proteins was not absolutely required for the ...
In the yeast Saccharomyces cerevisiae, the G protein beta gamma subunits are essential for pheromone signaling. The Galpha subunit Gpa1 can also promote signaling, but the effectors in this pathway are not well characterized. To identify candidate Gpa1 effectors, we expressed the constitutively active Gpa1(Q323L) mutant in each of nearly 5000 gene-deletion strains and measured mating-specific responses. Our analysis reveals a requirement for both the catalytic (Vps34) and regulatory (Vps15) subunits of the sole phosphatidylinositol 3-kinase in yeast. We demonstrate that Gpa1 is present at endosomes, where it interacts directly with both Vps34 and Vps15 and stimulates increased production of phosphatidylinositol 3-phosphate. Notably, Vps15 binds to GDP-bound Gpa1 and is predicted to have a seven-WD repeat structure similar to that of known G protein beta subunits. These findings reveal two new components of the pheromone signaling pathway. ...
This gene encodes a member of the guanylate-binding protein (GBP) family. GBPs specifically bind guanine nucleotides (GMP, GDP, and GTP) and contain two of the three consensus motifs found in typical GTP-binding proteins. The encoded protein interacts with a member of the germinal center kinase family. Multiple transcript variants encoding different isoforms have been been found for this gene. [provided by RefSeq, Jan 2016 ...
Looking for online definition of guanine nucleotide-binding protein G(I)/G(S)/G(T) beta subunit 1 in the Medical Dictionary? guanine nucleotide-binding protein G(I)/G(S)/G(T) beta subunit 1 explanation free. What is guanine nucleotide-binding protein G(I)/G(S)/G(T) beta subunit 1? Meaning of guanine nucleotide-binding protein G(I)/G(S)/G(T) beta subunit 1 medical term. What does guanine nucleotide-binding protein G(I)/G(S)/G(T) beta subunit 1 mean?
Small GTP-binding proteins (G proteins) are monomeric G proteins with a low molecular weight of 20 to 40 kDa. A small G protein acts as a molecular switch that cycles between inactive GDP-bound and active GTP-bound forms. Thus far, ,100 small G proteins have been identified in eukaryotes from yeast to humans. The small G proteins in this superfamily are structurally classified into ≥5 families: the Ras, Rho, Rab, Sar/Arf, and Ran families. In general, the Ras family mainly regulates gene expression, the Rho family regulates both cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate intracellular vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization during the cell cycle.1. Multiple ...
Agonist binding to guanine nucleotide-binding protein (G protein)-coupled receptors in membranes of myeloid differentiated human leukemia (HL-60) cells is inhibited by guanine nucleotides, most potently by the GTP analog guanosine 5-(gamma-thio)triphosphate (GTP gamma S). In order to study whether GTP gamma S formed locally from adenosine 5-(gamma-thio)triphosphate (ATP gamma S) and GDP by nucleoside diphosphokinase has any advantage over exogenously added GTP gamma S in binding to and activating G proteins, regulation of complement component 5a (C5a) binding to its receptors, as well as formation of GTP gamma S, was studied in membranes of HL-60 cells. ...
Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFNγ-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host proteins is central to a successful immune response directed against numerous PV-resident pathogens. However, the mechanism by which IRGs and GBPs cooperatively detect and destroy PVs is unclear. We find that host cell priming with IFNγ prompts IRG-dependent association of Toxoplasma- and Chlamydia-containing vacuoles with ubiquitin through regulated translocation of the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and deposition of GBPs to PVs, thereby conferring cell-autonomous immunity. Hypervirulent strains of Toxoplasma gondii evade this ...
Signaling by kinases and phosphatases that act on serine, threonine, and tyrosine residues of proteins is among the most extensively studied regulatory mechanisms in mammalian cells, and research focused in this area is ongoing. We are just beginning to appreciate that such signaling mechanisms are extended and enriched by the reversible phosphorylation of histidine residues. The most exciting developments in this field to date come from studies on the β subunit of heterotrimeric guanosine triphosphate-binding proteins (G proteins), the enzyme adenosine 5′-triphosphate-citrate lyase, and now the Ca2+-activated K+ channel KCa3.1, all of which are targeted by nucleoside diphosphate kinase (which phosphorylates histidines) and protein histidine phosphatase (which dephosphorylates phosphorylated histidines).. ...
TY - JOUR. T1 - Inhibiting ras signaling in the therapy of breast cancer. AU - Li, Tianhong. AU - Sparano, Joseph A.. PY - 2003/2. Y1 - 2003/2. N2 - Ras is a small guanosine triphosphate-binding protein that plays an important role in signal transduction pathways that influence cellular proliferation, apoptosis, cytoskeletal organization, and other important biological processes. Prenylation of Ras proteins by the enzyme farnesyltransferase renders the protein hydrophobic, causing localization to the inner surface of the cell membrane, where it exerts its biological effects. Ras mutations that result in constitutive activation of the Ras pathway are common in certain human cancers, and transfection of cell lines with mutant Ras renders them tumorigenic. Farnesyltransferase inhibitors (FTIs) were initially developed to inhibit growth of cancers harboring Ras mutations, but preclinical data suggests that they also have ...
Caspase-11 directly detects LPS within the host cell cytosol (6). To explain how LPS gains access to the host cell cytosol, four distinct LPS delivery pathways were proposed: (i) some intracellular Gram-negative bacteria escape vacuoles to enter the host cell cytosol, where they release LPS (30); (ii) host GBPs execute membranolytic activities to extrude intracellular Gram-negative bacteria from PVs and extract LPS through bacteriolysis (10, 19-21); (iii) endocytosed bacterial OMVs release LPS into the host cell cytosol potentially through fusion with or transport across endosomal membranes (15, 31); and (iv) circulating free LPS (in the form of aggregates or bound to LPS-binding proteins) is consumed in vivo by an undefined cell population able to present LPS for caspase-11-mediated recognition (4, 5). Here, we present evidence that GBPs play previously unknown roles in the latter two pathways.. GBPs assist ...
G protein-coupled receptors (GPCRs) which are 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. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and animals. 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. G protein-coupled receptors are involved in many diseases, and are also the target ...
Nuclear envelope assembly is promoted by phosphoinositide- specific phospholipase C with selective recruitment of phosphatidylinositol-enriched membranes Nuclear envelope (NE) formation in a cell-free egg extract proceeds by precursor membrane vesicle binding to chromatin in an ATP-dependent manner, followed by a GTP-induced NE assembly step. The requirement for GTP in the latter step of this process can be mimicked by addition of bacterial PI-PLC [phosphoinositide (PtdIns)-specific phospholipase C]. The NE assembly process is here dissected in relation to the requirement for endogenous phosphoinositide metabolism, employing recombinant eukaryotic PI-PLC, inhibitors and direct phospholipid analysis using ESI-MS (electrospray ionization mass spectrometry). PtdIns (phosphatidylinositol) species analysis by ESI-MS indicates that the chromatin-bound NE precursor vesicles are enriched for ...
MAP4K component of the MAPK pathway required for the mating pheromone response, haploid invasive growth and diploid pseudohyphal development. Links the pheromone response G-protein beta gamma subunits to downstream signaling components. Needed for mating in haploid cells, induction of a mating-specific gene FUS1, induction of mating-specific morphologies, and pheromone-induced proliferation arrest. Required for the regulation of the actin polarization and bud emergence during cell cycle in G1. Involved in the high osmolarity glycerol (HOG) response. Phosphorylates Thr-307 and Ser-302 or Ser-306 of STE11 and Ser-357 of MYO3. Phosphorylates histone H2B to form H2BS10ph during meiosis and H(2)O(2)-induced apoptosis. Its interaction with CDC42 is required for both invasive growth and the formation of pseudohyphae. Its interaction with STE4 is required for the pheromone signaling.
Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) has been identified recently as a novel regulator of estrogen signalling in breast cancer cells. Despite being a potential target for new breast cancer treatment, its amino acid sequence suggests no association with any well-characterized protein family and provides little clues as to its molecular function. In this paper, we predicted the structure, function and interactions of BIG3 using a range of bioinformatic tools. Homology search results showed that BIG3 had distinct features from its paralogues, BIG1 and BIG2, with a unique region between the two shared domains, Sec7 and DUF1981. Although BIG3 contains Sec7 domain, the lack of the conserved motif and the critical glutamate residue suggested no potential guaninyl-exchange factor (GEF) activity. Fold recognition tools predicted BIG3 to adopt an α-helical repeat structure similar to that of the armadillo (ARM) family. ...
The quantitative determination of pertussis-toxin-sensitive guanine-nucleotide-binding proteins (G-proteins) in cell membranes is still a problem. Pertussis-toxin-catalysed [32P]ADP-ribosylation strongly relies on the substrate quality of the alpha-subunits and is influenced by the concentration of nucleotides, beta gamma-subunits, the physicochemical properties of the membranes influencing the availability of Gi alpha for pertussis toxin, and covalent modification of Gi alpha. Quantification of immunoreactive material on Western blots can be only imprecisely performed by two-dimensional densitometry. In order to generate a method for quantification of pertussis-toxin-sensitive G-proteins in membranes we have developed a fast and sensitive radioimmunoassay. The C-terminal decapeptide of retinal transducin alpha (KENLKDCGLF) was 125I-labelled and used as tracer. Polyclonal antiserum (DS 4) was raised against ...
387554453 - EP 1118621 A4 2003-06-25 - NOVEL G PROTEIN-COUPLED RECEPTOR PROTEIN AND DNA THEREOF - [origin: WO0020456A1] A human-origin G protein-coupled receptor protein or its peptide fragment or its salt, a nucleic acid encoding this receptor protein and its derivative, etc. The human hippocampus-origin G protein-coupled receptor protein or the nucleic acid encoding the same and its derivative are usable in determining a ligand (an agonist) to the G protein-coupled receptor protein, as preventives and/or remedies for diseases in association with dysfunction of the G protein-coupled receptor protein, as gene diagnostics, in a method for screening a compound capable of varying the expression dose of the G protein-coupled receptor protein or its peptide fragment, etc.[origin: WO0020456A1] A ...
In this study, we have shown that basal MOR activity is detectable in mouse brain tissue and that it is up-regulated by morphine treatment. A role for basal MOR signaling in narcotic dependence is buttressed by the finding that changes in basal MOR activity persist for prolonged time periods, consistent with prolonged signs of antagonist-induced withdrawal after exposure to morphine.. The basal signaling activity of MOR was detected with the use of inverse agonists, β-CNA and BNTX (Wang et al., 2001b). Since basal MOR signaling spontaneously increases receptor/G protein coupling, inverse agonists are expected to decreased basal receptor/G protein coupling. We used two assays to test basal MOR activity, [35S]GTPγS binding and adenylyl cyclase activity assays. [35S]GTPγS binding measures direct receptor/G protein coupling, ...
PST receptors were purified and characterized in the liver, hepatoma membranes, as well as the signal transduction (55, 62, 63). This receptor appears to mediate the dual signaling mechanism in liver (57). PST stimulation activates pertussis toxin-insensitive G protein (Gαq/11), leading to the activation of phospholipase C b3 isoform (PLC-b3) (69), and therefore mediates the glycogenolytic effect in the liver by increasing cytoplasmic free calcium and stimulating PKC, while the pertussis toxin-sensitive G protein (Gai1,2) leads to the activation of guanylatecyclase (51). In the signaling pathway, hydrolysis of phosphatidylinositol 4,5-bisphosphate by Ca2+-mobilizing hormones leads to the formation of two second messengers i.e., inositol-1,4,5-triphosphate (InsP3) and diacylglycerol (DAG). The primary function of InsP3 is to mobilize Ca2+ from intracellular stores (60), whereas DAG stimulates PKC (58).. Active PST receptors were solubilized ...
rho GTP-Binding Proteins: A large family of MONOMERIC GTP-BINDING PROTEINS that are involved in regulation of actin organization, gene expression and cell cycle progression. This enzyme was formerly listed as EC 3.6.1.47.
The guanosine triphosphate (GTP)-binding proteins include signal-transducing heterotrimeric G proteins (for example, Gs, Gi), smaller GTP-binding proteins that function in protein sorting, and the oncogenic protein p21ras. The T cell receptor complexes CD4-p56lck and CD8-p56lck were found to include a 32- to 33-kilodalton phosphoprotein (p32) that was recognized by an antiserum to a consensus GTP-binding region in G proteins. Immunoprecipitated CD4 and CD8 complexes bound GTP and hydrolyzed it to guanosine diphosphate (GDP). The p32 protein was covalently linked to [alpha-32P]GTP by ultraviolet photoaffinity ...
A wide range of extracellular signals are transduced by G protein-coupled receptors (GPCRs). When activated by ligands, GPCRs can activate associated heterotrimeric guanine nucleotide-binding proteins (G proteins), which in turn act on various effectors. Increasing evidence indicates that GPCRs also signal independently of heterotrimeric G proteins. Several GPCRs directly interact with Src-family kinases. Here, we discuss the evidence for direct interaction and activation of Src-family kinases by GPCRs and data that suggest that agonist dosage provides a mechanism by which GPCRs can switch between G protein-dependent and G protein-independent signaling.. ...
The lipoglycoproteins of the WNT family act on seven transmembrane-spanning Class Frizzled receptors. Here, we show that WNT-5A evokes a proliferative response in a mouse microglia-like cell line (N13), which is sensitive to pertussis toxin, thus implicating the involvement of heterotrimeric G proteins of the G(i/o) family. We continue to show that WNT-5A stimulation of N13 membranes and permeabilized cells evokes the exchange of GDP for GTP of pertussis toxin-sensitive G proteins employing [gamma-(35)S]GTP assay and activity state-specific antibodies to GTP-bound G(i) proteins. Our functional analysis of the PTX-sensitivity of WNT-induced G protein activation and PCR analysis of G protein and FZD expression patterns suggest that WNT-5A stimulation leads to the activation of G(i2/3) proteins ...
Previous studies on immortalized B lymphoblasts from patients with EH and enhanced Na+-H+ exchanger activity have revealed an enhanced activation of PTX-sensitive G proteins.7 This conclusion was mainly based on two findings. First, HT lymphoblasts displayed enhanced [Ca2+]i signals upon stimulation with platelet-activating factor and somatostatin. Pretreatment with PTX strongly reduced these agonist-evoked Ca2+ signals, and the residual Ca2+ responses were no longer different between NT and HT cell lines. Second, both receptor-mediated stimulation and direct (by mastoparan-7) stimulation of GTPγS binding to PTX-sensitive G proteins were significantly increased in HT lymphoblasts.7 Unfortunately, B lymphoblasts apparently do not express functional receptors that are selectively coupled to PTX-insensitive G proteins, eg, Gq or Gs. Therefore, our proposal of a selective enhancement of signal ...
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 is a protein that in humans is encoded by the GNB3 gene. Heterotrimeric guanine nucleotide-binding proteins ( G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. A single-nucleotide polymorphism (C825T) in this gene is associated with essential hypertension and obesity. This polymorphism is also associated with the occurrence of the splice variant GNB3-s, which appears to have increased activity. GNB3-s is an example of alternative splicing caused by a nucleotide change outside of the splice donor and ...
We studied the effects of various beta-adrenoceptor (beta AR) antagonists and local anesthetics (LAs), i.e. substances possessing one basic and one lipophilic domain each, on activation of regulatory heterotrimeric guanine nucleotide-binding proteins (G-proteins). In membranes of differentiated HL-60 cells, propranolol activated high-affinity GTP hydrolysis with a half-maximal effect at 0.19 mM and a maximum at 1 mM. There was a close correlation between the log Q values (logarithm of the octanol: water partition coefficient) of beta AR antagonists and the logarithm of their effectiveness at activating GTPase (EC 3.6.1.-) in HL-60 membranes. The lipophilic LA, tetracaine, was also an effective activator of GTPase in HL-60 membranes, whereas more hydrophilic LAs were less stimulatory (bupivacaine and lidocaine) or even ...
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Several studies have demonstrated that AngII infusion leads to the formation of AAAs in mice.12,13,50 AngII exerts its diverse bioactive effects primarily by activating the AT1a receptor in mice, which plays a critical role in AngII-induced AAA development.17 In addition to mediating traditional G-protein-dependent signaling, the AT1a receptor is involved in G-protein-independent signaling by forming a complex with the multifunctional scaffolding protein βarr2.19,24 In the present study, we investigated a role for βarr2 in AngII-induced AAA formation and found that βarr2 deficiency significantly attenuates AAA formation in mice both on a hyperlipidemic apoE background and on a normolipidemic C57BL/6 background (Figure 1). These studies suggest that G-protein-independent, βarr2-dependent signaling for the AT1a receptor plays a major role in AngII-induced AAA formation.. Although our present studies showed that βarr2 deficiency attenuated ...
The Escherichia coli guanosine triphosphate (GTP)-binding proteins Ffh and FtsY have been proposed to catalyze the cotranslational targeting of proteins to the bacterial plasma membrane. A mutation was introduced into the GTP-binding domain of FtsY that altered its nucleotide specificity from GTP to xanthosine triphosphate (XTP). The mutant FtsY protein stimulated GTP hydrolysis by a ribonucleoprotein consisting of Ffh and 4.5S RNA in a reaction that required XTP, and it hydrolyzed XTP in a reaction that required both the Ffh-4.5S ribonucleoprotein and GTP. Thus, nucleotide triphosphate hydrolysis by Ffh and FtsY is likely to occur in reciprocally coupled reactions in which the two ...
beta Karyopherins: Nucleocytoplasmic transport molecules that bind to ALPHA KARYOPHERINS in the CYTOSOL and are involved in transport of molecules through the NUCLEAR PORE COMPLEX. Once inside the CELL NUCLEUS beta karyopherins interact with RAN GTP-BINDING PROTEIN and dissociate from alpha karyopherins. Beta karyopherins bound to RAN GTP-BINDING PROTEIN are then re-transported to the cytoplasm where hydrolysis of the GTP of RAN GTP-BINDING PROTEIN causes release of karyopherin beta.
Inositol phosphate accumulation and adenylate cyclase activity were investigated in the cortex of young and aged ethanol-treated rats. Three months of ethanol treatment of young rats decreased maximal stimulation of inositol phosphate accumulation by carbachol by 26%, from 494 ± 76% of basal turnover in control animals to 396 ± 54% in ethanol-treated animals (mean ± SD). In aged rats ethanol-related changes were no longer observed but age-related changes were evident. EC50 was significantly higher than in young animals and maximal stimulation was significantly lower. Basal adenylate cyclase activity in cortical membranes of all groups of animals was not different. Forskolin-stimulated adenylate cyclase activity was not affected by ethanol treatment, but was higher in aged animals. The activity of forskolin-stimulated adenylate cyclase in the presence of carbachol was higher in both young and aged ethanol-treated animals, when compared to young controls. These results suggest that both ethanol ...
Breast cancer is the most common malignancy in women worldwide. Although the endocrine therapy that targets estrogen receptor α (ERα) signaling has been well established as an effective adjuvant treatment for patients with ERα-positive breast cancers, long-term exposure may eventually lead to the development of acquired resistance to the anti-estrogen drugs, such as fulvestrant and tamoxifen. A better understanding of the mechanisms underlying antiestrogen resistance and identification of the key molecules involved may help in overcoming antiestrogen resistance in breast cancer. The whole-genome gene expression and DNA methylation profilings were performed using fulvestrant-resistant cell line 182R-6 and tamoxifen-resistant cell line TAMR-1 as a model system. In addition, qRT-PCR and Western blot analysis were performed to determine the levels of mRNA and protein molecules. MTT, apoptosis and cell cycle analyses were performed to examine the effect of either guanine ...
In vivo administration of pertussis toxin is often used to study the involvement of guanine nucleotide binding proteins in signal transduction. Especially when it is administered in the brain the effect is often poor. This could be due to the fact that pertussis toxin does not reach the area of interest. To evaluate the extent to which pertussis toxin is distributed in rat brain after intraventricular injection, different techniques were used. Immunohistochemical studies with an antibody against pertussis toxin showed that immunoreactivity was limited to periventricular brain structures less than 0.5 mm from the lumen. The highest immunoreactivity was seen 16-24 h after injection. After 96 h the labeling was very weak. The proportion of guanine nucleotide binding proteins that were ADP-ribosylated by in vivo injection of pertussis toxin into the ventricles as assessed by in vitro [32P]-back-ADP-ribosylation ...
The ability of morphine to alleviate pain is mediated through a heterotrimeric guanine nucleotide binding protein (G protein)-coupled heptahelical receptor (GPCR), the mu opioid receptor (muOR). The efficiency of GPCR signaling is tightly regulated and ultimately limited by the coordinated phosphorylation of the receptors by specific GPCR kinases and the subsequent interaction of the phosphorylated receptors with beta-arrestin 1 and beta-arrestin 2. Functional deletion of the beta-arrestin 2 gene in mice resulted in remarkable potentiation and prolongation of the analgesic effect of morphine, suggesting that muOR desensitization was impaired. These results provide evidence in vivo for the physiological importance of beta-arrestin 2 in regulating the function of a specific GPCR, the muOR. Moreover, they suggest that inhibition of beta-arrestin 2 function might lead to enhanced analgesic effectiveness of morphine and provide ...
The guanosine triphosphate (GTP)-loaded form of the guanosine triphosphatase (GTPase) Ras initiates multiple signaling pathways by binding to various effectors, such as the kinase Raf and phosphatidylinositol 3-kinase (PI3K). Ras activity is increased by guanine nucleotide exchange factors that stimulate guanosine diphosphate release and GTP loading and is inhibited by GTPase-activating proteins that stimulate GTP hydrolysis. KRAS is the most frequently mutated RAS gene in cancer. Here, we report that monoubiquitination of lysine-147 in the guanine nucleotide-binding motif of wild-type K-Ras could lead to enhanced GTP loading. Furthermore, ubiquitination increased the binding of the ...
Previously we used mass spectrometry to show that the yeast G protein alpha subunit Gpa1 is ubiquitinated at Lys-165, located within a subdomain not present in other G alpha proteins (Marotti, L. A., Jr., Newitt, R., Wang, Y., Aebersold, R., and Dohlman, H. G. (2002) Biochemistry 41, 5067-5074). Here we describe the functional role of Gpa1 ubiquitination. We find that Gpa1 expression is elevated in mutants deficient in either proteasomal or vacuolar protease function. Vacuolar protease pep4 mutants accumulate monoubiquitinated Gpa1, and much of the protein is localized within the vacuolar compartment. In contrast, proteasome-defective rpt6/cim3 mutants accumulate polyubiquitinated Gpa1, and in this case the protein exhibits cytoplasmic localization. Cells that lack Ubp12 ubiquitin-processing protease activity accumulate both mono- and polyubiquitinated forms of Gpa1. In this case, Gpa1 accumulates in both the cytoplasm and vacuole. Finally, ...
The signal recognition particle (SRP) consists of one RNA and six protein subunits. The N-terminal domain of the 54K subunit contains a putative GTP-binding site, whereas the C-terminal domain binds signal sequences and SRP RNA. Binding of SRP to the signal sequence as it emerges from the ribosome creates a cytosolic targeting complex containing the nascent polypeptide chain, the translating ribosome, and SRP. This complex is directed to the endoplasmic reticulum membrane as a result of its interaction with the SRP receptor, a membrane protein composed of two subunits, SR alpha and SR beta, each of which also contains a GTP-binding domain. In the presence of GTP, SRP receptor binding to SRP causes the latter to dissociate ...
We have demonstrated previously the potent activation of PLD by the chemokine IL-8 in T lymphocytes (18). We have now extended our findings to include the C-C chemokine RANTES in demonstrating that in the Jurkat T cell line, the activation of this enzyme occurs at subnanomolar concentrations and is dependent on the activation of small GTP-binding protein cofactors. RANTES-induced PLD activation is consistently maximal at 1 nM, a concentration corresponding to the optimal chemotaxis-inducing dose in normal T lymphocytes. Interestingly, PLD activation in T lymphocytes and Jurkat T cells appears to be an important biologic consequence of chemokine action and more readily measurable (at nanomolar concentrations) than readouts of receptor activation such as calcium flux. It was also apparent that RANTES is the only chemokine tested to date (RANTES, MIP-1α, MIP-1β, MCP-1, MCP-3, lymphotactin) that induces as robust a response as ...
We recently identified dynamin as a third nucleotide-sensitive microtubule-associated protein in brain tissue, in addition to kinesin and cytoplasmic dynein. Molecular cloning analysis has revealed that dynamin contains the three consensus elements characteristic of GTP-binding proteins, and biochemical results support a role for GTP in dynamin function. Dynamin is also homologous to the Mx proteins, involved in interferon-induced viral resistance, and the product of the yeast VPS1 gene, involved in vacuolar protein sorting. These results identify a novel class of GTP-utilizing proteins, with apparently diverse functions. ...
1. Guanosine 5′-[gamma-thio]triphosphate (GTP[S]), if added before GTP, blocks both Ca2+ efflux promoted by GTP and the effect of GTP on enhancement of inositol 1,4,5-triphosphate (IP3)-promoted Ca2+ release from preloaded microsomal vesicles. If, however, GTP[S] is added after GTP, it does not reverse the Ca2+ efflux promoted by GTP, nor does it inhibit IP3-promoted Ca2+ release. 2. The effect of GTP in enhancing IP3-promoted Ca2+ release is maintained after washing the microsomal vesicles free of added GTP. After this treatment, enhancement of IP3-promoted Ca2+ efflux can be observed in the absence of poly(ethylene glycol). 3. Electron microscopy shows that during GTP ...
Metabotropic glutamate receptors (mGluRs) are coupled to effector systems through GTP-binding proteins (G-proteins) and appear to mediate slow synaptic responses in the CNS. Although mGluR-mediated increases in phosphoinositide hydrolysis have been well characterized, other mechanisms for signal transduction employed by mGluRs are poorly understood. We recently reported that the selective mGluR agonist 1- aminocyclopentane-1 S,3R-dicarboxylic acid (1S,3R-ACPD) increases cAMP accumulation in rat hippocampal slices. We have now investigated the mechanisms involved in this response. A number of G-protein-linked receptors that are not directly coupled to adenylate cyclase increase cAMP accumulation by potentiating cAMP responses to other agonists. Furthermore, previous studies suggest that glutamate increases cAMP accumulation by a mechanism that is dependent upon the presence ...
Sphingosine 1-phosphate (S1P) is one of several bioactive phospholipids that exert profound mitogenic and morphogenic actions. Originally characterized as a second messenger, S1P is now recognized to achieve many of its effects through cell surface, G protein-coupled receptors. We used a subunit-selective [35S]GTPγS binding assay to investigate whether the variety of actions exerted through Edg-1, a recently identified receptor for S1P, might be achieved through multiple G proteins. We found, employing both Sf9 and HEK293 cells, that Edg-1 activates only members of the Gi family, and not Gs, Gq, G12, or G13. We additionally established that Edg-1 activates Gi in response not only to S1P but also sphingosylphosphorylcholine; no effects of lysophosphatidic acid through Edg-1 were evident. Our assays further revealed a receptor(s) for S1P endogenous to HEK293 cells that mediates activation of ...
GUANOSINE TRIPHOSPHATE | C10H16N5O14P3 | CID 6830 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.
As shown above, the morphology of the mitotic figure of arsenic-treated cells had features found with both Taxol and Colcemid. These observations correlate with recent findings on the three-dimensional structure of tubulin (18) that show that when the GTP binding site is unoccupied, two cysteine residues, Cys-12 and Cys-213, are in close proximity in the three-dimensional structure, separating after GTP binding occurs. Reaction of trivalent arsenic with these vicinal cysteine residues would inactivate the GTP binding site. This is further supported by an earlier finding that two cysteines in tubulin can be cross-linked after the removal of GTP (19) . These features provide a biochemical basis for the action of arsenic as a noncompetitive inhibitor of ...
Guanine is one of the five main nucleobases found in the nucleic acids DNA and RNA. Guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with conjugated double bonds. Being unsaturated, the bicyclic molecule is planar. The guanine nucleoside is called guanosine. The first isolation of guanine was reported in 1844 from the excreta of sea birds, known as guano, which was used as a source of fertilizer. High affinity binding of guanine nucleotides and the ability to hydrolyze bound GTP to GDP are characteristics of an extended family of intracellular proteins. Guanine nucleotide-binding regulatory proteins may be involved in the activation of phospholipases C and A2 by hormones and other ligands. The binding of hormones to receptors that activate phospholipase C is decreased ...
Vasopressin is the key regulator of water homeostasis in vertebrates. Central to its antidiuretic action in mammals is the redistribution of the water channel aquaporin 2 (AQP2) from intracellular vesicles to the apical membrane of kidney epithelial cells, an event initiated by an increase in cAMP and activation of protein kinase A. The subsequent steps of the signaling cascade are not known. To identify proteins involved in the AQP2 shuttle we exploited a recently developed cell line (CD8) derived from the rabbit cortical collecting duct and stably transfected with rat AQP2 cDNA. Treatment of CD8 cells with pertussis toxin (PTX) inhibited both the vasopressin-induced increase in water permeability and the redistribution of AQP2 from an intracellular compartment to the apical membrane. ADP-ribosylation studies revealed the presence of at least two major PTX substrates. Correspondingly, two alpha subunits of PTX-sensitive G ...
The researchers compared the results of prior single-particle electron microscopy analysis of the β2AR-Gs complex to the structure predicted by their model and found good agreement. They also used continuous wave electron paramagnetic resonance spectroscopy (CW-EPR) and peptide amide hydrogen-deuterium exchange mass spectrometry data to calculate changes in the solvent accessibility of key residues in the free versus receptor-bound Gα subunit. The results of these calculations agreed well with predictions based on the model. To further test the models validity, they selected an amino acid in the GTPase domain and another in the helical domain of Gi. They expressed a Gi protein bearing mutations in both of these amino acids to cysteine and then attached a sulfur-accessible nitroxide probe to each cysteine. The altered protein allowed them to use DEER to assess the changes in the distance between the GTPase ...
Guanyl nucleotide binding-proteins, or G-proteins, are ubiquitous molecules that are involved in cellular signal transduction mechanisms. Because a role has been established for cAMP in meiosis and G-proteins participate in cAMP-generating systems by stimulating or inhibiting adenylate cyclase, the present study was conducted to examine the possible involvement of G-proteins in the resumption of meiotic maturation. Cumulus cell-free mouse oocytes (denuded oocytes) were maintained in meiotic arrest in a transient and dose-dependent manner when microinjected with the nonhydrolyzable GTP analog, GTP gamma S. This effect was specific for GTP gamma S, because GppNHp, GTP, and ATP gamma S were without effect. Three compounds, known to interact with ...
βarrestin (βarr)-1 and -2 (βarrs) (or Arrestin-2 and -3, respectively) are universal G protein-coupled receptor (GPCR) adapter proteins expressed abundantly in extra-retinal tissues, including the myocardium. Both were discovered in the lab of the 2012 Nobel Prize in Chemistry co-laureate Robert Lefkowitz, initially as terminators of signaling from the β-adrenergic receptor (βAR), a process known as functional desensitization. They are now known to switch GPCR signaling from G protein-dependent to G protein-independent, which, in the case of βARs and angiotensin II type 1 receptor (AT1R), might be beneficial, e.g., anti-apoptotic, for the heart. However, the specific role(s) of each βarr isoform in cardiac GPCR signaling and function (or dysfunction in disease), remain unknown. The current consensus is that, whereas both βarr isoforms can desensitize and internalize cardiac GPCRs, they play quite different (even opposing in certain ...
FUNCTION: Guanine nucleotide-exchange factor (GEF) required for the formation or budding of transport vesicles from the ER. This function involves the cytoplasmic domain of the protein, which is thought to interact with the small GTP-binding protein SAR1. Required for autophagy. MISCELLANEOUS: In the process of transport, SEC12 itself may migrate to the Golgi apparatus and function in subsequent transport events. MISCELLANEOUS: Present with 6160 molecules/cell in log phase SD medium ...
The bacterial homologues of the signal recognition particle (SRP) and its receptor, the Ffh*4.5S RNA ribonucleoprotein complex and the FtsY protein, respectively, form a unique complex in which both Ffh and FtsY act as GTPase activating proteins for one another, resulting in the mutual stimulation of GTP hydrolysis by both proteins. Previous work showed that 4.5S RNA enhances the GTPase activity in the presence of both Ffh and FtsY, but it was not clear how this was accomplished. In this work, kinetic and thermodynamic analyses of the GTPase reactions of Ffh and FtsY have provided insights into the role of 4.5S RNA in the GTPase cycles of Ffh and FtsY. We found that 4.5S RNA accelerates the association between Ffh and FtsY 400-fold in their ...
Regulator of G protein signaling (RGS) proteins accelerate GTP hydrolysis by Gα subunits and thus facilitate termination of signaling initiated by G protein-coupled receptors (GPCRs). RGS proteins hold great promise as disease intervention points, given their signature role as negative regulators of GPCRs-receptors to which the largest fraction of approved medications are currently directed. RGS proteins share a hallmark RGS domain that interacts most avidly with Gα when in its transition state for GTP hydrolysis; by binding and stabilizing switch regions I and II of Gα, RGS domain binding consequently accelerates Gα-mediated GTP hydrolysis. The human genome encodes more than three dozen RGS domain-containing ...
Summary is not available for the mouse gene. This summary is for the human ortholog.] Regulator of G protein signaling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 4 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain. Regulator of G protein signaling 4 protein is 37% identical to RGS1 and 97% identical to rat Rgs4. This protein negatively regulate signaling upstream or at the level of the heterotrimeric G protein and is localized in ...
TY - JOUR. T1 - ADP ribosylation factor 6 regulates neuronal migration in the developing cerebral cortex through FIP3/arfophilin-1-dependent endosomal trafficking of N-cadherin. AU - Hara, Yoshinobu. AU - Fukaya, Masahiro. AU - Hayashi, Kanehiro. AU - Kawauchi, Takeshi. AU - Nakajima, Kazunori. AU - Sakagami, Hiroyuki. PY - 2016. Y1 - 2016. N2 - During neural development, endosomal trafficking controls cell shape and motility through the polarized transport of membrane proteins related to cellcell and cellextracellular matrix interactions. ADP ribosylation factor 6 (Arf6) is a critical small GTPase that regulates membrane trafficking between the plasma membrane and endosomes. We herein demonstrated that the knockdown of endogenous Arf6 in mouse cerebral cortices led to impaired neuronal migration in the intermediate zone and cytoplasmic retention of N-cadherin and syntaxin12 in migrating neurons. Rescue experiments with ...
The beta-adrenergic receptor kinase (beta ARK) phosphorylates the agonist-occupied beta-adrenergic receptor to promote rapid receptor uncoupling from Gs, thereby attenuating adenylyl cyclase activity. Beta ARK-mediated receptor desensitization may reflect a general molecular mechanism operative on many G-protein-coupled receptor systems and, particularly, synaptic neurotransmitter receptors. Two distinct cDNAs encoding beta ARK isozymes were isolated from rat brain and sequenced. The regional and cellular distributions of these two gene products, termed beta ARK1 and beta ARK2, were determined in brain by in situ hybridization and by immunohistochemistry at the light and electron microscopic levels. The beta ARK isozymes were found to be expressed primarily in neurons distributed throughout the CNS. Ultrastructurally, beta ARK1 and beta ARK2 immunoreactivities were present both in association with postsynaptic densities and, presynaptically, with axon terminals. The beta ARK isozymes have a ...
Functional selectivity, which highlights the ability of ligands to differentially activate the signalling pathways linked to G protein-couple receptors (GPCRs) has provided an avenue for developing ligands with greater safety profiles. Pilocarpine (Pilo), a non-selective muscarinic acetylcholine receptor (mAChR) agonist has been shown to differentially activate G protein subtypes linked to the M3 mAChR. In this study the pharmacology of Pilo was further investigated using a number of readouts. When compared to methacholine (MCh), a reference agonist, Pilo appeared to preferentially stimulate inositol phosphates production than global receptor phosphorylation. The ligand also appeared to preferentially promote phosphorylation of Ser412 at the third intracellular loop of the receptor than Ser577 at the C-terminal tail. This differential phosphorylation may be linked to the fact that these residues are phosphorylated by distinct protein ...
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Video created by Icahn School of Medicine at Mount Sinai for the course Introduction to Systems Biology. Module description goes here. 2000+ courses from schools like Stanford and Yale - no application required. Build career skills in data ...
In biology, small GTPases are small (20-25 kDa) proteins that bind to guanosine triphosphate (GTP). This family of proteins is homologous to Ras GTPases and also called the Ras superfamily GTPases. Together with heterotrimeric G-proteins they constitute the G-proteins. They are all GTPases and share common features, but small GTPases have slightly different structures and mechanisms of action. A typical G-protein is active when bound to GTP and inactive when bound to GDP (i.e. when the GTP is hydrolyzed to GDP). The GDP can be then replaced by free GTP. Therefore, a G-protein can be switched on and off. ...
Ver más] The small GTP-binding protein ADP-ribosylation factor 1 (ARF1) is an essential component of the molecular machinery that catalyzes the formation of membranebound transport intermediates. By using an in vitro assay that reproduces recruitment of cytosolic proteins onto purified, high salt-washed Golgi membranes, we have analyzed the role of cAMP-dependent protein kinase A (PKA) on ARF1 incorporation. Addition to this assay of either pure catalytic subunits of PKA (C-PKA) or cAMP increased ARF1 binding. By contrast, ARF1 association was inhibited following C-PKA inactivation with either PKA inhibitory peptide or RIIa as well as after cytosol depletion of C-PKA. C-PKA also stimulated recruitment and activation of a recombinant form of human ARF1 in the absence of additional cytosolic components. The binding step could ...
Addresses: Bilgin N, Univ Uppsala, Ctr Biomed, Dept Biochem, Box 576, S-75123 Uppsala, Sweden. Uppsala Univ, Ctr Biomed, Dept Biol Mol, S-75124 Uppsala, Sweden. Inst Biol Struct, F-38027 Grenoble 1, France. DESY, European Mol Biol Lab, D-22603 Hamburg, GeAvailable from: 2008-10-17 Created: 2008-10-17 Last updated: 2011-01-14 ...
The time course of cAMP production by S49 cell membranes in the presence of forskolin and a nonhydrolyzable GTP analog can yield information about the regulation of adenylate cyclase by both the inhibitory and stimulatory GTP-binding proteins (Gi and Gs). The time courses are complex and interpretation in terms of the activities of G1 and Gs requires a quantitative hypothesis. We present a general quantitative hypothesis that defines adenylate cyclase as existing in a distribution of two states, active and inactive. Gi and Gs, in their active states, alter the equilibrium of this distribution. Two distinct models are derived based on this hypothesis to accommodate two different proposed mechanisms for the action of Gi to inhibit adenylate cyclase: 1) a direct interaction between Gi and the catalytic subunit of adenylate cyclase and 2) a direct interaction ...
It has been debated whether the potassium channel of the atrium is activated by the alpha subunit or by the beta gamma subunits of guanine nucleotide binding (G) proteins, which dissociate on activation with guanosine triphosphate (GTP). Therefore, the channel-activating effectiveness of these subunits on isolated guinea pig atrial cells was tested. The activated alpha K subunit from human erythrocytes activated the channel in subpicomolar concentrations. The beta gamma dimer from bovine brain activated the channel in nanomolar concentrations. These results support the view that, physiologically, the alpha subunit activates the channel. ...
Ahnert-Hilger, G.; Wegenhorst, U.; Stecher, B.; Spicher, K.; Rosenthal, W. und Gratzl, Manfred (1992): Exocytosis from permeabilized bovine adrenal chromaffin cells is differently modulated by guanosine 5-[gamma-thio]triphosphate and guanosine 5-[beta gamma-imido]triphosphate. Evidence for the involvement of various guanine nucleotide-binding proteins. In: Biochemical Journal, Vol. 284: S. 321-326 [PDF, 3MB] ...
G protein-coupled receptors (GPCRs) relay diverse extracellular signals into cells by catalyzing nucleotide release from heterotrimeric G proteins, but the mechanism underlying this quintessential molecular signaling event has remained unclear. Here we use atomic-level simulations to elucidate the nucleotide-release mechanism. We find that the G protein α subunit Ras and helical domains-previously observed to separate widely upon receptor binding to expose the nucleotide-binding site-separate spontaneously and frequently even in the absence of a receptor. Domain separation is necessary but not sufficient for rapid nucleotide release. Rather, receptors catalyze nucleotide release by favoring an internal structural rearrangement of the Ras domain that weakens its nucleotide affinity. We use double electron-electron resonance spectroscopy and protein ...
Title:Application of BRET for Studying G Protein-Coupled Receptors. VOLUME: 14 ISSUE: 5. Author(s):Agnieszka A. Kaczor, Magdalena Makarska-Bialokoz, Jana Selent, Rocio A. de la Fuente, Maria Marti-Solano and Marian Castro. Affiliation:Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin, Poland.. Keywords:BRET, G protein-coupled receptors, G protein-coupled receptor dimers.. Abstract:G protein-coupled receptors (GPCRs) constitute one of the largest classes of cell surface receptors. GPCR biology has been a subject of widespread interest owing to the functional relevance of these receptors and their potential importance in the development of new drugs. At present, over 30% of all launched drugs target these receptors. GPCRs have been considered for a long ...
Regulation of neuronal voltage-activated Ca2+ channels by neurotransmitters and intracellular signaling pathways is an important step in the control of neurotransmitter release, synaptic transmission, and neuronal plasticity. In the present study, we have determined the effect of a novel anti-dementia drug FK960 on voltage-activated Ca2+ channels in isolated rat hippocampal neurons. Our results demonstrate for the first time that FK960 modulates the G protein-mediated inhibitory effect of somatostatin on Ca2+ channels and, furthermore, enhances the basal Ca2+ currents in hippocampal neurons.. It has been suggested that somatostatin receptors inhibit N-type Ca2+ channels via PTX-sensitive G proteins through a direct membrane-delimited model (Shapiro and Hille, 1993; Hille et al., 1995; Zhang et al., 1996). Somatostatin-induced inhibition of Ca2+ currents in these isolated hippocampal neurons is mediated by activation of G proteins because PTX ...
gs99, invoking micro-intelligence isnt needed to explain the arrival of activated nucleotides during replication. The Polymerase doesnt send out for the right nucleotide triphosphate; instead, random nucleotide triphosphates bump into the template nucleotide. If the nucleotide triphosphate hydrogen bonds correctly with the template nucleotide, the new phosphodiester linkage forms. If the nucleotide triphosphate is the wrong one then usually it will not slip into the correct orientation to form the new bond, so it is quickly displaced and another random activated nucleotide slips into position at the polymerase active site and bumps against the template nucleotide. Eventually (in a tiny fraction of a second) a correct nucleotide is fitted and reacted and the polymerase advances. If a mistake is made (and this sometimes happens), it is almost always caught by the proofreading function of the polymerase and corrected. If not, a mutation has occurred (a rare event). The process is driven by ...
1. General Function. Rab1 is a small GTP binding protein that is expressed in virtually all mammalian cells, fish, worms and flies and is homologous to the yeast protein Ypt1 (3). It is essential for ER to Golgi transport and has also been implicated in intra Golgi transport (22, 30). There are two isoforms Rab1a (205 aa) and Rab1b (201aa) which are 92% identical at the amino acid level with most differences in the carboxyl terminus (28). These two isoforms are generally localized in the same cellular regions and have similar biochemical properties and functions. Rab1a may also play a role in transcytosis (14). In addition to localization by immunoflourescence in tissue culture cells, Rab1a has been localized by immunogold labeling to vesicles between the ER and Golgi region and over Golgi stacks in NRK cells (23).. The vesicular transport activity of Rab1 is dependent on its ...
Controls Rho proteins homeostasis. Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Retains Rho proteins such as CDC42, RAC1 and RHOA in an inactive cytosolic pool, regulating their stability and protecting them from degradation. Actively involved in the recycling and distribution of activated Rho GTPases in the cell, mediates extraction from membranes of both inactive and activated molecules due its exceptionally high affinity for prenylated forms. Through the modulation of Rho proteins, may play a role in cell motility regulation. In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of ...
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.
TY - JOUR. T1 - Modulation of forskolin binding to rat brain membranes. AU - Seamon, K. B.. AU - Vaillancourt, Richard. AU - Daly, J. W.. PY - 1985. Y1 - 1985. N2 - High affinity binding sites for [3H]forskolin have been identified in rat brain membranes. These sites have a K(d) of 15 nM and a B(max) of about 200 fmol/mg protein. The binding of [3H]forskolin to those high affinity sites in rat brain membranes is increased about two-fold by addition of MgCl2 or MnCl2. Smaller increases are observed in the presence of calcium, sodium, or potassium. The binding of [3H]forskolin is also increased in the presence of NaF or GppNHp, agents that are known to activate adenylate cyclase through the stimulatory guanine nucleotide regulatory protein (N(s)). The increase in [3H]forskolin binding in the presence of NaF or ...
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.
Guanine nucleotides regulate binding of opiate agonists to membrane receptors by increasing agonist dissociation rates. The current study demonstrates that the ability of guanosine 5-triphosphate (GTP) and its nonhydrolyzable analogue guanylyl-5-imidodiphosphate (Gpp(NH)p) to inhibit opiate agonist binding to rat brain membranes can be altered by two methods: by preincubating with EDTA, and by preincubating at pH 4.5. EDTA pretreatment increased the potency of Gpp(NH)p in inhibiting [3H]morphine binding by 4-fold, with little apparent change in the maximum effect of Gpp(NH)p or on levels of binding itself. The effect of EDTA pretreatment was blocked by prior incubation of membranes with excess calcium or manganese but could not be reversed by any divalent cation if the EDTA incubation was longer than 10 min. EDTA pretreatment increased the ...
Research Summary. Research in my laboratory is centered around signalling events, particularly those that involve intracellular Ca2+ and the major Ca2+ -binding regulatory protein calmodulin. Two systems we are investigating are the regulation of protein synthesis and the control of endocytosis by Ca2+, both of which involve (different) calmodulin-regulated events. We are also interested in the mechanism of action of neurotrophic factors like nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) as they relate to the effects of these proteins on CNS neurons. Part of the action of these factors also involves Ca2+. Current projects. Neurotrophic factors and CNS neurons We have shown that primary cultures of rat embryonic hippocampal neurons can be used for biochemical investigations of the signal transduction pathways activated by BDNF and neurotrophin-3. These cells homogeneously express the ...
B pertussis produces numerous virulence factors, including toxins and attachment agents, many of which are antigenic and included in the acellular vaccine. The link of each virulence factor to clinical illness has been difficult to elucidate due to lack of an animal model for experimentation. However, a recently developed model in infant baboons has the potential to address unanswered questions. The bacteria attach to ciliated epithelial cells of the respiratory tract, induce ciliary paralysis and local inflammation, and thicken and decrease clearance of secretions. B pertussis is not invasive. Pertussis toxin, necessary but not sufficient to cause clinical pertussis, is secreted by the bacteria and affects G-protein function, which prevents migration of lymphocytes to the area of infection, and inhibits the function of neutrophils, macrophages, monocytes, and lymphocytes. Adenylate cyclase toxin invades phagocytes and induces high levels of cyclic adenosine monophosphate ...
Arginine adenosine-5′-diphosphoribosylation (ADP-ribosylation) is an enzyme-catalyzed potentially reversible posttranslational changes where the ADP-ribose moiety is transferred from NAD+ towards the guanidino CHR2797 moiety of arginine. proteins with binding companions e.g. toxin-catalyzed ADP-ribosylation of actin at R177 blocks actin polymerization sterically. In case there is the nucleotide-gated P2X7 ion route ADP-ribosylation at R125 near the ligand-binding site causes route Rabbit Polyclonal to SF3B3. gating. Arginine-specific ADP-ribosyltransferases (ARTs) bring a quality R-S-EXE theme that distinguishes these enzymes from structurally related enzymes which catalyze ADP-ribosylation of additional amino acid part chains DNA or little substances. Arginine-specific ADP-ribosylation could be inhibited by little molecule arginine analogues such as for example CHR2797 agmatine or meta-iodobenzylguanidine (MIBG) which ...
Guanine nucleotide-binding proteins (G-proteins) are known to act as important modulators of insulin release from the islets of Langerhans. We have recently found that the deoxynojirimycin-derivative emiglitate, a recognized inhibitor of intestinal α-glucosidehydrolase activity, is a powerful inhibitor of glucose-induced insulin release. With the use of isolated mouse islets the present investigation was performed in a primary attempt to elucidate whether this inhibitory mechanism in some way was linked to the β-cell G-protein system. Treatment of freshly isolated islets with pertussis toxin (PTX), which is known to inactivate the Gi-proteins, abolished the inhibitory effect of the α2-adrenoceptor agonist clonidine on insulin release stimulated by the phosphodiesterase inhibitor IBMX in the presence of the protein kinase C activator TPA and even changed it into an increase. Emiglitate did ...
GDP-dissociation inhibitors (GDIs) play a primary role in modulating the activity of GTPases. We recently reported the identification of a new GDI for the Rho-related GTPases named RhoGDIgamma. This gene is now designated ARHGDIG by HUGO. Here, in a detailed analysis of tissue expression of ARHGDIG, we observe high levels in the entire brain, with regional variations. The mRNA is also present at high levels in kidney and pancreas and at moderate levels in spinal cord, stomach, and pituitary gland. In other tissues examined, the mRNA levels are very low (lung, trachea, small intestine, colon, placenta) or undetectable. RT-PCR analysis of total RNA isolated from exocrine pancreas and islets shows that the gene is expressed in both tissues. We also report the genomic structure of ARHGDIG. The gene spans over 4 kb and is organized into six exons and five introns. The upstream region lacks a canonical TATA box and contains ...
Rhodopsin is a member of an ancient class of receptors that transduce signals through their interaction with guanine nucleotide-binding proteins (G proteins). We have mapped the sites of interaction of rhodopsin with its G protein, which by analogy suggests how other members of this class of receptors may interact with their G proteins. Three regions of rhodopsins cytoplasmic surface interact with the rod cell G protein transducin (Gt). These are (i) the second cytoplasmic loop, which connects rhodopsin helices III and IV, (ii) the third cytoplasmic loop, which connects rhodopsin helices V and VI, and (iii) a putative fourth cytoplasmic loop formed by amino acids 310-321, as the carboxyl-terminal sequence emerges from helix VII and anchors to the lipid bilayer via palmitoylcysteines 322 and 323. Evidence for these regions of ...
The NADPH oxidase generates microbicidal superoxide in phagocytes, and when defective it leads to chronic granulomatous disease (CGD). Oxidase specific proteins in the cytosol, p47phox and p67phox, as well as the small GTP binding protein p21rac are important for activation of superoxide production. Because the activity of this oxidase is normally tightly restricted to the phagocytic vacuole, and its temporal and spatial organisation might be regulated by cytoskeletal proteins, we examined the cytosolic phox proteins for interactions with cytoskeletal elements. p67phox copurified with a 57 kDa protein, identified as coronin, an actin binding protein that is important for movement and phagocytosis in Dictyostelium. Binding studies revealed ...
The nonselective alpha-adrenergic agonist oxymetazoline inhibits parathyroid hormone (PTH)-stimulated cAMP production in intact OK cells, an epithelial cell line derived from an American opossum kidney. This inhibition, however, is not blocked by alpha 2-adrenergic receptor antagonists. After excluding several alternate hypotheses to explain this anomalous activity of oxymetazoline, we hypothesized that oxymetazoline activates a receptor in OK cells that is negatively coupled to adenylate cyclase but distinct from the alpha 2-adrenergic receptor. Prior exposure of OK cells to pertussis toxin blocks the inhibitory response to oxymetazoline, suggesting involvement of a guanine nucleotide-binding regulatory protein. Screening various compounds for attenuation of PTH-stimulated adenylate cyclase showed that serotonin (5HT) is a potent and fully efficacious agonist. Desensitization of alpha 2-receptor-mediated inhibition of cAMP production by epinephrine did not ...
Myc-DDK-tagged ORF clone of Homo sapiens GDP dissociation inhibitor 2 (GDI2), transcript variant 2 as transfection-ready DNA - 10 µg - OriGene - cdna clones
Recent clinical studies have revealed that increased serum triglyceride (TG) levels are closely related to atherosclerosis, independently of serum levels of high-density lipoproteins (HDL) and low-density lipoproteins (LDL). Among triglyceride-rich lipoproteins (TRLs), remnant lipoproteins (RLPs) are considered to be atherogenic and an independent coronary risk factor. We previously reported that monocytes cultured in the presence of RLPs increased their adhesion to vascular endothelial cells. The underlying mechanism involved activation of RhoA, a member of small GTP binding proteins, resulting in activation of focal adhesion kinase (FAK) and s1-integrin. It is also known that RLPs enter vessel walls. In another study, we reported that RLPs induced smooth muscle cell (SMC) proliferation, independently of oxidative stress. Recently, we identified the ...
By using MT1 homodimers and MT1/MT2 heterodimers as model GPCRs, we are extending here two emerging concepts: the pre‐assembly of GPCR‐interacting complexes and the asymmetric function and organization of GPCR dimers. In addition, we are providing a new functional justification for GPCR dimerization that applies to homo‐ and heterodimers, namely the possibility of simultaneous and direct binding of GPCR‐interacting proteins (GIPs) to the same GPCR dimer composed of two asymmetric protomers. Heterotrimeric G proteins are central, although not exclusive signal transducers of GPCRs. An increasing number of reports suggests the formation of pre‐assembled receptor-G‐protein complexes, which rearrange upon agonist activation of the receptor (Bunemann et al, 2003; Galés et al, 2006; Audet et al, 2008). This central complex is surrounded by a number of other GIPs that might either compete with the G ...
Proteins that hydrolyze guanine triphosphate to yield guanine diphosphate. This is a class of proteins that belongs to a family of high energy phosphate hydrolases. Members of this family play major roles in biological signal transduction pathways.
Guanosine triphosphate, labeled on the alpha phosphate group with 32P, is typically used in reactions involving enzymes that will incorporate the ribonucleoside monophosphate (base, sugar, and alpha-labeled phosphate) into a chain of RNA. Common applications include:. ...
Guanine nucleotide-binding proteins (G proteins) ares involved as modulators or transducers in various transmembranes signaling ...
2. Ans. is other than B & E. IN the presence of GTP & all the process has -deltaG & the original AA to Prot reaction has been combined with the GTP hydrolysis as its individual deltaG is positive. MOre than that for deltaG to be positive u cant have -deltaH along with +deltaS. Im seeing for more info ...
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Novel regulatory mechanisms for the Dbl family guanine nucleotide exchange factor Cool‐2/α‐Pix | The EMBO JournalNovel regulatory mechanisms for the Dbl family guanine nucleotide exchange factor Cool‐2/α‐Pix | The EMBO Journal

... bound and GTPbound states (Boguski and McCormick, 1993). Rho family proteins, such as Cdc42 and Rac, are activated by a number ... B) Monomeric Cool‐2 shows GEF activity toward Cdc42 or Rac. The interaction of a G protein βγ subunit complex with PAK and the ... bound Cdc42 or Rac and the Cool‐2 monomer. The βγ subunit complex of large GTPbinding proteins, by interacting with PAK, ... bound Cdc42 or Rac to bind and undergo nucleotide exchange. The binding of Cbl‐b to the SH3 domain of monomeric Cool‐2 also ...
more infohttp://emboj.embopress.org/content/23/17/3492.long

Ethylene Rapidly Up-Regulates the Activities of Both Monomeric GTP-Binding Proteins and Protein Kinase(s) in Epicotyls of Pea |...Ethylene Rapidly Up-Regulates the Activities of Both Monomeric GTP-Binding Proteins and Protein Kinase(s) in Epicotyls of Pea |...

1992) The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70:401-410. ... ethylene affects the activation of both monomeric GTP-binding proteins (monomeric G-proteins) and protein kinases. For ... Ethylene Rapidly Up-Regulates the Activities of Both Monomeric GTP-Binding Proteins and Protein Kinase(s) in Epicotyls of Pea. ... ethylene promoted GTP binding to proteins in the appropriate range of molecular masses for monomeric G-proteins (20-30 kD); ...
more infohttp://www.plantphysiol.org/node/23738.full.print

Superfamily of monomeric GTP-binding proteins in plants: 1. Role of rop proteins in the control of plant growth and development...Superfamily of monomeric GTP-binding proteins in plants: 1. Role of rop proteins in the control of plant growth and development...

Role of rop proteins in the control of plant growth and development, Russian Journal of Plant Physiology" on DeepDyve, the ... "Superfamily of monomeric GTP-binding proteins in plants: 1. ... The Small GTP-Binding Protein Rac Is a Regulator of Cell Death ... Superfamily of monomeric GTP-binding proteins in plants: 1. Role of rop proteins in the control... Novikova, G.; Moshkov, I. ... Superfamily of monomeric GTP-binding proteins in plants: 1. Role of rop proteins in the control of plant growth and development ...
more infohttps://www.deepdyve.com/lp/springer_journal/superfamily-of-monomeric-gtp-binding-proteins-in-plants-1-role-of-rop-bJUCGEA0QQ

Rac3 - WikipediaRac3 - Wikipedia

Rac3 (Ras-related C3 botulinum toxin substrate 3) is a small (~21 kDa) monomeric GTP-binding protein G protein and is an ... It is a member of the Rac subfamily of the Rho family of small G proteins and is encoded by the gene RAC3. Courjal F, Chuchana ... RAC3 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH). ...
more infohttps://en.wikipedia.org/wiki/Rac3

RhoG - WikipediaRhoG - Wikipedia

Other proteins known to bind RhoG in its GTP-bound state include the microtubule-associated protein kinectin, Phospholipase D1 ... RhoG (Ras homology Growth-related) (or ARGH) is a small (~21 kDa) monomeric GTP-binding protein (G protein), and is an ... is sufficient to promote GTP-loading of Rac. RhoG-mediated Rac signalling has been shown to promote neurite outgrowth and cell ... Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG". The Journal of ...
more infohttps://en.wikipedia.org/wiki/RhoG

Angiotensin II Signal Transduction Through Small GTP-Binding Proteins | HypertensionAngiotensin II Signal Transduction Through Small GTP-Binding Proteins | Hypertension

Small GTP-binding proteins (G proteins) are monomeric G proteins with a low molecular weight of 20 to 40 kDa. A small G protein ... Rac regulates cardiovascular superoxide through diverse molecular interactions: more than a binary GTP switch. Am J Physiol ... Also, eIF4E is released from eIF4E binding protein/PHAS-I on phosphorylation of eIF4E binding protein/PHAS-I regulated through ... Angiotensin II Signal Transduction Through Small GTP-Binding Proteins. Haruhiko Ohtsu, Hiroyuki Suzuki, Hidekatsu Nakashima, ...
more infohttp://hyper.ahajournals.org/content/48/4/534

Relationship between p38 mitogen-activated protein kinase and small GTPase Rac for the activation of NADPH oxidase in bovine...Relationship between p38 mitogen-activated protein kinase and small GTPase Rac for the activation of NADPH oxidase in bovine...

Monomeric GTP-Binding Proteins NADPH Oxidase Phosphatidylinositol 3-Kinase p38 Mitogen-Activated Protein Kinases ... Furthermore, SB203580 abolished the OZ-elicited activation of Rac, which was assessed by detecting the GTP-bound form of this ... Furthermore, SB203580 abolished the OZ-elicited activation of Rac, which was assessed by detecting the GTP-bound form of this ... Furthermore, SB203580 abolished the OZ-elicited activation of Rac, which was assessed by detecting the GTP-bound form of this ...
more infohttps://kyushu-u.pure.elsevier.com/en/publications/relationship-between-p38-mitogen-activated-protein-kinase-and-sma

Protocols and Video Articles Authored by Xuehua XuProtocols and Video Articles Authored by Xuehua Xu

Imaging G Protein-coupled Receptor-mediated Chemotaxis and its Signaling Events in Neutrophil-like HL60 Cells ... Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum, ... The coupling of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) with G proteins is ... Diverse chemokines bind to their receptors to activate small G protein Rac through an evolutionarily conserved mechanism. Elmo ...
more infohttps://www.jove.com/author/Xuehua_Xu

p21-Activated Kinases | Profiles RNSp21-Activated Kinases | Profiles RNS

... that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN ... Mitogen-Activated Protein Kinase Phosphatases. *Mitogen-Activated Protein Kinases. *Monomeric GTP-Binding Proteins ...
more infohttps://profiles.rush.edu/display/18192

KRAS elisa kit | Human v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ELISA Kit-NP 004976.2KRAS elisa kit | Human v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ELISA Kit-NP 004976.2

Molecular Function: protein binding; GDP binding; GTP binding; GMP binding; protein complex binding; LRR domain binding. ... Protein type: G protein; G protein, monomeric; Motility/polarity/chemotaxis; Oncoprotein; G protein, monomeric, Ras. ... KRas: Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Interacts with PHLPP. Interacts (active GTP-bound form ... positive regulation of Rac protein signal transduction; negative regulation of cell differentiation; Ras protein signal ...
more infohttps://www.mybiosource.com/kras-human-elisa-kits/v-ki-ras2-kirsten-rat-sarcoma-viral-oncogene-homolog/936810

FERONIA receptor-like kinase regulates RHO GTPase signaling of root hair development | PNASFERONIA receptor-like kinase regulates RHO GTPase signaling of root hair development | PNAS

RHO GTPases are a large family of related monomeric GTP-binding proteins that serve diverse signaling functions (1). Plant RAC/ ... Moreover, ROP2 maltose-binding protein (MBP) efficiently pulled down pFER-expressed FER-GFP from seedling microsomal proteins ... It is known that most ROPGEFs preferentially bind to GDP-bound RAC/ROPs versus the GTP-bound activated form (19, 20), ... 3J) are preferentially pulled down by GDP-bound RAC/ROPs but not as efficiently by the GTP-bound form (19, 20). Together with ...
more infohttp://www.pnas.org/content/107/41/17821

Purification, crystallization and preliminary X-ray crystallographic analysis of a rice Rac/Rop GTPase, OsRac1.  - PubMed - NCBIPurification, crystallization and preliminary X-ray crystallographic analysis of a rice Rac/Rop GTPase, OsRac1. - PubMed - NCBI

Plant Proteins/isolation & purification*. *rac GTP-Binding Proteins/chemistry*. *rac GTP-Binding Proteins/isolation & ... OsRac1, a rice Rac/Rop protein, is a key regulator of reactive oxygen species (ROS) production and induces immune responses. ... The cross represents the peak-top position of OsRac1, assuming the molecular weight of the monomeric form containing GMPPNP and ... Plant small Rac/Rop GTPases have recently received broad attention as it is becoming clear that these enzymes regulate various ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/%20%20%20%2024419631

cdc42 GTP-Binding Protein | Profiles RNScdc42 GTP-Binding Protein | Profiles RNS

A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions ... cdc42 GTP-Binding Protein. *cdc42 GTP-Binding Protein, Saccharomyces cerevisiae. *rac GTP-Binding Proteins ... G25K GTP-Binding Protein, Placental Isoform*G25K GTP-Binding Protein, Placental Isoform ... "cdc42 GTP-Binding Protein" by people in this website by year, and whether "cdc42 GTP-Binding Protein" was a major or minor ...
more infohttps://profiles.umassmed.edu/display/127488

rho GTP-Binding Proteins
      - rho GTP-Binding Protein
     Summary Report | CureHunterrho GTP-Binding Proteins - rho GTP-Binding Protein Summary Report | CureHunter

A large family of MONOMERIC GTP-BINDING PROTEINS that are involved in regulation of actin organization, gene expression and ... rho GTP-Binding Proteins: 320*rhoA GTP-Binding Protein: 46. *rac GTP-Binding Proteins: 15 ... GTP-Binding Proteins: 5070*Monomeric GTP-Binding Proteins: 286*rho GTP-Binding Proteins: 320*rhoA GTP-Binding Protein: 46 ... rho GTP-Binding Protein; P21 (rho)Protein; rho Protein P21; G-Proteins, rho; GTP-Binding Protein, rho; GTP-Binding Proteins, ...
more infohttp://www.curehunter.com/public/keywordSummaryD020741.do

mediaTUM - Medien- und PublikationsservermediaTUM - Medien- und Publikationsserver

Plant Proteins/genetics/metabolism; Protein Interaction Mapping; Protein-Serine-Threonine Kinases/genetics/metabolism; ... Certain plant receptor-like cytoplasmic kinases were reported to interact with small monomeric G-proteins of the RHO of plant ( ... We identified a barley (Hordeum vulgare) partial cDNA of a ROP binding protein kinase (HvRBK1) in yeast (Saccharomyces ... Barley HvRBK1 is an active kinase in vitro, and activity is enhanced by CA HvRACB or GTP-loaded HvRAC1. Hence, HvRBK1 might act ...
more infohttp://mediatum.ub.tum.de/1379833

Phosphoinositide 3-kinase targeting by the β galactoside binding protein cytokine negates akt gene expression and leads...Phosphoinositide 3-kinase targeting by the β galactoside binding protein cytokine negates akt gene expression and leads...

Previously we have shown that the β galactoside binding protein (βGBP) cytokine, an antiproliferative molecule, induces ... The role of the PI3K signalling network in cell proliferation, cell survival and, through PI3K interaction with Rac proteins, ... We have recently shown that monomeric β-galactoside binding protein (βGBP), a molecule that we first discovered to be an ... to the SH3 domains of Grb2 and the conversion of GDP-Ras to active GTP-Ras which mediates the activation of effector pathways ...
more infohttps://0-breast--cancer--research-biomedcentral-com.brum.beds.ac.uk/articles/10.1186/bcr2217

ES domain oligomerization is necessary and sufficient f | Open-iES domain oligomerization is necessary and sufficient f | Open-i

Recombinant Fusion Proteins/genetics/metabolism. *cdc42 GTP-Binding Protein/genetics/metabolism. *rac GTP-Binding Proteins/ ... Summary of motogenic activity of monomeric, dimeric, and trimeric ES domain derivatives. Mentions: HUVECs were plated into ... Recombinant Fusion Proteins/genetics/metabolism. *cdc42 GTP-Binding Protein/genetics/metabolism. *rac GTP-Binding Proteins/ ... This motogenic activity required ES domain oligomerization, was dependent on rac, cdc42, and mitogen-activated protein kinase, ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC2199214_JCB0008119.f3ef&req=4

Regulation by GEFs | MigrationsRegulation by GEFs | Migrations

In the same vein as my recent post on kinase structures and autoinhibition of multimodular signaling proteins, last weeks ... GTP) into the diphosphate form (GDP). The GTP-bound form is generally the "active" form, whereas GDP-bound G proteins are " ... the Rho family of monomeric GTPases. Rho GTPases include Rho, Rac and Cdc42, which all effect the cytoskeleton (and therefore ... "inactive." Thus, GTP hydrolysis turns the cell off, until the GDP dissociates from the G protein. This makes a GTPase a ...
more infohttps://migration.wordpress.com/2007/06/20/regulation-by-gefs/

Elevated Phospholipase D Activity in H-Ras- but Not K-Ras-Transformed Cells by the Synergistic Action of RalA and ARF6 |...Elevated Phospholipase D Activity in H-Ras- but Not K-Ras-Transformed Cells by the Synergistic Action of RalA and ARF6 |...

... and Rho family monomeric GTP-binding proteins and protein kinase C α. J. Biol. Chem. 272:3860-3868. ... Differential activation of the Rac pathway by Ha-Ras and K-Ras. J. Biol. Chem. 276:15609-15615. ... Ral-BD is the Ral binding domain of Ral-BP1 that binds activated GTP-bound Ral proteins (76, 77). Activated Ral proteins were ... Neutrophil phospholipase D is activated by a membrane-associated Rho family small molecular weight GTP-binding protein. J. Biol ...
more infohttps://mcb.asm.org/content/23/2/645?ijkey=3bfcb7d1725258cfbcd7d15f9c864e6144372e0d&keytype2=tf_ipsecsha

Integrated G Proteins Signaling in Plants | Shaul Yalovsky | SpringerIntegrated G Proteins Signaling in Plants | Shaul Yalovsky | Springer

The Role of Seven-Transmembrane Domain MLO Proteins, Heterotrimeric G-Proteins, and Monomeric RAC/ROPs in Plant Defense ... Unconventional GTP-Binding Proteins in Plants. Ding, Lei (et al.). Pages 279-303 ... Protein-Lipid Modifications and Targeting of ROP/RAC and Heterotrimeric G Proteins ... Integrated G Proteins Signaling in Plants. Editors: Yalovsky, Shaul, Baluska, Frantisek, Jones, Alan (Eds.) ...
more infohttp://www.springer.com/us/book/9783642035234

ARF6 elisa kit | Human ADP ribosylation factor 6 (ARF6) ELISA Kit-NP 001654.1ARF6 elisa kit | Human ADP ribosylation factor 6 (ARF6) ELISA Kit-NP 001654.1

Molecular Function: GTPase activity; protein binding; GTP binding; thioesterase binding. Biological Process: myeloid cell ... Protein type: Motility/polarity/chemotaxis; G protein, monomeric, ARF; G protein, monomeric. Chromosomal Location of Human ... regulation of Rac protein signal transduction; protein transport; positive regulation of actin filament polymerization; cell ... The ARF genes encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera ...
more infohttps://www.mybiosource.com/prods/ELISA-Kit/Human/ADP-ribosylation-factor-6-ARF6/ARF6/datasheet.php?products_id=7221883

The GDP Exchange Factor AND-34 Is Expressed in B Cells, Associates With HEF1, and Activates Cdc42 | The Journal of ImmunologyThe GDP Exchange Factor AND-34 Is Expressed in B Cells, Associates With HEF1, and Activates Cdc42 | The Journal of Immunology

Significantly higher levels of GTP-bound Cdc42 (Fig. 7⇓A, right panel) but not Rac (Fig. 7⇓B, right panel) or Rho (Fig. 7⇓C, ... Proteins were released from the beads by boiling in protein sample buffer for 5 min and separated on a SDS-PAGE gel. After ... but it is possible that signaling within the Cas family member complexes is altered by conversion from dimeric to monomeric ... 7⇓F). Of note, levels of GTP-bound Rac were constitutively high in murine B cell lines, reducing the sensitivity of this assay ...
more infohttp://www.jimmunol.org/content/170/2/969?ijkey=5e163188919689daab370c4d49dd15de6a53e605&keytype2=tf_ipsecsha

KRAS (Kirsten rat sarcoma 2 viral oncogene homolog)KRAS (Kirsten rat sarcoma 2 viral oncogene homolog)

analogously to other GTP-binding proteins (such as Translation Elongation Factor EFTu or signal transducing G-Proteins) RAS ... GABAergic positive regulation of Rac protein signal transduction response to isolation stress endocrine signaling positive ... genes encode small monomeric proteins of low molecular mass (20-30 kDa) which share at least 30% homology to RAS proteins. ... pathway GTPase activity protein binding GTP binding cytoplasm mitochondrion cytosol plasma membrane focal adhesion Ras protein ...
more infohttp://atlasgeneticsoncology.org/Genes/GC_KRAS.html

KRAS (Kirsten rat sarcoma 2 viral oncogene homolog)KRAS (Kirsten rat sarcoma 2 viral oncogene homolog)

analogously to other GTP-binding proteins (such as Translation Elongation Factor EFTu or signal transducing G-Proteins) RAS ... GABAergic positive regulation of Rac protein signal transduction response to isolation stress endocrine signaling positive ... genes encode small monomeric proteins of low molecular mass (20-30 kDa) which share at least 30% homology to RAS proteins. ... pathway GTPase activity protein binding GTP binding cytoplasm mitochondrion cytosol plasma membrane focal adhesion Ras protein ...
more infohttp://www.atlasgeneticsoncology.org/Genes/KRASID91.html

rho GTP-Binding Proteins | Harvard Catalyst Profiles | Harvard Catalystrho GTP-Binding Proteins | Harvard Catalyst Profiles | Harvard Catalyst

cdc42 GTP-Binding Protein. *cdc42 GTP-Binding Protein, Saccharomyces cerevisiae. *rac GTP-Binding Proteins ... A large family of MONOMERIC GTP-BINDING PROTEINS that are involved in regulation of actin organization, gene expression and ... "rho GTP-Binding Proteins" by people in Harvard Catalyst Profiles by year, and whether "rho GTP-Binding Proteins" was a major or ... "rho GTP-Binding Proteins" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ...
more infohttps://connects.catalyst.harvard.edu/Profiles/display/Concept/rho%20GTP-Binding%20Proteins
  • The first are known as Guanine nucleotide exchange factors (GEFs) and these facilitate the exchange of GDP for GTP so as to promote subsequent RhoG-mediated signalling. (wikipedia.org)
  • A third group, known as Guanine nucleotide dissociation inhibitors (GDIs), inhibit dissociation of GDP and thus lock the G protein in its inactive state. (wikipedia.org)
  • Prototypically, the growth factor receptor on activation recruits a Ras guanine nucleotide exchange factor (GEF), Sos, via adaptor proteins Shc and Grb2. (ahajournals.org)
  • They shuttle between the GDP-bound inactive state and the GTP-bound activated state and their activation is predominantly mediated by a family of guanine nucleotide exchange factors (GEFs) referred to as ROPGEFs. (pnas.org)
  • In studies involving the Arabidopsis ROOT HAIR DEFECTIVE2 ( RHD2 / RBOHC ) gene encoding a NADPH oxidase and SUPERCENTIPEDE, which encodes a RAC/ROP negative regulator, guanine nucleotide dissociation inhibitor (GDI) (see Fig. S1 A ), Dolan and colleagues provided compelling evidence for a RAC/ROP-mediated NADPH oxidase-dependent pathway for ROS-regulated root hair development ( 16 , 17 ). (pnas.org)
  • Although relying on guanine nucleotide exchange for activation is conserved for RAC/ROPs ( Fig. S1 A ), their activation is largely dependent on a unique guanine exchange factor (GEF) family referred to as ROPGEFs ( 19 - 21 ). (pnas.org)
  • In the same vein as my recent post on kinase structures and autoinhibition of multimodular signaling proteins, last week's Nature had a post on Rewiring cellular morphology pathways with synthetic guanine nucleotide exchange factors (Yeh et al. (wordpress.com)
  • 2007). Here, instead of kinases as the signaling regulators inside the cell, we're talking about a class of proteins called guanine nucleotide exchange factors (GEFs). (wordpress.com)
  • The ARF genes encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The product of this gene is localized to the plasma membrane, and regulates vesicular trafficking, remodelling of membrane lipids, and signaling pathways that lead to actin remodeling. (mybiosource.com)
  • Interestingly, ARF6 protein levels were elevated in H-Ras- but not K-Ras-transformed cells. (asm.org)
  • Unlike Rho G-proteins, which undergo prenylation and methylation at their COOH-terminal cysteine residues, ARF6 undergoes myristoylation ( 1 , 2 ). (diabetesjournals.org)
  • OsRac1, a rice Rac/Rop protein, is a key regulator of reactive oxygen species (ROS) production and induces immune responses. (nih.gov)
  • Previously we have shown that the β galactoside binding protein (βGBP) cytokine, an antiproliferative molecule, induces functional inhibition of class 1A and class 1B PI3K. (beds.ac.uk)
  • Integrin signaling also induces formation of a complex of p130Cas, the adapter protein Crk, and a third molecule, DOCK 180, that is required for membrane ruffling, a component of cell migration ( 13 , 14 ). (jimmunol.org)
  • Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum Xuehua Xu 1 , Tian Jin 1 1 Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health Here, we describe detailed live cell imaging methods for investigating chemotaxis. (jove.com)
  • Imaging G Protein-coupled Receptor-mediated Chemotaxis and its Signaling Events in Neutrophil-like HL60 Cells Xi Wen 1 , Tian Jin 1 , Xuehua Xu 1 1 Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health Visual chemotaxis assays are essential for a better understanding of how eukaryotic cells control chemoattractant-mediated directional cell migration. (jove.com)
  • Here, we quantitatively measure temporal and spatial changes of receptor occupancy, G-protein activation by FRET imaging, and PIP3 levels by monitoring the dynamics of PH(Crac)-GFP translocation in single living cells in response to different chemoattractant fields. (jove.com)
  • Using the Arabidopsis ROPGEF1 as bait, we identified members of a receptor-like kinase (RLK) family as potential upstream regulators for RAC/ROP signaling. (pnas.org)
  • Angiotensin II (AngII), the vasoactive hormone of the renin-angiotensin system, initiates its cellular effects through activation of its cognate seven transmembrane-spanning G protein-coupled receptor, angiotensin type 1A (AT 1A ) receptor (AT 1A R). Interaction of AngII with the AT 1A R initiates conformational changes in the receptor, producing activation of its targeted G protein, G q/11 . (aspetjournals.org)
  • We have shown previously that nuclear localization of the receptor may be dependent upon a putative nuclear localization sequence within the carboxyl tail and that localization to the nuclear area from the plasma membrane involves clathrin-coated pits and is associated with the ability of AngII to induce COX-2 protein expression (Morinelli et al. (aspetjournals.org)
  • We show that the fer phenotypes correlated with reduced levels of active RAC/ROPs and NADPH oxidase-dependent, auxin-regulated ROS accumulation in roots and root hairs and that up-regulating RAC/ROP signaling in fer countered the mutant phenotypes. (pnas.org)
  • Interaction between RAC/ROPs and NADPH oxidase underlies activation of pathogen-elicited reactive oxygen species (ROS)-mediated defense response in rice ( 7 ). (pnas.org)
  • Given their involvement in diverse biological processes, RAC/ROPs may act as integration points for crosstalk between multiple signaling pathways ( 2 ). (pnas.org)
  • also called RAC) family in planta and to be activated by this interaction in vitro. (tum.de)
  • Protein interaction of the constitutively activated (CA) barley HvROPs CA HvRACB and CA HvRAC1 with full-length HvRBK1 was verified in yeast and in planta. (tum.de)
  • Protein interaction of the constitutively activated (CA) barley HvROPs CA HvRACB and CA HvRAC1 wi. (tum.de)
  • We propose that Tuba facilitates dorsal ruffling of melanoma cells through direct interaction with actin-regulatory proteins and the recruitment of signaling molecules to lipid microdomains for the coordinated assembly of a cytoskeletal network. (biologists.org)
  • There is evidence suggesting that PLD acts downstream from G-proteins, but a direct interaction of specific members has not been shown. (embl-heidelberg.de)
  • Together, such posttranslational modification steps have been proven to be essential for the targeting and association of these proteins with their membranous sites for optimal effector interaction ( 1 - 5 ). (diabetesjournals.org)
  • However, very little is known with regard to potential regulation by G-protein regulatory factors (e.g., the guanosine diphosphate-dissociation inhibitor [GDI]) of insulin secretion from the islet β-cell. (diabetesjournals.org)
  • The first one involves the ability of the GDI to prevent dissociation of GDP from Rho G-proteins. (diabetesjournals.org)
  • Phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002, blocked not only p38 MAPK activation but also Rac activation. (elsevier.com)
  • Well characterised examples include the dual specificity GEF TRIO which is able to promote nucleotide exchange on RhoG and Rac (via its GEFD1 domain) and also on RhoA via a separate GEF domain (GEFD2). (wikipedia.org)
  • Several RAC/ROP effectors have been identified (see Fig. S1 A ). These include a family of CRIB-domain proteins (RICs) and a coiled-coil domain protein (ICR1). (pnas.org)
  • The proposed model for RhoG-dependent Rac activation involves recruitment of the ELMO/Dock180 complex to activated RhoG at the plasma membrane and this relocalisation, together with an ELMO-dependent conformational change in Dock180, is sufficient to promote GTP-loading of Rac. (wikipedia.org)
  • OZ stimulation induced the translocation of p47 phox and Rac to the plasma membrane and SB203580 completely blocked the translocation of Rac, but only partially blocked that of p47 phox . (elsevier.com)
  • Ligands for RTKs include soluble or membrane bound peptide or protein hormones such as insulin, epidermal growth factor (EGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF) and many more GFs. (johanneswilbertz.com)
  • Bound proteins have been eluted in 5 × 1% SDS sample buffer and examined by 12% SDS Page and western blot with anti RhoA antibody evaluation. (micrornamimic.com)
  • In plants, multiple transmembrane spanning NADPH oxidases, homologous to the catalytic gp91 phox subunit of the mammalian enzyme, have been found to underlie several RAC/ROP-mediated, ROS-regulated growth and stress-induced responses. (pnas.org)
  • These results provide a first indication for a direct regulation of PLDalpha by a heterotrimeric G-protein alpha-subunit in plants. (embl-heidelberg.de)
  • The cross represents the peak-top position of OsRac1, assuming the molecular weight of the monomeric form containing GMPPNP and Mg 2+ ion. (nih.gov)
  • When the G-protein was included in the PLD assay, a strong dosage-dependent inhibition of the PLD activity was observed. (embl-heidelberg.de)
  • Similarly, up-regulating RAC/ROP activity by overexpressing a constitutively active RAC/ROP in transgenic Arabidopsis seedlings also induced ectopic accumulation of NADPH oxidase-derived ROS and defective root hairs ( 18 ). (pnas.org)
  • Palmitoylation of rPLD1 is not necessary for catalytic activity, since N-terminal truncation mutants lacking the first 168 or 319 amino acids exhibit high basal activity although they cannot be stimulated by protein kinase C (PKC). (embl-heidelberg.de)
  • Its minimal effector region (amino acids 30-40) is identical to Ras, but the protein differs at nine amino acids within the extended effector region comprising amino acids 23-46 (2) . (aacrjournals.org)
  • NADPH oxidase-derived reactive oxygen species (ROS) are emerging as important regulators for growth and development and play a crucial role in mediating RAC/ROP-regulated root hair development, a polarized cell growth process. (pnas.org)
  • Specifically, they showed that NADPH oxidase-derived ROS is required for polarized root hair growth and regulated RAC/ROP activity controls production and spatially regulated accumulation of ROS at the tip of emerging and elongating root hairs. (pnas.org)
  • Collagen XVIII (c18) is a triple helical endothelial/epithelial basement membrane protein whose noncollagenous (NC)1 region trimerizes a COOH-terminal endostatin (ES) domain conserved in vertebrates, Caenorhabditis elegans and Drosophila. (nih.gov)
  • Identification of novel membrane-bound phospholipase D from Streptoverticillium cinnamoneum, possessing only hydrolytic activity. (embl-heidelberg.de)
  • A membrane-bound phospholipase D (PLD) has been identified and isolated in a soluble form from an actinomycete, Streptoverticillium cinnamoneum. (embl-heidelberg.de)
  • Barley HvRBK1 is an active kinase in vitro, and activity is enhanced by CA HvRACB or GTP-loaded HvRAC1. (tum.de)