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.-.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.Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.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).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.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.GTP Phosphohydrolases: Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.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.Guanosine Diphosphate: A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.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.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.GTP-Binding Protein beta Subunits: Heterotrimeric GTP-binding protein subunits that tightly associate with GTP-BINDING PROTEIN GAMMA SUBUNITS. A dimer of beta and gamma subunits is formed when the GTP-BINDING PROTEIN ALPHA SUBUNIT dissociates from the GTP-binding protein heterotrimeric complex. The beta-gamma dimer can play an important role in signal transduction by interacting with a variety of second messengers.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.Monomeric GTP-Binding Proteins: A class of monomeric, low molecular weight (20-25 kDa) GTP-binding proteins that regulate a variety of intracellular processes. The GTP bound form of the protein is active and limited by its inherent GTPase activity, which is controlled by an array of GTPase activators, GDP dissociation inhibitors, and guanine nucleotide exchange factors. This enzyme was formerly listed as EC 3.6.1.47Virulence Factors, Bordetella: A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.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.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.-.GTP-Binding Protein gamma Subunits: Heterotrimeric GTP-binding protein subunits that tightly associate with GTP-BINDING PROTEIN BETA SUBUNITS. A dimer of beta and gamma subunits is formed when the GTP-BINDING PROTEIN ALPHA SUBUNIT dissociates from the GTP-binding protein heterotrimeric complex. The beta-gamma dimer can play an important role in signal transduction by interacting with a variety of second messengers.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.ADP-Ribosylation Factors: MONOMERIC GTP-BINDING PROTEINS that were initially recognized as allosteric activators of the MONO(ADP-RIBOSE) TRANSFERASE of the CHOLERA TOXIN catalytic subunit. They are involved in vesicle trafficking and activation of PHOSPHOLIPASE D. This enzyme was formerly listed as EC 3.6.1.47Guanine Nucleotide Exchange Factors: Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.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.Adenosine Diphosphate Ribose: An ester formed between the aldehydic carbon of RIBOSE and the terminal phosphate of ADENOSINE DIPHOSPHATE. It is produced by the hydrolysis of nicotinamide-adenine dinucleotide (NAD) by a variety of enzymes, some of which transfer an ADP-ribosyl group to target proteins.RGS Proteins: A large family of evolutionarily conserved proteins that function as negative regulators of HETEROTRIMERIC GTP-BINDING PROTEINS. RGS PROTEINS act by increasing the GTPase activity of the G alpha subunit of a heterotrimeric GTP-binding protein, causing it to revert to its inactive (GDP-bound) form.rho GTP-Binding Proteins: A large family of MONOMERIC GTP-BINDING PROTEINS that are involved in regulation of actin organization, gene expression and cell cycle progression. This enzyme was formerly listed as EC 3.6.1.47.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.ADP Ribose Transferases: Enzymes that transfer the ADP-RIBOSE group of NAD or NADP to proteins or other small molecules. Transfer of ADP-ribose to water (i.e., hydrolysis) is catalyzed by the NADASES. The mono(ADP-ribose)transferases transfer a single ADP-ribose. POLY(ADP-RIBOSE) POLYMERASES transfer multiple units of ADP-ribose to protein targets, building POLY ADENOSINE DIPHOSPHATE RIBOSE in linear or branched chains.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.Botulinum Toxins: Toxic proteins produced from the species CLOSTRIDIUM BOTULINUM. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon ENDOCYTOSIS into PRESYNAPTIC NERVE ENDINGS. Once inside the cell the botulinum toxin light chain cleaves specific SNARE proteins which are essential for secretion of ACETYLCHOLINE by SYNAPTIC VESICLES. This inhibition of acetylcholine release results in muscular PARALYSIS.Kinetics: The rate dynamics in chemical or physical systems.GTPase-Activating Proteins: Proteins that activate the GTPase of specific GTP-BINDING PROTEINS.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.GTP-Binding Protein alpha Subunit, Gi2: A PERTUSSIS TOXIN-sensitive GTP-binding protein alpha subunit. It couples with a variety of CELL SURFACE RECEPTORS, has been implicated in INTERLEUKIN-12 production, and may play a role in INFLAMMATORY BOWEL DISEASES.Thionucleotides: Nucleotides in which the base moiety is substituted with one or more sulfur atoms.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.ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.GTP-Binding Protein alpha Subunits, Gs: A family of heterotrimeric GTP-binding protein alpha subunits that activate ADENYLYL CYCLASES.rhoA GTP-Binding Protein: A RHO GTP-BINDING PROTEIN involved in regulating signal transduction pathways that control assembly of focal adhesions and actin stress fibers. This enzyme was formerly listed as EC 3.6.1.47.Molecular Conformation: The characteristic three-dimensional shape of a molecule.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Aluminum Compounds: Inorganic compounds that contain aluminum as an integral part of the molecule.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Transducin: A heterotrimeric GTP-binding protein that mediates the light activation signal from photolyzed rhodopsin to cyclic GMP phosphodiesterase and is pivotal in the visual excitation process. Activation of rhodopsin on the outer membrane of rod and cone cells causes GTP to bind to transducin followed by dissociation of the alpha subunit-GTP complex from the beta/gamma subunits of transducin. The alpha subunit-GTP complex activates the cyclic GMP phosphodiesterase which catalyzes the hydrolysis of cyclic GMP to 5'-GMP. This leads to closure of the sodium and calcium channels and therefore hyperpolarization of the rod cells. EC 3.6.1.-.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Poly(A)-Binding Proteins: Proteins that bind to the 3' polyadenylated region of MRNA. When complexed with RNA the proteins serve an array of functions such as stabilizing the 3' end of RNA, promoting poly(A) synthesis and stimulating mRNA translation.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.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Wasp Venoms: Venoms produced by the wasp (Vespid) family of stinging insects, including hornets; the venoms contain enzymes, biogenic amines, histamine releasing factors, kinins, toxic polypeptides, etc., and are similar to bee venoms.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.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 Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.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.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.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Guanine NucleotidesPhosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.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.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.Fluorides: Inorganic salts of hydrofluoric acid, HF, in which the fluorine atom is in the -1 oxidation state. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Sodium and stannous salts are commonly used in dentifrices.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.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).)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.GTP-Binding Protein Regulators: Proteins that regulate the signaling activity of GTP-BINDING PROTEINS. They are divided into three categories depending upon whether they stimulate GTPase activity (GTPASE-ACTIVATING PROTEINS), inhibit release of GDP; (GUANINE NUCLEOTIDE DISSOCIATION INHIBITORS); or exchange GTP for GDP; (GUANINE NUCLEOTIDE EXCHANGE FACTORS).GTP Cyclohydrolase: (GTP cyclohydrolase I) or GTP 7,8-8,9-dihydrolase (pyrophosphate-forming) (GTP cyclohydrolase II). An enzyme group that hydrolyzes the imidazole ring of GTP, releasing carbon-8 as formate. Two C-N bonds are hydrolyzed and the pentase unit is isomerized. This is the first step in the synthesis of folic acid from GTP. EC 3.5.4.16 (GTP cyclohydrolase I) and EC 3.5.4.25 (GTP cyclohydrolase II).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.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.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).Circular Dichroism: A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)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.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.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Phospholipase C beta: A phosphoinositide phospholipase C subtype that is primarily regulated by its association with HETEROTRIMERIC G-PROTEINS. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of C-terminal extension of 400 residues.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.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.Bacterial Proteins: Proteins found in any species of bacterium.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).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.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.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.Tacrolimus Binding Proteins: A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS. EC 5.2.1.-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.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.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Protein Multimerization: The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Fungal Proteins: Proteins found in any species of fungus.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Rhodopsin: A purplish-red, light-sensitive pigment found in RETINAL ROD CELLS of most vertebrates. It is a complex consisting of a molecule of ROD OPSIN and a molecule of 11-cis retinal (RETINALDEHYDE). Rhodopsin exhibits peak absorption wavelength at about 500 nm.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.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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Poly(A)-Binding Protein I: A poly(A) binding protein that has a variety of functions such as mRNA stabilization and protection of RNA from nuclease activity. Although poly(A) binding protein I is considered a major cytoplasmic RNA-binding protein it is also found in the CELL NUCLEUS and may be involved in transport of mRNP particles.Protein-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.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.Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.Thermodynamics: A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)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.Spectrometry, Fluorescence: Measurement of the intensity and quality of fluorescence.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Molecular Weight: The sum of the weight of all the atoms in a molecule.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.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.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.Proto-Oncogene Proteins p21(ras): Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC 3.6.1.47.Insulin-Like Growth Factor Binding Proteins: A family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (Int J Gynaecol Obstet 1992;39(1):3-9)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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.RNA-Binding Proteins: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.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.Cross-Linking Reagents: Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.Arabidopsis Proteins: Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.Cholera Toxin: An ENTEROTOXIN from VIBRIO CHOLERAE. It consists of two major protomers, the heavy (H) or A subunit and the B protomer which consists of 5 light (L) or B subunits. The catalytic A subunit is proteolytically cleaved into fragments A1 and A2. The A1 fragment is a MONO(ADP-RIBOSE) TRANSFERASE. The B protomer binds cholera toxin to intestinal epithelial cells, and facilitates the uptake of the A1 fragment. The A1 catalyzed transfer of ADP-RIBOSE to the alpha subunits of heterotrimeric G PROTEINS activates the production of CYCLIC AMP. Increased levels of cyclic AMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells.PhosphoproteinsGene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Multiprotein Complexes: Macromolecular complexes formed from the association of defined protein subunits.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.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.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.Protein Phosphatase 2: A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.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.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.ADP-Ribosylation Factor 1: ADP-RIBOSYLATION FACTOR 1 is involved in regulating intracellular transport by modulating the interaction of coat proteins with organelle membranes in the early secretory pathway. It is a component of COAT PROTEIN COMPLEX I. This enzyme was formerly listed as EC 3.6.1.47.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Pheromones: Chemical substances, excreted by an organism into the environment, that elicit behavioral or physiological responses from other organisms of the same species. Perception of these chemical signals may be olfactory or by contact.Hydrogen Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.Replication Protein A: A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.Arabidopsis: A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.Guanosine Monophosphate: A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.Receptors, Muscarinic: One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Fluorescence Resonance Energy Transfer: A type of FLUORESCENCE SPECTROSCOPY using two FLUORESCENT DYES with overlapping emission and absorption spectra, which is used to indicate proximity of labeled molecules. This technique is useful for studying interactions of molecules and PROTEIN FOLDING.Fatty Acid-Binding Proteins: Intracellular proteins that reversibly bind hydrophobic ligands including: saturated and unsaturated FATTY ACIDS; EICOSANOIDS; and RETINOIDS. They are considered a highly conserved and ubiquitously expressed family of proteins that may play a role in the metabolism of LIPIDS.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.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.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).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.cdc42 GTP-Binding Protein: A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions including cytoskeletal changes, filopodia formation and transport through the GOLGI APPARATUS. This enzyme was formerly listed as EC 3.6.1.47.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Peptide Elongation Factor Tu: A protein found in bacteria and eukaryotic mitochondria which delivers aminoacyl-tRNA's to the A site of the ribosome. The aminoacyl-tRNA is first bound to a complex of elongation factor Tu containing a molecule of bound GTP. The resulting complex is then bound to the 70S initiation complex. Simultaneously the GTP is hydrolyzed and a Tu-GDP complex is released from the 70S ribosome. The Tu-GTP complex is regenerated from the Tu-GDP complex by the Ts elongation factor and GTP.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.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.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.Cercopithecus 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.Arrestins: Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors.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)Nuclear Magnetic Resonance, Biomolecular: NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.rac GTP-Binding Proteins: A sub-family of RHO GTP-BINDING PROTEINS that is involved in regulating the organization of cytoskeletal filaments. This enzyme was formerly listed as EC 3.6.1.47.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Nerve Tissue ProteinsTransglutaminases: Transglutaminases catalyze cross-linking of proteins at a GLUTAMINE in one chain with LYSINE in another chain. They include keratinocyte transglutaminase (TGM1 or TGK), tissue transglutaminase (TGM2 or TGC), plasma transglutaminase involved with coagulation (FACTOR XIII and FACTOR XIIIa), hair follicle transglutaminase, and prostate transglutaminase. Although structures differ, they share an active site (YGQCW) and strict CALCIUM dependence.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.Solutions: The homogeneous mixtures formed by the mixing of a solid, liquid, or gaseous substance (solute) with a liquid (the solvent), from which the dissolved substances can be recovered by physical processes. (From Grant & Hackh's Chemical Dictionary, 5th ed)Molecular Dynamics Simulation: A computer simulation developed to study the motion of molecules over a period of time.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.beta-Adrenergic Receptor Kinases: G-protein-coupled receptor kinases that mediate agonist-dependent PHOSPHORYLATION and desensitization of BETA-ADRENERGIC RECEPTORS.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Hexanols: Isomeric forms and derivatives of hexanol (C6H11OH).Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Protein Interaction Domains and Motifs: Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS.Peptide Elongation Factor G: Peptide Elongation Factor G catalyzes the translocation of peptidyl-tRNA from the A to the P site of bacterial ribosomes by a process linked to hydrolysis of GTP to GDP.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.GTP Phosphohydrolase-Linked Elongation Factors: Factors that utilize energy from the hydrolysis of GTP to GDP for peptide chain elongation. EC 3.6.1.-.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Trypsin: A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.Periplasmic Binding Proteins: Periplasmic proteins that scavenge or sense diverse nutrients. In the bacterial environment they usually couple to transporters or chemotaxis receptors on the inner bacterial membrane.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.
In the GTP-bound conformation, Ras has a high affinity for numerous effectors which allow it to carry out its functions. These ... Ras activates several pathways, of which the mitogen-activated protein (MAP) kinase cascade has been well-studied. This cascade ... which is related in structure to the Gα subunit of heterotrimeric G proteins (large GTPases). G proteins function as binary ... transmits signals downstream and results in the transcription of genes involved in cell growth and division. Another Ras- ...
The GPCR can then activate an associated G protein by exchanging the GDP bound to the G protein for a GTP. The G protein's α ... proteins to continue the signal transduction cascade while the freed GPCR is able to rebind to another heterotrimeric G protein ... in which calcium-modulated protein calmodulin (CaM) binds Ca2+, undergoes a change in conformation, and activates CaM kinase II ... The ERK2 mitogen-activated protein kinase, a key signal transduction mediator downstream of receptor activation in many ...
... the conformation of the receptor changes to activate the G protein, causing Gα to bind a molecule of GTP and dissociate from ... Subsequent to this, the receptors' kinase domains are activated, initiating phosphorylation signaling cascades of downstream ... family of integral transmembrane proteins that possess seven transmembrane domains and are linked to a heterotrimeric G protein ... Ligand binding to the extracellular domain of integrins changes the protein's conformation, clustering it at the cell membrane ...
"Analysis of RhoA-binding proteins reveals an interaction domain conserved in heterotrimeric G protein beta subunits and the ... The conformations of the Switch domains are modified depending on the binding of either GDP or GTP to RhoA. The nature of the ... Riento K, Guasch RM, Garg R, Jin B, Ridley AJ (June 2003). "RhoE binds to ROCK I and inhibits downstream signaling". Mol. Cell ... activity has been linked within several cancer applications due to its significant involvement in cancer signaling cascades. ...
The GPCR can then activate an associated G protein by exchanging the GDP bound to the G protein for a GTP. The G protein's α ... in the tail conformation),[39][40] and heterotrimeric G protein exist and may account for protein signaling from endosomes.[41] ... proteins to continue the signal transduction cascade while the freed GPCR is able to rebind to another heterotrimeric G protein ... The ERK2 mitogen-activated protein kinase, a key signal transduction mediator downstream of receptor activation in many ...
nucleotide binding. • LRR domain binding. • GDP binding. • protein complex binding. • GTP binding. • GMP binding. • protein ... "Calmodulin binds to K-Ras, but not to H- or N-Ras, and modulates its downstream signaling". Molecular and Cellular Biology. 21 ... MAPK cascade. • axon guidance. • Fc-epsilon receptor signaling pathway. • positive regulation of nitric-oxide synthase activity ... 5p21: REFINED CRYSTAL STRUCTURE OF THE TRIPHOSPHATE CONFORMATION OF H-RAS P21 AT 1.35 ANGSTROMS RESOLUTION: IMPLICATIONS FOR ...
We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their ... InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... GTP binding changes the conformation of switch regions within the alpha subunit, which allows the bound trimeric G protein ( ... The dissociated subunits activate the downstream pheromone signalling MAP kinase cascade that induce changes necessary to ...
guanine nucleotide-binding protein G(i) subunit alpha-2. Names. GTP-binding regulatory protein Gi alpha-2 chain. adenylate ... short for guanine nucleotide-binding proteins, are a family of proteins involved in second messenger cascades. G proteins are ... When a ligand binds to a G protein-coupled receptor, it stabilises a conformation ... ... G-protein activation, organism-specific biosystemReceptor activated heterotrimeric G proteins consist of the Galpha and the ...
... couples to a heterotrimeric GTP-binding protein (G protein), and eventually activates a mitogen-activated protein kinase (MAPK ... The Gα subunit of the G protein interacts directly with the downstream MAPK to down-regulate the mating signal. This strategy ... The ribozyme exists either in an undocked conformation or in one of four distinct docked states. Individual molecules exhibit a ... The yeast mating response to pheromones involves transmission of signals through a cascade that begins at a cell surface ...
In the GTP-bound conformation, Ras has a high affinity for numerous effectors which allow it to carry out its functions. These ... Ras activates several pathways, of which the mitogen-activated protein (MAP) kinase cascade has been well-studied. This cascade ... which is related in structure to the Gα subunit of heterotrimeric G proteins (large GTPases). G proteins function as binary ... transmits signals downstream and results in the transcription of genes involved in cell growth and division. Another Ras- ...
The GPCR can then activate an associated G protein by exchanging the GDP bound to the G protein for a GTP. The G proteins α ... proteins to continue the signal transduction cascade while the freed GPCR is able to rebind to another heterotrimeric G protein ... in which calcium-modulated protein calmodulin (CaM) binds Ca2+, undergoes a change in conformation, and activates CaM kinase II ... The ERK2 mitogen-activated protein kinase, a key signal transduction mediator downstream of receptor activation in many ...
... This article or section includes a list of references or external links, but its sources remain unclear because it ... GTP) bound state, ultimately going on to regulate downstream cell processes. ... Heterotrimeric G proteins share a common mode of action, i.e., activation in response to a conformation change in the G-protein ... G proteins, short for guanine nucleotide-binding proteins, are a family of proteins involved in second messenger cascades. ...
G proteins from a diverse family of regulatory GTPases which, in the GTP-bound state, bind to and activate downstream effectors ... Comparison of GTP- and GDP-bound conformations of G proteins reveals how specific contacts between the gamma-phosphate of GTP ... Signaling pathways using heterotrimeric guanine-nucleotide-binding-proteins (G proteins) trigger physiological responses ... It also activates serum response factor possibly via a kinase cascade and mediates a growth signal to nuclei. Two signalling ...
fadA is an α subunit of a heterotrimeric G protein, putatively the target for the RGS domain of flbA (133). When bound to GTP, ... the PacC protein is in an inactive conformation and is unable to bind target sites. At alkaline pHs, the PacC protein is ... Some proteins acting downstream of PKA in the G-protein signaling pathway also interact with components of the MAP kinase ... cerevisiae indicate that cAMP-dependent protein kinases might positively regulate signaling in the MAP kinase cascade (83). ...
... of animal heterotrimeric GTP binding regulatory proteins (G proteins) (Ross and Higashijima, 1994). Because G proteins are also ... 1992). Membrane-bound conformation of mastoparan-X, a G-protein-activating peptide. Biochemistry 31, 5654-5660. ... agonist/antagonist results only allow us to place PLC activation and Ca2+ influx/release downstream of the putative G protein- ... protein-dependent activation of the phosphoinositide second messenger pathway might be part of the signal transduction cascade ...
Research Grants about gq g11 gtp binding protein alpha subunits ... point downstream from receptor activation of the heterotrimeric ... These results suggest that the IP3 transduction cascade is involved in the response of the sugar receptor cell of the fly... ... Furthermore, the heterologous desensitization of mGluR1a is dependent upon the splice variant being in an active conformation ... heterotrimeric gtp binding proteins , gtp binding protein alpha subunits , gq g11 gtp binding protein alpha subunits ...
... bound (inactive) and GTP-bound (active) conformations, which appear to be tightly regulated by various G-protein regulatory ... In a manner akin to the heterotrimeric G-proteins, small G-proteins cycle between their guanosine diphosphate (GDP)- ... suggested potential cross-talk between multiple small G-proteins (e.g., ARF6 and Rac1) in the signaling cascade underlying ... They reported that activation of ARF6 is critical for the activation of downstream signaling steps involving Rac1. Recent ...
... can itself mediate Cdc42 activation downstream of heterotrimeric GTP-binding protein (G protein)-coupled receptors, which are ... These factors engage cell surface receptors, initiating a cascade of events, including the activation of G proteins or tyrosine ... Integrin affinity is regulated in large part by alterations in the conformation of the integrin extracellular domains that ... When bound to GTP, they are active and interact with their downstream target proteins, which include protein kinases, lipid- ...
A-kinase anchoring proteins (AKAPs) directly bind PKA and recruit it to specific subcellular loci targeting the kinase activity ... and thereby provide discrete spatiotemporal control of downstream phosphorylation events. AKAPs also scaffold other signalling ... A-kinase anchoring proteins (AKAPs) directly bind PKA and recruit it to specific subcellular loci targeting the kinase activity ... Here, we will focus on mechanisms for targeting protein-protein interaction, disruptors that modulate down-stream cAMP ...
A G protein becomes activated upon the receptor-stimulated binding of GTP to its α subunit and continues to modulate the ... proteins or by the G protein effectors (reviewed in refs. 3-6). The phototransduction cascade of vertebrate photoreceptors ... Heterotrimeric G proteins act as molecular switches that relay excitation from activated receptors to effector molecules, such ... polyclonal antibodies raised against the RGS9c domain have an ability to interact with RGS9 in its native conformation and to ...
... activating heterotrimeric G-proteins (Gαβγ) by promoting the replacement of bound GDP with GTP in the Gα protein. The activated ... and their downstream signaling cascades (Vincent et al., 2008; Willoughby and Cooper, 2008). Most of these GEIs are FRET-based ... The binding partner selectively recognizes the GTP-bound, activated conformation of the GTPase, leading to a dynamic FRET ... GPCR and Heterotrimeric G Protein Signaling. G protein coupled receptors (GPCRs) are critical components of the membrane-bound ...
Oncogene ect2 is related to regulators of small GTP-binding proteins. Nature. 1993; 362: 462-465. ... Several intracellular signaling cascades are activated by VEGF on receptor binding.7 VEGF-driven endothelial proliferation is ... The BTB-kelch protein KLEIP is an essential downstream regulator of VEGF/bFGF-induced migration and sprouting angiogenesis, and ... Zeng H, Zhao D, Mukhopadhyay D. KDR stimulates endothelial cell migration through heterotrimeric G protein Gq/11-mediated ...
The binding of GTP rigidifies small GTPases in an active conformation that interacts with specific effector proteins and ... homology downstream of Sec7 (HDS) lipid-binding domains, or SH2 and SH3 domains related to protein-protein interactions [25]. ... the heterotrimeric G proteins, and the RAS superfamily of small monomeric GTPases [13, 14]. Whereas heterotrimeric G proteins ... These receptors mediate intracellular signalling cascades through activation of two superfamilies of G proteins, ...
It has been shown that 12-HETE activates small GTP binding proteins: cell division cycle 42 (Cdc42) and ras-related C3 ... the angiotensin II receptor type1 is stabilized in its active conformation and stimulates heterotrimeric G proteins (most ... Regulation of tyrosine kinase cascades by G-protein-coupled receptors. Current opinion in cell biology 1999 Apr;11(2):177-83 ... Phosphorylated and activated Akts stimulates several downstream effectors, which regulate cell survival, cell cycle, glucose ...
... by extracellular signals activates heterotrimeric G proteins by promoting the binding of GTP to their α subunits. G proteins ... Striatal neurons express a staggering number of GPCRs whose activation results in the engagement of downstream signaling ... by extracellular signals activates heterotrimeric G proteins by promoting the binding of GTP to their α subunits. G proteins ... RGS proteins accelerate GTP hydrolysis by the α subunits of G proteins, thus promoting deactivation of GPCR signaling. In this ...
... camp-dependent protein kinase) G-protein signal cascade Structure of G-proteins Small GTP-binding proteins, ... A Ligand-Binding Ion Channel Classes of Receptor Proteins in Eukaryotes, Heterotrimeric G Proteins Signaling View the ... each specific for a particular set of receptors and for a particular set of downstream target proteins in the plasma membrane ... to adopt a new shape that allows it to interact with its target protein The beta gamma complex doesn t change its conformation, ...
... of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream ... coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein ... The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 ... and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream ...
... unit that is bound to the G subunit for a guanine triphosph ate (GTP). This nucleotide exchange causes the heterotrimeric G ... Since the Y7.53A receptor is going to have identical conformations presented to both G proteins, it can be said that G Sand G Q ... The downstream target of a particular GPCR is determined by its location in the body and the G protein to which it is coupled. ... In the periphery of the body the G/IP3 signaling cascade, which has made HH1R receptors synonymous with allergic responses, is ...
G protein signaling systems include three components: the receptor itself, a GTP-binding protein (G protein), and an ... to the family of receptors that bind to heterotrimeric "G proteins." Many different G proteins are known to interact with ... We decided to investigate the downstream signaling consequences of ICAM-2 binding to LFA-1. ICAM-2 Induces p44/42 MAPK Activity ... When a hormone or other first messenger binds to a receptor, the receptor changes conformation and this alters its interaction ...
Therefore, fusion proteins of the WASP GTPase binding domain with a reporter protein selectively identifies GTP-Cdc42. To ... The assays take advantage of downstream effectors that only bind the GTP-bound form of the GTPases and that are specific for ... to keep the protein in an inactive conformation. Upon binding of activated Rho proteins, the DAD is released and the ability of ... The protein Slg1 is linked to the PKC pathway by the finding that this MAP kinase cascade is activated by heat stress via Slg1p ...
As is the case with G-Protein-coupled receptors, proteins that bind GTP play a major role in transmission of signal from the ... The kinase domain of the receptors is subsequently activated, initiating signaling cascades of phosphorylation of downstream ... and are linked to a guanine nucleotide-binding protein (or heterotrimeric G protein). Many receptors make up this family, ... Once the GPCR recognizes a ligand, the shape (conformation) of the receptor changes to mechanically activate the G protein, and ...
  • The third biochemical activity involves the ability of GDI to sequester back Cdc42, Rac, and Rho from its putative membranous site, thereby inhibiting its interaction with their respective effector proteins ( 1 , 2 , 6 - 16 ). (diabetesjournals.org)
  • G proteins exert their effects by influencing the activity of key effector proteins in this region, including ion channels, second messenger enzymes, and protein kinases. (frontiersin.org)
  • Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and furthermore, through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion. (embl.de)
  • Emerging evidence suggests that such cellular events are delicately controlled by G-proteins, which have been implicated in cytoskeletal remodeling to facilitate granule movement ( 3 - 5 ). (diabetesjournals.org)
  • GEFs and GAPs are multidomain proteins that control cellular events in time and space through interaction with other proteins and lipids inside the cells. (hindawi.com)
  • BTB-kelch proteins are intracellular proteins that control cellular architecture and cellular functions. (ahajournals.org)
  • BTB-kelch proteins are regulators of the cytoskeleton acting as modulators of cellular architecture, cellular organization, and cell migration. (ahajournals.org)
  • They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. (uniprot.org)
  • Apart from Ras, they also target other cellular proteins that require farnesylation to become activated, e.g. (embl.de)
  • Although importance of PLC enzymes for key cellular functions is well established, the PLC proteins belonging to the ε, ζ and η subfamilies were identified and characterized only during the last decade. (jcancer.org)
  • equivalents in the POLH machinery p25 in the correlation of this protein mRNA and lysyl for the XP cellular flow( XPV) in metabolic Edition polyubiquitin beta-catenin acids. (evakoch.com)
  • A variety of cellular stresses are known to affect the activity of protein kinases. (ubc.ca)
  • Rho/Rac proteins are involved in a wide variety of cellular functions such as cell polarity, vesicular trafficking, the cell cycle and transcriptomal dynamics . (wikidoc.org)
  • There are two protein products of the KRAS gene in mammalian cells that result from the use of alternative exon 4 (exon 4A and 4B respectively): K-Ras4A and K-Ras4B, these proteins have different structure in their C-terminal region and use different mechanisms to localize to cellular membranes including the plasma membrane . (wikipedia.org)
  • The cytoskeleton is a highly dynamic network of filamentous proteins that enables the active transport of cellular cargo, transduces force, and when assembled into higher-order structures, forms the basis for motile cellular structures that promote cell movement. (mechanobio.info)
  • PKA (Protein Kinase-A) is a second messenger-dependent enzyme that has been implicated in a wide range of cellular processes, including transcription, metabolism, cell cycle progression and. (qiagen.com)
  • The ubiquitin-proteasome system (UPS) is involved in selective targeting of innumerable cellular proteins through a complex pathway that plays important roles in a broad array of processes. (pharmaceuticalintelligence.com)
  • Using CRISPR-Cas9 to engineer a cellular model of melanoma initiation from primary human melanocytes, we discovered that a lineage-restricted transcription factor, BRN2, is downstream of CDKN2A and directly regulated by E2F1. (scicrunch.org)
  • Bromodomain-containing proteins are epigenetic modulators involved in a wide range of cellular processes, from recruitment of transcription factors to pathological disruption of gene regulation and cancer development. (ox.ac.uk)
  • G proteins carry lipid modifications on one or more of their subunits to target them to the plasma membrane and to contribute to protein interactions. (ebi.ac.uk)
  • This result highlights the usefulness of these compounds as invaluable tools for the study of Ras signal transduction processes and the plasma membrane localization of the Ras proteins. (embl.de)
  • To grow, eukaryotic cells must expand by inserting glycerolipids, sphingolipids, sterols, and proteins into their plasma membrane, and maintain the proper levels and bilayer distribution. (mdpi.com)
  • The exchange of GDP for GTP on Gpa1 alters its interaction with the G protein beta subunit Ste4, leading to dissociation of the G protein beta-gamma dimer Ste4-Ste18. (ebi.ac.uk)
  • Together, such posttranslational modification steps have been proven to be essential for the targeting and association of these proteins with their membranous sites for optimal effector interaction ( 1 - 5 ). (diabetesjournals.org)
  • PAK5 preferentially binds to CDC42 in the presence of GTP and the CRIB motif is essential for this interaction. (sdbonline.org)
  • The interaction appears to require at least two separated amino-acid sequences present specifically in the beta isoform of p110 and the GTP-bound form of Rab5. (embl-heidelberg.de)
  • These results suggest that there is a specific interaction between GTP-bound Rab5 and the p110beta/p85 PI 3-kinase, leading to efficient coupling of the lipid kinase product to its downstream target, protein kinase B. (embl-heidelberg.de)
  • As a consequence, mutant Gαs with substitutions at either residue remains GTP-bound, persisting in an active state that prolongs the effector protein interaction with dissociated Gαs or βγ. (biomedcentral.com)
  • ORF 1 was shown to bind actin and to be required for the stabilization of the ring canals within the egg chamber. (ahajournals.org)
  • Furthermore, overexpression of the Pkc1-controlled mitogen-activated protein (MAP) kinase Mpk1 suppresses the actin defect of tor2ts and rho1-2ts mutants. (sdbonline.org)
  • Thus, Tor2 signals to the actin cytoskeleton via Rho1, Pkc1 and the cell integrity MAP kinase cascade (Helliwell, 1998). (sdbonline.org)
  • Two molecules that directly stimulate actin polymerization are the WASP/WAVE proteins and the Diaphanous-related formins . (wikidoc.org)
  • Our previous GeneChip data showed that EdTx downregulated MPhi genes involved in actin cytoskeleton remodeling, including protein kinase A (PKA). (genes2cognition.org)
  • The Actin family is a diverse and evolutionarily ancient group of proteins that provide the supportive framework to the three-dimensional structure of eukaryotic cells. (qiagen.com)
  • The G1 subunits of SHC1 is However achieved modified with FGFR3, but this is first of Aldosterone process, and the cohesin-bound development now branched involved to mediate other activity. (evakoch.com)
  • Negative regulators identified included Megf8, Mgrn1, and an unannotated gene encoding a tetraspan protein we named Atthog. (stanford.edu)
  • During the sequencing of the genome of S. cerevisiae , a new gene encoding a protein with a Rho-GAP homology domain was identified. (sdbonline.org)
  • Such processes are usually rapid, lasting on the order of milliseconds in the case of ion flux, minutes for the activation of protein- and lipid-mediated kinase cascades, or hours and even days for gene expression. (chemeurope.com)
  • In a screen for viable mutations affecting adult central brain structures, the mushroom bodies tiny ( mbt ) gene of Drosophila, which encodes a protein related to p21-activated kinase (PAK), has been isolated. (sdbonline.org)
  • Both enantiomers are active in long-term responses such as changes in gene expression and protein synthesis. (medicinestuffs.com)
  • Many human cancers have mutations in a gene that encodes a protein called Ras, which promotes cell growth and division by controlling the activities of other proteins. (elifesciences.org)
  • Other mutations in the gene that encodes Ras are also found in cancer cells, but these are less common and it is not clear how they alter the activity of the protein. (elifesciences.org)
  • Overexpression of Ruk(l) in cultured primary neurons induces apoptosis, an effect that could be reversed by co-expression of constitutively activated forms of the p110 alpha catalytic subunit of PI 3-kinase or its downstream effector PKB/Akt. (embl-heidelberg.de)
  • The GTP-bound form interacts with its specific target and performs its cell functions. (sdbonline.org)
  • Using pharmacological activators and inhibitors, we have concluded that gliding motility is initiated when albumin interacts with the surface of the sporozoite and that this leads to a signal transduction cascade within the sporozoite, including the elevation of intracellular cAMP, the modulation of sporozoite motility by Ca 2+ and the release of microneme proteins. (pubmedcentralcanada.ca)
  • Here we show that a conserved motif in the human GW182 paralog TNRC6C interacts with the C-terminal domain of polyadenylate binding protein 1 (PABC) and present the crystal structure of the complex. (genes2cognition.org)
  • We report here of the development of techniques for the synthesis of a series of modified Ras proteins. (embl.de)
  • early with this, lung of SHC1 and FGFR1 IIIc is located in cytoskeletal proteins replacing synthesis. (evakoch.com)
  • The 70 kDa ribosomal protein S6 kinase (p70s6k) has been implicated in the control of cell proliferation and the onset of protein synthesis following mitogenic and hormonal stimulation. (ubc.ca)
  • The main rise in ABA caused by water loss occurs some 2-3 hour after the onset of wilting The ability of cycloheximide to block this process indicates a requirement for de novo protein synthesis and thus implicates an up-regu- lation of ABA biosynthesis in stressed tissues. (medicinestuffs.com)
  • Endoplasmic Reticulum-bound Ribosomes Reside in Stable Association with the Translocon Following Termination of Protein Synthesis The Journal of Biological Chemistry. (jove.com)
  • We report that ribosomes reside in stable association with the Sec61alpha-translocon following the termination stage of protein synthesis. (jove.com)
  • The number of Arf GAPs identified in PMNs is expanding, and dissecting their functions will provide important insights into the role of these proteins in PMN physiology. (hindawi.com)
  • GEFs control the release of GDP from the rho protein and the replacement with GTP . (wikidoc.org)
  • However, in recent years it has become apparent that several nonreceptor GEFs also exist, providing cells with a further level of control over G protein activity. (jmolecularsignaling.com)
  • Mutant, constitutively activated forms of Ras proteins are frequently found in cancer. (embl.de)
  • The expressions of constitutively active and dominant negative mutants of Rab5 in THP-1 cells induce the stimulation and inhibition, respectively, of protein kinase B activity, which is dependent on the PI 3-kinase product phosphatidylinositol 3,4,5-triphosphate. (embl-heidelberg.de)
  • A novel AR-interacting protein, provisionally termed PAK6, has been identified that shares a high degree of sequence similarity with p21-activated kinases (PAKs). (sdbonline.org)
  • PAK5 is a functional protein kinase but unlike PAK-I family kinases (PAK1, 2, and 3), the kinase activity of PAK5 does not seem to require the binding of CDC42. (sdbonline.org)
  • The N-terminal CR1 encodes a RAS-binding download( RBD) and a mixed model( CRD) that contain interactions with RAS and the helix inositol. (evakoch.com)
  • ROS production affects the redox-based modification of cysteine residues in redox proteins, which contribute to protein functions such as enzymatic activity, protein-protein interactions, oligomerization, and intracellular localization. (biomedcentral.com)
  • Tubulin dimers primarily use longitudinal interactions to bind to each other and to γ−TuRC during the nucleation phase. (mechanobio.info)
  • G proteins are important signal transducing molecules in cells. (chemeurope.com)
  • Furthermore, development of novel classes of small molecules involved in displacement of AKAP-bound signal molecules is now emerging. (frontiersin.org)
  • The number of proteins and other molecules participating in the events involving signal transduction increases as the process emanates from the initial stimulus, resulting in a "signal cascade," beginning with a relatively small stimulus that elicits a large response. (chemeurope.com)
  • The maleimide group provided the key to link chemically synthesized lipopeptide molecules in a specific and efficient manner to a truncated form of the H-Ras protein. (embl.de)
  • Most integrins bind to extracellular matrix (ECM) molecules, and they transmit signals that are critical in growth, development, tissue homeostasis, and host defense. (schoolbag.info)
  • Cells use heterotrimeric G proteins to transduce a wide variety of signals, including polypeptide hormones, small molecules, odorants, and light. (jmolecularsignaling.com)
  • The G α subunit will eventually hydrolyze the attached GTP to GDP by its inherent enzymatic activity, allowing it to re-associate with G βγ and starting a new cycle. (chemeurope.com)
  • PLCε protein has the biggest size among all PLC family members - 230 kDa and consists of several functional domains including core domain (consisting of EF, X and Y subdomains) which possesses an ability to hydrolyze PIP2, pleckstrin-homology PH and C2 domains, GTP-exchanging (CDC25-like) domain at the C-terminus and two Ras-associating domains at N-terminus [ 4 - 6 ]. (jcancer.org)
  • We have identified an adaptor protein, Ruk(l), which forms complexes with the PI 3-kinase holoenzyme in vitro and in vivo. (embl-heidelberg.de)
  • Bartkiewicz M, Houghton A, Baron R. Leucine zipper-mediated homodimerization of the adaptor protein c-Cbl. (labome.org)
  • Furthermore, access to bioconjugates that embody the correct structure of the protein but that may additionally carry different lipid groups or labels (i.e., fluorescent tags) by which the protein can be traced in biological systems, could provide invaluable reagents. (embl.de)
  • These modified Ras proteins carry a number of different, natural and non-natural lipid residues, and the process was extended to also provide access to a number of fluorescently labeled derivatives. (embl.de)
  • Furthermore, a preliminary study on the biological activity of the natural Ras protein derivative (containing the normal farnesyl and palmitoyl lipid residues) has shown full biological activity. (embl.de)
  • Loss of the CDKN2A protein product p16INK4A permitted metastatic dissemination of human melanoma lines in mice, a phenotype rescued by inhibition of BRN2. (scicrunch.org)
  • The covalent binding to the targeted proteins was confirmed by MS and time-dependent inhibition. (ox.ac.uk)