Guanine Nucleotide Exchange Factors: Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.Rho Guanine Nucleotide Exchange Factors: 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.ras Guanine Nucleotide Exchange Factors: A family of GUANINE NUCLEOTIDE EXCHANGE FACTORS that are specific for RAS PROTEINS.Guanine NucleotidesProto-Oncogene Proteins c-vav: Proto-oncogene proteins that are guanine nucleotide exchange factors for RHO GTPASES. They also function as signal transducing adaptor proteins.Guanosine Diphosphate: A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.ras-GRF1: 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.cdc42 GTP-Binding Protein: A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions including cytoskeletal changes, filopodia formation and transport through the GOLGI APPARATUS. This enzyme was formerly listed as EC 188.8.131.52.Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.rac1 GTP-Binding Protein: A rac GTP-binding protein involved in regulating actin filaments at the plasma membrane. It controls the development of filopodia and lamellipodia in cells and thereby influences cellular motility and adhesion. It is also involved in activation of NADPH OXIDASE. This enzyme was formerly listed as EC 184.108.40.206.rho GTP-Binding Proteins: A large family of MONOMERIC GTP-BINDING PROTEINS that are involved in regulation of actin organization, gene expression and cell cycle progression. This enzyme was formerly listed as EC 220.127.116.11.ADP-Ribosylation Factors: MONOMERIC GTP-BINDING PROTEINS that were initially recognized as allosteric activators of the MONO(ADP-RIBOSE) TRANSFERASE of the CHOLERA TOXIN catalytic subunit. They are involved in vesicle trafficking and activation of PHOSPHOLIPASE D. This enzyme was formerly listed as EC 18.104.22.168rac GTP-Binding Proteins: A sub-family of RHO GTP-BINDING PROTEINS that is involved in regulating the organization of cytoskeletal filaments. This enzyme was formerly listed as EC 22.214.171.124.rap1 GTP-Binding Proteins: 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 126.96.36.199.rhoA GTP-Binding Protein: A RHO GTP-BINDING PROTEIN involved in regulating signal transduction pathways that control assembly of focal adhesions and actin stress fibers. This enzyme was formerly listed as EC 188.8.131.52.Guanine Nucleotide-Releasing Factor 2: 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.GTPase-Activating Proteins: Proteins that activate the GTPase of specific GTP-BINDING PROTEINS.SOS1 Protein: A mammalian homolog of the DROSOPHILA SON OF SEVENLESS PROTEIN. It is a guanine nucleotide exchange factor for RAS PROTEINS.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.ADP-Ribosylation Factor 1: ADP-RIBOSYLATION FACTOR 1 is involved in regulating intracellular transport by modulating the interaction of coat proteins with organelle membranes in the early secretory pathway. It is a component of COAT PROTEIN COMPLEX I. This enzyme was formerly listed as EC 184.108.40.206.GTP Phosphohydrolases: Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.ral Guanine Nucleotide Exchange Factor: 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.Son of Sevenless 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.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Eukaryotic Initiation Factor-2B: A guanine nucleotide exchange factor that acts to restore EUKARYOTIC INITIATION FACTOR-2 to its GTP bound form.rab GTP-Binding Proteins: A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. EC 3.6.1.-.ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 220.127.116.11.Guanineral GTP-Binding Proteins: A family of ubiquitously expressed MONOMERIC GTP-BINDING PROTEINS that are involved in intracellular signal transduction. This enzyme was formerly listed as EC 18.104.22.168.rap GTP-Binding Proteins: A family of MONOMERIC GTP-BINDING PROTEINS that are related to RAS PROTEINS.This enzyme was formerly listed as EC 22.214.171.124.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Guanine Nucleotide Dissociation Inhibitors: Protein factors that inhibit the dissociation of GDP from GTP-BINDING PROTEINS.Nucleotides: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)rab5 GTP-Binding Proteins: A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in transport from the cell membrane to early endosomes. This enzyme was formerly listed as EC 126.96.36.199.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.GTP-Binding Protein alpha Subunits, G12-G13: 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.Coat Protein Complex I: 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.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesMonomeric GTP-Binding Proteins: A class of monomeric, low molecular weight (20-25 kDa) GTP-binding proteins that regulate a variety of intracellular processes. The GTP bound form of the protein is active and limited by its inherent GTPase activity, which is controlled by an array of GTPase activators, GDP dissociation inhibitors, and guanine nucleotide exchange factors. This enzyme was formerly listed as EC 188.8.131.52Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cell Cycle Proteins: 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'-O-(3-Thiotriphosphate): Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.p21-Activated Kinases: A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Eukaryotic Initiation Factor-2: 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.ran GTP-Binding Protein: A monomeric GTP-binding protein involved in nucleocytoplasmic transport of proteins into the nucleus and RNA into the cytoplasm. This enzyme was formerly listed as EC 184.108.40.206.HSP110 Heat-Shock Proteins: 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.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Proto-Oncogene Proteins p21(ras): Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC 220.127.116.11.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.rab1 GTP-Binding Proteins: 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 18.104.22.168.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Brefeldin A: A fungal metabolite which is a macrocyclic lactone exhibiting a wide range of antibiotic activity.NIH 3T3 Cells: 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/)Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.rho-Specific Guanine Nucleotide Dissociation Inhibitors: A subcategory of guanine nucleotide dissociation inhibitors that are specific for RHO GTP-BINDING PROTEINS.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.Oncogene Proteins: Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).src Homology Domains: Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.A Kinase Anchor Proteins: 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.Kinetics: The rate dynamics in chemical or physical systems.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Stress Fibers: 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.Fungal Proteins: Proteins found in any species of fungus.cdc42 GTP-Binding Protein, Saccharomyces cerevisiae: 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 22.214.171.124.Golgi Apparatus: 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)GRB2 Adaptor Protein: A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).Recombinant Proteins: Proteins prepared by recombinant DNA technology.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.ras GTPase-Activating Proteins: PROTEINS that specifically activate the GTP-phosphohydrolase activity of RAS PROTEINS.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.PhosphoproteinsCercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.GTP-Binding Protein alpha Subunits: The GTPase-containing subunits of heterotrimeric GTP-binding proteins. When dissociated from the heterotrimeric complex these subunits interact with a variety of second messenger systems. Hydrolysis of GTP by the inherent GTPase activity of the subunit causes it to revert to its inactive (heterotrimeric) form. The GTP-Binding protein alpha subunits are grouped into families according to the type of action they have on second messenger systems.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Vesicular Transport Proteins: 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, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.rhoB GTP-Binding Protein: 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 126.96.36.199.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Heterotrimeric GTP-Binding Proteins: 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.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Guanylyl Imidodiphosphate: A non-hydrolyzable analog of GTP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It binds tightly to G-protein in the presence of Mg2+. The nucleotide is a potent stimulator of ADENYLYL CYCLASES.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Proto-Oncogene Proteins c-crk: 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.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Serum Response Element: 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.Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.Pseudopodia: A dynamic actin-rich extension of the surface of an animal cell used for locomotion or prehension of food.Peptide Elongation Factor 1: 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.Son of Sevenless Protein, Drosophila: A guanine nucleotide exchange factor from DROSOPHILA. Sevenless refers to genetic mutations in DROSOPHILA that cause loss of the R7 photoreceptor which is required to see UV light.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Phosphatidylinositol Phosphates: Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.GTP-Binding Protein alpha Subunits, Gi-Go: A family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.Endosomes: Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Adaptor Proteins, Vesicular Transport: A class of proteins involved in the transport of molecules via TRANSPORT VESICLES. They perform functions such as binding to the cell membrane, capturing cargo molecules and promoting the assembly of CLATHRIN. The majority of adaptor proteins exist as multi-subunit complexes, however monomeric varieties have also been found.Cytokinesis: The process by which the CYTOPLASM of a cell is divided.Oncogene Protein p21(ras): Transforming protein encoded by ras oncogenes. Point mutations in the cellular ras gene (c-ras) can also result in a mutant p21 protein that can transform mammalian cells. Oncogene protein p21(ras) has been directly implicated in human neoplasms, perhaps accounting for as much as 15-20% of all human tumors. This enzyme was formerly listed as EC 188.8.131.52.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Cell Surface Extensions: Specialized structures of the cell that extend the cell membrane and project out from the cell surface.Receptor, EphA8: 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.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Green Fluorescent Proteins: 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.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.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).Retroviridae Proteins, Oncogenic: Retroviral proteins that have the ability to transform cells. They can induce sarcomas, leukemias, lymphomas, and mammary carcinomas. Not all retroviral proteins are oncogenic.Cell Adhesion: Adherence of cells to surfaces or to other cells.rho-Associated Kinases: 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.PC12 Cells: 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.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Nerve Tissue Proteinsrho Guanine Nucleotide Dissociation Inhibitor alpha: An abundantly-expressed rho GDP-dissociation inhibitor subtype that regulates a broad variety of RHO GTPASES.trans-Golgi Network: 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.Protein Prenylation: A post-translational modification of proteins by the attachment of an isoprenoid to the C-terminal cysteine residue. The isoprenoids used, farnesyl diphosphate or geranylgeranyl diphosphate, are derived from the same biochemical pathway that produces cholesterol.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Cell Polarity: 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.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Focal Adhesions: 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.Cyclic AMP-Dependent Protein Kinases: 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.Thionucleotides: Nucleotides in which the base moiety is substituted with one or more sulfur atoms.Genes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Oncogene Protein v-crk: 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.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Multiprotein Complexes: Macromolecular complexes formed from the association of defined protein subunits.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cell Shape: The quality of surface form or outline of CELLS.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.GTP-Binding Protein alpha Subunits, Gq-G11: 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.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 184.108.40.206.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Ephrin-A1: 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.Neurites: 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.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Neuropeptides: Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Cell Transformation, Neoplastic: 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.Pertussis Toxin: One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.Peptide Initiation Factors: Protein factors uniquely required during the initiation phase of protein synthesis in GENETIC TRANSLATION.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Blood Proteins: Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.RNA, Transfer, Met: 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).Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Microfilament Proteins: 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.HSP70 Heat-Shock Proteins: 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.Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.Peptide Chain Initiation, Translational: 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.Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.Growth Cones: 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.Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.PDZ Domains: 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.Phosphoinositide Phospholipase C: 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.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.GTP-Binding Protein alpha Subunits, Gs: A family of heterotrimeric GTP-binding protein alpha subunits that activate ADENYLYL CYCLASES.Protein Interaction Mapping: Methods for determining interaction between PROTEINS.Myosin Type II: 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.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Luminescent Proteins: 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.Proto-Oncogene Proteins c-raf: 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.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.