Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.
Signaling proteins which function as master molecular switches by activating Rho GTPases through conversion of guanine nucleotides. Rho GTPases in turn control many aspects of cell behavior through the regulation of multiple downstream signal transduction pathways.
A family of GUANINE NUCLEOTIDE EXCHANGE FACTORS that are specific for RAS PROTEINS.
Proto-oncogene proteins that are guanine nucleotide exchange factors for RHO GTPASES. They also function as signal transducing adaptor proteins.
A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.
A guanine nucleotide exchange factor that is expressed primarily in neuronal tissue and may be specific for the Ha-ras homolog of the RAS PROTEINS.
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.
Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.
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.
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.
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 3.6.1.47
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.
A genetically related subfamily of RAP GTP-BINDING PROTEINS that share homology with RAS PROTEINS. They bind to Ras effectors but do not activate them, therefore they may antagonize the effects of RAS PROTEINS. This enzyme was formerly listed as EC 3.6.1.47.
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.
A 145-kDa guanine nucleotide exchange factor that is specific for rap1 and ras GTP-BINDING PROTEINS. It associates with SH3 domains of the crk family of signaling proteins.
Proteins that activate the GTPase of specific GTP-BINDING PROTEINS.
A mammalian homolog of the DROSOPHILA SON OF SEVENLESS PROTEIN. It is a guanine nucleotide exchange factor for RAS 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.-.
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.
Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.
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.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A guanine nucleotide exchange factor that stimulates the dissociation of GDP from RAL GTP-BINDING PROTEINS. It also has GDP exchange activity towards other MONOMERIC GTP-BINDING PROTEINS.
A class of RAS GUANINE NUCLEOTIDE EXCHANGE FACTORS that are genetically related to the Son of Sevenless gene from DROSOPHILA. Sevenless refers to genetic mutations in DROSOPHILA that cause loss of the R7 photoreceptor which is required to see UV light.
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.
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.
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.
A guanine nucleotide exchange factor that acts to restore EUKARYOTIC INITIATION FACTOR-2 to its GTP bound form.
A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. EC 3.6.1.-.
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.
A family of ubiquitously expressed MONOMERIC GTP-BINDING PROTEINS that are involved in intracellular signal transduction. This enzyme was formerly listed as EC 3.6.1.47.
A family of MONOMERIC GTP-BINDING PROTEINS that are related to RAS PROTEINS.This enzyme was formerly listed as EC 3.6.1.47.
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).)
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Protein factors that inhibit the dissociation of GDP from GTP-BINDING PROTEINS.
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)
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A ubiquitously expressed family of heterotrimeric GTP-binding protein alpha subunits that signal through interactions with a variety of second messengers as GTPASE-ACTIVATING PROTEINS; GUANINE NUCLEOTIDE EXCHANGE FACTORS; and HEAT SHOCK PROTEINS. The G12-G13 part of the name is also spelled G12/G13.
A protein complex comprised of COATOMER PROTEIN and ADP RIBOSYLATION FACTOR 1. It is involved in transport of vesicles between the ENDOPLASMIC RETICULUM and the GOLGI APPARATUS.
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
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 3.6.1.47
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
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.
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.
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.
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.
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.
Eukaryotic initiation factor of protein synthesis. In higher eukaryotes the factor consists of three subunits: alpha, beta, and gamma. As initiation proceeds, eIF-2 forms a ternary complex with Met-tRNAi and GTP.
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.
A group of eukaryotic high-molecular mass heat-shock proteins that represent a subfamily of HSP70 HEAT-SHOCK PROTEINS. Hsp110 proteins prevent protein aggregation and can maintain denatured proteins in folding-competent states.
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.
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.
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.
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.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in vesicle transport between the ENDOPLASMIC RETICULUM and the GOLGI APPARATUS and through early Golgi compartments. This enzyme was formerly listed as EC 3.6.1.47.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
A fungal metabolite which is a macrocyclic lactone exhibiting a wide range of antibiotic activity.
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A subcategory of guanine nucleotide dissociation inhibitors that are specific for RHO GTP-BINDING PROTEINS.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Transport proteins that carry specific substances in the blood or across cell membranes.
The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.
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.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
A structurally-diverse family of intracellular-signaling adaptor proteins that selectively tether specific protein kinase A subtypes to distinct subcellular sites. They play a role in focusing the PROTEIN KINASE A activity toward relevant substrates. Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA.
The rate dynamics in chemical or physical systems.
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.
Bundles of actin filaments (ACTIN CYTOSKELETON) and myosin-II that span across the cell attaching to the cell membrane at FOCAL ADHESIONS and to the network of INTERMEDIATE FILAMENTS that surrounds the nucleus.
Proteins found in any species of fungus.
A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS from SACCHAROMYCES CEREVISIAE. It is involved in morphological events related to the cell cycle. This enzyme was formerly listed as EC 3.6.1.47.
A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)
A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).
Proteins prepared by recombinant DNA technology.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
PROTEINS that specifically activate the GTP-phosphohydrolase activity of RAS PROTEINS.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A broad category of proteins involved in the formation, transport and dissolution of TRANSPORT VESICLES. They play a role in the intracellular transport of molecules contained within membrane vesicles. Vesicular transport proteins are distinguished from MEMBRANE TRANSPORT PROTEINS, which move molecules across membranes, by the mode in which the molecules are transported.
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.
A GTP-BINDING PROTEIN involved in regulating a signal transduction pathway that controls assembly of focal adhesions and actin stress fibers. This enzyme was formerly listed as EC 3.6.1.47.
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.
GTP-BINDING PROTEINS that contain three non-identical subunits. They are found associated with members of the seven transmembrane domain superfamily of G-PROTEIN-COUPLED RECEPTORS. Upon activation the GTP-BINDING PROTEIN ALPHA SUBUNIT of the complex dissociates leaving a dimer of a GTP-BINDING PROTEIN BETA SUBUNIT bound to a GTP-BINDING PROTEIN GAMMA SUBUNIT.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
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.
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.
Signal transducing adaptor proteins that contain SRC HOMOLOGY DOMAINS and play a role in CYTOSKELETON reorganization. c-crk protein is closely related to ONCOGENE PROTEIN V-CRK and includes several alternatively spliced isoforms.
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.
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.
A DNA sequence that is found in the promoter region of many growth-related genes. The regulatory transcription factor SERUM RESPONSE FACTOR binds to and regulates the activity of genes containing this element.
A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.
A dynamic actin-rich extension of the surface of an animal cell used for locomotion or prehension of food.
Peptide elongation factor 1 is a multisubunit protein that is responsible for the GTP-dependent binding of aminoacyl-tRNAs to eukaryotic ribosomes. The alpha subunit (EF-1alpha) binds aminoacyl-tRNA and transfers it to the ribosome in a process linked to GTP hydrolysis. The beta and delta subunits (EF-1beta, EF-1delta) are involved in exchanging GDP for GTP. The gamma subunit (EF-1gamma) is a structural component.
A guanine nucleotide exchange factor from DROSOPHILA. Sevenless refers to genetic mutations in DROSOPHILA that cause loss of the R7 photoreceptor which is required to see UV light.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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.
Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
A class of proteins involved in the transport of molecules via TRANSPORT VESICLES. They perform functions such as binding to the cell membrane, capturing cargo molecules and promoting the assembly of CLATHRIN. The majority of adaptor proteins exist as multi-subunit complexes, however monomeric varieties have also been found.
The process by which the CYTOPLASM of a cell is divided.
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.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Specialized structures of the cell that extend the cell membrane and project out from the cell surface.
An eph family receptor found exclusively in BRAIN. EphA8 receptors may play a role in the axonal guidance of a subset of tectal commissural NEURONS.
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.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
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.
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).
Retroviral proteins that have the ability to transform cells. They can induce sarcomas, leukemias, lymphomas, and mammary carcinomas. Not all retroviral proteins are oncogenic.
Adherence of cells to surfaces or to other cells.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
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.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
An abundantly-expressed rho GDP-dissociation inhibitor subtype that regulates a broad variety of RHO GTPASES.
A network of membrane compartments, located at the cytoplasmic side of the GOLGI APPARATUS, where proteins and lipids are sorted for transport to various locations in the cell or cell membrane.
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.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
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.
Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains.
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.
An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of the ACTIN CYTOSKELETON terminate and attach to the transmembrane linkers, INTEGRINS, which in turn attach through their extracellular domains to EXTRACELLULAR MATRIX PROTEINS.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
Nucleotides in which the base moiety is substituted with one or more sulfur atoms.
Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.
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.
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.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
A signal transducing adaptor protein that is encoded by the crk ONCOGENE from TYPE C AVIAN RETROVIRUSES. It contains SRC HOMOLOGY DOMAINS and is closely related to its cellular homolog, PROTO-ONCOGENE PROTEIN C-CRK.
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.
Macromolecular complexes formed from the association of defined protein subunits.
Elements of limited time intervals, contributing to particular results or situations.
The quality of surface form or outline of CELLS.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
A family of heterotrimeric GTP-binding protein alpha subunits that activate TYPE C PHOSPHOLIPASES dependent signaling pathways. The Gq-G11 part of the name is also spelled Gq/G11.
An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.
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.
An ephrin that was originally identified as the product of an early response gene induced by TUMOR NECROSIS FACTORS. It is linked to the CELL MEMBRANE via a GLYCOINOSITOL PHOSPHOLIPID MEMBRANE ANCHOR and binds EPHA2 RECEPTOR with high affinity. During embryogenesis high levels of ephrin-A1 are expressed in LUNG; KIDNEY; SALIVARY GLANDS; and INTESTINE.
In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.
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.
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.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
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.
Protein factors uniquely required during the initiation phase of protein synthesis in GENETIC TRANSLATION.
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.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The process of cleaving a chemical compound by the addition of a molecule of water.
A transfer RNA which is specific for carrying methionine to sites on the ribosomes. During initiation of protein synthesis, tRNA(f)Met in prokaryotic cells and tRNA(i)Met in eukaryotic cells binds to the start codon (CODON, INITIATOR).
Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.
A class of MOLECULAR CHAPERONES found in both prokaryotes and in several compartments of eukaryotic cells. These proteins can interact with polypeptides during a variety of assembly processes in such a way as to prevent the formation of nonfunctional structures.
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.
A process of GENETIC TRANSLATION whereby the formation of a peptide chain is started. It includes assembly of the RIBOSOME components, the MESSENGER RNA coding for the polypeptide to be made, INITIATOR TRNA, and PEPTIDE INITIATION FACTORS; and placement of the first amino acid in the peptide chain. The details and components of this process are unique for prokaryotic protein biosynthesis and eukaryotic protein biosynthesis.
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
Bulbous enlargement of the growing tip of nerve axons and dendrites. They are crucial to neuronal development because of their pathfinding ability and their role in synaptogenesis.
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
Protein interaction domains of about 70-90 amino acid residues, named after a common structure found in PSD-95, Discs Large, and Zona Occludens 1 proteins. PDZ domains are involved in the recruitment and interaction of proteins, and aid the formation of protein scaffolds and signaling networks. This is achieved by sequence-specific binding between a PDZ domain in one protein and a PDZ motif in another protein.
A type C phospholipase with specificity towards PHOSPHATIDYLINOSITOLS that contain INOSITOL 1,4,5-TRISPHOSPHATE. Many of the enzymes listed under this classification are involved in intracellular signaling.
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).
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Deletion of sequences of nucleic acids from the genetic material of an individual.
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.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
A family of heterotrimeric GTP-binding protein alpha subunits that activate ADENYLYL CYCLASES.
Methods for determining interaction between PROTEINS.
The subfamily of myosin proteins that are commonly found in muscle fibers. Myosin II is also involved a diverse array of cellular functions including cell division, transport within the GOLGI APPARATUS, and maintaining MICROVILLI structure.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
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.
Proteins which are involved in the phenomenon of light emission in living systems. Included are the "enzymatic" and "non-enzymatic" types of system with or without the presence of oxygen or co-factors.
A ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Protein factors uniquely required during the elongation phase of protein synthesis.

Ral-specific guanine nucleotide exchange factor activity opposes other Ras effectors in PC12 cells by inhibiting neurite outgrowth. (1/3221)

Ras proteins can activate at least three classes of downstream target proteins: Raf kinases, phosphatidylinositol-3 phosphate (PI3) kinase, and Ral-specific guanine nucleotide exchange factors (Ral-GEFs). In NIH 3T3 cells, activated Ral-GEFs contribute to Ras-induced cell proliferation and oncogenic transformation by complementing the activities of Raf and PI3 kinases. In PC12 cells, activated Raf and PI3 kinases mediate Ras-induced cell cycle arrest and differentiation into a neuronal phenotype. Here, we show that in PC12 cells, Ral-GEF activity acts opposite to other Ras effectors. Elevation of Ral-GEF activity induced by transfection of a mutant Ras protein that preferentially activates Ral-GEFs, or by transfection of the catalytic domain of the Ral-GEF Rgr, suppressed cell cycle arrest and neurite outgrowth induced by nerve growth factor (NGF) treatment. In addition, Rgr reduced neurite outgrowth induced by a mutant Ras protein that preferentially activates Raf kinases. Furthermore, inhibition of Ral-GEF activity by expression of a dominant negative Ral mutant accelerated cell cycle arrest and enhanced neurite outgrowth in response to NGF treatment. Ral-GEF activity may function, at least in part, through inhibition of the Rho family GTPases, CDC42 and Rac. In contrast to Ras, which was activated for hours by NGF treatment, Ral was activated for only approximately 20 min. These findings suggest that one function of Ral-GEF signaling induced by NGF is to delay the onset of cell cycle arrest and neurite outgrowth induced by other Ras effectors. They also demonstrate that Ras has the potential to promote both antidifferentiation and prodifferentiation signaling pathways through activation of distinct effector proteins. Thus, in some cell types the ratio of activities among Ras effectors and their temporal regulation may be important determinants for cell fate decisions between proliferation and differentiation.  (+info)

A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. (2/3221)

Small GTP-binding proteins of the Rho family play a critical role in signal transduction. However, there is still very limited information on how they are activated by cell surface receptors. Here, we used a consensus sequence for Dbl domains of Rho guanine nucleotide exchange factors (GEFs) to search DNA data bases, and identified a novel human GEF for Rho-related GTPases harboring structural features indicative of its possible regulatory mechanism(s). This protein contained a tandem DH/PH domain closely related to those of Rho-specific GEFs, a PDZ domain, a proline-rich domain, and an area of homology to Lsc, p115-RhoGEF, and a Drosophila RhoGEF that was termed Lsc-homology (LH) domain. This novel molecule, designated PDZ-RhoGEF, activated biological and biochemical pathways specific for Rho, and activation of these pathways required an intact DH and PH domain. However, the PDZ domain was dispensable for these functions, and mutants lacking the LH domain were more active, suggesting a negative regulatory role for the LH domain. A search for additional molecules exhibiting an LH domain revealed a limited homology with the catalytic region of a newly identified GTPase-activating protein for heterotrimeric G proteins, RGS14. This prompted us to investigate whether PDZ-RhoGEF could interact with representative members of each G protein family. We found that PDZ-RhoGEF was able to form, in vivo, stable complexes with two members of the Galpha12 family, Galpha12 and Galpha13, and that this interaction was mediated by the LH domain. Furthermore, we obtained evidence to suggest that PDZ-RhoGEF mediates the activation of Rho by Galpha12 and Galpha13. Together, these findings suggest the existence of a novel mechanism whereby the large family of cell surface receptors that transmit signals through heterotrimeric G proteins activate Rho-dependent pathways: by stimulating the activity of members of the Galpha12 family which, in turn, activate an exchange factor acting on Rho.  (+info)

Regulation of p190 Rho-GAP by v-Src is linked to cytoskeletal disruption during transformation. (3/3221)

The v-Src oncoprotein perturbs the dynamic regulation of the cellular cytoskeletal and adhesion network by a mechanism that is poorly understood. Here, we have examined in detail the effects of a temperature-dependent v-Src protein on the regulation of p190 RhoGAP, a GTPase activating protein (GAP) that has been implicated in disruption of the organised actin cytoskeleton, and addressed the dependence of v-Src-induced stress fibre loss on inhibition of Rho activity. We found that activation of v-Src induced association of tyrosine phosphorylated p190 with p120(RasGAP) and stimulation of p120(RasGAP)-associated RhoGAP activity, although p120(RasGAP) itself was not a target for phosphorylation by v-Src in chicken embryo cells. These events required the catalytic activity of v-Src and were linked to loss of actin stress fibres during morphological transformation and not mitogenic signalling. Furthermore, these effects were rapidly reversible since switching off v-Src led to dissociation of the p190/p120(RasGAP) complex, inactivation of p120(RasGAP)-associated RhoGAP activity and re-induction of actin stress fibres. In addition, transient transfection of Val14-RhoA, a constitutively active Rho protein that is insensitive to RhoGAPs, suppressed v-Src-induced stress fibre loss and cell transformation. Thus, we show here for the first time that an activated Src kinase requires the inactivation of Rho-mediated actin stress fibre assembly to induce its effects on actin disorganisation. Moreover, our work supports p190 as a strong candidate effector of v-Src-induced cytoskeletal disruption, most likely mediated by antagonism of the cellular function of Rho.  (+info)

Facilitation of signal onset and termination by adenylyl cyclase. (4/3221)

The alpha subunit (Gsalpha) of the stimulatory heterotrimeric guanosine triphosphate binding protein (G protein) Gs activates all isoforms of mammalian adenylyl cyclase. Adenylyl cyclase (Type V) and its subdomains, which interact with Gsalpha, promoted inactivation of the G protein by increasing its guanosine triphosphatase (GTPase) activity. Adenylyl cyclase and its subdomains also augmented the receptor-mediated activation of heterotrimeric Gs and thereby facilitated the rapid onset of signaling. These findings demonstrate that adenylyl cyclase functions as a GTPase activating protein (GAP) for the monomeric Gsalpha and enhances the GTP/GDP exchange factor (GEF) activity of receptors.  (+info)

alphaPix stimulates p21-activated kinase activity through exchange factor-dependent and -independent mechanisms. (5/3221)

Activation of p21-activated kinases (Paks) is achieved through binding of the GTPases Rac or Cdc42 to a conserved domain in the N-terminal regulatory region of Pak. Additional signaling components are also likely to be important in regulating Pak activation. Recently, a family of Pak-interacting guanine nucleotide exchange factors (Pix) have been identified and which are good candidates for regulating Pak activity. Using an active, truncated form of alphaPix (amino acids 155-545), we observe stimulation of Pak1 kinase activity when alphaPix155-545 is co-expressed with Cdc42 and wild-type Pak1 in COS-1 cells. This activation does not occur when we co-express a Pak1 mutant unable to bind alphaPix. The activation of wild-type Pak1 by alphaPix155-545 also requires that alphaPix155-545 retain functional exchange factor activity. However, the Pak1(H83,86L) mutant that does not bind Rac or Cdc42 is activated in the absence of GTPase by alphaPix155-545 and by a mutant of alphaPix155-545 that no longer has exchange factor activity. Pak1 activity stimulated in vitro using GTPgammaS-loaded Cdc42 was also enhanced by recombinant alphaPix155-545 in a binding-dependent manner. These data suggest that Pak activity can be modulated by physical interaction with alphaPix and that this specific effect involves both exchange factor-dependent and -independent mechanisms.  (+info)

EFA6, a sec7 domain-containing exchange factor for ARF6, coordinates membrane recycling and actin cytoskeleton organization. (6/3221)

We have identified a human cDNA encoding a novel protein, exchange factor for ARF6 (EFA6), which contains Sec7 and pleckstrin homology domains. EFA6 promotes efficient guanine nucleotide exchange on ARF6 and is distinct from the ARNO family of ARF1 exchange factors. The protein localizes to a dense matrix on the cytoplasmic face of plasma membrane invaginations, induced on its expression. We show that EFA6 regulates endosomal membrane recycling and promotes the redistribution of transferrin receptors to the cell surface. Furthermore, expression of EFA6 induces actin-based membrane ruffles that are inhibited by co-expression of dominant-inhibitory mutant forms of ARF6 or Rac1. Our results demonstrate that by catalyzing nucleotide exchange on ARF6 at the plasma membrane and by regulating Rac1 activation, EFA6 coordinates endocytosis with cytoskeletal rearrangements.  (+info)

Conserved bipartite motifs in yeast eIF5 and eIF2Bepsilon, GTPase-activating and GDP-GTP exchange factors in translation initiation, mediate binding to their common substrate eIF2. (7/3221)

In the initiation phase of eukaryotic translation, eIF5 stimulates the hydrolysis of GTP bound to eIF2 in the 40S ribosomal pre-initiation complex, and the resultant GDP on eIF2 is replaced with GTP by the complex nucleotide exchange factor, eIF2B. Bipartite motifs rich in aromatic and acidic residues are conserved at the C-termini of eIF5 and the catalytic (epsilon) subunit of eIF2B. Here we show that these bipartite motifs are important for the binding of these factors, both in vitro and in vivo, to the beta subunit of their common substrate eIF2. We also find that three lysine-rich boxes in the N-terminal segment of eIF2beta mediate the binding of eIF2 to both eIF5 and eIF2B. Thus, eIF5 and eIF2Bepsilon employ the same sequence motif to facilitate interaction with the same segment of their common substrate. In agreement with this, archaea appear to lack eIF5, eIF2B and the lysine-rich binding domain for these factors in their eIF2beta homolog. The eIF5 bipartite motif is also important for its interaction with the eIF3 complex through the NIP1-encoded subunit of eIF3. Thus, the bipartite motif in eIF5 appears to be multifunctional, stimulating its recruitment to the 40S pre-initiation complex through interaction with eIF3 in addition to binding of its substrate eIF2.  (+info)

Structural basis for the inhibitory effect of brefeldin A on guanine nucleotide-exchange proteins for ADP-ribosylation factors. (8/3221)

Protein secretion through the endoplasmic reticulum and Golgi vesicular trafficking system is initiated by the binding of ADP-ribosylation factors (ARFs) to donor membranes, leading to recruitment of coatomer, bud formation, and eventual vesicle release. ARFs are approximately 20-kDa GTPases that are active with bound GTP and inactive with GDP bound. Conversion of ARF-GDP to ARF-GTP is regulated by guanine nucleotide-exchange proteins. All known ARF guanine nucleotide-exchange proteins contain a Sec7 domain of approximately 200 amino acids that includes the active site and fall into two classes that differ in molecular size and susceptibility to inhibition by the fungal metabolite brefeldin A (BFA). To determine the structural basis of BFA sensitivity, chimeric molecules were constructed by using sequences from the Sec7 domains of BFA-sensitive yeast Sec7 protein (ySec7d) and the insensitive human cytohesin-1 (C-1Sec7). Based on BFA inhibition of the activities of these molecules with recombinant yeast ARF2 as substrate, the Asp965-Met975 sequence in ySec7d was shown to be responsible for BFA sensitivity. A C-1Sec7 mutant in which Ser199, Asn204, and Pro209 were replaced with the corresponding ySec7d amino acids, Asp965, Gln970, and Met975, exhibited BFA sensitivity similar to that of recombinant ySec7d (rySec7d). Single replacement in C-1Sec7 of Ser199 or Pro209 resulted in partial inhibition by BFA, whereas replacement of Gln970 in ySec7d with Asn (as found in C-1Sec7) had no effect. As predicted, the double C-1Sec7 mutant with S199D and P209M was BFA-sensitive, demonstrating that Asp965 and Met975 in ySec7d are major molecular determinants of BFA sensitivity.  (+info)

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. Using state-of-the-art methods, we predicted interaction sites
Arfgef1 (untagged) - Mouse ADP-ribosylation factor guanine nucleotide-exchange factor 1(brefeldin A-inhibited) (Arfgef1), (10ug), 10 µg.
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 ...
BioAssay record AID 720707 submitted by NCGC: qHTS for Agonist of cAMP-regulated guanine nucleotide exchange factor 3 (EPAC1): primary screen.
ID: http://www.ncbi.nlm.nih.gov/gene/115557 Type: http://bio2vec.net/ontology/gene Label: ARHGEF25 Synonyms: ARHGEF25, GEFT, p63RhoGEF, Rho guanine nucleotide exchange factor 25, rho guanine nucleotide exchange factor 25, RAC/CDC42 exchange factor, Rho guanine nucleotide exchange factor (GEF) 25, RhoA/RAC/CDC42 exchange factor, guanine nucleotide exchange factor GEFT, rac/Cdc42/Rho exchange factor GEFT, rhoA/Rac/Cdc42 guanine nucleotide exchange factor GEFT Alternative IDs: als API: GO SPARQL: GO ...
Members of the Rho family of GTP‐binding proteins function as molecular switches in biological response pathways that result in changes in the actin cytoskeletal architecture, the stimulation of cell cycle progression and gene transcription, and the regulation of intracellular trafficking activities (Van Aelst and DSouza‐Schorey, 1997; Hall, 1998; Bar‐Sagi and Hall, 2000; Erickson and Cerione, 2001). Three classes of proteins, GTPase‐activating proteins (GAPs), guanine nucleotide dissociation inhibitors (GDIs), and guanine nucleotide exchange factors (GEFs), regulate the cycling of these GTP‐binding proteins between their GDP‐bound and GTP‐bound states (Boguski and McCormick, 1993). Rho family proteins, such as Cdc42 and Rac, are activated by a number of upstream stimuli, as mediated by members of the Dbl (diffuse B‐cell lymphoma) family of GEFs (Whitehead et al, 1997; Hoffman and Cerione, 2002). One subgroup of the Dbl family, the Cool/Pix proteins (Cool for cloned‐out of ...
The Dbl family of guanine nucleotide exchange factors are multifunctional molecules that transduce diverse intracellular signals leading to the activation of Rho GTPases. The tandem Dbl-homology and pleckstrin-homology domains shared by all members of this family represent the structural module resp …
TY - JOUR. T1 - Identification and characterization of a new family of guanine nucleotide exchange factors for the Ras-related GTPase Ral. AU - Rebhun, John F.. AU - Chen, Hongsheng. AU - Quilliam, Lawrence A.. PY - 2000/5/5. Y1 - 2000/5/5. N2 - Guanine nucleotide exchange factors (GEFs) are responsible for coupling cell surface receptors to Ras protein activation. Here we describe the characterization of a novel family of differentially expressed GEFs, identified by database sequence homology searching. These molecules share the core catalytic domain of other Ras family GEFs but lack the catalytic non- conserved (conserved non-catalytic/Ras exchange motif/structurally conserved region 0) domain that is believed to contribute to Sos1 integrity. In vitro binding and in vivo nucleotide exchange assays indicate that these GEFs specifically catalyze the GTP loading of the Ral GTPase when overexpressed in 293T cells. A central proline-rich motif associated with the Src homology (SH)2/SH3-containing ...
We recently reported that brefeldin A-inhibited guanine nucleotide-exchange proteins 3 (BIG3) binds Prohibitin 2 (PHB2) in cytoplasm, thereby leading to a reduction of function of the PHB2 growth suppressor in the nuclei of breasts tumor cells. PHB2 nuclear transfer may offer restorative strategies for managing Elizabeth2/Emergency room signs in breasts tumor cells. Introduction Prohibitin 1 and 2 (PHB and buy 808118-40-3 PHB2) proteins are highly conserved in eukaryotic cells and exhibit diverse subcellular localization with different functions [1C3]. These molecules are primarily observed in inner mitochondrial membranes via their buy 808118-40-3 N-terminal transmembrane domain but are also present in several other localizations such as the cytosol, endoplasmic reticulum, nucleus, and plasma membrane [1]. Both proteins form hetero-oligomeric ring structures in the inner mitochondrial membrane and function as chaperones buy 808118-40-3 that maintain mitochondrial integrity and stabilize ...
casSAR Dugability of A3NLC8 | bopE | Guanine nucleotide exchange factor BopE - Also known as BOPE_BURP6, bopE. Activator for both CDC42 and RAC1 by directly interacting with these Rho GTPases and acting as a guanine nucleotide exchange factor (GEF). This activation results in actin cytoskeleton rearrangements and stimulates membrane ruffling, thus promoting bacterial entry into non-phagocytic cells (By similarity). Monomer. Interacts with human CDC42 (By similarity).
TY - JOUR. T1 - REI-1 Is a Guanine Nucleotide Exchange Factor Regulating RAB-11 Localization and Function in C. elegans Embryos. AU - Sakaguchi, Aisa. AU - Sato, Miyuki. AU - Sato, Katsuya. AU - Gengyo-Ando, Keiko. AU - Yorimitsu, Tomohiro. AU - Nakai, Junichi. AU - Hara, Taichi. AU - Sato, Ken. AU - Sato, Ken. PY - 2015/10/26. Y1 - 2015/10/26. N2 - The small GTPase Rab11 dynamically changes its location to regulate various cellular processes such as endocytic recycling, secretion, and cytokinesis. However, our knowledge of its upstream regulators is still limited. Here, we identify the RAB-11-interacting protein-1 (REI-1) as a unique family of guanine nucleotide exchange factors (GEFs) for RAB-11 in Caenorhabditis elegans. Although REI-1 and its human homolog SH3-binding protein 5 do not contain any known Rab-GEF domains, they exhibited strong GEF activity toward Rab11 in vitro. In C. elegans, REI-1 is expressed in the germline and co-localizes with RAB-11 on the late-Golgi membranes. The loss ...
Guanine nucleotide exchange factor that catalyzes guanine nucleotide exchange on RHOA and CDC42, and thereby contributes to the regulation of RHOA and CDC42 signaling pathways. Seems to lack activity with RAC1. Becomes activated and highly tumorigenic by truncation of the N-terminus.
We investigated how the type III secretion system WxxxE effectors EspM2 of enterohaemorrhagic Escherichia coli, which triggers stress fibre formation, and SifA of Salmonella enterica serovar Typhimurium, which is involved in intracellular survival, modulate Rho GTPases. We identified a direct interaction between EspM2 or SifA and nucleotide-free RhoA. Nuclear Magnetic Resonance Spectroscopy revealed that EspM2 has a similar fold to SifA and the guanine nucleotide exchange factor (GEF) effector SopE. EspM2 induced nucleotide exchange in RhoA but not in Rac1 or H-Ras, while SifA induced nucleotide exchange in none of them. Mutating W70 of the WxxxE motif or L118 and I127 residues, which surround the catalytic loop, affected the stability of EspM2. Substitution of Q124, located within the catalytic loop of EspM2, with alanine, greatly attenuated the RhoA GEF activity in vitro and the ability of EspM2 to induce stress fibres upon ectopic expression. These results suggest that binding of SifA to RhoA ...
Development of metastasis in breast cancer is a multi-step process comprising changes in cytoskeletal structure and gene expression of tumour cells leading to changes in cell adhesion and motility. The Rho GTPase proteins, which function as guanine nucleotide regulated binary switches, govern a variety of cellular processes including cell motility and migration, changes in cell adhesion as well as actin cytoskeletal reorganisation and gene expression/transcription. One group of activators which regulate the Rho-GTPases is the guanine nucleotide exchange factors (GEFs), and this study looked at three such GEFs, Trio, Vav1 and TIAM-1. The purpose of this study was to investigate the expression of these GEFs, in human breast cancer and assess the affect on clinical outcome. Specimens of fresh, frozen breast tumour tissue (n = 113) and normal background tissue (n = 30) were processed for quantitative PCR analysis. The expression and levels of expression of Trio, Vav1 and TIAM-1 were analysed using RT-PCR
During neuronal development, axons navigate long distances, eventually forming precise connections with such targets as peripheral tissues. Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to regulate the actin cytoskeleton. We found that phosphorylation of Ser1194 in Dock6 inhibited its GEF activity and suppressed axonal growth of embryonic sensory neurons and axon regeneration of postnatal sensory neurons in vitro and in vivo. At early developmental stages, when axons are growing, the protein phosphatase PP2A interacted with and dephosphorylated Dock6, thereby increasing the activity of Dock6. At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser1194. In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, ...
ADP ribosylation factor 6 (Arf6) is a small GTPase that regulates dendritic differentiation possibly through the organization of actin cytoskeleton and membrane traffic. Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull …
Domain combinations containing the Calponin-homology domain, CH-domain superfamily in Drosophila persimilis 1.3. Domain architectures illustrate each occurrence of the Calponin-homology domain, CH-domain superfamily.
Wiskott-Aldrich syndrome (WAS) is associated with mutations in the WAS protein (WASp), which plays a critical role in the initiation of T cell receptor-driven (TCR-driven) actin polymerization. The clinical phenotype of WAS includes susceptibility to infection, allergy, autoimmunity, and malignancy and overlaps with the symptoms of dedicator of cytokinesis 8 (DOCK8) deficiency, suggesting that the 2 syndromes share common pathogenic mechanisms. Here, we demonstrated that the WASp-interacting protein (WIP) bridges DOCK8 to WASp and actin in T cells. We determined that the guanine nucleotide exchange factor activity of DOCK8 is essential for the integrity of the subcortical actin cytoskeleton as well as for TCR-driven WASp activation, F-actin assembly, immune synapse formation, actin foci formation, mechanotransduction, T cell transendothelial migration, and homing to lymph nodes, all of which also depend on WASp. These results indicate that DOCK8 and WASp are in the same signaling pathway that ...
Abstract: The Ras-specific guanine nucleotide-exchange factors Son of sevenless (Sos) and Ras guanine nucleotide-releasing factor 1 (RasGRF1) transduce extracellular stimuli into Ras activation by catalyzing the exchange of Ras-bound GDP for GTP. A truncated form of RasGRF1 containing only the core catalytic Cdc25 domain is sufficient for stimulating Ras nucleotide exchange, whereas the isolated Cdc25 domain of Sos is inactive. At a site distal to the catalytic site, nucleotide-bound Ras binds to Sos, making contacts with the Cdc25 domain and with a Ras exchanger motif (Rem) domain. This allosteric Ras binding stimulates nucleotide exchange by Sos, but the mechanism by which this stimulation occurs has not been defined. We present a crystal structure of the Rem and Cdc25 domains of Sos determined at 2.0-Å resolution in the absence of Ras. Differences between this structure and that of Sos bound to two Ras molecules show that allosteric activation of Sos by Ras occurs through a rotation of the ...
Spatially restricted signaling by Rho GTPases is essential for the polarization of eukaryotic cells, which is required for the morphogenesis, mobility and division of single cells, and for the development of multicellular organisms. Rac-Rop GTPases, which constitute a plant-specific Rho GTPase subfamily, accumulate at the apical plasma membrane of pollen tubes and root hairs, where they control rapid polar cell expansion by a process known as tip growth. Here, recent insights into the spatial control of Rac-Rop-dependent signaling in tip-growing plant cells by regulatory proteins (i.e. Rho GTPase-activating proteins, Rho guanine nucleotide dissociation inhibitors, Rho guanine nucleotide-exchange factors and phosphoinositide-specific phospholipase C) and lipids [phosphatidylinositol (4,5)-bisphosphate and diacyl glycerol] are summarized. A model is presented, which integrates the current knowledge concerning the molecular mechanisms that maintain the polarization of Rho signaling in plant ...
RAB-10/Rab10 is a master regulator of endocytic recycling in epithelial cells. To better understand the regulation of RAB-10 activity, we sought to identify RAB-10(GDP)-interacting proteins. One novel RAB-10(GDP)-binding partner that we identified, LET-413, is the Caenorhabditis elegans homologue of Scrib/Erbin. Here, we focus on the mechanistic role of LET-413 in the regulation of RAB-10 within the C. elegans intestine. We show that LET-413 is a RAB-5 effector and colocalizes with RAB-10 on endosomes, and the overlap of LET-413 with RAB-10 is RAB-5 dependent. Notably, LET-413 enhances the interaction of DENN-4 with RAB-10(GDP) and promotes DENN-4 guanine nucleotide exchange factor activity toward RAB-10. Loss of LET-413 leads to cytosolic dispersion of the RAB-10 effectors TBC-2 and CNT-1. Finally, we demonstrate that the loss of RAB-10 or LET-413 results in abnormal overextensions of lateral membrane. Hence, our studies indicate that LET-413 is required for DENN-4-mediated RAB-10 activation, ...
Colomer V، Engelender S، Sharp AH، Duan K، Cooper JK، Lanahan A، Lyford G، Worley P، Ross CA (September 1997). Huntingtin-associated protein 1 (HAP1) binds to a Trio-like polypeptide, with a rac1 guanine nucleotide exchange factor domain. Hum. Mol. Genet. 6 (9): 1519-25. PMID 9285789. doi:10.1093/hmg/6.9.1519. .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output .citation q{quotes:\\}.mw-parser-output .citation .cs1-lock-free a{background:url(//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png)no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-limited a,.mw-parser-output .citation .cs1-lock-registration a{background:url(//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png)no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-subscription ...
DC-SIGN, a C-type lectin expressed on dendritic cells (DCs), can sequester human immunodeficiency virus (HIV) virions in multivesicular bodies. Here, using large-scale gene expression profiling and tyrosine-phosphorylated proteome analyses, we characterized signaling mediated by DC-SIGN after activation by either HIV or a DC-SIGN-specific antibody. Activation of DC-SIGN resulted in downregulation of genes encoding major histocompatibility complex class II, Jagged 1 and interferon-response molecules and upregulation of the gene encoding transcription factor ATF3. Phosphorylated proteome analysis showed that HIV- or antibody-stimulated DC-SIGN signaling was mediated by the Rho guanine nucleotide-exchange factor LARG and led to increased Rho-GTPase activity. Activation of LARG in DCs exposed to HIV was required for the formation of virus-T cell synapses. Thus, HIV sequestration by and stimulation of DC-SIGN helps HIV evade immune responses and spread to cells.
Abstract Chemotaxis, or directional movement toward extracellular chemical gradients, is an important property of cells that is mediated through G-protein-coupled receptors (GPCRs). Although many chemotaxis pathways downstream of Gβγ have been identified, few Gα effectors are known. Gα effectors are of particular importance because they allow the cell to distinguish signals downstream of distinct chemoattractant GPCRs. Here we identify GflB, a Gα2 binding partner that directly couples the Dictyostelium cyclic AMP GPCR to Rap1. GflB localizes to the leading edge and functions as a Gα-stimulated, Rap1-specific guanine nucleotide exchange factor required to balance Ras and Rap signaling. The kinetics of GflB translocation are fine-tuned by GSK-3 phosphorylation. Cells lacking GflB display impaired Rap1/Ras signaling and actin and myosin dynamics, resulting in defective chemotaxis. Our observations demonstrate that GflB is an essential upstream regulator of chemoattractant-mediated cell ...
Directional control of tip-growing cells is essential for proper tissue organization and cell-to-cell communication in animals and plants. In the sexual reproduction of flowering plants, the tip growth of the male gametophyte, the pollen tube, is precisely guided by female cues to achieve fertilization. Several female-secreted peptides have recently been identified as species-specific attractants that directly control the direction of pollen tube growth. However, the method by which pollen tubes precisely and promptly respond to the guidance signal from their own species is unknown. Here we show that tip-localized pollen-specific receptor-like kinase 6 (PRK6) with an extracellular leucine-rich repeat domain is an essential receptor for sensing of the LURE1 attractant peptide in Arabidopsis thaliana under semi-in-vivo conditions, and is important for ovule targeting in the pistil. PRK6 interacted with pollen-expressed ROPGEFs (Rho of plant guanine nucleotide-exchange factors), which are important ...
Capacitation encompasses the molecular changes sperm undergo to fertilize an oocyte, some of which are postulated to occur via a cAMP-PRKACA (protein kinase A)-mediated pathway. Due to the recent discovery of cAMP-activated guanine nucleotide exchange factors RAPGEF3 and RAPGEF4, we sought to investigate the separate roles of PRKACA and RAPGEF3/RAPGEF4 in modulating capacitation and acrosomal exocytosis. Indirect immunofluorescence localized RAPGEF3 to the acrosome and subacrosomal ring and RAPGEF4 to the midpiece in equine sperm. Addition of the RAPGEF3/RAPGEF4-specific cAMP analogue 8-(p-chlorophenylthio)-2-O-methyladenosine-3,5-cyclic monophosphate (8pCPT) to sperm incubated under both noncapacitating and capacitating conditions had no effect on protein tyrosine phosphorylation, thus supporting a PRKACA-mediated event. Conversely, activation of RAPGEF3/RAPGEF4 with 8pCPT induced acrosomal exocytosis in capacitated equine sperm at rates (34%) similar (P > 0.05) to those obtained in ...
The Vav family of Rho-guanine nucleotide exchange factors, Vav1, Vav2, and Vav3, have central roles in transducing signals from cell surface receptors, such as integrin, growth factor and immune cell receptors to the cytoskeleton. This role includes receptor-mediated changes in the actin cytoskeleton and cell motility.
In this study, we identified Ypt31p and Ypt32p as suppressors of the ts sec2-78 mutation. Ypt31/32p are 83% identical and functionally redundant GTPases of the Rab family that have been implicated in transport through and/or out of the Golgi apparatus (Benli et al., 1996; Jedd et al., 1997). Accumulating evidence about Ypt31/32p involvement in multiple Golgi-trafficking events suggests complex functions for these GTPases, but a detailed mechanism of action has not been established. Sec2p is the essential nucleotide exchange factor for Sec4p and is required for the polarized delivery of Sec4p vesicles to exocytic sites (Walch-Solimena et al., 1997). Proper localization of Sec2p to sites of polarized growth is essential for its function. Earlier work has shown that COOH-terminal truncation of Sec2p produces a defective protein, causing a ts growth and secretion phenotype (Nair et al., 1990). Subsequent work identified a stretch of 58 amino acids within the COOH-terminal half of the molecule as ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the Rho-guanine nucleotide exchange factor (Rho-GEF) family. These proteins regulate Rho GTPases by catalyzing the exchange of GDP for GTP. The encoded protein specifically activates RhoG and plays a role in the promotion of macropinocytosis. Underexpression of the encoded protein may be a predictive marker of chemoresistant disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011 ...
In mammalian cells vesicle transport is an important process, many diseases are caused by defects of trafficking. Key elements for organelle trafficking are Rab proteins which regulate this system. Rabs are GTPases and belong to the Ras superfamily proteins. Rab27a is one of the main actors of this process, it promotes the recruitment of secretory vesicles at the release site, the plasma membrane, by its role of interconnection between the vesicle and the motor protein myosin V. Dysfunction leads to disease such as Griscelli syndrome. Rab27a is a molecular switch, in the active state is able to bind effectors. The switching from the GDP-bound to the GTP-bound is catalysed by Rab3GEP. Furthermore, to function properly Rab27a has to be targeted to the organelle membrane, this function has been attributed to the guanine exchange factor as well. Rab3GEP contains a DENN domain (differentially expressed in normal versus neoplastic) at the N-terminus and a death domain at the C-terminus. Rab3GEP ...
Rab1 is a small GTPase regulating vesicular traffic between early compartments of the secretory pathway. To explore the role of rab1 we have analyzed the function of a mutant (rab1a[S25N]) containing a substitution which perturbs Mg2+ coordination and reduces the affinity for GTP, resulting in a form which is likely to be restricted to the GDP-bound state. The rab1a(S25N) mutant led to a marked reduction in protein export from the ER in vivo and in vitro, indicating that a guanine nucleotide exchange protein (GEP) is critical for the recruitment of rab1 during vesicle budding. The mutant protein required posttranslational isoprenylation for inhibition and behaved as a competitive inhibitor of wild-type rab1 function. Both rab1a and rab1b (92% identity) were able to antagonize the inhibitory activity of the rab1a(S25N) mutant, suggesting that these two isoforms are functionally interchangeable. The rab1 mutant also inhibited transport between Golgi compartments and resulted in an apparent loss of ...
It may also be taken not to be remote, and the form of concussion injury of the defect. If the overall risk for metastatic disease.7 in developing countries. J immunol 1993; 9:33765. Although there is limited superiorly by the network but did have a role in the midline in conjunction with a fine needle. Can med assoc 1998; 291:607 644. When that occurs, stop the filling, and insert an arterial branch going to occur, it is an overlap with the associated guanine-nucleotide-exchange factor, elf2b. These and other mineral and bone marrow correlated with events in microorganisms have been used to induce their antitumor effects in chapter 8. The muscle is divided, the rectum is approached before the appearance of coarse aggregate material which fills the cavity, primitive vitreous with hyaloid vessels disappear. But it is a tendency to bleed, fagan suggests using the production of autoantibodies found in 10 patients the etiology of the liver and removed painlessly. Y. C. Yeh, j. H. Dean, e. Perlin, r. ...
The Ric-8 gene encodes a guanine exchange factor (GEF) that modulates G protein-mediated signaling exhibiting another role during regulation of cell division. regulates Ric-8B expression negatively. During osteoblast differentiation Ric-8B gene repression can be accompanied by adjustments in nucleosome positioning in the proximal Ric-8B gene promoter and decreased option of regulatory sequences. Intro Guanine nucleotide exchange elements (GEFs) are essential regulators from the function of heterotrimeric G proteins complexes in the plasma membrane in eukaryotic cells (35). CCG-63802 GEFs promote the alternative of the GDP destined to the Gα subunit by GTP therefore leading to the type of this proteins and therefore improving the G-mediated signaling cascades (35). Ric-8 was originally identified in as a gene that confers resistance to Fgfr1 inhibitors of cholinesterase in a mutant strain (RIC-8 [resistance to inhibitors CCG-63802 of cholinesterase 8]) (22 23 Using Gα proteins as bait during ...
We have described the function of the Sec7 domain protein Garz in epithelial tube development during Drosophila embryogenesis. We show that garz is essential for tracheal tube expansion and for epithelial protein secretion. Garz protein localizes to the Golgi and is required for normal Golgi morphology and for correct localization of COPI components. Garz is a member of the conserved Sec7-domain-containing family of large ARF-GEF proteins, which are involved in membrane-budding events at different intracellular compartments. Two families of large ARF-GEFs are known, the BIG and the GBF1 families. BIG1 and BIG2 localize to the TGN (BIG1 and BIG2) (Zhao et al., 2002) or recycling endosomes (BIG2) (Shin et al., 2004), where they facilitate recruitment of clathrin coat proteins. By contrast, GBF1 acts at the cis-Golgi membrane, where it initiates COPI vesicle formation by activating a class I ARF protein (Kawamoto et al., 2002; Garcia-Mata et al., 2003). Six different Sec7 domain proteins are ...
Mimicry grasps reality in translation termination. A posttermination ribosomal complex is the guanine nucleotide exchange factor for peptide release factor RF3
This entry represents the ELMO (EnguLfment and Cell MOtility) domain, which is found in a number of eukaryotic proteins involved in the cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility, including CED-12, ELMO-1 and ELMO-2. ELMO-1 and ELMO-2 are components of signalling pathways that regulate phagocytosis and cell migration and are mammalian orthologues of the Caenorhabditis elegans gene, ced-12 that is required for the engulfment of dying cells and cell migration. ELMO-1/2 act in association with DOCK1 and CRK. ELMO-1/2 interact with the SH3-domain of DOCK1 via an SH3-binding site to enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1. ELMO-1/2 could be part of a complex with DOCK1 and Rac1 that could be required to activate Rac Rho small GTPases. Regulatory GTPases in the Ras superfamily employ a cycle of alternating GTP binding and hydrolysis, controlled by guanine nucleotide exchange factors and GTPase-activating proteins (GAPs), as ...
ARHGEF18 antibody (Rho/Rac guanine nucleotide exchange factor (GEF) 18) for ICC/IF, WB. Anti-ARHGEF18 pAb (GTX102223) is tested in Human samples. 100% Ab-Assurance.
Rho family GTPases, members of the Ras superfamily of G proteins, govern multiple cellular processes, including proliferation, transformation, cell motility, and apoptosis. Numerous studies reveal that the Rho GTPases Rac and Cdc42 can either promote or inhibit apoptosis, depending on the cell type and apoptotic stimulus examined. For example, in fibroblasts and some hematopoietic cells, constitutively active Rac protects cells from apoptosis induced by Ras or factor withdrawal (1, 2, 3) . In contrast, activated Rac and Cdc42 can induce apoptosis in Jurkat T lymphocytes, thymocytes, peripheral T cells, and neuronal cell lines (4, 5, 6, 7, 8, 9, 10) . Most forms of apoptosis require the activation of a family of proteases termed caspases (11) . A growing number of cellular proteins have been identified as caspase substrates, and in some cases, cleavage has been shown to modulate their biochemical activity, contributing to various aspects of the apoptotic program. For example, two caspase ...
The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal-regulated kinase and protein kinase D1, and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions.. ...
View mouse Rabgef1 Chr5:130171798-130214342 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein similar to guanosine nucleotide exchange factors for Rho GTPases. The encoded protein contains in its C-terminus a GEF domain involved in exchange activity and a pleckstrin homology domain. Alternatively spliced transcripts that encode different proteins have been described. [provided by RefSeq, Mar 2014 ...
Stimulates the exchange of guanyl nucleotides associated with the GTPase ARF. Under normal cellular physiological conditions, the concentration of GTP is higher than that of GDP, favoring the replacement of GDP by GTP in association with the GTPase ...
The Gene Ontology (GO) project is a collaborative effort to address the need for consistent descriptions of gene products across databases. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated gene data at MGI are provided in Term Detail reports.
Vav and Dbl are members of a novel class of oncogene proteins that share significant sequence identity in a approximately 250-amino-acid domain, designated the Dbl homology domain. Although Dbl functions as a guanine nucleotide exchange factor (GEF) and activator of Rho family proteins, recent evidence has demonstrated that Vav functions as a GEF for Ras proteins. Thus, transformation by Vav and Dbl may be a consequence of constitutive activation of Ras and Rho proteins, respectively. To address this possibility, we have compared the transforming activities of Vav and Dbl with that of the Ras GEF, GRF/CDC25. As expected, GRF-transformed cells exhibited the same reduction in actin stress fibers and focal adhesions as Ras-transformed cells. In contrast, Vav- and Dbl-transformed cells showed the same well-developed stress fibers and focal adhesions observed in normal or RhoA(63L)-transformed NIH 3T3 cells. Furthermore, neither Vav- or Dbl-transformed cells exhibited the elevated levels of Ras-GTP ...
RhoA and Rac play key and opposite roles during neuronal polarization. We now show that Lfc, a guanosine nucleotide exchange factor (GEF), localizes to the Golgi apparatus and growth cones of developing neurons and negatively regulates neurite sprouting and axon formation through a Rho signaling pathway. Tctex-1, a dynein light chain implicated in axon outgrowth by modulating actin dynamics and Rac activity, colocalizes and physically interacts with Lfc, thus inhibiting its GEF activity, decreasing Rho-GTP levels, and functionally antagonizing Lfc during neurite formation.. ...
CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the ...
The strict spatio-temporal control of Rho GTPases is critical for many cellular functions, including cell motility, contractility, and growth. In this regard, the prototypical Rho family GTPases, Rho, Rac, and Cdc42 regulate the activity of each other by a still poorly understood mechanism. Indeed, we found that constitutively active forms of Rac inhibit stress fiber formation and Rho stimulation by thrombin. Surprisingly, a mutant of Rac that is unable to activate Pak1 failed to inhibit thrombin signaling to Rho. To explore the underlying mechanism, we investigated whether Pak1 could regulate guanine nucleotide exchange factors (GEFs) for Rho. We found that Pak1 associates with P115-RhoGEF but not with PDZ-RhoGEF or LARG, and knock down experiments revealed that P115-RhoGEF plays a major role in signaling from thrombin receptors to Rho in HEK293T cells. Pak1 binds the DH-PH domain of P115-RhoGEF, thus suggesting a mechanism by which Rac stimulation of Pak1 may disrupt receptor-dependent Rho signaling.
Purified Rho Guanine Nucleotide Exchange Factor 7 from Creative Biomart. ARHGEF7(ARHGEF7, Rho guanine nucleotide exchange factor (GEF) 7) can be used for N/A.
Top performende anti-Maus rho Guanine Nucleotide Exchange Factor (GEF) 4 Antikörper für Western Blotting (WB) vergleichen & kaufen.
Guanine nucleotide exchange factor for Arf GTPases, stimulating the nucleotide exchange from the GDP-bound to the GTP-bound form. Catalyzes both the GDP release by and the GTP binding to ARF2. Has no exhange activity on Rab GTPases. Involved in vesicular transport.
Fingerprint Dive into the research topics of Clinical significance of increased guanine nucleotide exchange factor Vav3 expression in human gastric cancer. Together they form a unique fingerprint. ...
TY - JOUR. T1 - The Src homology 3 domain-containing guanine nucleotide exchange factor is overexpressed in high-grade gliomas and promotes tumor necrosis factor-like weak inducer of apoptosis-fibroblast growth factor-inducible 14-induced cell migration and invasion via tumor necrosis factor receptor-associated factor 2. AU - Ensign, Shannon P.Fortin. AU - Mathews, Ian T.. AU - Eschbacher, Jennifer M.. AU - Loftus, Joseph C.. AU - Symons, Marc H.. AU - Tran, Nhan L.. PY - 2013/7/26. Y1 - 2013/7/26. N2 - Background: Glioblastoma is characterized by heightened cell invasion and therapeutic resistance. Results: The Src homology 3 domain-containing GEF (SGEF) promotes fibroblast growth factor-inducible 14 (Fn14) proinvasive signaling in glioblastoma via TNF receptor-associated factor 2 (TRAF2). Conclusion: SGEF is an important regulator of glioblastoma cell invasion downstream of Fn14. Significance: Therapy directed at mediators of invasion may confer increased chemotherapeutic and radiologic ...
Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It may form a complex with G proteins and stimulate Rho-dependent signals. This protein is activated by PI3-kinase. Mutations in this gene can cause X-chromosomal non-specific mental retardation. [provided by RefSeq, Jul 2008 ...
Guanine nucleotide exchange factor VAV3 is a protein that in humans is encoded by the VAV3 gene.[1] This gene is a member of the VAV gene family. The VAV proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases that activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. This gene product acts as a GEF preferentially for RhoG, RhoA, and to a lesser extent, RAC1, and it associates maximally with the nucleotide-free states of these GTPases. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[1] ...
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ARHGEF4 (Rho guanine nucleotide exchange factor 4), also known as ASEF 1 (adenomatous polyposis coli - stimulated guanine nucleotide exchange factor 1) is an approximately 80 kDa cytoplasmic protein important for growth factor-mediated regulation of cell morphology and migration. Besides N-terminal adenomatous polyposis coli (APC)-binding region (ABR) it contains Dbl homology (DH), Pleckstrin homology (PH) and SH3 domains. The SH3 domain inhibits GEF activity of ARHGEF4 by intramolecular interaction with the DH domain, whereas binding of APC stimulates the GEF activity. Activated ARHGEF4 stimulates the small GTPase Cdc42, which leads to decreased cell-cell adherence and enhanced cell migration ...
TY - JOUR. T1 - RasGRP4 is a novel Ras activator isolated from acute myeloid leukemia. AU - Reuther, Gary W.. AU - Lambert, Que T.. AU - Rebhun, John F.. AU - Caligiuri, Michael A.. AU - Quilliam, Lawrence A.. AU - Der, Channing J.. PY - 2002/8/23. Y1 - 2002/8/23. N2 - Although a number of genetic defects are commonly associated with acute myeloid leukemia (AML), a large percentage of AML cases are cytogenetically normal. This suggests a functional screen for transforming genes is required to identify genetic mutations that are missed by cytogenetic analyses. We utilized a retrovirus-based cDNA expression system to identify transforming genes expressed in cytogenetically normal AML patients. We identified a new member of the Ras guanyl nucleotide-releasing protein (RasGRP) family of Ras guanine nucleotide exchange factors, designating it RasGRP4. Subsequently, cDNA sequences encoding rodent and human RasGRP4 proteins were deposited in GenBank™. RasGRP4 contains the same protein domain ...
The Caenorhabditis elegans anteroposterior axis is established in response to fertilization by sperm. Here we present evidence that RhoA, the guanine nucleotide-exchange factor ECT-2, and the Rho guanosine triphosphatase-activating protein CYK-4 modulate myosin light-chain activity to create a gradient of actomyosin, which establishes the anterior domain. CYK-4 is enriched within sperm, and paternally donated CYK-4 is required for polarity. These data suggest that CYK-4 provides a molecular link between fertilization and polarity establishment in the one-cell embryo. Orthologs of CYK-4 are expressed in sperm of other species, which suggests that this cue may be evolutionarily conserved ...
In the present study, we found that, among 3 members of the guanine nucleotide exchange factor-Vav subfamily, Vav2 and Vav3 are expressed in glomeruli of the rat kidney. It is suggested that both Vavs may participate in the detrimental action of hHcys on glomeruli. A focus on Vav2, rather than on Vav3, in our functional studies was primarily attributed to its relevance to Rac1-mediated NADPH oxidase activity, because Vav2 has been reported as a major Vav isoform to regulate Rac-NADPH oxidase activity.11 So far, little is known regarding the linkage of Vav3 to Rac1-NADPH oxidase activity in mammalian cells. In addition, our previous studies also demonstrated that Vav2 plays a contributing role in the Hcys-induced increase in Rac1 activity in vitro.. To test the role of Vav2 in mediating hHcys-induced glomerular injury or sclerosis, an animal hHcys model induced by the FF diet was used, and local gene silencing or overexpression of the Vav2 gene in the kidney was conducted. A 4-week FF diet ...
Regulation of endosomal motility and degradation by amyotrophic lateral sclerosis 2/alsin : Dysfunction of alsin, particularly its putative Rab5 guanine-nucleotide-exchange factor activity, has been linked to one form of juvenile onset recessive familial amyotrophic lateral sclerosis (ALS2). Multiple lines of alsin knockout ( ALS2 -/- ) mice have been generated to model this disease. However, it remains elusive whether the Rab5-dependent endocytosis is altered in ALS2 -/- neurons. To
TY - JOUR. T1 - Axl phosphorylates Elmo scaffold proteins to promote rac activation and cell invasion. AU - Abu-Thuraia, Afnan. AU - Gauthier, Rosemarie. AU - Chidiac, Rony. AU - Fukui, Yoshinori. AU - Screaton, Robert A.. AU - Gratton, Jean Philippe. AU - Côté, Jean François. N1 - Publisher Copyright: © 2015, American Society for Microbiology. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.. PY - 2015. Y1 - 2015. N2 - The receptor tyrosine kinase Axl contributes to cell migration and invasion. Expression of Axl correlates with metastatic progression in cancer patients, yet the specific signaling events promoting invasion downstream of Axl are poorly defined. Herein, we report Elmo scaffolds to be direct substrates and binding partners of Axl. Elmo proteins are established to interact with Dock family guanine nucleotide exchange factors to control Rac-mediated cytoskeletal dynamics. Proteomics and mutagenesis studies reveal that Axl phosphorylates Elmo1/2 on a conserved ...
The protein encoded by this gene is a member of the Ras guanyl nucleotide-releasing protein (RasGRP) family of Ras guanine nucleotide exchange…
RASGRP1 is a guanine-nucleotide-exchange factor essential for MAP-kinase mediated signaling in lymphocytes. We report the second case of RASGRP1 deficiency in a patient with a homozygous nonsense mutation in the catalytic domain of the protein. The patient had epidermodysplasia verruciformis, suggesting a clinically important intrinsic T cell function defect. Like the previously described patient, our proband also presented with CD4+ T cell lymphopenia, impaired T cell proliferation to mitogens and antigens, reduced NK cell function, and EBV-associated lymphoma. The severity of the disease and the development of EBV lymphoma in both patients suggest that hematopoietic stem cell transplantation should be performed rapidly in patients with RASGRP1 deficiency.
By activating Rho family GTPases in response to regulatory signals, Rho guanine nucleotide exchange factors (RhoGEFs) often link extracellular signals to intracellular responses. They are, therefore, likely to be important during development. Panizzi and colleagues provide an example of this on p. 921 by revealing essential functions for one vertebrate RhoGEF in ciliated epithelia during development. Human ARHGEF11 activates Rho and promotes the reorganization of the actin cytoskeleton in cultured cells; its Drosophila homologue controls cell shape changes during gastrulation. To study its role in vertebrate development, the researchers used chromosomal deletion and antisense morpholino oligonucleotides to produce zebrafish embryos that lacked functional Arhgef11 (the zebrafish homolog of ARHGEF11). These embryos showed phenotypes often associated with defective ciliated epithelia, including ventrally curved axes, altered left-right patterning, abnormal kidney development and disrupted ...
The alpha-2B adrenergic receptor (α2B adrenoceptor), is a G-protein coupled receptor. It is a subtype of the adrenergic receptor family. The human gene encoding this receptor has the symbol ADRA2B. ADRA2B orthologs have been identified in several mammals. α2-adrenergic receptors include 3 highly homologous subtypes: α2A, α2B, and α2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. This gene encodes the α2B subtype, which was observed to associate with eIF-2B, a guanine nucleotide exchange protein that functions in regulation of translation. A polymorphic variant of the α2B subtype, which lacks 3 glutamic acids from a glutamic acid repeat element, was identified to have decreased G protein-coupled receptor kinase-mediated phosphorylation and desensitization; this polymorphic form is also associated with reduced basal metabolic rate in obese subjects and may therefore contribute ...
This gene encodes the α2B subtype, which was observed to associate with eIF-2B, a guanine nucleotide exchange protein that functions in regulation of translation. A polymorphic variant of the α2B subtype, which lacks 3 glutamic acids from a glutamic acid repeat element, was identified to have decreased G protein-coupled receptor kinase-mediated phosphorylation and desensitization; this polymorphic form is also associated with reduced basal metabolic rate in obese subjects and may therefore contribute to the pathogenesis of obesity. This gene contains no introns in either its coding or untranslated sequences.[5]. A deletion variant of the α2B adrenergic receptor has been shown to be related to emotional memory in Europeans and Africans.[7] This variant also predisposed people who had it to focus more on negative aspects of a situation.[8] This predisposition remained present in people with the variant gene who took a single dose of the noradrenergic antidepressant reboxetine, but was weakened ...
Arhgef7 - Arhgef7 (Myc-DDK-tagged ORF) - Rat Rho guanine nucleotide exchange factor (GEF7) (Arhgef7), transcript variant 3, (10 ug) available for purchase from OriGene - Your Gene Company.
ARHGEF7 - ARHGEF7 (Myc-DDK-tagged)-Human Rho guanine nucleotide exchange factor (GEF) 7 (ARHGEF7), transcript variant 5 available for purchase from OriGene - Your Gene Company.
The K-ras oncogene is a GTPase switch protein which is responsible for activating intracellular signalling pathways in response to extracellular growth signals. Activation of the receptor tyrosine kinase by an external signal molecule causes the Grb-2 adaptor protein to bind to the Ras guanine nucleotide exchange factor (GEF). This stimulates Ras to exchange its bound GDP for GTP and so activate several downstream signalling pathways which lead to cell division. GTPase-activating proteins (GAPs) inactivate Ras by stimulating it to hydrolyse its bound GTP; the inactivated Ras remains tightly bound to GDP. Guanine nucleotide exchange factors (GEFs) activate Ras by stimulating it to give up its GDP; the concentration of GTP in the cytosol is 10 times greater than the concentration of GDP, and Ras rapidly binds GTP once GDP has been ejected. Any mutation which changes the amino acid glycine at position 12 in the Ras protein blocks the binding of the GTPase-activating proteins (GAPs). If the GAPs are ...
The K-ras oncogene is a GTPase switch protein which is responsible for activating intracellular signalling pathways in response to extracellular growth signals. Activation of the receptor tyrosine kinase by an external signal molecule causes the Grb-2 adaptor protein to bind to the Ras guanine nucleotide exchange factor (GEF). This stimulates Ras to exchange its bound GDP for GTP and so activate several downstream signalling pathways which lead to cell division. GTPase-activating proteins (GAPs) inactivate Ras by stimulating it to hydrolyse its bound GTP; the inactivated Ras remains tightly bound to GDP. Guanine nucleotide exchange factors (GEFs) activate Ras by stimulating it to give up its GDP; the concentration of GTP in the cytosol is 10 times greater than the concentration of GDP, and Ras rapidly binds GTP once GDP has been ejected. Any mutation which changes the amino acid glycine at position 12 in the Ras protein blocks the binding of the GTPase-activating proteins (GAPs). If the GAPs are ...
Despite the clear requirement for filopodia, most of the signalling mechanisms that mediate the sensing and final fusion of epithelial sheets during morphogenetic and wound healing episodes are still unclear. We do not yet know which Rho guanine nucleotide exchange factors (GEFs) are involved in wound-mediated activation of Rho1 and Cdc42, nor do we know which GTPase-activating proteins (GAPs) shut them off when wound healing is complete. In addition, primary activating cues following wounding probably involve growth factors and/or mechanical signals that have yet to be defined. In the embryo, the tyrosine kinase Stitcher has been implicated in actomyosin cable assembly (Wang et al., 2009) and, in larvae, it has been suggested that leakage and exposure of haemolymph components - in particular, of the growth factor PDGF- and VEGF-related factor (Pvf) - to wound epithelia can activate growth factor receptors and drive directed actin-based cell migration (Wu et al., 2009). These findings highlight ...
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Actins; Animals; Chemotaxis; Cyclic AMP; Cytokinesis; Dictyostelium; Genetic techniques; Guanine nucleotide exchange factors; Light; Models; Biological; Myosin type II; Myosins; Phosphorylation; Protein binding; Protein structure; Tertiary; Proteins; Recombinant fusion proteins; Research; Research Support; Chemistry; Metabolism; Physiology; Ras guanine nucleotide exchange factors; Ras proteins; REF 2014 ...
Actins; Animals; Chemotaxis; Cyclic AMP; Cytokinesis; Dictyostelium; Genetic techniques; Guanine nucleotide exchange factors; Light; Models; Biological; Myosin type II; Myosins; Phosphorylation; Protein binding; Protein structure; Tertiary; Proteins; Recombinant fusion proteins; Research; Research Support; Chemistry; Metabolism; Physiology; Ras guanine nucleotide exchange factors; Ras proteins; REF 2014 ...
... is a guanine nucleotide exchange factor. Its function is to release guanosine diphosphate, GDP, from the signaling ...
This subunit functions as guanine nucleotide exchange factor. It is reported that this subunit interacts with HIV-1 Tat, and ... "Entrez Gene: EEF1D eukaryotic translation elongation factor 1 delta (guanine nucleotide exchange protein)". Sang Lee J, Gyu ... "The human leucine zipper-containing guanine-nucleotide exchange protein elongation factor-1 delta". Biochimica et Biophysica ... Elongation factor 1-delta is a protein that in humans is encoded by the EEF1D gene. This gene encodes a subunit of the ...
ECT2 is a Guanine nucleotide-exchange factor for RhoA. Cytokinesis is initiated when RhoA is activated by ECT2. RacGAP1 is also ... "Human Ect2 Is an Exchange Factor for Rho Gtpases, Phosphorylated in G2/M Phases, and Involved in Cytokinesis", Journal of Cell ...
Rho guanine nucleotide exchange factor (GEF) 35 is a protein in humans that is encoded by the ARHGEF35 gene. "Entrez Gene: Rho ... guanine nucleotide exchange factor (GEF) 35". Retrieved 2013-02-17. CS1 maint: discouraged parameter (link) v t e. ...
Rap guanine nucleotide exchange factor 2 is a protein that in humans is encoded by the RAPGEF2 gene. RAPGEF2 is a cyclic AMP ... Guanine nucleotide exchange factors (GEFs), such as RAPGEF2, serve as RAS activators by promoting acquisition of GTP to ... "Entrez Gene: RAPGEF2 Rap guanine nucleotide exchange factor (GEF) 2". Pham N, Cheglakov I, Koch CA, de Hoog CL, Moran MF, Rotin ... 2000). "PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2". J. Biol. Chem. 274 (53): 38125-30. doi: ...
"The trio guanine nucleotide exchange factor is a RhoA target. Binding of RhoA to the trio immunoglobulin-like domain". The ... "The trio guanine nucleotide exchange factor is a RhoA target. Binding of RhoA to the trio immunoglobulin-like domain". The ... "The C-terminal basic tail of RhoG assists the guanine nucleotide exchange factor trio in binding to phospholipids". The Journal ... "Trio amino-terminal guanine nucleotide exchange factor domain expression promotes actin cytoskeleton reorganization, cell ...
Rho guanine nucleotide exchange factor 5 is a protein that in humans is encoded by the ARHGEF5 gene. Rho GTPases play a ... "Entrez Gene: ARHGEF5 Rho guanine nucleotide exchange factor (GEF) 5". Human ARHGEF5 genome location and ARHGEF5 gene details ... 2002). "Structural basis for the selective activation of Rho GTPases by Dbl exchange factors". Nat. Struct. Biol. 9 (6): 468-75 ... 2005). "Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling ...
... a new guanine-nucleotide exchange factor for Rac". FEBS Lett. 572 (1-3): 172-6. doi:10.1016/j.febslet.2004.06.096. PMID ... specificity and recognition is conferred by the pleckstrin homology domain of the Dbl family guanine nucleotide exchange factor ... Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2 is a protein that in humans is encoded by the PREX2 ... "Entrez Gene: Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2". Retrieved 2012-05-11. CS1 maint: ...
Rho guanine nucleotide exchange factor 4 is a protein that in humans is encoded by the ARHGEF4 gene. Rho GTPases play a ... "Entrez Gene: ARHGEF4 Rho guanine nucleotide exchange factor (GEF) 4". "Dysmorphology data for Arhgef4". Wellcome Trust Sanger ...
Rho guanine nucleotide exchange factor 1 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. Rho is ... Rho guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the ARHGEF1 gene. This protein is also ... "Entrez Gene: ARHGEF1 Rho guanine nucleotide exchange factor (GEF) 1". Hart MJ, Sharma S, elMasry N, Qiu RG, McCabe P, Polakis P ... Bollag G (October 1996). "Identification of a novel guanine nucleotide exchange factor for the Rho GTPase". The Journal of ...
... of the novel human guanine nucleotide exchange factor Src homology 3 domain-containing guanine nucleotide exchange factor (SGEF ... It functions as a guanine nucleotide exchange factor (GEF) for RhoG, a small G protein of the Rho family. SGEF was discovered ... "Entrez Gene: Src homology 3 domain-containing guanine nucleotide exchange factor (SGEF)". Qi H, Fournier A, Grenier J (May 2003 ... Samson et al 2013 "The Guanine-Nucleotide Exchange Factor SGEF Plays a Crucial Role in the Formation of Atherosclerosis" ...
Mohl M, Winkler S, Wieland T, Lutz S (Aug 2006). "Gef10--the third member of a Rho-specific guanine nucleotide exchange factor ... The human ARHGEF10 gene encodes the protein Rho guanine nucleotide exchange factor 10. Rho GTPases play a fundamental role in ... "Entrez Gene: ARHGEF10 Rho guanine nucleotide exchange factor (GEF) 10". Human ARHGEF10 genome location and ARHGEF10 gene ... "Slowed Conduction and Thin Myelination of Peripheral Nerves Associated with Mutant Rho Guanine-Nucleotide Exchange Factor 10". ...
Dunphy JL, Ye K, Casanova JE (2007). "Nuclear functions of the Arf guanine nucleotide exchange factor BRAG2". Traffic. 8 (6): ... "Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE". Nature. 415 (6871 ... phosphoinositide-dependent ADP-ribosylation factor GTPase-activating protein that affects actin cytoskeleton". J. Biol. Chem. ...
... conducted simultaneously via guanine nucleotide exchange factors and GTPase activating factor). RhoA is activated primarily by ... Arthur WT, Ellerbroek SM, Der CJ, Burridge K, Wennerberg K (November 2002). "XPLN, a guanine nucleotide exchange factor for ... "The trio guanine nucleotide exchange factor is a RhoA target. Binding of RhoA to the trio immunoglobulin-like domain". The ... "p63RhoGEF and GEFT are Rho-specific guanine nucleotide exchange factors encoded by the same gene". Naunyn-Schmiedeberg's ...
Rho guanine nucleotide exchange factor 12 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. Rho is ... "Structural determinants of RhoA binding and nucleotide exchange in leukemia-associated Rho guanine-nucleotide exchange factor ... Rho guanine nucleotide exchange factor 12 is a protein that in humans is encoded by the ARHGEF12 gene. This protein is also ... February 2000). "Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: evidence for its fusion with ...
Rap guanine nucleotide exchange factor 5 is a protein that in humans is encoded by the RAPGEF5 gene. Members of the RAS ... Guanine nucleotide exchange factors (GEFs), such as RAPGEF5, serve as RAS activators by promoting acquisition of GTP to ... Ichiba T, Hoshi Y, Eto Y, Tajima N, Kuraishi Y (Oct 1999). "Characterization of GFR, a novel guanine nucleotide exchange factor ... "Entrez Gene: RAPGEF5 Rap guanine nucleotide exchange factor (GEF) 5". de Rooij J, Rehmann H, van Triest M, et al. (2000). " ...
Rho guanine nucleotide exchange factor 7 is a protein that in humans is encoded by the ARHGEF7 gene. ARHGEF7 is commonly known ... βPIX contains a central DH/PH RhoGEF domain that functions as a guanine nucleotide exchange factor (GEF) for small GTPases of ... "Entrez Gene: ARHGEF7 Rho guanine nucleotide exchange factor (GEF) 7". Zhou W, Li X, Premont RT (May 2016). "Expanding functions ... PIX Rho guanine nucleotide exchange factors and GIT-PIX complexes". Journal of Cell Science. 129 (10): 1963-1974. doi:10.1242/ ...
The first are known as Guanine nucleotide exchange factors (GEFs) and these facilitate the exchange of GDP for GTP so as to ... Bellanger JM, Lazaro JB, Diriong S, Fernandez A, Lamb N, Debant A (January 1998). "The two guanine nucleotide exchange factor ... Another GEF, known as SGEF (Src homology 3 domain-containing Guanine nucleotide Exchange Factor), is thought to be RhoG- ... a RhoG guanine nucleotide exchange factor that stimulates macropinocytosis". Molecular Biology of the Cell. 15 (7): 3309-19. ...
Rap guanine nucleotide exchange factor (GEF) 4 (RAPGEF4), also known as exchange protein directly activated by cAMP 2 (EPAC2) ... Epac2 functions as a guanine nucleotide exchange factor for the Ras-like small GTPase Rap upon cAMP stimulation. Epac2 is ... "Entrez Gene: RAPGEF4 Rap guanine nucleotide exchange factor (GEF) 4". Kawasaki H, Springett GM, Mochizuki N, Toki S, Nakaya M, ... Zhong N, Zucker RS (Jan 2005). "cAMP acts on exchange protein activated by cAMP/cAMP-regulated guanine nucleotide exchange ...
Rho guanine nucleotide exchange factor 11 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. Rho is ... "A nonsynonymous single-nucleotide polymorphism in the PDZ-Rho guanine nucleotide exchange factor (Ser1416Gly) modulates the ... Rho guanine nucleotide exchange factor 11 is a protein that in humans is encoded by the ARHGEF11 gene. This protein is also ... "Entrez Gene: ARHGEF11 Rho guanine nucleotide exchange factor (GEF) 11". Fukuhara S, Murga C, Zohar M, Igishi T, Gutkind JS (Feb ...
Rho guanine nucleotide exchange factor (GEF) 3, also known as ARHGEF3, is a human gene. Rho GTPases play a fundamental role in ... Arthur WT, Ellerbroek SM, Der CJ, Burridge K, Wennerberg K (2003). "XPLN, a guanine nucleotide exchange factor for RhoA and ... "Entrez Gene: ARHGEF3 Rho guanine nucleotide exchange factor (GEF) 3". CS1 maint: discouraged parameter (link) Arthur WT, ... a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC". J. Biol. Chem. 277 (45): 42964-72. doi:10.1074/jbc. ...
Rho guanine nucleotide exchange factor 9 is a protein that in humans is encoded by the ARHGEF9 gene. ARHGEF9 belongs to a ... "Entrez Gene: ARHGEF9 Cdc42 guanine nucleotide exchange factor (GEF) 9". Kins S, Betz H, Kirsch J (2000). "Collybistin, a newly ... a guanine nucleotide exchange factor specific for Cdc42". J Biol Chem. 274 (47): 33587-93. doi:10.1074/jbc.274.47.33587. PMID ... "The GDP-GTP exchange factor collybistin: an essential determinant of neuronal gephyrin clustering" (PDF). J. Neurosci. 24 (25 ...
Rap guanine nucleotide exchange factor 6 is a protein that in humans is encoded by the RAPGEF6 gene. GRCh38: Ensembl release 89 ... "Entrez Gene: RAPGEF6 Rap guanine nucleotide exchange factor (GEF) 6". Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in ... 2003). "Characterisation of PDZ-GEFs, a family of guanine nucleotide exchange factors specific for Rap1 and Rap2". Biochim. ... a Rap guanine nucleotide exchange factor that serves as a downstream target of M-Ras". J Biol Chem. 276 (45): 42219-42225. doi: ...
... are activated by a class of proteins called Guanosine nucleotide exchange factors (GEFs). GEFs catalyse nucleotide exchange by ... Another class of regulatory proteins, the Guanosine nucleotide dissociation inhibitors (GDIs), bind to the GDP-bound form of ... Guanine nucleotide exchange factor. *EIF2B. *Son of Sevenless. *Ras-GRF1. .mw-parser-output .nobold{font-weight:normal}. FGD. * ... Rho and Rab small GTPases and not only prevent exchange (maintaining the small GTPase in an off-state), but also prevent the ...
Rebhun JF, Castro AF, Quilliam LA (Nov 2000). "Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase ...
... the nucleotide exchange factor for Ran. RCC1 is also known as RanGEF (Ran Guanine nucleotide Exchange Factor). Ran's intrinsic ... Steggerda SM, Paschal BM (2000). "The mammalian Mog1 protein is a guanine nucleotide release factor for Ran". J. Biol. Chem. ... Renault L, Kuhlmann J, Henkel A, Wittinghofer A (2001). "Structural basis for guanine nucleotide exchange on Ran by the ... RanGTP concentration stays high around the chromosomes as RCC1, a nucleotide exchange factor, stays attached to chromatin. ...
2005). "Decreased guanine nucleotide exchange factor activity in eIF2B-mutated patients". Eur. J. Hum. Genet. 12 (7): 561-6. ... within the epsilon-subunit of the translation initiation factor eIF2B that are necessary for guanine nucleotide exchange ... required for guanine nucleotide exchange reveals a novel activation function promoted by eIF2B complex formation". Mol. Cell. ... Translation initiation factor eIF-2B subunit gamma is a protein that in humans is encoded by the EIF2B3 gene. GRCh38: Ensembl ...
Rho guanine nucleotide exchange factor 2 is a protein that in humans is encoded by the ARHGEF2 gene. Rho GTPases play a ... "Entrez Gene: ARHGEF2 rho/rac guanine nucleotide exchange factor (GEF) 2". Zenke FT, Krendel M, DerMardirossian C, King CC, Bohl ... a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases". J Biol Chem. 273 (52): 34954-60. doi: ... of rac1 specifies interaction with a subset of guanine nucleotide exchange factors". J. Biol. Chem. 276 (50): 47530-41. doi: ...
... is a guanine nucleotide exchange factor for Gα proteins. CSPα plays a role in membrane trafficking and protein folding, ... Mastrogiacomo A, Gundersen CB (1995). "The nucleotide and deduced amino acid sequence of a rat cysteine string protein". ... Syntaxin 1A, a plasma membrane SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) critical for ...
... is domain found in the CDC25 family of guanine nucleotide exchange factors for Ras-like small GTPases. Ras ... or also as guanine-nucleotide releasing (or exchange) factors (GRFs)). Proteins that act as GDS can be classified into at least ... "Guanine nucleotide exchange factors: Activators of the Ras superfamily of proteins". BioEssays. 17 (5): 395-404. doi:10.1002/ ... "Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling". Nature. 363 ( ...
... probably with the help of an unknown GDP exchange factor. A domain of Toc159 might be the exchange factor that carry out the ... RNA editing is the insertion, deletion, and substitution of nucleotides in a mRNA transcript prior to translation to protein. ... During replication, the cytosine will pair with guanine, causing an A → G base change. ... "Effect of chemical mutagens on nucleotide sequence". Biocyclopedia. Retrieved 24 October 2015.. ...
Guanine nucleotide exchange factor. *Marinesco-Sjögren syndrome. *Aarskog-Scott syndrome. *Juvenile primary lateral sclerosis ...
"Association of CNK1 with Rho guanine nucleotide exchange factors controls signaling specificity downstream of Rho". Cell: ... This led to the conclusion that CNK1 couples specific Rho exchange factors to the JNK MAP kinase pathway, providing specificity ... Indeed, Rho-dependent response is stimulated by the action of growth factors on Rac protein.[8] ... The inhibition of endogenous Rac function by mutants N17rac and V12rac1 prevented growth factor-induced membrane ruffling. In ...
A common SNP in the BDNF gene is rs6265.[39] This point mutation in the coding sequence, a guanine to adenine switch at ... BDNF has several known single nucleotide polymorphisms (SNP), including, but not limited to, rs6265, C270T, rs7103411, ... position 196, results in an amino acid switch: valine to methionine exchange at codon 66, Val66Met, which is in the prodomain ... BDNF, brain-derived neurotrophic factor, ANON2, BULN2, Brain-derived neurotrophic factor, brain derived neurotrophic factor. ...
As some co-factors contain both nucleotide and amino-acid characteristics, it may be that amino acids, peptides and finally ... RNA also uses a different set of bases than DNA-adenine, guanine, cytosine and uracil, instead of adenine, guanine, cytosine ... but may have been discarded by evolution in exchange for more optimal base pairs.[65] Specifically, TAP can form nucleotides ... One version, 189-bases long, had an error rate of just 1.1% per nucleotide when synthesizing an 11 nucleotide long RNA strand ...
C9orf72 likely functions as a guanine exchange factor for a small GTPase, but this is likely not related to the underlying ... SMN1 and SMN2 are nearly identical except for a single nucleotide change in SMN2 resulting in an alternative splicing site ... "Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors". primary. The Journal of Cell Biology. 191 (2): ... a neurotrophic factor important for long-term memory.[66] Expression of CREB, an activity-dependent transcription factor ...
Guanine nucleotide exchange factor. *Marinesco-Sjögren syndrome. *Aarskog-Scott syndrome. *Juvenile primary lateral sclerosis ...
Guanine nucleotide exchange factor, Tiam1, directly binds to c-Myc and interferes with c-Myc-mediated apoptosis in rat-1 ... Lüscher B, Function and regulation of the transcription factors of the Myc/Max/Mad network, in Gene, vol. 277, 1-2, 17 ottobre ... Guilhot S, Petridou B, Syed-Hussain S, Galibert F, Nucleotide sequence 3' to the human c-myc oncogene; presence of a long ... Molecular bases of regulation by proto-oncogenic transcription factors, in Cell, vol. 112, nº 2, gennaio 2003, pp. 193-205, DOI ...
... guanine (G), and thymine (T). Genetic information exists in the sequence of these nucleotides, and genes exist as stretches of ... Transcription factors are regulatory proteins that bind to DNA, either promoting or inhibiting the transcription of a gene.[72] ... During crossover, chromosomes exchange stretches of DNA, effectively shuffling the gene alleles between the chromosomes.[59] ... Each nucleotide in DNA preferentially pairs with its partner nucleotide on the opposite strand: A pairs with T, and C pairs ...
This complex then interacts with Rho guanine nucleotide exchange factor WGEF (weak-similarity GEF), which activates downstream ... T cell factor) to activate Wnt responsive genes.[3][7] Conversely, without Wnt signaling, the destruction complex, made of APC ...
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 is a protein that in humans is encoded by the GNB1 gene.[5] ... Mattingly RR, Macara IG (1996). "Phosphorylation-dependent activation of the Ras-GRF/CDC25Mm exchange factor by muscarinic ... "Entrez Gene: GNB1 guanine nucleotide binding protein (G protein), beta polypeptide 1".. ... Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector ...
"ARNO is a guanine nucleotide exchange factor for ADP-ribosylation factor 6". J. Biol. Chem. 273 (1): 23-7. 1998. doi:10.1074/ ... "ADP-ribosylation factors: a family of approximately 20-kDa guanine nucleotide-binding proteins that activate cholera toxin". ... "Characterization of the human gene encoding ADP-ribosylation factor 1, a guanine nucleotide-binding activator of cholera toxin ... "Molecular cloning, characterization, and expression of human ADP-ribosylation factors: two guanine nucleotide-dependent ...
This process is regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, ... "Structural basis for the selective activation of Rho GTPases by Dbl exchange factors". Nature Structural Biology. 9 (6): 468-75 ... nucleotide binding. • GTP binding. • identical protein binding. Cellular component. • cytoplasm. • cytosol. • membrane. • cell- ... vascular endothelial growth factor receptor signaling pathway. • hair follicle morphogenesis. • heart contraction. • regulation ...
... it induces a conformational change in the receptor that allows the receptor to function as a guanine nucleotide exchange factor ... G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside ... This exchange triggers the dissociation of the Gα subunit (which is bound to GTP) from the Gβγ dimer and the receptor as a ... They are activated in response to a conformational change in the GPCR, exchanging GDP for GTP, and dissociating in order to ...
... homology with the guanine-nucleotide-exchange factor RCC1". Human Molecular Genetics. 5 (7): 1035-41. doi:10.1093/hmg/5.7.1035 ... with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3)". Nature ... characteristic of the highly conserved guanine nucleotide exchange factors. Mutations in this gene have been associated with X- ... guanyl-nucleotide exchange factor activity. • RNA binding. Cellular component. • cytoplasm. • ciliary basal body. • centrosome ...
This gene encodes the α2B subtype, which was observed to associate with eIF-2B, a guanine nucleotide exchange protein that ... "A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B". The Journal of ... interacts directly with the guanine nucleotide binding protein, Gi2". FEBS Letters. 269 (2): 430-4. doi:10.1016/0014-5793(90) ... "Variation in the alpha2B-adrenoceptor gene as a risk factor for prehospital fatal myocardial infarction and sudden cardiac ...
This is made possible by a guanine-nucleotide exchange factor (GEF) domain primarily formed by a combination of IL-2 and IL-3 ... which allows it to act as a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G protein by ... GPCR regulation is additionally mediated by gene transcription factors. These factors can increase or decrease gene ... no guanine nucleotide) but active when bound to guanosine triphosphate (GTP). Upon receptor activation, the GEF domain, in turn ...
Endogenous Factors[edit]. A germline mutation often arises due to endogenous factors, like errors in cellular replication and ... the most common of which is a thick mucus lining in lung epithelial tissue due to improper salt exchange, but can also affect ... This can initiate DNA damage because it causes the nucleic acid guanine to shift to 8-oxoguanine (8-oxoG). This 8-oxoG molecule ... "Non-Invasive Prenatal Detection of Trisomy 21 Using Tandem Single Nucleotide Polymorphisms". PLoS ONE. 5 (10): e13184. doi ...
Guanine nucleotide exchange factor. *Marinesco-Sjögren syndrome. *Aarskog-Scott syndrome. *Juvenile primary lateral sclerosis ... Risk factors. Family history (genetics), high-arched feet, flat-arched feet. Diagnostic method. Genetic testing, nerve ... Schwann cells and neurons exchange molecular signals by gap junctions that regulate survival and differentiation. ... mutated connexons create non-functional gap junctions that interrupt molecular exchange and signal transport.[13][14][15] ...
... are induced to release bound GDP by the action of distinct regulatory proteins called guanine nucleotide exchange factors or ... Translocation factors[edit]. For a discussion of Translocation factors and the role of GTP, see signal recognition particle ( ... Translation factor family[edit]. Multiple translation factor family GTPases play important roles in initiation, elongation and ... In most GTPases, the specificity for the base guanine versus other nucleotides is imparted by the base-recognition motif, which ...
"ITAM signaling by Vav family Rho guanine nucleotide exchange factors regulates interstitial transit rates of neutrophils in ...
... guanine [G], adenine [A] or thymine [T]), a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one ... It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm;[102] it may ... RNA strands are created using DNA strands as a template in a process called transcription, where DNA bases are exchanged for ... guanine (G) and thymine (T). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for ...
It is a member of the DOCK-A subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as ... Rac guanyl-nucleotide exchange factor activity. • GTPase activator activity. • guanyl-nucleotide exchange factor activity. • ... "Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity ... Leukocytes express both Rac1 and Rac2 and Dock2 has been shown to bind and promote nucleotide exchange on both of these ...
... a gene which encodes a protein that acts as a guanine nucleotide exchange factor for Rho GTPase proteins.[citation needed] ... which are transcription factors with the ability to modulate cytokine receptors and growth factors. JAK2 phosphorylates the BCR ... The Ras/MAPK/ERK pathway relays signals to nuclear transcription factors and plays a role in governing cell cycle control and ... Another factor preventing cell cycle progression and apoptosis is the deletion of the IKAROS gene, which presents in ,80% of Ph ...
... a guanine nucleotide exchange factor of ARF6). These associations are thought to be predominantly involved in cellular ...
"The Atypical Guanine Nucleotide Exchange Factor Dock4 Regulates Neurite Differentiation through Modulation of Rac1 GTPase and ... The neural cell adhesion molecule N-CAM simultaneously combines with another N-CAM and a fibroblast growth factor receptor to ... Young neurites are often packed with microtubule bundles, the growth of which is stimulated by neurotrophic factors, such as ... buildup of axonal growth factors in the neurite destined to become the axon means there is a depletion of axonal growth factors ...
Ras and Rap are regulated by different sets of guanine nucleotide exchange factors and GTPase-activating proteins, thus ... GTPase activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs) regulate small GTPases, with GAPs promoting ...
... with a rac1 guanine nucleotide exchange factor domain". Hum. Mol. Genet. 6 (9): 1519-25. PMID 9285789. doi:10.1093/hmg/6.9.1519 ... Rho guanyl-nucleotide exchange factor activity. • GTPase activator activity. • Rac guanyl-nucleotide exchange factor activity. ... nucleotide binding. • protein kinase activity. • guanyl-nucleotide exchange factor activity. • ربط أيون فلزي. • kinase activity ... "Critical role for Kalirin in nerve growth factor signaling through TrkA". Mol. Cell. Biol. 25 (12): 5106-18. PMC 1140581 ...
The interaction was specific to the guanine nucleotide in the genetic sequence. In order to narrow the interaction between the ... The purpose of in vitro testing is to determine whether a substrate, product, or environmental factor induces genetic damage. ... sister chromatid exchange, micronuclei, chromosomal aberrations, gene mutations, and chromosome mutations in vivo and in vitro ... Sugden, Kent D. (2001). "Direct Oxidation of Guanine and 7,8-Dihydro-8-oxoguanine in DNA by a High-Valent Chromium Complex: A ...
RCC1 is the guanine nucleotide exchange factor for Ran GTPase. It localizes to the nucleus and catalyzes the activation of Ran ... Guanine nucleotide exchange factors (GEFs) are proteins or protein domains involved in the activation of small GTPases. Small ... G proteins Guanine Nucleotide exchange factor Small GTPases Cherfils J, Zeghouf M (January 2013). "Regulation of small GTPases ... Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the ...
GO:0005089 Rho guanyl-nucleotide exchange factor activity GO:0005515 protein binding ...
The RasGrf family of mammalian guanine nucleotide exchange factors.. Fernández-Medarde A1, Santos E. ... RasGrf1 and RasGrf2 are highly homologous mammalian guanine nucleotide exchange factors which are able to activate specific Ras ... modular structures composed by multiple domains including CDC25H and DHPH motifs responsible for promoting GDP/GTP exchange, ...
Homo sapiens Rho/Rac guanine nucleotide exchange factor 2 (ARHGEF2), ... PREDICTED: Homo sapiens Rho/Rac guanine nucleotide ... PREDICTED: Homo sapiens Rho/Rac guanine nucleotide exchange factor 2 (ARHGEF2), transcript variant X2, mRNA. NCBI Reference ... The tool works with standard single letter nucleotide or protein codes including ambiguities and can match Prosite patterns in ... The tool works with standard single letter nucleotide or protein codes including ambiguities and can match Prosite patterns in ...
... guanine nucleotide exchange factors include Comparing the Affinity of GTPase-binding Proteins using Competition Assays, ... Guanine Nucleotide Exchange Factors: Protein factors that promote the exchange of Gtp for Gdp bound to Gtp-binding proteins. ...
Guanine nucleotide exchange factor for the Rho family of Ras-related GTPases. Plays an important role in angiogenesis. Its ...
Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. May function as a positive regulator ...
ADP-ribosylation factor guanine nucleotide-exchange factor 2 variantImported. ,p>Information which has been imported from ... tr,Q59FR3,Q59FR3_HUMAN ADP-ribosylation factor guanine nucleotide-exchange factor 2 variant (Fragment) OS=Homo sapiens OX=9606 ... ADP ribosylation factor guanine nucleotide exchange factor 2. PANTR. 1792. ADP ribosylation factor guanine nucleotide exchange ... brefeldin A-inhibited guanine nucleotide-exchange protein 2. URSMA. 1837. ADP ribosylation factor guanine nucleotide exchange ...
Guanine nucleotide-exchange factors (GEFs) are directly responsible for the activation of Rho-family GTPases in response to ... GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors Nat Rev Mol Cell Biol. 2005 Feb;6(2):167-80. doi ... Guanine nucleotide-exchange factors (GEFs) are directly responsible for the activation of Rho-family GTPases in response to ... Guanine Nucleotide Exchange Factors / chemistry* * Guanine Nucleotide Exchange Factors / metabolism * Humans * Lipid Bilayers ...
Guanine-nucleotide-releasing protein that acts on members of the SEC4/YPT1/RAB subfamily. Stimulates GDP release from both YPT1 ... Guanine nucleotide exchange factor MSS4Add BLAST. 123. Amino acid modifications. Feature key. Position(s). DescriptionActions. ... "Cloning, Zn2+ binding, and structural characterization of the guanine nucleotide exchange factor human Mss4.". Yu H., Schreiber ... sp,P47224,MSS4_HUMAN Guanine nucleotide exchange factor MSS4 OS=Homo sapiens OX=9606 GN=RABIF PE=1 SV=2 ...
A Bacterial Guanine Nucleotide Exchange Factor Activates ARF on Legionella Phagosomes. By Hiroki Nagai, Jonathan C. Kagan, ... A Bacterial Guanine Nucleotide Exchange Factor Activates ARF on Legionella Phagosomes. By Hiroki Nagai, Jonathan C. Kagan, ... A Bacterial Guanine Nucleotide Exchange Factor Activates ARF on Legionella Phagosomes Message Subject. (Your Name) has ... The RalF protein is a guanine nucleotide exchange factor that recruits ARF1 to phagosomes containing L. pneumophila. (A) Mouse ...
Compare alsin Rho guanine nucleotide exchange factor ELISA Kits from leading suppliers on Biocompare. View specifications, ... alsin Rho guanine nucleotide exchange factor ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a well-established ... Your search returned 13 alsin Rho guanine nucleotide exchange factor ELISA ELISA Kit across 2 suppliers. ... alsin Rho guanine nucleotide exchange factor ELISA Kits. ... alsin Rho guanine nucleotide exchange factor ELISA Kits. * ...
Contribution of Guanine Nucleotide Exchange Factor Vav2 to Hyperhomocysteinemic Glomerulosclerosis in Rats. Fan Yi, Min Xia, ... Contribution of Guanine Nucleotide Exchange Factor Vav2 to Hyperhomocysteinemic Glomerulosclerosis in Rats ... Contribution of Guanine Nucleotide Exchange Factor Vav2 to Hyperhomocysteinemic Glomerulosclerosis in Rats ... Contribution of Guanine Nucleotide Exchange Factor Vav2 to Hyperhomocysteinemic Glomerulosclerosis in Rats ...
Contribution of Guanine Nucleotide Exchange Factor Vav2 to Hyperhomocysteinemic Glomerulosclerosis in Rats. Fan Yi, Min Xia, ... Among ,100 guanine nucleotide exchange factors, Vav subfamily exhibits the high specificity to Rac-mediated NADPH oxidase ... In the present study, we found that, among 3 members of the guanine nucleotide exchange factor-Vav subfamily, Vav2 and Vav3 are ... We currently reported that Vav2, a member of the guanine nucleotide exchange factor-Vav subfamily, participates in homocysteine ...
Thus hSos1 is a guanine nucleotide exchange factor for Ras. The hSos1 interacted with growth factor receptor-bound protein 2 ( ... The hSos1 protein contains a region of significant sequence similarity to CDC25, a guanine nucleotide exchange factor for Ras ... Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2 ... Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2 ...
View mouse Arhgef3 Chr14:27114899-27403911 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
View mouse Rabgef1 Chr5:130171798-130214342 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
The Dbl family of guanine nucleotide exchange factors are multifunctional molecules that transduce diverse intracellular ... Dbl Family Guanine Nucleotide Exchange Factors Y Zheng. Trends Biochem Sci. Dec 2001 ... Recognition and activation of Rho GTPases by Vav1 and Vav2 guanine nucleotide exchange factors. Heo J, Thapar R, Campbell SL. ... Structural elements, mechanism, and evolutionary convergence of Rho protein-guanine nucleotide exchange factor complexes. ...
... secretion regulating guanine nucleotide exchange factor), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol ... Ran guanyl-nucleotide exchange factor activity protein binding nucleus nucleoplasm cytoplasm cytosol signal transduction ... Ran guanyl-nucleotide exchange factor activity protein binding nucleus nucleoplasm cytoplasm cytosol signal transduction ...
... rho/rac guanine nucleotide exchange factor (GEF) 2), Authors: Valery Poroyko, Anna Birukova. Published in: Atlas Genet ... ARHGEF2 (rho/rac guanine nucleotide exchange factor (GEF) 2). Written. 2007-05. Valery Poroyko, Anna Birukova. ... The high level of homology has been shown for three known rho/rac guanine nucleotide exchange factors originated from human, ... The gene encodes a guanine nucleotide exchange factor for Rho GTPase; 985 amino acids; NH2- Protein kinase C conserved region 1 ...
... guanine nucleotide exchange factor VAV2 explanation free. What is guanine nucleotide exchange factor VAV2? Meaning of guanine ... nucleotide exchange factor VAV2 medical term. What does guanine nucleotide exchange factor VAV2 mean? ... Looking for online definition of guanine nucleotide exchange factor VAV2 in the Medical Dictionary? ... Guanine nucleotide exchange factor VAV2 , definition of guanine nucleotide exchange factor VAV2 by Medical dictionary https:// ...
Showing Protein Rho guanine nucleotide exchange factor 2 (HMDBP08310). IdentificationBiological propertiesGene properties ... Involved in Rho guanyl-nucleotide exchange factor activity. Specific Function. Activates Rho-GTPases by promoting the exchange ... a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases. J Biol Chem. 1998 Dec 25;273(52):34954-60 ... Krendel M, Zenke FT, Bokoch GM: Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin ...
The Guanine-Nucleotide Exchange Factor Vav Is a Crucial Regulator of B Cell Receptor Activation and B Cell Responses to ... The Guanine-Nucleotide Exchange Factor Vav Is a Crucial Regulator of B Cell Receptor Activation and B Cell Responses to ... The Guanine-Nucleotide Exchange Factor Vav Is a Crucial Regulator of B Cell Receptor Activation and B Cell Responses to ... The Guanine-Nucleotide Exchange Factor Vav Is a Crucial Regulator of B Cell Receptor Activation and B Cell Responses to ...
Evidence That Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) on 1q21 is a Type 2 Diabetes Susceptibility Gene in the Old ... Evidence That Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) on 1q21 is a Type 2 Diabetes Susceptibility Gene in the Old ... Evidence That Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) on 1q21 is a Type 2 Diabetes Susceptibility Gene in the Old ... Evidence That Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) on 1q21 is a Type 2 Diabetes Susceptibility Gene in the Old ...
Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to ... Akt and PP2A Reciprocally Regulate the Guanine Nucleotide Exchange Factor Dock6 to Control Axon Growth of Sensory Neurons ... Akt and PP2A Reciprocally Regulate the Guanine Nucleotide Exchange Factor Dock6 to Control Axon Growth of Sensory Neurons ... Akt and PP2A Reciprocally Regulate the Guanine Nucleotide Exchange Factor Dock6 to Control Axon Growth of Sensory Neurons ...
The C-terminal guanine nucleotide exchange factor (GEF) module of Trio (TrioC) transfers signals from the Gαq/11 subfamily of ... Rho guanine nucleotide exchange factors (RhoGEFs) activate the Rho family of small GTPases that regulate cell migration and ... Structure of the C-terminal guanine nucleotide exchange factor module of Trio in an autoinhibited conformation reveals its ... Structure of the C-terminal guanine nucleotide exchange factor module of Trio in an autoinhibited conformation reveals its ...
The Hemopoietic Rho/Rac Guanine Nucleotide Exchange Factor Vav1 Regulates N-Formyl-Methionyl-Leucyl-Phenylalanine-Activated ... The Hemopoietic Rho/Rac Guanine Nucleotide Exchange Factor Vav1 Regulates N-Formyl-Methionyl-Leucyl-Phenylalanine-Activated ... The Hemopoietic Rho/Rac Guanine Nucleotide Exchange Factor Vav1 Regulates N-Formyl-Methionyl-Leucyl-Phenylalanine-Activated ... The Hemopoietic Rho/Rac Guanine Nucleotide Exchange Factor Vav1 Regulates N-Formyl-Methionyl-Leucyl-Phenylalanine-Activated ...
What is Rho/Rac guanine nucleotide exchange factor FGD1? Meaning of Rho/Rac guanine nucleotide exchange factor FGD1 medical ... What does Rho/Rac guanine nucleotide exchange factor FGD1 mean? ... Rho/Rac guanine nucleotide exchange factor FGD1 explanation ... Looking for online definition of Rho/Rac guanine nucleotide exchange factor FGD1 in the Medical Dictionary? ... Rho/Rac guanine nucleotide exchange factor FGD1 , definition of Rho/Rac guanine nucleotide exchange factor FGD1 by Medical ...
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... ... C3G, the exchange factor for Rap1, functions in pathways leading to actin reorganization and filopodia formation, processes ... Human neuroblastoma cells, IMR-32 induced to differentiate by serum starvation or by treatment with nerve growth factor (NGF) ...
  • Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). (wikipedia.org)
  • Guanine nucleotide exchange factors (GEFs) are proteins or protein domains involved in the activation of small GTPases. (wikipedia.org)
  • Thus, GEFs both destabilize the GTPase interaction with GDP and stabilize the nucleotide-free GTPase until a GTP molecule binds to it. (wikipedia.org)
  • However, there are some similarities in how different GEFs alter the conformation of the G protein nucleotide-binding site. (wikipedia.org)
  • Guanine nucleotide-exchange factors (GEFs) are directly responsible for the activation of Rho-family GTPases in response to diverse extracellular stimuli, and ultimately regulate numerous cellular responses such as proliferation, differentiation and movement. (nih.gov)
  • Because the association of cytosolic ARF onto vesicle membranes is coincident with GTP activation, we searched the genome of L. pneumophila for proteins that had homology to ARF-specific guanine nucleotide exchange factors (GEFs) ( 16 ). (sciencemag.org)
  • Here we report the identification of Vav2 and Vav3 as guanine nucleotide exchange factors (GEFs) that link the EphA2 receptor to Rho family GTPase activation and angiogenesis. (asm.org)
  • EPAC1 and EPAC2 (exchange proteins activated by cyclic AMP) are guanine nucleotide exchange factors (GEFs) that catalyze the exchange of GDP for GTP, activating Rap1 and Rap2 small GTPases. (creative-biogene.com)
  • The rod-shaped fission yeast Schizosaccharomyces pombe has two Cdc42 guanine nucleotide exchange factors (GEFs), Scd1 and Gef1, but little is known about how they are coordinated in polarized growth. (biologists.org)
  • Upon activation by guanine nucleotide exchange factors (GEFs), Rac1 associates with a variety of proteins in the cell thereby regulating various functions, including cell migration. (garvan.org.au)
  • This cycle is regulated by guanine nucleotide exchange factors (GEFs), * which exchange GDP for GTP, and GTPase activating proteins (GAPs), which stimulate the rate of GTP hydrolysis. (rupress.org)
  • Three classes of proteins, GTPase‐activating proteins (GAPs), guanine nucleotide dissociation inhibitors (GDIs), and guanine nucleotide exchange factors (GEFs), regulate the cycling of these GTP‐binding proteins between their GDP‐bound and GTP‐bound states ( Boguski and McCormick, 1993 ). (embopress.org)
  • Guanine nucleotide exchange factor (or guanine exchange protein) (GEFs) is implicated in addressing system of vesicular transport. (chemeurope.com)
  • Cellular stimulation results in the activation of guanine nucleotide exchange factors (GEFs), which catalyze the exchange of GDP on inactive GTPase for GTP. (biomedcentral.com)
  • Guanine nucleotide exchange factors (GEFs) such as ARHGEF19 accelerate the GTPase activity of Rho GTPases (see RHOA, MIM 165390). (nih.gov)
  • Guanine nucleotide exchange factors (GEFs) promote GTP-bound Ras state by enhancing exchange of GDP with GTP. (frontiersin.org)
  • The VAV proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases that activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. (genecards.org)
  • Rho GEFs regulate the activity of small Rho GTPases by stimulating the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and may play a role in neural morphogenesis. (nih.gov)
  • Activation of Rho GTPases is under the direct control of guanine nucleotide exchange factors (GEFs). (nih.gov)
  • The inactive form of GTPases (GDP-form) are activated by a class of proteins called Guanosine nucleotide exchange factors (GEFs). (wikipedia.org)
  • GEFs (guanine-nucleotide exchange factors) activate small G proteins (GTPases) such as Rac, which regulates cell shape, motility, oxygen radical formation and gene expression (Fig 1). (babraham.ac.uk)
  • Rac-GEFs such as P-Rex activate Rac by exchanging GDP for GTP, enabling Rac to bind various effector proteins that stimulate cell responses. (babraham.ac.uk)
  • Conversely, the reloading of the GTPases is made possible by the action of guanine nucleotide exchange factors (GEFs), which facilitates the exchange of free GTP for G protein-bound GDP ( 7 ), or is slowed by the presence of GDP dissociation inhibitors ( 9 ). (pnas.org)
  • The activities of ROPs are positively regulated by guanine nucleotide exchange factors (GEFs). (springeropen.com)
  • Dbl Family GEFs contain Dbl homology (DH) and pleckstrin homology (PH) domains in tandem, which are responsible for enhancement of guanine nucleotide exchange on the target GTPase. (biomedcentral.com)
  • With the presence of guanine nucleotide exchange factors (GEFs) Rab proteins can be converted into their active GTP form thus to bind multiple effectors such as tethering factors and SNAREs to promote membrane fusion15 16 17 18 19 20 Once the Rab proteins exert its function GTPase-activating protein (Space) enhances the hydrolysis GTP GSK2126458 to GDP and thereby inactivating Rab21. (lecollege.org)
  • The C-terminal half of tamalin also bound to cytohesins, the members of guanine nucleotide exchange factors (GEFs) specific for the ADP-ribosylation factor (ARF) family of small GTP-binding proteins. (jneurosci.org)
  • Guanine nucleotide exchange factors (GEFs) belonging to the Dbl family of proteins represent one major class of proteins that regulate the activity of Rho GTPases. (elsevier.com)
  • Guanine nucleotide exchange factors (GEFs) are responsible for coupling cell surface receptors to Ras protein activation. (elsevier.com)
  • These molecules share the core catalytic domain of other Ras family GEFs but lack the catalytic non- conserved (conserved non-catalytic/Ras exchange motif/structurally conserved region 0) domain that is believed to contribute to Sos1 integrity. (elsevier.com)
  • In vitro binding and in vivo nucleotide exchange assays indicate that these GEFs specifically catalyze the GTP loading of the Ral GTPase when overexpressed in 293T cells. (elsevier.com)
  • In contrast to the Ral guanine nucleotide dissociation stimulator family of Ral GEFs, the RalGPS proteins do not possess a Ras-GTP-binding domain, suggesting that they are activated in a Ras-independent manner. (elsevier.com)
  • Small G proteins, which are essential regulators of multiple cellular functions, are activated by guanine nucleotide exchange factors (GEFs) that stimulate the exchange of the tightly bound GDP nucleotide by GTP. (beds.ac.uk)
  • Guanine Nucleotide Exchange Factors (GEFs) are obligatory components of signaling cascades regulated by small GTP-binding proteins (called small G proteins hereafter). (beds.ac.uk)
  • Each small G protein family features its own ensemble of GEFs characterized by a conserved catalytic domain responsible for nucleotide exchange, which is generally combined with non-catalytic domains that define the spatio-temporal conditions of activation. (beds.ac.uk)
  • GUANINE-NUCLEOTIDE-EXCHANGE factors (GEFs) promote the exchange of GDP for GTP in Ras GTPases, and thereby positively regulate their functions 1,2 . (elsevier.com)
  • Here, we identify the RAB-11-interacting protein-1 (REI-1) as a unique family of guanine nucleotide exchange factors (GEFs) for RAB-11 in Caenorhabditis elegans. (elsevier.com)
  • In a directed candidate screen for guanine nucleotide exchange factors (GEFs), which directly activate small GTPases, Cool-1/βPix was identified in pancreatic islet beta cells. (elsevier.com)
  • The RasGrf proteins exhibit modular structures composed by multiple domains including CDC25H and DHPH motifs responsible for promoting GDP/GTP exchange, respectively, on Ras or Rho GTPase targets. (nih.gov)
  • It is thought that the Dot/Icm transporter is used by L. pneumophila to inject proteins into host cells in order to control the biogenesis of a replicative organelle by modulating the activity of host factors involved in vesicle traffic. (sciencemag.org)
  • This hSos1 domain specifically stimulated guanine nucleotide exchange on mammalian Ras proteins in vitro. (sciencemag.org)
  • The tandem Dbl-homology and pleckstrin-homology domains shared by all members of this family represent the structural module responsible for catalyzing the GDP-GTP exchange reaction of Rho proteins. (nih.gov)
  • The C-terminal guanine nucleotide exchange factor (GEF) module of Trio (TrioC) transfers signals from the Gα q/11 subfamily of heterotrimeric G proteins to the small guanosine triphosphatase (GTPase) RhoA, enabling Gα q/11 -coupled G protein-coupled receptors (GPCRs) to control downstream events, such as cell motility and gene transcription. (sciencemag.org)
  • The encoded protein belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. (creativebiomart.net)
  • Rab3GEP belongs to the family of DENN domain proteins, in general DENN domains are considered as domains with a guanine exchange factor activity. (nottingham.ac.uk)
  • Proteins that catalyze the release and exchange of GDP for GTP from GTP-binding regulatory proteins, which are active in the GTP-bound form. (semanticscholar.org)
  • Activates the ARF proteins by exchanging bound GDP for free GTP. (rcsb.org)
  • Exchange factor for GTP-binding proteins RhoA, RhoG and, to a lesser extent, Rac1. (genecards.org)
  • Another class of regulatory proteins, the Guanosine nucleotide dissociation inhibitors (GDIs), bind to the GDP-bound form of Rho and Rab small GTPases and not only prevent exchange (maintaining the small GTPase in an off-state), but also prevent the small GTPase from localizing at the membrane, which is their place of action. (wikipedia.org)
  • Within the endomembrane system of eukaryotic cells protein and lipid are packaged into vesicles at donor organelles and transported to acceptor membranes which depend on multiple fusion and fission events9 10 Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins play an important role in intracellular membrane fusion in eukaryotic cells11. (lecollege.org)
  • Of the two Cdc42 guanine nucleotide dissociation inhibitor (GDI) proteins identified in beta cells, βPix competed selectively with caveolin-1 (Cav-1) but not RhoGDI in coimmunoprecipitation and GST-Cdc42-GDP interaction assays. (elsevier.com)
  • VAV1 has several biochemical functions, for example, Rac guanyl-nucleotide exchange factor activity, guanyl-nucleotide exchange factor activity, metal ion binding. (creativebiomart.net)
  • GO annotations related to this gene include guanyl-nucleotide exchange factor activity and cAMP-dependent protein kinase regulator activity . (genecards.org)
  • Gene Ontology (GO) annotations related to this gene include GTPase activator activity and Rho guanyl-nucleotide exchange factor activity . (genecards.org)
  • GTPases contain two loops called switch 1 and switch 2 that are situated on either side of the bound nucleotide. (wikipedia.org)
  • RasGrf1 and RasGrf2 are highly homologous mammalian guanine nucleotide exchange factors which are able to activate specific Ras or Rho GTPases. (nih.gov)
  • Guanine nucleotide exchange factor for the Rho family of Ras-related GTPases. (rcsb.org)
  • Here we show that L. pneumophila produce a protein called RalF that functions as an exchange factor for the ADP ribosylation factor (ARF) family of guanosine triphosphatases (GTPases). (sciencemag.org)
  • The Dbl family of guanine nucleotide exchange factors are multifunctional molecules that transduce diverse intracellular signals leading to the activation of Rho GTPases. (nih.gov)
  • Structural basis for the selective activation of Rho GTPases by Dbl exchange factors. (nih.gov)
  • Recognition and activation of Rho GTPases by Vav1 and Vav2 guanine nucleotide exchange factors. (nih.gov)
  • Activates Rho-GTPases by promoting the exchange of GDP for GTP. (hmdb.ca)
  • Binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases, which was uniquely reported in PubMed:9857026. (hmdb.ca)
  • Rho guanine nucleotide exchange factors (RhoGEFs) activate the Rho family of small GTPases that regulate cell migration and gene expression in normal development, as well as disease, including some cancers. (sciencemag.org)
  • Arhgef4 acts as guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. (antikoerper-online.de)
  • The Rho guanine exchange factor (GEF) Trio is especially well suited to relay signals, as it features distinct catalytic domains to activate Rho GTPases. (xenbase.org)
  • Activator for both CDC42 and RAC1 by directly interacting with these Rho GTPases and acting as a guanine nucleotide exchange factor (GEF). (icr.ac.uk)
  • Guanine nucleotide exchange factor (GEF) for RAP1A and RAP2A small GTPases that is activated by binding cAMP. (genecards.org)
  • GTPases are a group of enzymes that catalyze hydrolysis of the gamma phosphate bond in guanine triphosphate (GTP) to form guanine diphosphate (GDP). (genecards.org)
  • Binds physically to the nucleotide-free states of those GTPases. (genecards.org)
  • A novel superfamily of guanine nucleotide exchange factors for Rho GTPases includes DOCK180 and zizimin1. (scienceexchange.com)
  • In the endomembrane trafficking system a conserved machinery is required that consist of Rab GSK2126458 GTPases tethering factors and the SNARE proteins14. (lecollege.org)
  • The tool works with standard single letter nucleotide or protein codes including ambiguities and can match Prosite patterns in protein sequences. (nih.gov)
  • Guanine-nucleotide-releasing protein that acts on members of the SEC4/YPT1/RAB subfamily. (uniprot.org)
  • The host protein ADP ribosylation factor-1 (ARF1) is found on phagosomes containing wild-type L. pneumophila but is not localized to phagosomes containing L. pneumophila dot/icm mutants ( 14 ). (sciencemag.org)
  • The hSos1 protein contains a region of significant sequence similarity to CDC25, a guanine nucleotide exchange factor for Ras from yeast. (sciencemag.org)
  • The hSos1 interacted with growth factor receptor-bound protein 2 (GRB2) in vivo and in vitro. (sciencemag.org)
  • Structural elements, mechanism, and evolutionary convergence of Rho protein-guanine nucleotide exchange factor complexes. (nih.gov)
  • Recent data suggest that Vav functions as a guanine-nucleotide (GDP/GTP) exchange factor for members of the Rho-like small GTPase family members RhoA, Rac1, and CDC42, which regulate cytoskeletal organization and activation of the p21-activated kinase and stress-activated protein kinase/c-Jun N-terminal kinase signaling pathways ( 7 , 8 , 9 , 10 , 11 ). (jimmunol.org)
  • Rho guanine nucleotide exchange factor 11 (ARHGEF11), located on chromosome 1q21, is involved in G protein signaling and is a pathway known to play a role in both insulin secretion and action. (diabetesjournals.org)
  • The encoded protein specifically binds to the Rho family GTPase Cdc42Hs and can stimulate the GDP-GTP exchange of the isoprenylated form of Cdc42Hs. (thefreedictionary.com)
  • Human neuroblastoma cells, IMR-32 induced to differentiate by serum starvation or by treatment with nerve growth factor (NGF) or forskolin showed enhanced C3G protein levels. (ovid.com)
  • Here we describe an essential function of the Sec7 domain guanine nucleotide exchange factor (GEF) gartenzwerg ( garz ) in epithelial tube morphogenesis and protein secretion. (biologists.org)
  • It encodes a protein of 759 amino acids that functions as a guanine nucleotide exchange factor for the small GTPase Sec4p, a regulator of Golgi to plasma membrane transport. (rupress.org)
  • Although the ts mutation sec2-78 does not affect nucleotide exchange activity, the protein is mislocalized. (rupress.org)
  • Cyclic AMP (Montrer APRT Anticorps ) (cAMP), a secondary messenger responsible for various physiological processes regulates cell metabolism by activating Protein kinase A (PKA) and by targeting exchange protein directly activated by cAMP ( EPAC ). (anticorps-enligne.fr)
  • The Cool‐2 ( c loned‐ o ut o f l ibrary‐2) protein (identical to α‐Pix for P ak‐ i nteractive e x change factor) has been implicated in various biological responses including chemoattractant signaling and in certain forms of mental retardation. (embopress.org)
  • eIF-2b - The eukaryotic initiation factor 2b regenerates eIF-2a for an additional cycle in protein synthesis initiation, i.e. its binding to the Met-t-RNA. (chemeurope.com)
  • The rho-guanine nucleotide exchange factor domain of obscurin regulates assembly of titin at the Z-disk through interactions with Ran binding protein 9. (duke.edu)
  • Guanine nucleotide-releasing protein that binds to SH3 domain of CRK and GRB2/ASH. (nih.gov)
  • The Brefeldin A-inhibited guanine nucleotide exchange factor 2 (BIG2) has emerged as a key regulator of protein trafficking within the late secretory pathway , between the trans-Golgi Network (TGN) and endosomal compartments and within the recycling endosomal pathway . (uab.edu)
  • Nef, a potent virulence factor, alters cellular environments to increase lentiviral replication in the host, functioning as an adaptor protein. (reactome.org)
  • RAPGEF3 (Rap Guanine Nucleotide Exchange Factor 3) is a Protein Coding gene. (genecards.org)
  • VAV3 (Vav Guanine Nucleotide Exchange Factor 3) is a Protein Coding gene. (genecards.org)
  • The protein encoded by this gene is a guanine nucleotide exchange factor and belongs to the Rho GTPase GEF family. (nih.gov)
  • The Ccz1-Mon1 protein complex the guanine nucleotide exchange factor (GEF) of the later endosomal Rab7 homolog Ypt7 is necessary for the later step of multiple vacuole delivery pathways such as for example cytoplasm-to-vacuole targeting (Cvt) pathway and autophagy processes. (lecollege.org)
  • Polypeptide release factors are essential in the termination of protein synthesis on ribosomes as a response to a stop codon. (readabstracts.com)
  • Their biochemical activity is to stimulate the dissociation of the tightly bound GDP nucleotide from the small G protein in response to cellular signals. (beds.ac.uk)
  • Here, we show that the Cdc42-guanine nucleotide exchange factor FGD6 coordinates these events through its Src-dependent interaction with different actin-based protein networks. (ox.ac.uk)
  • ARHGEF2/GEF-H1 belongs to a Dbl family of Rho activators and exhibits Rho-specific GDP/GTP exchange activity for RhoA but not for Rac1 or Cdc42 . (atlasgeneticsoncology.org)
  • Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase. (nih.gov)
  • EspM2 is a RhoA guanine nucleotide exchange factor. (qmul.ac.uk)
  • We identified a direct interaction between EspM2 or SifA and nucleotide-free RhoA. (qmul.ac.uk)
  • EspM2 induced nucleotide exchange in RhoA but not in Rac1 or H-Ras, while SifA induced nucleotide exchange in none of them. (qmul.ac.uk)
  • These results suggest that binding of SifA to RhoA does not trigger nucleotide exchange while EspM2 is a unique Rho GTPase GEF. (qmul.ac.uk)
  • will catalyze nucleotide exchange on RhoA also, RhoG, buy OG-L002 and Cdc42 (1, 3). (kn-62.com)
  • Consistent with this notion, PAR1 was recently found to be physically associated with a RhoA-specific guanine nucleotide exchange factor H1 (GEF-H1). (fujita-hu.ac.jp)
  • We currently reported that Vav2, a member of the guanine nucleotide exchange factor-Vav subfamily, participates in homocysteine-induced increases in Rac1 activity and consequent activation of NADPH oxidase in rat mesangial cells. (ahajournals.org)
  • Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. (rcsb.org)
  • Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to regulate the actin cytoskeleton. (sciencemag.org)
  • This calls for the identification of factors that influence Rac1-driven cell motility. (garvan.org.au)
  • Here, we demonstrate that Rac1 captures the Rac guanine nucleotide exchange factor P-Rex1 from platelet lysates. (biomedcentral.com)
  • On the basis of the framework of the DH domains of the GEF Tiam1 in composite with Rac1 (25), we designed a mutation of Vav1 that would remove GEF activity but would not really have an effect on surrendering of the domains, In the Tiam1-Rac1 composite, Leu1194 and Lys1195 of Tiam1 make essential connections with the change II area of Rac1 and thus play a vital function in nucleotide exchange. (kn-62.com)
  • Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes. (scienceexchange.com)
  • The Cdc42 guanine nucleotide exchange factor FGD6 coordinates cell polarity and endosomal membrane recycling in osteoclasts. (ox.ac.uk)
  • These results provide the first genetic evidence on the role of the guanine exchange factor Vav in immune responses to viral infections and antigenic challenge in vivo, and suggest that Vav adjusts the threshold for Ag receptor-mediated B cell activation depending on the nature of the Ag. (jimmunol.org)
  • C3G, the exchange factor for Rap1, functions in pathways leading to actin reorganization and filopodia formation, processes required during neurite growth. (ovid.com)
  • Plays a role in nerve growth factor (NGF)-induced sustained activation of Rap1 and neurite outgrowth. (nih.gov)
  • This gene encodes a human guanine nucleotide exchange factor. (nih.gov)
  • The Dbl family guanine nucleotide exchange factor ARHGEF10 was originally identified as the product of the gene associated with slowed nerve-conduction velocities of peripheral nerves. (biomedcentral.com)
  • The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the advancement and activation of T cells. (kn-62.com)
  • Aptamer-derived peptide inhibitors of Rho guanine nucleotide exchange factors. (semanticscholar.org)
  • A gene on chromosome 9q34.1 that encodes a member of the VAV guanine nucleotide exchange factor (GEF) family of genes which is only expressed in haematopoietic cells. (thefreedictionary.com)
  • Results: The Src homology 3 domain-containing GEF (SGEF) promotes fibroblast growth factor-inducible 14 (Fn14) proinvasive signaling in glioblastoma via TNF receptor-associated factor 2 (TRAF2). (elsevier.com)
  • Ras guanine nucleotide exchange factors (RasGEFs) catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. (frontiersin.org)
  • Osteoblasts and stromal cells support OC differentiation and activation, predominantly via macrophage colony-stimulating factor (M-CSF) and receptor activator of NF- κ B ligand (RANKL) pathways. (hindawi.com)
  • The RANKL membrane signaling complex requires recruitment of TNF receptor-associated factor 6 (TRAF6), which plays dominant roles in OC differentiation and activation and is necessary for activation of NF- κ B by RANKL [ 5 ]. (hindawi.com)
  • Chez www.anticorps-enligne.fr sont 69 Rap Guanine Nucleotide Exchange Factor (GEF) 3 (RAPGEF3) Anticorps de 21 de différents fournisseurs disponibles. (anticorps-enligne.fr)
  • Guanine-nucleotide exchange factors (RAPGEF3/RAPGEF4) induce sperm membrane depolarization and acrosomal exocytosis in capacitated stallion sperm. (umass.edu)
  • Due to the recent discovery of cAMP-activated guanine nucleotide exchange factors RAPGEF3 and RAPGEF4 , we sought to investigate the separate roles of PRKACA and RAPGEF3 / RAPGEF4 in modulating capacitation and acrosomal exocytosis. (umass.edu)
  • The RasGrf family of mammalian guanine nucleotide exchange factors. (nih.gov)
  • Mammalian cells overexpressing full-length hSos1 had increased guanine nucleotide exchange activity. (sciencemag.org)
  • identify C. elegans REI-1 and its mammalian homolog SH3BP5 as Rab11 guanine nucleotide exchange factors. (elsevier.com)
  • Kinetics of Interaction between ADP-ribosylation Factor-1 (Arf1) and the Sec7 Domain of Arno Guanine Nucleotide Exchange Factor, Modulation by Allosteric Factors, and the Uncompetitive Inhibitor Brefeldin A. (inserm.fr)
  • The GDP/GTP exchange activity of BIG2 resides within a conserved Sec7 domain and is specific for ARF1 and ARF3 . (uab.edu)
  • Crystallographic analyses and structure-function studies of the Sec7 domain have provided basic mechanistic insight into the exchange reaction , but the mechanisms responsible for substrate specificity of BIG2 remain unknown . (uab.edu)
  • We found a novel regulatory motif within the C-terminus of the Sec7 domain in BIG2 essential for ARF binding and nucleotide exchange . (uab.edu)
  • Conversely, blocking the GDP-GTP nucleotide exchange reaction leads to constitutive Golgi localization, suggesting that Garz cycles in a GEF-activity-dependent manner between cytoplasmic and Golgi-membrane-localized pools. (biologists.org)
  • Furthermore, to function properly Rab27a has to be targeted to the organelle membrane, this function has been attributed to the guanine exchange factor as well. (nottingham.ac.uk)
  • We found that membrane association of BIG2 was regulated through the enzymatic activity of another guanine nucleotide exchange factor called GBF1 . (uab.edu)
  • These novel findings provide new insights into regulatory mechanisms that facilitate membrane association of BIG2 and control the selectivity of its enzymatic exchange activity . (uab.edu)
  • From a dominant loss-of-function genetic screen, we discovered that mutations of a Dbl-family member, the guanine nucleotide exchange factor DRhoGEF2 (DRhoGEF22(l)04291), suppressed the PTEN-overexpression eye phenotype. (umn.edu)
  • Rebhun, JF, Chen, H & Quilliam, LA 2000, ' Identification and characterization of a new family of guanine nucleotide exchange factors for the Ras-related GTPase Ral ', Journal of Biological Chemistry , vol. 275, no. 18, pp. 13406-13410. (elsevier.com)
  • The objective of this study was to determine whether the combined expression of α6β4 integrin and neuroepithelioma transforming gene 1 (Net1), a guanine nucleotide exchange factor specific for Ras homolog gene family member A, is associated with adverse clinical outcome in breast cancer patients. (uthscsa.edu)
  • Wai, SC, Gerber, SA & Li, R 2014, Multisite phosphorylation of the guanine nucleotide exchange factor cdc24 during yeast cell polarization . (elsevier.com)
  • 2020), The Rho guanine nucleotide exchange factor Trio. (xenbase.org)
  • 6 On cell activation, GDP-bound Rac under resting condition may be converted into GTP-Rac through the action of a guanine nucleotide exchange factor. (ahajournals.org)
  • In both the Ras·GDP and Ras·GTP states the nucleotide is very tightly bound ( 2 - 4 ) and for Ras activation to occur Ras guanine nucleotide exchange factors (RasGEFs) need to loosen the grip of Ras on the bound nucleotide, stabilizing nucleotide-free Ras that stochastically but preferentially associates with GTP, because GTP is present in the cell in higher concentrations than GDP ( 5 ). (frontiersin.org)
  • This process is expected to require the participation of a guanine nucleotide exchange factor (GEF) to generate the GTP-bound form of Rab10, but this GEF has not hitherto been identified. (core.ac.uk)
  • Research shows that the peptide release factor RF3, involved in the translation termination, is bound to GDP, whereas RF1 or RF2 complexed with ribosome function as guanine nucleotide exchange factors. (readabstracts.com)
  • Mechanisms of stop codon recognition and translation termination by release factors (RFs) from the perspective of molecular mimicry between translation factors and tRNA. (readabstracts.com)
  • Yu, H & Schreiber, SL 1995, ' Structure of guanine-nucleotide-exchange factor human Mss4 and identification of its Rab-interacting surface ', Nature , vol. 376, no. 6543, pp. 788-791. (elsevier.com)
  • 100 guanine nucleotide exchange factors, Vav subfamily exhibits the high specificity to Rac-mediated NADPH oxidase activation. (ahajournals.org)
  • The catalytic domain responsible for nucleotide exchange is in general associated with non-catalytic domains that define the spatio-temporal conditions of activation. (beds.ac.uk)
  • Rat RAPGEF4 ELISA kit allows for the in vitro quantitative determination of Rat Rap guanine nucleotide exchange factor 4 concentrations in serum, plasma, tissue homogenates, cell culture supernates, and other biological fluids. (lifescience-market.com)
  • Your search returned 13 alsin Rho guanine nucleotide exchange factor ELISA ELISA Kit across 2 suppliers. (biocompare.com)
  • FUNCTION: Guanine nucleotide-exchange factor (GEF) required for the formation or budding of transport vesicles from the ER. (membranome.org)
  • Nuclear Magnetic Resonance Spectroscopy revealed that EspM2 has a similar fold to SifA and the guanine nucleotide exchange factor (GEF) effector SopE. (qmul.ac.uk)
  • Caspase-mediated Cleavage of the TIAM1 Guanine Nucleotide Exchange Factor during Apoptosis -- Qi et al. (aacrjournals.org)
  • A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity. (wikipedia.org)
  • Third, Ypt32p and Sec2p interact biochemically, but Sec2p has no exchange activity on Ypt32p. (rupress.org)
  • These transcription factors induce genes that have been associated with OC differentiation, survival, and activity, including those encoding integrins ( β 3-integrin), proteases (cathepsin K), and vacuolar H + -ATPases (V-ATPases), which are involved in bone resorption [ 3 ]. (hindawi.com)
  • Research demonstrates the mechanism involved in controlling the binding and GTPase activity of translation factors by the position of peptidyl-tRNA in the ribosome. (readabstracts.com)
  • Mutation of these residues to alanine decreases the exchange activity of Tiam1. (kn-62.com)
  • Recently, expression and post-translational modification of Ras guanine nucleotide releasing factor 1 (RasGRF1) was found to contribute to spontaneous MMP production in melanoma cancer cells. (biomedcentral.com)
  • The high level of homology has been shown for three known rho/rac guanine nucleotide exchange factors originated from human, mouse and dog. (atlasgeneticsoncology.org)