Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.
Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.
Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.
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
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'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.
A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. EC 3.6.1.-.
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
A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.
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
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.
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
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.
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.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
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.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Nucleotides in which the base moiety is substituted with one or more sulfur atoms.
Proteins that activate the GTPase of specific GTP-BINDING PROTEINS.
Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.
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.
Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.
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
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
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.
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.
The rate dynamics in chemical or physical systems.
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.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
(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 (GTP cyclohydrolase I) and EC (GTP cyclohydrolase II).
A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS. EC 5.2.1.-
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.
The process of cleaving a chemical compound by the addition of a molecule of water.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A 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.
Proteins prepared by recombinant DNA technology.
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.
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)
Established cell cultures that have the potential to propagate indefinitely.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
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.
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.
Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.
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.
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.
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.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A protein kinase encoded by the Saccharomyces cerevisiae CDC28 gene and required for progression from the G1 PHASE to the S PHASE in the CELL CYCLE.
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.
Proteins found in any species of fungus.
A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS from SACCHAROMYCES CEREVISIAE. It is involved in morphological events related to the cell cycle. This enzyme was formerly listed as EC
A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.
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.-.
A protein found in bacteria and eukaryotic mitochondria which delivers aminoacyl-tRNA's to the A site of the ribosome. The aminoacyl-tRNA is first bound to a complex of elongation factor Tu containing a molecule of bound GTP. The resulting complex is then bound to the 70S initiation complex. Simultaneously the GTP is hydrolyzed and a Tu-GDP complex is released from the 70S ribosome. The Tu-GTP complex is regenerated from the Tu-GDP complex by the Ts elongation factor and GTP.
Transglutaminases 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.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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.
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.
Proteins found in any species of bacterium.
Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A poly(A) binding protein that is involved in promoting the extension of the poly A tails of MRNA. The protein requires a minimum of ten ADENOSINE nucleotides in order for binding to mRNA. Once bound it works in conjunction with CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR to stimulate the rate of poly A synthesis by POLY A POLYMERASE. Once poly-A tails reach around 250 nucleotides in length poly(A) binding protein II no longer stimulates POLYADENYLATION. Mutations within a GCG repeat region in the gene for poly(A) binding protein II have been shown to cause the disease MUSCULAR DYSTROPHY, OCULOPHARYNGEAL.
ADP-RIBOSYLATION FACTOR 1 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
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.
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.
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
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
Factors that utilize energy from the hydrolysis of GTP to GDP for peptide chain elongation. EC 3.6.1.-.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
A family of high molecular weight GTP phosphohydrolases that play a direct role in vesicle transport. They associate with microtubule bundles (MICROTUBULES) and are believed to produce mechanical force via a process linked to GTP hydrolysis. This enzyme was formerly listed as EC
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.
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).
The sum of the weight of all the atoms in a molecule.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
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.
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.
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.
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.
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.
A carbon-nitrogen ligase. During purine ribonucleotide biosynthesis, this enzyme catalyzes the synthesis of adenylosuccinate from GTP; IMP; and aspartate with the formation of orthophosphate and GDP. EC
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).
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.
A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.
A family of GTP-binding proteins that were initially identified in YEASTS where they were shown to initiate the process of septation and bud formation. Septins form into hetero-oligomeric complexes that are comprised of several distinct septin subunits. These complexes can act as cytoskeletal elements that play important roles in CYTOKINESIS, cytoskeletal reorganization, BIOLOGICAL TRANSPORT, and membrane dynamics.
Protein factors uniquely required during the elongation phase of protein synthesis.
Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).
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.
A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.
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
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
Multicomponent ribonucleoprotein structures found in the CYTOPLASM of all cells, and in MITOCHONDRIA, and PLASTIDS. They function in PROTEIN BIOSYNTHESIS via GENETIC TRANSLATION.
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.
A family of secreted multidomain proteins that were originally identified by their association with the latent form of TRANSFORMING GROWTH FACTORS. They interact with a variety of EXTRACELLULAR MATRIX PROTEINS and may play a role in the regulation of TGB-beta bioavailability.
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.
A protein involved in transport between the ENDOPLASMIC RETICULUM and the GOLGI APPARATUS. This enzyme was formerly listed as EC
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.
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.
Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
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.
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
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
A general transcription factor that plays a major role in the activation of eukaryotic genes transcribed by RNA POLYMERASES. It binds specifically to the TATA BOX promoter element, which lies close to the position of transcription initiation in RNA transcribed by RNA POLYMERASE II. Although considered a principal component of TRANSCRIPTION FACTOR TFIID it also takes part in general transcription factor complexes involved in RNA POLYMERASE I and RNA POLYMERASE III transcription.
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
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.
One of the six homologous proteins that specifically bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions. The function of this protein is not completely defined. However, several studies demonstrate that it inhibits IGF binding to cell surface receptors and thereby inhibits IGF-mediated mitogenic and cell metabolic actions. (Proc Soc Exp Biol Med 1993;204(1):4-29)
A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in calcium-dependent EXOCYTOSIS. This enzyme was formerly listed as EC
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.
Proteins which bind with RETINOL. The retinol-binding protein found in plasma has an alpha-1 mobility on electrophoresis and a molecular weight of about 21 kDa. The retinol-protein complex (MW=80-90 kDa) circulates in plasma in the form of a protein-protein complex with prealbumin. The retinol-binding protein found in tissue has a molecular weight of 14 kDa and carries retinol as a non-covalently-bound ligand.
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.
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)
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.
A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.
A calbindin protein found in many mammalian tissues, including the UTERUS, PLACENTA, BONE, PITUITARY GLAND, and KIDNEYS. In intestinal ENTEROCYTES it mediates intracellular calcium transport from apical to basolateral membranes via calcium binding at two EF-HAND MOTIFS. Expression is regulated in some tissues by VITAMIN D.
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.
A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
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.
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.
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.
An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC
The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Proteins that are involved in the peptide chain termination reaction (PEPTIDE CHAIN TERMINATION, TRANSLATIONAL) on RIBOSOMES. They include codon-specific class-I release factors, which recognize stop signals (TERMINATOR CODON) in the MESSENGER RNA; and codon-nonspecific class-II release factors.
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).)
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
An alpha-globulin found in the plasma of man and other vertebrates. It is apparently synthesized in the liver and carries vitamin D and its metabolites through the circulation and mediates the response of tissue. It is also known as group-specific component (Gc). Gc subtypes are used to determine specific phenotypes and gene frequencies. These data are employed in the classification of population groups, paternity investigations, and in forensic medicine.
A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
A RNA-binding protein that binds to polypyriminidine rich regions in the INTRONS of messenger RNAs. Polypyrimidine tract-binding protein may be involved in regulating the ALTERNATIVE SPLICING of mRNAs since its presence on an intronic RNA region that is upstream of an EXON inhibits the splicing of the exon into the final mRNA product.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Proteins obtained from the species Schizosaccharomyces pombe. 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.
Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)
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.
A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
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.
The process by which two molecules of the same chemical composition form a condensation product or polymer.
A sterol regulatory element binding protein that regulates expression of GENES involved in FATTY ACIDS metabolism and LIPOGENESIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING.
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
Proteins obtained from ESCHERICHIA COLI.
A subtype of dynamin found primarily in the NEURONS of the brain.
The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.
Peptide Elongation Factor 2 catalyzes the translocation of peptidyl-tRNA from the A site to the P site of eukaryotic ribosomes by a process linked to the hydrolysis of GTP to GDP.
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.
Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).
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.
Elements of limited time intervals, contributing to particular results or situations.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.
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.
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.
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.
A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.
Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.
Techniques to partition various components of the cell into SUBCELLULAR FRACTIONS.
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.
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.
The process by which a DNA molecule is duplicated.
Periplasmic proteins that bind MALTOSE and maltodextrin. They take part in the maltose transport system of BACTERIA.
A family of ribonucleoproteins that were originally found as proteins bound to nascent RNA transcripts in the form of ribonucleoprotein particles. Although considered ribonucleoproteins they are primarily classified by their protein component. They are involved in a variety of processes such as packaging of RNA and RNA TRANSPORT within the nucleus. A subset of heterogeneous-nuclear ribonucleoproteins are involved in additional functions such as nucleocytoplasmic transport (ACTIVE TRANSPORT, CELL NUCLEUS) of RNA and mRNA stability in the CYTOPLASM.
Measurement of the intensity and quality of fluorescence.
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.
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.
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
Specialized cells that detect and transduce light. They are classified into two types based on their light reception structure, the ciliary photoreceptors and the rhabdomeric photoreceptors with MICROVILLI. Ciliary photoreceptor cells use OPSINS that activate a PHOSPHODIESTERASE phosphodiesterase cascade. Rhabdomeric photoreceptor cells use opsins that activate a PHOSPHOLIPASE C cascade.

Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity. (1/1676)

We previously reported that the role of reactive oxygen intermediates (ROIs) in NF-kappaB activation by proinflammatory cytokines was cell specific. However, the sources for ROIs in various cell types are yet to be determined and might include 5-lipoxygenase (5-LOX) and NADPH oxidase. 5-LOX and 5-LOX activating protein (FLAP) are coexpressed in lymphoid cells but not in monocytic or epithelial cells. Stimulation of lymphoid cells with interleukin-1beta (IL-1beta) led to ROI production and NF-kappaB activation, which could both be blocked by antioxidants or FLAP inhibitors, confirming that 5-LOX was the source of ROIs and was required for NF-kappaB activation in these cells. IL-1beta stimulation of epithelial cells did not generate any ROIs and NF-kappaB induction was not influenced by 5-LOX inhibitors. However, reintroduction of a functional 5-LOX system in these cells allowed ROI production and 5-LOX-dependent NF-kappaB activation. In monocytic cells, IL-1beta treatment led to a production of ROIs which is independent of the 5-LOX enzyme but requires the NADPH oxidase activity. This pathway involves the Rac1 and Cdc42 GTPases, two enzymes which are not required for NF-kappaB activation by IL-1beta in epithelial cells. In conclusion, three different cell-specific pathways lead to NF-kappaB activation by IL-1beta: a pathway dependent on ROI production by 5-LOX in lymphoid cells, an ROI- and 5-LOX-independent pathway in epithelial cells, and a pathway requiring ROI production by NADPH oxidase in monocytic cells.  (+info)

Myelin and collapsin-1 induce motor neuron growth cone collapse through different pathways: inhibition of collapse by opposing mutants of rac1. (2/1676)

Precise growth cone guidance is the consequence of a continuous reorganization of actin filament structures within filopodia and lamellipodia in response to inhibitory and promoting cues. The small GTPases rac1, cdc42, and rhoA are critical for regulating distinct actin structures in non-neuronal cells and presumably in growth cones. Collapse, a retraction of filopodia and lamellipodia, is a typical growth cone behavior on contact with inhibitory cues and is associated with depolymerization and redistribution of actin filaments. We examined whether small GTPases mediate the inhibitory properties of CNS myelin or collapsin-1, a soluble semaphorin, in chick embryonic motor neuron cultures. As demonstrated for collapsin-1, CNS myelin-evoked growth cone collapse was accompanied by a reduction of rhodamine-phalloidin staining most prominent in the growth cone periphery, suggesting actin filament disassembly. Specific mutants of small GTPases were capable of desensitizing growth cones to CNS myelin or collapsin-1. Adenoviral-mediated expression of constitutively active rac1 or rhoA abolished CNS myelin-induced collapse and allowed remarkable neurite extension on a CNS myelin substrate. In contrast, expression of dominant negative rac1 or cdc42 negated collapsin-1-induced growth cone collapse and promoted neurite outgrowth on a collapsin-1 substrate. These findings suggest that small GTPases can modulate the signaling pathways of inhibitory stimuli and, consequently, allow the manipulation of growth cone behavior. However, the fact that opposite mutants of rac1 were effective against different inhibitory stimuli speaks against a universal signaling pathway underlying growth cone collapse.  (+info)

Activation of the Cdc42-associated tyrosine kinase-2 (ACK-2) by cell adhesion via integrin beta1. (3/1676)

Activated Cdc42-associated kinase-2 (ACK-2) is a non-receptor tyrosine kinase that appears to be a highly specific target for the Rho-related GTP-binding protein Cdc42. In order to understand better how ACK-2 activity is regulated in cells, we have expressed epitope-tagged forms of this tyrosine kinase in COS-7 and NIH3T3 cells. We find that ACK-2 can be activated by cell adhesion in a Cdc42-dependent manner. However, unlike the focal adhesion kinase, which also is activated by cell adhesion, the activation of ACK-2 is F-actin-independent and does not require cell spreading. In addition, overexpression of ACK-2 in COS-7 cells did not result in the stimulation of extracellular signal-regulated kinase activity but rather activated the c-Jun kinase. Both anti-integrin beta1 antibody and RGD peptides inhibited the activation of ACK-2 by cell adhesion. In addition, ACK-2 was co-immunoprecipitated with integrin beta1. Overall, these findings suggest that ACK-2 interacts with integrin complexes and mediates cell adhesion signals in a Cdc42-dependent manner.  (+info)

Rho GTPases control polarity, protrusion, and adhesion during cell movement. (4/1676)

Cell movement is essential during embryogenesis to establish tissue patterns and to drive morphogenetic pathways and in the adult for tissue repair and to direct cells to sites of infection. Animal cells move by crawling and the driving force is derived primarily from the coordinated assembly and disassembly of actin filaments. The small GTPases, Rho, Rac, and Cdc42, regulate the organization of actin filaments and we have analyzed their contributions to the movement of primary embryo fibroblasts in an in vitro wound healing assay. Rac is essential for the protrusion of lamellipodia and for forward movement. Cdc42 is required to maintain cell polarity, which includes the localization of lamellipodial activity to the leading edge and the reorientation of the Golgi apparatus in the direction of movement. Rho is required to maintain cell adhesion during movement, but stress fibers and focal adhesions are not required. Finally, Ras regulates focal adhesion and stress fiber turnover and this is essential for cell movement. We conclude that the signal transduction pathways controlled by the four small GTPases, Rho, Rac, Cdc42, and Ras, cooperate to promote cell movement.  (+info)

Inhibition of myosin light chain kinase by p21-activated kinase. (5/1676)

p21-activated kinases (PAKs) are implicated in the cytoskeletal changes induced by the Rho family of guanosine triphosphatases. Cytoskeletal dynamics are primarily modulated by interactions of actin and myosin II that are regulated by myosin light chain kinase (MLCK)-mediated phosphorylation of the regulatory myosin light chain (MLC). p21-activated kinase 1 (PAK1) phosphorylates MLCK, resulting in decreased MLCK activity. MLCK activity and MLC phosphorylation were decreased, and cell spreading was inhibited in baby hamster kidney-21 and HeLa cells expressing constitutively active PAK1. These data indicate that MLCK is a target for PAKs and that PAKs may regulate cytoskeletal dynamics by decreasing MLCK activity and MLC phosphorylation.  (+info)

Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to shear stress. (6/1676)

Shear stress, the tangential component of hemodynamic forces, plays an important role in endothelial remodeling. In this study, we investigated the role of Rho family GTPases Cdc42 and Rho in shear stress-induced signal transduction and cytoskeleton reorganization. Our results showed that shear stress induced the translocation of Cdc42 and Rho from cytosol to membrane. Although both Cdc42 and Rho were involved in the shear stress-induced transcription factor AP-1 acting on the 12-O-tetradecanoyl-13-phorbol-acetate-responsive element (TRE), only Cdc42 was sufficient to activate AP-1/TRE. Dominant-negative mutants of Cdc42 and Rho, as well as recombinant C3 exoenzyme, attenuated the shear stress activation of c-Jun NH2-terminal kinases (JNKs), suggesting that Cdc42 and Rho regulate the shear stress induction of AP-1/TRE activity through JNKs. Shear stress-induced cell alignment and stress fiber formation were inhibited by the dominant-negative mutants of Rho and p160ROCK, but not by the dominant-negative mutant of Cdc42, indicating that the Rho-p160ROCK pathway regulates the cytoskeletal reorganization in response to shear stress.  (+info)

Nucleotide binding to the G12V-mutant of Cdc42 investigated by X-ray diffraction and fluorescence spectroscopy: two different nucleotide states in one crystal. (7/1676)

The 2.5 A crystal structure of the full length human placental isoform of the Gly12 to Val mutant Cdc42 protein (Cdc42(G12V)) bound to both GDP/Mg2+ and GDPNH2 (guanosine-5'-diphospho-beta-amidate) is reported. The crystal contains two molecules in the asymmetric unit, of which one has bound GDP/Mg2+, while the other has bound GDPNH2 without a Mg2+ ion. Crystallization of the protein was induced via hydrolysis of the Cdc42 x GppNHp complex by the presence of contaminating alkaline phosphatase activity in combination with the crystallization conditions. This prompted us to compare the binding characteristics of GDPNH2 vs. GDP. The amino group of GDPNH2 drastically reduces the affinity to Cdc42 in comparison with that of GDP, causes the loss of the Mg2+ ion, and apparently also increases the conformational flexibility of the protein as seen in the crystal. Both the switch I and switch II regions are visible in the electron density of the GDP-bound molecule, but not in the molecule bound to GDPNH2. The C-terminus containing the CaaX-motif is partly ordered in both molecules due to an intramolecular disulfide bond formed between Cys105/Cys188 and Cys305/Cys388, respectively.  (+info)

The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. (8/1676)

Although small GTP-binding proteins of the Rho family have been implicated in signaling to the actin cytoskeleton, the exact nature of the linkage has remained obscure. We describe a novel mechanism that links one Rho family member, Cdc42, to actin polymerization. N-WASP, a ubiquitously expressed Cdc42-interacting protein, is required for Cdc42-stimulated actin polymerization in Xenopus egg extracts. The C terminus of N-WASP binds to the Arp2/3 complex and dramatically stimulates its ability to nucleate actin polymerization. Although full-length N-WASP is less effective, its activity can be greatly enhanced by Cdc42 and phosphatidylinositol (4,5) bisphosphate. Therefore, N-WASP and the Arp2/3 complex comprise a core mechanism that directly connects signal transduction pathways to the stimulation of actin polymerization.  (+info)

The Ras guanine-nucleotide exchange factor Ras-GRF/Cdc25(Mn) harbors a complex array of structural motifs that include a Dbl-homology (DH) domain, usually found in proteins that interact functionally with the Rho family GTPases, and the role of which is not yet fully understood. Here, we present evidence that Ras-GRF requires its DH domain to translocate to the membrane, to stimulate exchange on Ras, and to activate mitogen-activated protein kinase (MAPK). In an unprecedented fashion, we have found that these processes are regulated by the Rho family GTPase Cdc42. We show that GDP- but not GTP-bound Cdc42 prevents Ras-GRF recruitment to the membrane and activation of Ras/MAPK, although no direct association of Ras-GRF with Cdc42 was detected. We also demonstrate that catalyzing GDP/GTP exchange on Cdc42 facilitates Ras-GRF-induced MAPK activation. Moreover, we show that the potentiating effect of ionomycin on Ras-GRF-mediated MAPK stimulation is also regulated by Cdc42. These results provide the ...
Here, we report a novel mechanism of PDZ (PSD-95/Dlg/ZO-1) domain regulation that distorts a conserved element of PDZ ligand recognition. The polarity regulator Par-6 assembles a conserved multiprotein complex and is directly modulated by the Rho GTPase Cdc42. Cdc42 binds the adjacent Cdc42/Rac interactive binding (CRIB) and PDZ domains of Par-6, increasing C-terminal ligand binding affinity by 10-fold. By solving structures of the isolated PDZ domain and a disulfide-stabilized CRIB-PDZ, we detected a conformational switch that controls affinity by altering the configuration of the conserved GLGF loop. As a result, lysine 165 is displaced from the PDZ core by an adjacent hydrophobic residue, disrupting coordination of the PDZ ligand-binding cleft. Stabilization of the CRIB:PDZ interface restores K165 to its canonical location in the binding pocket. We conclude that a unique dipeptide switch in the Par-6 PDZ transmits a signal for allosteric activation to the ligand-binding pocket. ...
Genghis khan was isolated in a search for proteins that physically interact with the Drosophila small GTPases Rac1 and Cdc42. Gek does not bind to Cdc42N17, a dominant negative mutant that preferentially stays in the GDP-bound state. The ability of Gek to bind Cdc42 in its GTP-bound form (but not in its GDP-bound form) suggests that Gek is an effector of Cdc42. A mutation in the Cdc42 effector domain (A35), which is important for signaling to downstream targets, eliminates Gek binding. Gek does not bind to Drosophila Rac. Deletion of three residues in Gek, which correspond to three conserved residues of the Cdc42/Rac interactive binding (CRIB) domain, disrupt Geks binding to Cdc42. Gek exhibits kinase activity using histone as a substrate (Luo, 1997).. Cdc42, a Rho family GTPase that acts through Gek The small GTPases of the Rac/Rho/Cdc42 subfamily are implicated in actin cytoskeleton-membraneinteraction in mammalian cells and budding yeast. The in vivo functions of these GTPases ...
Many putative downstream effectors of the small GTPases Cdc42 and Rac contain a GTPase binding domain (GBD), also called p21 binding domain (PBD), which has been shown to specifically bind the GTP bound form of Cdc42 or Rac, with a preference for Cdc42 [1,2]. The most conserved region of GBD/PBD domains is the N-terminal Cdc42/Rac interactive binding motif (CRIB), which consists of about 16 amino acids with the consensus sequence I-S-x-P-x(2,4)-F-x-H-x(2)-H-V-G [3]. Although the CRIB motif is necessary for the binding to Cdc42 and Rac, it is not sufficient to give high-affinity binding [4,5]. A less well conserved inhibitory switch (IS) domain responsible for maintaining the proteins in a basal (autoinhibited) state is located C-terminaly of the CRIB-motif [6,7,8]. GBD domains can adopt related but distinct folds depending on context. Although GBD domains are largely unstructured in the free state, the IS domain forms an N-terminal β hairpin that immediately follows the conserved CRIB motif and ...
S. pombe cdc42+ suppressed the S. cerevisiae cdc24-4ts mutation and the S. cerevisiae BEM3 and RGA1 GAPs reversed this suppression: Previous studies have shown that S. cerevisiae CDC42 on a low-copy vector was able to suppress the cdc24-4ts mutation in the presence of 1 m sorbitol (Bender and Pringle 1989). Presumably, levels of activated GTP-bound Cdc42p are reduced in the cdc24-4 mutant at 37° and suppression is through an increase in levels of GTP-bound Cdc42p upon overexpression. Addition of a high-copy vector containing either the S. cerevisiae BEM3 or RGA1-encoded GAP reverses this suppression, presumably by inactivation of the Cdc42-GTP to a GDP-bound state (Bi and Pringle 1996). S. pombe cdc42+ under S. cerevisiae CDC42 promoter control was inserted into a low-copy S. cerevisiae plasmid (pRS315-cdc42+) and transformed into cdc24-4ts strain Y147. This plasmid was able to suppress the cdc24-4ts mutant at 37° in the presence of 1 m sorbitol (Figure 1). In addition, high-copy plasmids ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of a family of p21-stimulated serine/threonine protein kinases, which contain an amino-terminal Cdc42/Rac interactive binding (CRIB) domain and a carboxyl-terminal kinase domain. These kinases function in a number of cellular processes, including cytoskeleton rearrangement, apoptosis, and the mitogen-activated protein (MAP) kinase signaling pathway. The protein encoded by this gene interacts with androgen receptor (AR) and translocates to the nucleus, where it is involved in transcriptional regulation. Changes in expression of this gene have been linked to prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015 ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of a family of p21-stimulated serine/threonine protein kinases, which contain an amino-terminal Cdc42/Rac interactive binding (CRIB) domain and a carboxyl-terminal kinase domain. These kinases function in a number of cellular processes, including cytoskeleton rearrangement, apoptosis, and the mitogen-activated protein (MAP) kinase signaling pathway. The protein encoded by this gene interacts with androgen receptor (AR) and translocates to the nucleus, where it is involved in transcriptional regulation. Changes in expression of this gene have been linked to prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015 ...
p21-activated kinase 6 (PAK6) is a member of the PAK family of serine/threonine kinases. These kinases have a highly conserved amino-terminal Cdc42/Rac interactive binding domain and a carboxyl-terminal kinase domain. PAK kinases are implicated in the regulation of a number of cellular processes, including cytoskeleton
Kaur R., Liu X., Gjoerup O., Zhang A., Yuan X., Balk S.P., Schneider M.C., Lu M.L.. The p21-activated kinases (PAKs) contain an N-terminal Cdc42/Rac interactive binding domain, which in the group 1 PAKs (PAK1, 2, and 3) regulates the activity of an adjacent conserved autoinhibitory domain. In contrast, the group 2 PAKs (PAK4, 5, and 6) lack this autoinhibitory domain and are not activated by Cdc42/Rac binding, and the mechanisms that regulate their kinase activity have been unclear. This study found that basal PAK6 kinase activity was repressed by a p38 mitogen-activated protein (MAP) kinase antagonist and could be strongly stimulated by constitutively active MAP kinase kinase 6 (MKK6), an upstream activator of p38 MAP kinases. Mutation of a consensus p38 MAP kinase target site at serine 165 decreased PAK6 kinase activity. Moreover, PAK6 was directly activated by MKK6, and mutation of tyrosine 566 in a consensus MKK6 site (threonine-proline-tyrosine, TPY) in the activation loop of the PAK6 ...
J:149918 Fuchs S, Herzog D, Sumara G, Buchmann-Moller S, Civenni G, Wu X, Chrostek-Grashoff A, Suter U, Ricci R, Relvas JB, Brakebusch C, Sommer L, Stage-specific control of neural crest stem cell proliferation by the small rho GTPases Cdc42 and Rac1. Cell Stem Cell. 2009 Mar 6;4(3):236-47 ...
Prerequisites for all modes of cell migration are cell-substratum interactions that require a sophisticated interplay of membrane dynamics and cytoskeletal rearrangement. Generally, a migrating cell is polarized with a distinct rear and front, from which it extends a wide and thin membrane protrusion- lamellipodium, small fingerlike projections- filopodia, and membrane blisters- blebs. The development of these structures is primarily driven by cytoskeletal contractions and actin polymerization, which are under regulation of several actin-binding proteins and the small GTPases Cdc42, Rac and Rho. Lamellipodia and filopodia are assumed to arise from polymerizing actin, pushing the membrane forward through a Brownian-ratchet mechanism. However, other models based on shifts in the local hydrostatic pressure have also been suggested since blebs are initially void of actin. Recently, fluxes of water through membrane-anchored water channels, aquaporins (AQPs), have been implicated in cell motility, ...
CDC42 is a member of the Rho GTPase family that regulates multiple cellular activities, including actin polymerization. The protein encoded by this gene is a CDC42 binding protein that mediates actin cytoskeleton reorganization at the plasma membrane. This protein is secreted and is primarily found in bone marrow. [provided by RefSeq, Jul 2008 ...
Active Cdc42 ELISA Activation Assay - colorimetric format offers a sensitive and accurate dection of active Cdc42 GTPase. Additional assays for small GTPases including Rho, Ras, Cdc42, Rac, Ral, Arf also available in pull-down and G-LISA formats.
摘 要:胚胎干细胞的生长、增殖、分化和形状改变等过程受微环境、机械力等多种因素的影响。胚胎干细胞能够感知微小机械力刺激,并将其转化成生物化学信号,进而通过F-肌动蛋白、肌球蛋白-II、Cdc42、Rho和Src等产生一系列分子水平的应答反应,最终导致基因差异表达。胚胎干细胞应答外力基本过程的研究对于胚胎早期发育和分化机制研究、克隆和再生药物的研制与开发等均有重要意义。该文就机械力对胚胎干细胞结构、形态和分化的影响及其潜在机制等进行论述 ...
The Dbl family of guanine nucleotide exchange factors are multifunctional molecules that transduce diverse intracellular signals leading to the activation of Rho GTPases. The tandem Dbl-homology and pleckstrin-homology domains shared by all members of this family represent the structural module resp …
TY - JOUR. T1 - Genetically encoded photoswitching of actin assembly through the Cdc42-WASP-Arp2/3 complex pathway. AU - Leung, Daisy W.. AU - Otomo, Chinatsu. AU - Chory, Joanne. AU - Rosen, Michael K.. PY - 2008/9/2. Y1 - 2008/9/2. N2 - General methods to engineer genetically encoded, reversible, light-mediated control over protein function would be useful in many areas of biomedical research and technology. We describe a system that yields such photo-control over actin assembly. We fused the Rho family GTPase Cdc42 in its GDP-bound form to the photosensory domain of phytochrome B (PhyB) and fused the Cdc42 effector, the Wiskott-Aldrich Syndrome Protein (WASP), to the light-dependent PhyB-binding domain of phytochrome interacting factor 3 (Pif3). Upon red light illumination, the fusion proteins bind each other, activating WASP, and consequently stimulating actin assembly by the WASP target, the Arp2/3 complex. Binding and WASP activation are reversed by far-red illumination. Our approach, in ...
Many signaling pathways control cell shape, and these pathways ultimately do so, at least in part, by regulating polymerization of actin. Members of the WASP (Wiskott-Aldrich syndrome protein) family appear to integrate such signals and are thus subject to a complex array of regulatory mechanisms. Activation of WASP through the Rho family GTPase Cdc42 and interaction with phosphatidylinositol 4,5-bisphosphate (PIP2) stimulate the Arp2/3 complex, which in turn promotes nucleation of actin filaments. Papers by Higgs and Pollard and Rohatgi et al. characterizing native WASP from bovine thymus and in vitro-translated N-WASP (where N refers to neuronal, even though this family member is widely expressed) and the Commentary by Zigmond provide new details of this multifaceted regulation. The NH2-terminus of WASP appears to interact with the COOH-terminus and block binding to Arp2/3. Activation by Cdc42 and PIP2 reduces the autoinhibitory binding and exposes the Arp2/3 binding region. Rohatgi et al. use ...
RhoA of the Rho Family Small GTPases Is Essential for B Lymphocyte Development. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
The member of Rho family of small GTPases Cdc42 plays important and conserved roles in cell polarity and motility. The Cdc42ep family proteins have been identified to bind to Cdc42, yet how they interact with Cdc42 to regulate cell migration remains to be elucidated. In this study, we focus on Cdc42ep1, which is expressed predominantly in the highly migratory neural crest cells in frog embryos. Through morpholino-mediated knockdown, we show that Cdc42ep1 is required for the migration of cranial neural crest cells. Loss of Cdc42ep1 leads to rounder cell shapes and the formation of membrane blebs, consistent with the observed disruption in actin organization and focal adhesion alignment. As a result, Cdc42ep1 is critical for neural crest cells to apply traction forces at the correct place to migrate efficiently. We further show that Cdc42ep1 is localized to two areas in neural crest cells: in membrane protrusions together with Cdc42 and in perinuclear patches where Cdc42 is absent. Cdc42 directly ...
Prerequisites for all modes of cell migration are cell-substratum interactions that require a sophisticated interplay of membrane dynamics and cytoskeletal rearrangement. Generally, a migrating cell is polarized with a distinct rear and front, from which it extends a wide and thin membrane protrusion- lamellipodium, small fingerlike projections- filopodia, and membrane blisters- blebs. The development of these structures is primarily driven by cytoskeletal contractions and actin polymerization, which are under regulation of several actin-binding proteins and the small GTPases Cdc42, Rac and Rho. Lamellipodia and filopodia are assumed to arise from polymerizing actin, pushing the membrane forward through a Brownian-ratchet mechanism. However, other models based on shifts in the local hydrostatic pressure have also been suggested since blebs are initially void of actin. Recently, fluxes of water through membrane-anchored water channels, aquaporins (AQPs), have been implicated in cell motility, ...
The constant self renewal and differentiation of adult intestinal stem cells maintains a functional intestinal mucosa for a lifetime. However, the molecular mechanisms that regulate intestinal stem cell division and epithelial homeostasis are largely undefined. We report here that the small GTPases Cdc42 and Rab8a are critical regulators of these processes in mice. Conditional ablation of Cdc42 in the mouse intestinal epithelium resulted in the formation of large intracellular vacuolar structures containing microvilli (microvillus inclusion bodies) in epithelial enterocytes, a phenotype reminiscent of human microvillus inclusion disease (MVID), a devastating congenital intestinal disorder that results in severe nutrient deprivation. Further analysis revealed that Cdc42-deficient stem cells had cell division defects, reduced capacity for clonal expansion and differentiation into Paneth cells, and increased apoptosis. Cdc42 deficiency impaired Rab8a activation and its association with multiple ...
Rho GTPases are reported DISCUSSION In the present study we investigated the effect of ionizing radiation (IR) on the expression of the
This gene encodes a member of the DBL family of guanine nucleotide exchange factors. The encoded protein has been proposed to regulate the actin cytoskeleton by specifically activating the Rho-family GTPase Cdc42. An interaction between the encoded protein and a Listeria protein has been shown to mediate Listeria infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015 ...
Rho GTPases comprise a family of molecular switches that control signal transduction pathways in eukaryotic cells. A conformational change induced upon binding GTP promotes an interaction with target (effector) proteins to generate a cellular response. A highly conserved function of Rho GTPases from yeast to humans is to control the actin cytoskeleton, although, in addition, they promote a wide range of other cellular activities. Changes in the actin cytoskeleton drive many dynamic aspects of cell behaviour, including morphogenesis, migration, phagocytosis and cytokinesis, and the dysregulation of Rho GTPases is associated with numerous human diseases and disorders. ...
DOCK-C subfamily proteins (DOCK6-8) partially conserve the Cdc42-interacting residues of DOCK939 and the Rac1-interacting residues of DOCK2.40 To understand the mechanism underlying the Cdc42 specificity of DOCK8, we performed X-crystallographic analysis of the complex between the DOCK8 DHR-2 domain and the dominant-negative T17N mutant of Cdc42 (supplemental Table 1). Two lobes (lobes B and C) of DOCK8 DHR-2 generate a cooperative interface with Cdc42 (Figure 6C) in a manner similar to DOCK9 DHR-2.39 Based on the DOCK6 structural model, it was predicted that Met1932 of DOCK6 would be incompatible with the aromatic side chain at position 56 (Phe, Tyr, or Trp) that is conserved in nearly all of the Rho family of GTPases.40 However, the DOCK8 DHR-2·Cdc42 complex structure revealed that DOCK8 Met1976, corresponding to Met1932 of DOCK6, assumes a bent side-chain conformation and thereby avoids the putative steric hindrance with the Phe56 side chain of Cdc42 (Figure 6D). When the structure of Rac1 ...
Zou W, Greenblatt MB, Shim JH, Kant S, Zhai B, Lotinun S, Brady N, Hu DZ, Gygi SP, Baron R, Davis RJ, Jones D, Glimcher LH. MLK3 regulates bone development downstream of the faciogenital dysplasia protein FGD1 in mice. J Clin Invest. 2011 Nov; 121(11):4383-92 ...
H Si, H Lu... Z Chen TNF-α modulates genome-wide redistribution of ΔNp63α/TAp73 and NF-κB cREL interactive binding on TP53 and AP-1 motifs to promote an oncogenic gene program in squamous cancer. Oncogene 35:44 5781-5794 ...
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Cdc42 and Rac1 have distinct but overlapping binding sites on PICK1.Upper panel: GST pulldowns were carried out using purified his6flagCdc42 or his6mycRac1 and
Dr Arjun Srinivasan, the associate director of the CDC, said that the misuse and overuse of antibiotics have rendered them powerless to fight continuously evolving infections like MRSA.
Information on what to do if you have been exposed to TB, and links for patients and health care providers. Provided by the Centers for Disease Control and Prevention (CDC).
I logged on to this site after following a link from CDC. I was curious about CD and considering a change from LL. After reading the ridiculous opinions of...
This is by far the craziest most uncertain time I have ever experienced in my lifetime and to make things worse the FACTS keep changing
Just in time for World Breastfeeding Week (yes, there is one), the CDC has released a report (.pdf) showing that only a small percentage of U.S. hospitals - 4 …. ...
COVID-19: Keep you and your loved ones safe. Visit the CDC Guidance for Older Adults, or call 1-833-MY-Senior for resources in your area. ...
PAK5兔多克隆抗体(ab110069)可与大鼠, 人样本反应并经WB, IHC实验严格验证,被1篇文献引用。所有产品均提供质保服务,中国75%以上现货。
PAK4兔多克隆抗体(ab17974)可与人样本反应并经WB, IP实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
Members of the Rho family of GTP‐binding proteins function as molecular switches in biological response pathways that result in changes in the actin cytoskeletal architecture, the stimulation of cell cycle progression and gene transcription, and the regulation of intracellular trafficking activities (Van Aelst and DSouza‐Schorey, 1997; Hall, 1998; Bar‐Sagi and Hall, 2000; Erickson and Cerione, 2001). Three classes of proteins, GTPase‐activating proteins (GAPs), guanine nucleotide dissociation inhibitors (GDIs), and guanine nucleotide exchange factors (GEFs), regulate the cycling of these GTP‐binding proteins between their GDP‐bound and GTP‐bound states (Boguski and McCormick, 1993). Rho family proteins, such as Cdc42 and Rac, are activated by a number of upstream stimuli, as mediated by members of the Dbl (diffuse B‐cell lymphoma) family of GEFs (Whitehead et al, 1997; Hoffman and Cerione, 2002). One subgroup of the Dbl family, the Cool/Pix proteins (Cool for cloned‐out of ...
TY - JOUR. T1 - Cdc42 overexpression induces hyperbranching in the developing mammary gland by enhancing cell migration. AU - Bray, Kristi. AU - Gillette, Melissa. AU - Young, Jeanette. AU - Loughran, Elizabeth. AU - Hwang, Melissa. AU - Sears, James C.. AU - Vargo-Gogola, Tracy. PY - 2013/9/30. Y1 - 2013/9/30. N2 - Introduction: The Rho GTPase Cdc42 is overexpressed and hyperactivated in breast tumors compared to normal breast tissue. Cdc42 regulates key processes that are critical for mammary gland morphogenesis and become disrupted during the development, progression, and metastasis of breast cancer. However, the contribution of Cdc42 to normal and neoplastic mammary gland development in vivo remains poorly understood. We were therefore interested in investigating the effects of Cdc42 overexpression on mammary gland morphogenesis as a first step toward understanding how its overexpression may contribute to mammary tumorigenesis.Methods: We developed a tetracycline-regulatable Cdc42 ...
TY - JOUR. T1 - Axl phosphorylates Elmo scaffold proteins to promote rac activation and cell invasion. AU - Abu-Thuraia, Afnan. AU - Gauthier, Rosemarie. AU - Chidiac, Rony. AU - Fukui, Yoshinori. AU - Screaton, Robert A.. AU - Gratton, Jean Philippe. AU - Côté, Jean François. N1 - Publisher Copyright: © 2015, American Society for Microbiology. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.. PY - 2015. Y1 - 2015. N2 - The receptor tyrosine kinase Axl contributes to cell migration and invasion. Expression of Axl correlates with metastatic progression in cancer patients, yet the specific signaling events promoting invasion downstream of Axl are poorly defined. Herein, we report Elmo scaffolds to be direct substrates and binding partners of Axl. Elmo proteins are established to interact with Dock family guanine nucleotide exchange factors to control Rac-mediated cytoskeletal dynamics. Proteomics and mutagenesis studies reveal that Axl phosphorylates Elmo1/2 on a conserved ...
In yeast, Cdc42 is required to polarize the site of bud formation, and several in vitro studies show that it may also be required for efficient polarization of eukaryotic cells (Etienne-Manneville, 2004). Furthermore, for monocytes in culture, blocking Cdc42 signaling leads to a failure to receive and respond to chemotactic cues (Allen et al., 1998; Chou et al., 2003; Srinivasan et al., 2003). However, our in vivo studies in the fly embryo reveal no significant effect on the numbers of hemocytes recruited to laser wounds after 1 h in Cdc42 mutant embryos. This finding is true also for embryos expressing the dominant-negative Cdc42N17 and Cdc42S89 transgenes specifically in hemocytes (Fig. 3 a). Both developmental dispersal of hemocytes and their recruitment to sites of tissue damage appears grossly normal. But on closer inspection, we observe that hemocyte motility is abnormal. During the migratory phase, and once hemocytes have reached the wound, we frequently see cells with several leading ...
Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase alpha. Serine/Threonine Kinases (STKs), DMPK-like subfamily, DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK) alpha isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. MRCKalpha is expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. ...
Objectives: The Rho subfamily of small GTPases, including RhoA, Rac1, and Cdc42, regulates diverse cellular functions, including polarity and migration. Our prior studies established an essential role for Cdc42 in vascular network assembly, demonstrating that the genetic inactivation of Cdc42 yields defective vascular morphogenesis due to impaired migration of endothelial precursor cells. We have further shown that protein kinase Ciota and glycogen synthase kinase-3 Beta are downstream effectors of Cdc42 involved in mediating vascular network assembly. The objective of this study was to elucidate the guanine nucleotide exchange factors (GEFs) that activate Cdc42; specifically, we investigated the role of Zizimin1 and its effects on Cdc42 and vasculogenesis.. Methods: We performed affinity pulldown assays using a nucleotide-free Cdc42 G15A mutant that specifically binds to Cdc42 GEFs. Mass spectrometric analysis identified Zizimin1 as a candidate Cdc42 GEF.. Results: During vasculogenesis in ...
Several studies have identified Rho family GTPases (i.e. Rho, Rac, Cdc42) as mediators of diverse critical cellular processes, such as actin cytoskeleton remodeling, gene transcription, cell-cell adhesion, and cell cycle progression. However, more recent data highlight an essential role for Rho GTPases as regulators of neuronal morphology and neuronal survival. In particular, Rac GTPase generally induces neurite outgrowth and promotes neuronal survival while Rho GTPase typically provokes neurite retraction and induces neuronal apoptosis. However, the precise signaling pathways that regulate neuronal survival downstream of Rho GTPases and the potential involvement of dysregulated activity of Rho GTPases as a causative factor in the progression of neurodegenerative diseases remains to be elucidated. Consistent with a pro-survival function for Rac in neurons, inhibition of Rac with Clostridium difficle toxin B (ToxB) or expression of a dominant negative Rac1 mutant significantly induces activation of the
The sequential and regulated recruitment of leukocytes into tissues by chemoattractants is essential for effective clearance of pathogens and healing. The Rho GTPases Cdc42, Rac, and Rho are important for establishing and maintaining migratory polarity. Most chemoattractants for phagocytes signal either through seven transmembrane G-protein-coupled receptors (GPCRs) or tyrosine kinase receptors. Y721 is the most important for chemotaxis because it recruits phospholipase-C-γ (PL C-γ) and the p85 subunit of class 1A PI3Ks, both of which are implicated in the initiation of chemotaxis. Several intracellular signaling complexes contribute to the polarization of phagocytes in response to chemoattractants, and they probably act together to allow optimal chemotaxis. Cdc42 is implicated in multiple types of cell polarity, including axon specification, yeast mating, and epithelial polarity. There are several PLC isoforms, of which PLCβ2 and PLCβ3 are activated by GPCR signaling in neutrophils, whereas PLCβ
PAK proteins are involved in the regulation of cellular processes such as gene transcription, cell morphology, motility and apoptosis (Bagrodia and Cerione, 1999; Daniels and Bokoch, 1999; Jaffer and Chernoff, 2002). Our results illustrate that different PAK proteins fulfil distinct functions in the same cell. In the developing photoreceptor cells, D-PAK is required in growth cones to control axon guidance (Hing et al., 1999) whereas Mbt is localised at AJs and is required for cell morphogenesis.. One major difference between group I and group II PAKs is the regulation of kinase activity. For group I PAK proteins it has been shown that binding of GTP-bound Cdc42 or Rac releases the inhibitory effect of the KID on catalytic activity (Buchwald et al., 2001; Chong et al., 2001; Lei et al., 2000). The lack of an obvious KID in group II PAKs (Fig. 5C) is reflected by their distinct biochemical properties. In contrast to group I PAKs, a slightly reduced rather than enhanced kinase activity is observed ...
The Rho family of GTPases is a family of small (~21 kDa) signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants. Three members of the family have been studied in detail: Cdc42, Rac1, and RhoA. All G proteins are molecular switches, and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions. Identification of the Rho family of GTPases began in the mid-1980s. The first identified Rho member was RhoA, isolated serendipitously in 1985 from a low stringency cDNA screening. Rac1 and Rac2 were identified next, in 1989 followed by Cdc42 in 1990. Eight additional mammalian Rho members were identified from biological screenings until the late 1990s, a turning point in biology where availability of complete genome sequences allowed full ...
Rho GTPases are master regulators of many immunoreceptors, ranging from receptors required for differentiation and maturation of immune cells and for pathogen recognition to receptors involved in pathogen uptake and the subsequent host signaling responses. Several TLRs induce the activation of the Rho family GTPases Rac, Rho, and Cdc42. Almost every cell type, including professional innate immune cells such as macrophages, neutrophils, and dendritic cells, responds to TLR stimulation by activating Rho GTPases rapidly (8, 20, 31). Similarly, lung epithelial cells induce Rho GTPase activation when they encounter TLR ligands. It seems apparent that RhoA activation depends on the interaction of a specific TLR ligand with its cognate TLR, independently of the connecting adapters or the cellular compartment where TLR signaling occurs. A RhoA FRET probe was used to examine localized RhoA activity at early time points after initiation of TLR2 or TLR3 signaling. After 3-5 min of treatment with the TLR2 ...
May be involved in several stages of intracellular trafficking (By similarity). Could play an important role in the regulation of glucose transport by insulin. May act as a downstream effector of RHOQ/TC10 in the regulation of insulin-stimulated glucose transport.
This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein may pay a role in clathrin-mediated endocytosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2013 ...
Cdc42 is a member of the Rho GTPase family and functions as a molecular switch in regulating cell migration, proliferation, differentiation and survival. However, the role of Cdc42 in heart development remains largely unknown. To determine the function of Cdc42 in heart formation, we have generated a Cdc42 cardiomyocyte knockout (CCKO) mouse line by crossing Cdc42 flox mice with myosin light chain (MLC) 2a-Cre mice. The inactivation of Cdc42 in embryonic cardiomyocytes induced lethality after embryonic day 12.5. Histological analysis of CCKO embryos showed cardiac developmental defects that included thin ventricular walls and ventricular septum defects. Microarray and real-time PCR data also revealed that the expression level of p21 was significantly increased and cyclin B1 was dramatically decreased, suggesting that Cdc42 is required for cardiomyocyte proliferation. Phosphorylated Histone H3 staining confirmed that the inactivation of Cdc42 inhibited cardiomyocytes proliferation. In addition,
Most previous studies on the activation of Rho-like GTPases have relied on analyses of downstream cytoskeletal changes. In the new study, Sander et al. took advantage of the properties of two downstream effectors, Pak and Rhotekin, to confer specificity in a biochemical assay for Rho-like GTPase activity. Pak binds to GTP-, but not GDP-loaded Rac and Cdc42, and Rhotekin binds specifically to GTP-loaded Rho. Activation of Rac, or signaling by constitutively active mutants of Cdc42 and Rac, down-regulates endogenous Rho activity, but activation of Rho has no effect on Rac activity. The down-regulation of Rho by Rac causes an epithelioid, nonmigratory phenotype in NIH3T3 fibroblasts, an effect that can be reversed by expressing constitutively active Rho, indicating that the reciprocal balance of the two proteins determines cell morphology and migratory behavior. The scientists found a similar down-regulation of Rho by Rac in several other cell types, and are now trying to identify factors that ...
Bosse, T., Ehinger, J., Czuchra, A., Benesch, S., Steffen, A., Wu, X., Schloen, K., Niemann, Hartmut, Scita, G., Stradal, T. E., Brakebusch, C., and Rottner, K. Cdc42 and phosphoinositide 3-kinase drive Rac-mediated actin polymerization downstream of c-Met in distinct and common pathways. Mol Cell Biol 27.19 (2007): 6615-6628 ...
To further test the vector system, we designed both a synthetic siRNA and a pSUPER vector that target the same 19-nt sequence in theCDC20 transcript. As for CDH1, efficient suppression of endogenous CDC20 expression was achieved with both synthetic siRNA and with pSUPER-CDC20 (Fig. 2B). To measure the level of gene suppression accurately by the pSUPER system, we designed a construct to target polo like kinase-1 (PLK1). Introduction of pSUPER-PLK1 led to a significant decrease in PLK1 protein levels and a reduction in PLK1 kinase activity by a factor of 10 [Supplementary fig. 1A (4)]. To date, we were successful in knocking down the expression of more than 10 genes for which we designed a pSUPER siRNA vector, highlighting the efficiency with which genes can be targeted using this vector (6).. Next, we asked whether suppression of gene expression by the pSUPER vector is sufficient to affect cellular physiology. We designed a construct to knockdown p53, a transcription factor that is stabilized ...
Background Rho GTPase-activating protein which may be involved in clathrin-mediated endocytosis. GTPase activators for the Rho-type GTPases act by converting them to an inactive GDP-bound state. Has activity toward CDC42 and...
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The biosensors developed in the authors laboratory have been based on different designs, each imparting specific strengths and weaknesses
The biosensors developed in the authors laboratory have been based on different designs, each imparting specific strengths and weaknesses
médecine/sciences (M/S), revue internationale dans le domaine de la recherche biologique, médicale et en santé
médecine/sciences (M/S), revue internationale dans le domaine de la recherche biologique, médicale et en santé
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Complete information for CDC37 gene (Protein Coding), Cell Division Cycle 37, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Distributed via the CDC Health Alert NetworkMay 25, 2018, 1130 ET (11:30 AM ET)CDC HAN-00410The Centers for Disease Control and Prevention (CDC) is providing information on: 1) the current status of a multistate outbreak of coagulopathy from exposure ...
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Mark D. Bass is the author of these articles in the Journal of Visualized Experiments: Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound, Comparing the Affinity of GTPase-binding Proteins using Competition Assays
Homo sapiens CDC42 binding protein kinase alpha (DMPK-like) (CDC42BPA), transcript variant A, mRNA. (H00008476-R03) - Products - Abnova
Recombinant rho GTPase Activating Protein 19 (ARHGAP19) Protein (His tag). Species: Mouse. Source: Insect Cells. Order product ABIN3125177.
The CDC gets it wrong again - the sun doesnt cause melanoma Last year, I reported on the incompetent way the Centers for Disease Control (CDC) handed the
Cells depleted of Plk or cdc5-1 protein arrest at multiple points of M phase. (A) Growth of cdc5Δ mutant conditionally rescued by expressing either GAL1-HA-EGF
U.S. Centers for Disease Control and Prevention (CDC) has determined that sixty-five percent of those with cancer now survive five years or more after diagnosis.
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Antibiotic resistance is the ability of bacteria to resist the e ects of drug treatment. Simply put, germs continue to multiply because the drugs cannot kill them. For more than 30 years, the U.S. Centers for Disease Control and Prevention (CDC) has ...
PAK inhibitors (inhibiting targets of signaling pathways) used for various assays, some have entered clinical trials, which would be new cancer therapies.
View mouse Arhgap24 Chr5:102481391-102897937 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
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The p21-activated kises (PAKs) are serine-threonine kises that bind to the active forms of Cdc42 and Rac. They are divided into two groups, the first…
Rho family GTP-binding protein family members Rac1 and Cdc42, activated via DHPH RhoGEF domain. Rho family of GTPases Scaffold ... Like other GEFs, αPIX can promote both release of GDP from an inactive small GTP-binding protein and binding of GTP to promote ... 2003). "The Cbl proteins are binding partners for the Cool/Pix family of p21-activated kinase-binding proteins". FEBS Lett. 550 ... and activated Rac1 or Cdc42 binding to this PAK stimulates its protein kinase activity leading to downstream target protein ...
"The Arp2/3 complex mediates actin polymerization induced by the small GTP-binding protein Cdc42". Proceedings of the National ... Actin-related protein 3 is a protein that in humans is encoded by the ACTR3 gene. The specific function of this gene has not ... Winter D, Podtelejnikov AV, Mann M, Li R (Jul 1997). "The complex containing actin-related proteins Arp2 and Arp3 is required ... Higgs HN, Blanchoin L, Pollard TD (Nov 1999). "Influence of the C terminus of Wiskott-Aldrich syndrome protein (WASp) and the ...
Hoffman GR, Nassar N, Cerione RA (2000). "Structure of the Rho family GTP-binding protein Cdc42 in complex with the ... "Mapping the binding site for the GTP-binding protein Rac-1 on its inhibitor RhoGDI-1". Structure. 8 (1): 47-55. doi:10.1016/ ... "Mapping the binding site for the GTP-binding protein Rac-1 on its inhibitor RhoGDI-1". Structure. 8 (1): 47-55. doi:10.1016/ ... Li X, Bu X, Lu B, Avraham H, Flavell RA, Lim B (February 2002). "The hematopoiesis-specific GTP-binding protein RhoH is GTPase ...
Rho family GTP-binding protein family members Rac1 and Cdc42, activated via DHPH RhoGEF domain. The neuronal synapse adaptors ... Like other GEFs, βPIX can promote both release of GDP from an inactive small GTP-binding protein and binding of GTP to promote ... and activated Rac1 or Cdc42 binding to this PAK stimulates its protein kinase activity leading to downstream target protein ... "The Cbl proteins are binding partners for the Cool/Pix family of p21-activated kinase-binding proteins". FEBS Lett. 550 (1-3): ...
... and CDC42 (MIM 116952). GTPase-activating proteins (GAPs) bind activated forms of Rho GTPases and stimulate GTP hydrolysis. ... a new human GTPase-activating protein for Rac and Cdc42 similar to Drosophila rotundRacGAP gene product, is expressed in male ... Rac GTPase-activating protein 1 is an enzyme that in humans is encoded by the RACGAP1 gene. Rho GTPases control a variety of ... "Entrez Gene: RACGAP1 Rac GTPase activating protein 1". Ren K, Zhou D, Wang M, Li E, Hou C, Su Y, et al. (March 2021). "RACGAP1 ...
They serve as targets for the small GTP binding proteins CDC42 and Rac and have been implicated in a wide range of biological ... PAK1 p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast)". "Entrez Gene: PAK2 p21 (CDKN1A)-activated kinase 2". "Entrez ...
These proteins serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of ... ARG-binding protein 2γ, hepatitis B virus X protein, STE20-related kinase adaptor protein α, RhoI, Klotho, N-acetylglucosaminyl ... Seoh ML, Ng CH, Yong J, Lim L, Leung T (March 2003). "ArhGAP15, a novel human RacGAP protein with GTPase binding property". ... Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L (January 1994). "A brain serine/threonine protein kinase activated by Cdc42 and ...
"Entrez Gene: RALB v-ral simian leukemia viral oncogene homolog B (ras related; GTP binding protein)". Simicek M, Lievens S, ... RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity". J. Biol. Chem. 270 (38): 22473-7. doi:10.1074/jbc. ... "Identification and characterization of a novel protein interacting with Ral-binding protein 1, a putative effector protein of ... Hsieh CL, Swaroop A, Francke U (1990). "Chromosomal localization and cDNA sequence of human ralB, a GTP binding protein". Somat ...
... and Cdc42 regulate their activity by alternating between an active GTP-bound state, and an inactive GDP-bound state. Guanine ... Just I, Selzer J, von Eichel-Streiber C, Aktories K (March 1995). "The low molecular mass GTP-binding protein Rho is affected ... In Rac and Cdc42, the sugar moiety is transferred to the Thr-35. The glucosylation prevents proper binding of GTP and blocks ... TcdA acts preferentially on the GDP-bound form of the GTPase proteins since this configuration exposes the threonine residue ...
The example of substrate includes H-Ras, N-ras, R-Ras, RhoB, Cdc42 inform 2, Rab10, Galpha subunit of trimeric GTP binding ... Palmitoyl acyltransferase is a group of enzymes that transfer palmityl group to -SH group on cysteine on a protein. This ... The catalytic domain of the protein has aspartate-histidine-histidine-cystein (DHHC) in the core and therefore is called DHHC ... The addition of palmitoyl group increase the membrane association of the substrate protein while the removal by palmitoyl ...
The PAK proteins are a family of serine/threonine kinases that serve as targets for the small GTP binding proteins, CDC42 and ... The PAK proteins are a family of serine/threonine kinases that serve as targets for the small GTP binding proteins, CDC42 and ... Serine/threonine-protein kinase PAK 2 is an enzyme that in humans is encoded by the PAK2 gene. PAK2 is one of three members of ... The protein encoded by this gene is activated by proteolytic cleavage during caspase-mediated apoptosis, and may play a role in ...
Instead, it binds the active (GTP-bound) forms of RAC1 and CDC42 with higher affinity than GDP-bound forms, and stabilizes the ... Bashour AM, Fullerton AT, Hart MJ, Bloom GS (1997). "IQGAP1, a Rac- and Cdc42-binding protein, directly binds and cross-links ... This domain binds calmodulin, a protein known as a calcium sensor that can bind and regulate many target proteins. A GRD ( ... which mediates actin-binding and binds calponin. The WW, or poly-proline protein-protein domain, so named because of two ...
Rho small GTPases are inactive when bound to GDP but active when bound to GTP; RhoGEF domains in proteins are able to promote ... GDP release and GTP binding to activate specific Rho family members, including RhoA, Rac1 and Cdc42. The largest class of ... gene encodes a brain protein with homology to guanine nucleotide exchange proteins and GTPase-activating proteins". The Journal ... A distinct class of RhoGEFs is those proteins containing the DOCK/CZH/DHR-2 domain. This structure has no sequence similarity ...
... +GTP-Binding+Protein at the US National Library of Medicine Medical Subject Headings (MeSH) CDC42 Info with links in the ... "CDC42 (cell division cycle 42 (GTP binding protein, 25kDa))". Retrieved 2016-04-22. Stengel K, Zheng ... Cdc42 cycles between an active GTP-bound state and an inactive GDP-bound state. This process is regulated by guanine nucleotide ... a transcriptionally inducible adapter protein that binds GTP-Cdc42 and activates SAPK/JNK. A potential marker transcript for ...
... like many other small G-protein associating domains) and selectively binds GTP-bound Ras proteins only. (You can see this ... upon tyrosine phosphorylation by the Cdc42-regulated kinase ACK1". J. Biol. Chem. 275 (38): 29788-93. doi:10.1074/jbc. ... "The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors". Oncogene. 23 (2): 559-68 ... most importantly GTP-bound Ras. Activated small G-proteins can thus break up the intramolecular interactions: this results in a ...
TIAM1 modulates the activity of Rho GTP-binding proteins and connects extracellular signals to cytoskeletal activities. In ... Wennerberg K, Ellerbroek SM, Liu RY, Karnoub AE, Burridge K, Der CJ (Dec 2002). "RhoG signals in parallel with Rac1 and Cdc42 ... T-cell lymphoma invasion and metastasis-inducing protein 1 is a protein that in humans is encoded by the TIAM1 gene. TIAM1 is ... "Ca2+/calmodulin-dependent protein kinase II regulates Tiam1 by reversible protein phosphorylation". The Journal of Biological ...
Septins are a group of the highly conserved GTP binding proteins found in eukaryotes. Different septins form protein complexes ... Rac for lamellipodia and Cdc42 for filopodia. Functions include: Muscle contraction Cell movement Intracellular transport/ ... Actin structures are controlled by the Rho family of small GTP-binding proteins such as Rho itself for contractile acto-myosin ... The same holds true for the actin-like proteins and their structure and ATP binding domain. Cytoskeletal proteins are usually ...
Rac and Cdc42), leading to their activation since Rho proteins are inactive when bound to GDP but active when bound to GTP. ... DOCK family proteins are categorised into four subfamilies based on their sequence homology: DOCK-A subfamily Dock180 (also ... members contain a RhoGEF domain to function as guanine nucleotide exchange factors to promote GDP release and GTP binding to ... DOCK (Dedicator of cytokinesis) is a family of related proteins involved in intracellular signalling networks. DOCK family ...
The GTP-binding protein Rac is the regulator of this membrane ruffling. Changes in the Polyphosphoinositide metabolism and ... Rac1 and cdc42. Some bacteria such as enteropathogenic E. coli and enterohemorrhagic E. coli can induce membrane ruffling by ... A number of actin-binding and organizing proteins localize to membrane ruffles and potentially target to transducing molecules ...
The DAD binds the N-terminal GBD; this link is broken when GTP-bound Rho binds to the GBD and activates the protein. The ... Mammalian Drf3 contains a CRIB-like motif within its GBD for binding to Cdc42, which is required for Cdc42 to activate and ... including the actin-binding protein profilin, SH3 (Src homology 3) domain proteins, and WW domain proteins. The actin ... The FH2 domain is required for the self-association of formin proteins through the ability of FH2 domains to directly bind each ...
This protein has been shown to bind both CDC42 and TC10 GTPases in a GTP-dependent manner. When overexpressed in fibroblasts, ... "Entrez Gene: CDC42EP4 CDC42 effector protein (Rho GTPase binding) 4". Human CDC42EP4 genome location and CDC42EP4 gene details ... The product of this gene is a member of the CDC42-binding protein family. Members of this family interact with Rho family ... Cdc42 effector protein 4 is a protein that in humans is encoded by the CDC42EP4 gene. ...
... is a GTPase activating protein specific for RAC GTP-binding proteins. It is expressed primarily in the brain and may ... CHN1 is transferred to the plasma membrane and negatively regulates Rho-family small GTPases RAC1 and CDC42, thus causing the ... Buttery P, Beg AA, Chih B, Broder A, Mason CA, Scheiffele P (February 2006). "The diacylglycerol-binding protein α1-chimaerin ... the C-terminal RhoGAP domain and the central C1 domain similar to protein kinase C. When lipid diacylglycerol (DAG) binds to ...
The cooperative binding of CDC42 and PIP2 is thermodynamically favored; binding of one enhances binding of the other. CDC42 and ... WASp and N-WASP are analogs, they contain an N-terminal EVH1 domain, a C-terminal VCA domain and central B and GBD (GTP binding ... "Cdc42-interacting protein 4 mediates binding of the Wiskott-Aldrich syndrome protein to microtubules". The Journal of ... "Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the ...
... functions to enhance the GTPase activity of the Rho-GTPase proteins RhoA and Cdc42, promoting the hydrolysis of their bound GTP ... its ability to enhance activated GTP-bound Rho-GTPases' (specifically, RhoA and Cdc42) intrinsic ability to convert their GTP ... Constitutive activation of Cdc42 due to the absence of RhoGAP proteins such as DLC1 will contribute to the continual repetition ... Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans ...
Wang KL, Roufogalis BD (May 1999). "Ca2+/calmodulin stimulates GTP binding to the ras-related protein ral-A". The Journal of ... RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity". The Journal of Biological Chemistry. 270 (38): 22473 ... "Identification and characterization of a novel protein interacting with Ral-binding protein 1, a putative effector protein of ... "Identification and characterization of a novel protein interacting with Ral-binding protein 1, a putative effector protein of ...
... interacting only with the GTP bound forms of rho and rac 1. Displaying a distinctive protein organization, this protein defines ... myotonic dystrophy protein kinase (MDPK) and the CDC42 effector known as MRCK or GEK. Citron kinase, which resembles the ROCK ... This GTPase cycles between an inactive GDP-bound form and an active GTP-bound form, and this RhoA flux seems important for ... Madaule P, Furuyashiki T, Reid T, Ishizaki T, Watanabe G, Morii N, Narumiya S (Dec 1995). "A novel partner for the GTP-bound ...
... small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular ... GDI1 has been shown to interact with CDC42. GRCh38: Ensembl release 89: ENSG00000203879 - Ensembl, May 2017 GRCm38: Ensembl ... "Molecular cloning and characterization of a novel type of regulatory protein (GDI) for smg p25A, a ras p21-like GTP-binding ... GDIs slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound rabs. GDI1 is expressed ...
... a domain found in members of the Rho family of GTP-binding proteins. Functional studies in mice determined that this protein ... "Vestibular dysgenesis in mice lacking Abr and Bcr Cdc42/RacGAPs". Dev. Dyn. 223 (4): 517-25. doi:10.1002/dvdy.10071. PMID ... ABR, RhoGEF and GTPase activating protein is a protein that in humans is encoded by the ABR gene. This gene encodes a protein ... The protein encoded by this gene contains a GTPase-activating protein domain, ...
... belongs to a family of Rho-like GTPases that act as molecular switches by cycling from the active GTP-bound state to ... the inactive GDP-bound state. These proteins are key regulators of the actin cytoskeleton and are involved in cell signaling.[ ... "Entrez Gene: ARHGEF9 Cdc42 guanine nucleotide exchange factor (GEF) 9". Kins S, Betz H, Kirsch J (2000). "Collybistin, a newly ... "Identification of a gephyrin-binding motif in the GDP/GTP exchange factor collybistin". Biol. Chem. 382 (10): 1455-62. doi: ...
The cooperative binding of CDC42 and PIP2 is thermodynamically favored; binding of one enhances binding of the other.[9] CDC42 ... WASp and N-WASP are analogs, they contain an N-terminal EVH1 domain, a C-terminal VCA domain and central B and GBD (GTP binding ... SH3 domain binding. • protein binding. • identical protein binding. • actin binding. • protein kinase binding. • small GTPase ... "Cdc42-interacting protein 4 mediates binding of the Wiskott-Aldrich syndrome protein to microtubules". The Journal of ...
transcription factor binding. • GTP-dependent protein binding. • ‏GO:0001948 ربط بروتيني. • Rho GTPase binding. • protein ... "The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and ... "The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42.". Nat. Cell Biol. 2 (8): 531-9. PMID 10934474 ... Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein ...
"Regulator of G protein signalling"). Receptors stimulate GTP binding (turning the G protein on). RGS proteins stimulate GTP ... Wikimedia Commons has media related to G proteins.. *GTP-Binding Proteins at the US National Library of Medicine Medical ... G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside ... They are small (20-kDa to 25-kDa) proteins that bind to guanosine triphosphate (GTP). This family of proteins is homologous to ...
GBD domain binding. • profilin binding. • nucleotide binding. • GTP binding. • GTPase activity. • protein kinase binding. ... "The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42". Nat. Cell Biol. 2 (8): 531-9. doi:10.1038/ ... "Small GTP-binding protein TC10 differentially regulates two distinct populations of filamentous actin in 3T3L1 adipocytes". Mol ... GTP metabolic process. • small GTPase mediated signal transduction. • negative regulation of protein localization to plasma ...
... interacting only with the GTP bound forms of rho and rac 1. Displaying a distinctive protein organization, this protein defines ... myotonic dystrophy protein kinase (MDPK) and the CDC42 effector known as MRCK or GEK.[8] Citron kinase, which resembles the ... protein kinase activity. • PDZ domain binding. • SH3 domain binding. • scaffold protein binding. • metal ion binding. • kinase ... protein serine/threonine kinase activity. • GO:0001948 protein binding. • ATP binding. • Rho GTPase binding. ...
G protein signaling is terminated by hydrolysis of bound GTP to bound GDP.[2][3] This can occur through the intrinsic GTPase ... bound to GTP) only for a short time before deactivating themselves by converting bound GTP to bound GDP.[2][3] However, many ... Artificial GTP analogues like GTP-γ-S, β,γ-methylene-GTP, and β,γ-imino-GTP that cannot be hydrolyzed can lock the GTPase in ... They are also called small or monomeric guanine nucleotide-binding regulatory proteins, small or monomeric GTP-binding proteins ...
GTP-binding protein regulators. *see GTP-binding protein regulators. Other. *Activating transcription factor 6 ... Cyclins, when bound with the dependent kinases, such as the p34/cdc2/cdk1 protein, form the maturation-promoting factor. MPFs ... S cyclins bind to Cdk and the complex directly induces DNA replication. The levels of S cyclins remain high, not only ... Protein cyclin A governs this process by keeping the process going until the errors are eliminated. In normal cells, persistent ...
enzyme binding. • protein binding. • thioesterase binding. • protein kinase binding. • nucleotide binding. • GTP binding. • Rab ... Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein ... histone deacetylase binding. • Rho GDP-dissociation inhibitor binding. • GTP-dependent protein binding. • GTPase activity. • ... "Interaction of Nck-associated protein 1 with activated GTP-binding protein Rac". The Biochemical Journal. 322 (3): 873-8. doi: ...
Hall, A. (1994). „Small GTP-binding proteins and the regulation of actin cytoskeleton". Annu. Rev. Cell Biol. 10: 31-54. PMID ... Ras · Rab (Rab27) · Arf (Arf6) · Ran · Rheb · Ro familija (RhoA, RhoB, CDC42, Rac1) · Rap ... Tipični G-protein je aktivan kada je vezan za GTP i neaktivan kad je vezan za GDP (i.e. kad je GTP hidrolizovan do GDP). GDP ... look at the regulation of Ras-related GTP-binding proteins". Curr. Opin. Struct. Biol. 7: 786-792. PMID 9434896.. ...
GDP binding. • GO:0032403 macromolecular complex binding. • GTP binding. • GMP binding. • GO:0001948 protein binding. • GTPase ... "Stimulation of Ras guanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm) upon tyrosine phosphorylation by the Cdc42- ... to a molecule of GTP. The K-Ras protein is turned off (inactivated) when it converts the GTP to GDP. When the protein is bound ... it is unlikely that drug-like small molecule inhibitors could compete with GTP/GDP binding. Other than where GTP/GDP binds, ...
Rho-related GTP-binding protein RhoJ is a protein that in humans is encoded by the RHOJ gene. ARHJ belongs to the Rho family of ... 2005). "Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes". ... small GTP-binding proteins. Rho proteins regulate the dynamic assembly of cytoskeletal components for several physiologic ... 2004). "The GTP/GDP Cycling of Rho GTPase TCL Is an Essential Regulator of the Early Endocytic Pathway". Mol. Biol. Cell. 14 ( ...
GTP-bound Cdc42, although this interaction required a small N-terminal region of Dock11 in addition to the DHR2 domain. Cdc42 ... Dock11 activates the small G protein Cdc42. Dock11 was identified as a protein which is highly expressed in Germinal center B ... Dock11 binds and activates nucleotide-free Cdc42 via its DHR2 domain and has also been reported to mediate positive feedback on ... Côté JF, Vuori K (August 2007). "GEF what? Dock180 and related proteins help Rac to polarize cells in new ways". Trends in Cell ...
A typical G-protein is active when bound to GTP and inactive when bound to GDP (i.e. when the GTP is hydrolyzed to GDP). The ... the human homolog of the yeast cell cycle gene CDC42". Mol Cell Biol. 10 (11): 5977-82. doi:10.1128/MCB.10.11.5977. ISSN 0270- ... GTP-binding protein regulators Wennerberg K, Rossman KL, Der CJ (March 2005). "The Ras superfamily at a glance". J. Cell Sci. ... Therefore, a G-protein can be switched on and off. GTP hydrolysis is accelerated by GTPase activating proteins (GAPs), while ...
... and their state of phosphorylation determines which proteins can bind. While many of the key polarity proteins are well ... For polarity sites to form, Cdc42 must be present and capable of cycling GTP, a process regulated by its guanine nucleotide ... Examples include the PAR complex (Cdc42, PAR3/ASIP, PAR6, atypical protein kinase C), Crumbs complex (Crb, PALS, PATJ, Lin7), ... PAR-1, the C. elegans-specific ring-finger-containing protein PAR-2, and LGL-1 (called posterior PAR proteins) are present ...
Logothetis DE, Kurachi Y, Galper J, Neer EJ, Clapham DE (1987). "The beta gamma subunits of GTP-binding proteins activate the ... "Heterotrimeric G protein betagamma subunits stimulate FLJ00018, a guanine nucleotide exchange factor for Rac1 and Cdc42". The ... and is a component of heterotrimeric G proteins. Heterotrimeric G proteins, also called guanosine nucleotide-binding proteins, ... Brandt DR, Ross EM (January 1985). "GTPase activity of the stimulatory GTP-binding regulatory protein of adenylate cyclase, Gs ...
... activates Cdc42 by exchanging GDP bound to Cdc42 for GTP and regulates the recruitment of Cdc42 to Golgi membranes. Levels ... "Faciogenital dysplasia protein (FGD1) regulates export of cargo proteins from the golgi complex via Cdc42 activation". Mol. ... The DH domain is required for the activation of Cdc42, through the catalytic exchange of GDP with GTP on Cdc42, while the PH ... The prolin-rich domain interacts with cortactin and actin-binding protein 1. FYVE-finger domains are conserved through ...
When GTP-bound, Rac will cause the formation of lamellipodia, and Cdc42 will cause the formation of filopodia, thus promoting ... Ridley, Anne J.; Hall, Alan (August 1992). "The small GTP-binding protein rho regulates the assembly of focal adhesions and ... Ridley, Anne J.; Hall, Alan (August 1992). "The small GTP-binding protein rho regulates the assembly of focal adhesions and ... When bound to GTP, Rho activates Rho-associated coiled-coil forming kinase (ROCK) and mammalian homologue of Drosophila ...
Aspenström P, Lindberg U, Hall A (1996). "Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the ... Zhang B, Zheng Y (April 1998). "Regulation of RhoA GTP hydrolysis by the GTPase-activating proteins p190, p50RhoGAP, Bcr, and ... Comparison of kinetic properties of Cdc42 binding to the Cdc42-interactive domains". J. Biol. Chem. 272 (35): 21999-2007. doi: ... "Cloning and expression of a human CDC42 GTPase-activating protein reveals a functional SH3-binding domain". J. Biol. Chem. 268 ...
It is a Cdc42/Rac1 GTPase regulator. ARHGAP31 encodes a GTPase-activating protein (GAP). A variety of cellular processes are ... regulated by Rho GTPases which cycle between an inactive form bound to GDP and an active form bound to GTP. This cycling ... Lamarche-Vane N, Hall A (1998). "CdGAP, a novel proline-rich GTPase-activating protein for Cdc42 and Rac". J. Biol. Chem. 273 ( ... 2006). "The human orthologue of CdGAP is a phosphoprotein and a GTPase-activating protein for Cdc42 and Rac1 but not RhoA". ...
NHE1-mediated H+ efflux is required for guanine nucleotide exchange factor (GEF)-catalyzed GTP binding to Cdc42, suggesting a ... Bustelo XR, Sauzeau V, Berenjeno IM (2007). "GTP-binding proteins of the Rho/Rac family: regulation, effectors and functions in ... This protein cannot be inactivated normally, through GTP hydrolysis, and is thus "stuck on". When a Rho protein activated in ... Because Rho proteins are G-proteins and plasma membrane bound, their location can be easily controlled. In each situation, ...
Davidson MM, Haslam RJ (1994). "Dephosphorylation of cofilin in stimulated platelets: roles for a GTP-binding protein and Ca2+ ... "Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha". J. Biol. Chem. 276 (25): 23092-6. ... Saito Y, Doi K, Yamagishi N, Ishihara K, Hatayama T (Feb 2004). "Screening of Hsp105alpha-binding proteins using yeast and ... Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and ...
... encoding protein FAM227A FBLN1 GTPBP1: GTP-binding protein 1 [email protected] IGLJ3 encoding protein Immunoglobulin lambda joining 3 ... encoding chromobox protein homolog 7 CDC42EP1: CDC42 effector protein 1 CECR1: Cat eye syndrome critical region protein 1 CHEK2 ... encoding protein Thyrotroph embryonic factor THAP7: encoding protein THAP domain-containing protein 7 THOC5: encoding protein ... ADM2: encoding protein ADM2 APOBEC3B: encoding protein Probable DNA dC->dU-editing enzyme APOBEC-3B ARFGAP3: encoding protein ...
The binding to receptors activates a signaling pathway involving some proteins of the small GTPase system (Cdc42, Rac, RhoA, ... This GTPase belongs to the superfamily of small GTP hydrolases, whose members play key roles in the amoeboid type of invasion, ... It was shown that ZEB1 and ZEB2 proteins with a zinc finger domain are able to directly bind to promoters, thereby inducing the ... This protein is known to be involved in the regulation of developing invadopodias, which are structures typical of malignant ...
... to activate small GTPases of the Rho family by facilitating release of GDP from an inactive Rho GTPase and binding of GTP to ... The DBL proto-oncogene is a protein that in humans is encoded by the MCF2 gene. The commonly-used name DBL is derived from " ... In particular, DBL activates the Rho family member Cdc42. Gene recombinations that result in the loss of N-terminal regions ... Srivastava SK, Wheelock RH, Aaronson SA, Eva A (December 1986). "Identification of the protein encoded by the human diffuse B- ...
GTP-binding proteins then were added. To avoid light scattering from the beads, GTP-binding proteins used here were eluted by ... Extracts were stimulated by Cdc42-GTPγS (25 nM), Cdc42-GDPβS (25 nM), and Rho-GTPγS (50 nM) (left) or by Cdc42-GTPγS at ... Actin polymerization also depends on the nucleotide bound to Cdc42: GTPγS-charged Cdc42 was active, but GDPβS-charged Cdc42 was ... The Arp2/3 complex mediates actin polymerization induced by the small GTP-binding protein Cdc42. Le Ma, Rajat Rohatgi, and Marc ...
The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway.. Coso OA1, Chiariello M ... GTP-Binding Proteins. *cdc42 GTP-Binding Protein, Saccharomyces cerevisiae. *rac GTP-Binding Proteins ... Taken together, these findings strongly support a critical role for Rac1 and Cdc42 in controlling the JNK signaling pathway. ... c-Jun amino-terminal kinases (JNKs) and mitogen-activated protein kinases (MAPKs) are closely related; however, they are ...
Functional analysis of the interaction between the small GTP binding protein Cdc42 and the Ste20 protein kinase in yeast.. ... but it has been demonstrated recently that binding of the small GTP binding protein Cdc42 is able to activate Ste20 in vitro. ... In contrast, a Ste20 mutant protein unable to bind Cdc42 was found diffusely throughout the cytoplasm, suggesting that Cdc42 is ... suggesting that binding of Cdc42 and Ste20 was not required to activate Ste20. Wild-type Ste20 protein was visualized as a ...
cdc42 GTP-Binding Protein [D12.776.157.325.515.700.050]. *cdc42 GTP-Binding Protein, Saccharomyces cerevisiae [D12.776.157.325. ... cdc42 GTP-Binding Protein [D12.644.360.525.700.050]. *cdc42 GTP-Binding Protein, Saccharomyces cerevisiae [D12.644.360.525. ... cdc42 GTP-Binding Protein [D12.776.476.525.700.050]. *cdc42 GTP-Binding Protein, Saccharomyces cerevisiae [D12.776.476.525. ... cdc42 GTP-Binding Protein, Saccharomyces cerevisiae*cdc42 GTP-Binding Protein, Saccharomyces cerevisiae ...
GTP binding protein, 25kDa)), Authors: Fátima Valdés-Mora, Teresa Gómez del Pulgar, Juan Carlos Lacal. Published in: Atlas ... BCL7A--CDC42 BTD--CDC42 C11ORF96--CDC42 CDC42--ABCF2 CDC42--ACK CDC42--CAPZB CDC42--CELA3A CDC42--CELA3B CDC42--CLEC2D CDC42-- ... CDC42 PRDM16--CDC42 RABEP1--CDC42 RAC--CDC42 RAC1--CDC42 RNF38--CDC42 STAU2--CDC42 TAOK1--CDC42 TC10--CDC42 TFRC--CDC42 USP48-- ... CDC42 GRHL2--CDC42 GRHL3--CDC42 HNRNPC--CDC42 IL1R2--CDC42 KDM1A--CDC42 KIF1B--CDC42 KLHL21--CDC42 LGALS3--CDC42 LRRC47--CDC42 ...
... "cdc42 GTP-Binding Protein" by people in this website by year, and whether "cdc42 GTP-Binding Protein" was a major or minor ... cdc42 GTP-Binding Protein*cdc42 GTP-Binding Protein. *GTP-Binding Protein, cdc42 ... G25K GTP-Binding Protein, Placental Isoform*G25K GTP-Binding Protein, Placental Isoform ... "cdc42 GTP-Binding Protein" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ...
G proteins. GTP-binding proteins, GDI, guanine-nucleotide dissociation inhibitor. GEF. guanine-nucleotide exchange factor. NBD ... GTPγS is an agonist with a broad spectrum and can activate any GTP-binding proteins in the extracts. To determine whether the ... Corequirement of Specific Phosphoinositides and Small GTP-binding Protein Cdc42 in Inducing Actin Assembly in Xenopus Egg ... Corequirement of Specific Phosphoinositides and Small GTP-binding Protein Cdc42 in Inducing Actin Assembly in Xenopus Egg ...
Atypical Protein Kinases Cλ and -ζ Associate with the GTP-Binding Protein Cdc42 and Mediate Stress Fiber Loss. Matthew P. ... GST-Cdc42 associates with aPKC in rat brain cytosol.GST fusions of the Rho family GTP-binding proteins RhoA, Rac1, and Cdc42 ... V12 Cdc42 bound well to aPKCs, wild-type Cdc42 bound less well, and little binding was detected with N17 Cdc42. The V12/T35A ... Atypical Protein Kinases Cλ and -ζ Associate with the GTP-Binding Protein Cdc42 and Mediate Stress Fiber Loss ...
Activation of Other Small G Proteins by Ang II. Cdc42 Activation by Ang II. Cdc42 regulates formation of filopodia in the ... Small GTP-binding proteins (G proteins) are monomeric G proteins with a low molecular weight of 20 to 40 kDa. A small G protein ... Also, eIF4E is released from eIF4E binding protein/PHAS-I on phosphorylation of eIF4E binding protein/PHAS-I regulated through ... Angiotensin II Signal Transduction Through Small GTP-Binding Proteins. Haruhiko Ohtsu, Hiroyuki Suzuki, Hidekatsu Nakashima, ...
... detectable GTPase activity but its high intrinsic guanine nucleotide exchange activity suggests it is constitutively GTP-bound ... Cdc42 protein signal transduction Source: GO_CentralInferred from biological aspect of ancestori*21873635 ... GTP-binding, Magnesium, Metal-binding, Nucleotide-binding. Enzyme and pathway databases. Reactome - a knowledgebase of ... Rho-related GTP-binding protein RhoUAdd BLAST. 258. Amino acid modifications. Feature key. Position(s). DescriptionActions. ...
CLIP-170 binds to the growing ends of microtubules and plays pivotal roles in orientation. We have found that IQGAP1, an ... effector of Rac1 and Cdc42, interacts with CLIP-170. In Vero fibroblasts, IQGAP1 localizes … ... cdc42 GTP-Binding Protein / metabolism* * rac1 GTP-Binding Protein / metabolism* * ras GTPase-Activating Proteins* ... Furthermore, expression of an IQGAP1 mutant defective in Rac1/Cdc42 binding induces multiple leading edges. These results ...
cdc42 GTP-Binding Protein / physiology * rac GTP-Binding Proteins / physiology * rho GTP-Binding Proteins / physiology ... Cdc42 activity is also not required for closure. Inhibition of Rho or Cdc42 results, however, in statistically significant ... cdc42 GTP-Binding Protein * rac GTP-Binding Proteins * rho GTP-Binding Proteins ... Although Rho and Cdc42 activities are not required for closure, they have a role in determining the regularity of closure. ...
protein binding. • thioesterase binding. • protein kinase binding. • nucleotide binding. • GTP binding. • identical protein ... "Protein Data Bank in Europe. EMBL-EBI. Retrieved 2016-04-22.. *^ "CDC42 (cell division cycle 42 (GTP binding protein, 25kDa))" ... Wikimedia Commons has media related to CDC42.. *cdc42+GTP-Binding+Protein at the US National Library of Medicine Medical ... ubiquitin protein ligase activity. • apolipoprotein A-I receptor binding. • GTP-dependent protein binding. • GTPase activity. • ...
... cdc42 GTP-Binding Proteincdc42 GTP-Binding Protein, Saccharomyces cerevisiae • Cell Membrane Permeability • Cell Polarity • ... Protein BindingProtein Isoforms • Protein Transport • Quail • Rats • Rats, Inbred SHR • Rats, Wistar • Renal Circulation • ... Saccharomyces cerevisiae • Saccharomyces cerevisiae Proteins • Septins • Signal Transduction • SNARE Proteins • Sodium • Sodium ... Membrane Transport Proteins • Mice • Microvessels • Models, Animal • Models, Biological • Models, Statistical • Models, ...
... cdc42 GTP-Binding Proteincdc42 GTP-Binding Protein, Saccharomyces cerevisiae • Cell Membrane Permeability • Cell Polarity • ... Protein BindingProtein Isoforms • Protein Transport • Quail • Rats • Rats, Inbred SHR • Rats, Wistar • Renal Circulation • ... Saccharomyces cerevisiae • Saccharomyces cerevisiae Proteins • Septins • Signal Transduction • SNARE Proteins • Sodium • Sodium ... Membrane Transport Proteins • Mice • Microvessels • Models, Animal • Models, Biological • Models, Statistical • Models, ...
Purchase G Protein Pathways, Part C: Effector Mechanisms, Volume 345 - 1st Edition. Print Book & E-Book. ISBN 9780121822460, ... Section VI: Small GTP-Binding Proteins: Assay of Cdc42, Rac, and Rho GTPase Activation by Affinity Methods. Assays of ADP- ... Regulation of Mitogen-Activated Protein Kinases by G-Protein-Coupled Receptors. Analysis of Protein Kinase B/Akt. Direct ... Overexpression of Tightly Regulated Proteins: Protein Phosphatase 2A Overexpression in NIH 3T3 Cells. Monitoring G-Protein- ...
Nucleotide binding to the G12V-mutant of Cdc42 investigated by X-ray diffraction and fluorescence spectroscopy: two different ... G25K GTP-BINDING PROTEIN protein, length: 191 (BLAST) Sequence Similarity Cutoff. Rank. Chains in Cluster. Cluster ID / Name. ... Structures of protein chains with identical sequences (sequence identity > 95%) are aligned, superimposed and clustered. ... This allows for the easy identification of regions and types of structural flexibility present in a protein of interest. ...
Cdc42 Gtp-binding Protein, Saccharomyces Cerevisiae. A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS from ... Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the ... Silent Information Regulator Proteins, Saccharomyces Cerevisiae. A set of nuclear proteins in SACCHAROMYCES CEREVISIAE that are ... Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at ...
Cdc42 antibody validated for WB. Referenced in 1 publication. Immunogen corresponding to synthetic peptide ... Ras like protein TC25 antibody. *Small GTP binding protein Cdc42 antibody. *TC25 antibody ... Cdc42/Rac is an important upstream regulator of the protein kinase cascade that controls the SAPK/JNK and p38 activity. Recent ... ab18758 detects recombinant human Rac and cdc42 proteins (Rho subfamily), and does not cross-react with members of the Ras or ...
FRZB (Frizzled-Related Protein): FRZB antibodies FRZB ELISA Kits FRZB Proteins IGFBP4 (Insulin-Like Growth Factor Binding ... This protein is highly similar to Saccharomyces cerevisiae Cdc 42, and is able to complement the yeast cdc42-1 mutant. The ... Protein 4): IGFBP4 antibodies IGFBP4 ELISA Kits IGFBP4 Proteins IGFBP5 (Insulin-Like Growth Factor Binding Protein 5): IGFBP5 ... IGFBP6 (Insulin-Like Growth Factor Binding Protein 6): IGFBP6 antibodies IGFBP6 ELISA Kits IGFBP6 Proteins ...
This protein is highly similar to Saccharomyces cerevisiae Cdc 42, and is able to complement the yeast cdc42-1 mutant. The ... FRZB (Frizzled-Related Protein): FRZB Antikörper FRZB ELISA Kits FRZB Proteine IGFBP4 (Insulin-Like Growth Factor Binding ... The protein encoded by this gene is a receptor protein tyrosine kinase and type I transmembrane protein that belongs to the ROR ... This protein also acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and was ...
0 (Cadherins); 0 (beta Catenin); EC (cdc42 GTP-Binding Protein). ... Prote na cdc42 de Liga o ao GTP/metabolismo. [Mh] Termos MeSH secund rio:. Animais. Caderinas/metabolismo. Ades o Celular. ... 0 (Membrane Proteins); 0 (PGRMC1 protein, mouse); 0 (PGRMC2 protein, mouse); 0 (Receptors, Progesterone). ... Trp-Asp (WD) repeat domain 1 (WDR1) is a highly conserved actin-binding protein across all eukaryotes and is involved in ...
Ack1 was identified as a 120-kDa protein that interacts with activated GTP-bound Cdc42. Structural studies have revealed sites ... ligand binding, nuclear translocation, DNA binding, and protein-protein interactions). The amino-terminal 485 amino acids of AR ... Subsequently, Ack1 binds and phosphorylates AR protein. The AR-Ack1 complex translocates to the nucleus and binds to the AREs ... TAD, transactivation domain; DBD, DNA-binding domain; LBD, ligand-binding domain. (D) Purified GST-AR and GST-cAR proteins were ...
The role of GTP-Binding Proteins in Endothelial Signaling. The effect of TNF on rac and Cdc42 on cell-cell adhesion and ... The effects of junctional protein phosphorylation on endothelial signaling and dysfunction.. *Robert Wood Johnson Minority ... Novel Roles for Junctional Proteins. Vascular endothelial cadherin and vascular endothelial growth factor signaling ...
EC GTP-Binding Protein, Saccharomyces cerevisiae From MEDLINE®/PubMed®, a database of the U.S. National Library ...
Categories: cdc42 GTP-Binding Protein Image Types: Photo, Illustrations, Video, Color, Black&White, PublicDomain, ...
This protein is highly similar to Saccharomyces cerevisiae Cdc 42, and is able to complement the yeast cdc42-1 mutant. The ... Microtubule associated proteins like MAP1, MAP2, MAP4, or MAPtau bind polymerized microtubules stabilize the polymerized form, ... Several common GTPase families like Rac and Rho promote microtubule assembly indirectly by facilitating GDP/GTP exchange on ... RHOA Proteins ROCK1 (rho-Associated, Coiled-Coil Containing Protein Kinase 1): ROCK1 antibodies ROCK1 ELISA Kits ROCK1 Proteins ...
CDC42. Cell division cycle 42 (GTP binding protein, 25kDa). NM_001039802. NM_001791. NM_044472. Gene Info. ... Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1). NM_018890. NM_006908. Gene Info. ... Telomeric repeat binding factor 2. NM_005652. Gene Info. TERF2IP. Telomeric repeat binding factor 2, interacting protein. NM_ ... PARP1 binding protein. NM_017915. Gene Info. PAXIP1. PAX interacting (with transcription-activation domain) protein 1. NM_ ...
Role of rop proteins in the control of plant growth and development, Russian Journal of Plant Physiology" on DeepDyve, the ... "Superfamily of monomeric GTP-binding proteins in plants: 1. ... Proteins That Require the Cdc42/Rac-Interactive Binding Motif ... Superfamily of monomeric GTP-binding proteins in plants: 1. Role of rop proteins in the control... Novikova, G.; Moshkov, I. ... Superfamily of monomeric GTP-binding proteins in plants: 1. Role of rop proteins in the control of plant growth and development ...
  • Biochemical studies of CDC42 show that, in response to external signals originating from cell surface receptors and cell adhesion molecules, GEFs engage CDC42 and form macromolecular complexes with scaffolding proteins and/or kinases and with specific effector molecules triggering a signalling cascade to direct cellular responses (Cerione, 2004). (
  • Most signals transmitted by Rho family members depend on the association of effector proteins with the GTP-bound form of Rac, Rho, or Cdc42. (
  • Recent efforts have focused on identifying the immediate effector molecules that interact with the activated GTP-binding proteins. (
  • Ras mediates its effect on cell proliferation mainly by activation of its effector Raf to initiate the mitogen-activated protein kinase (MAPK/extracellular signal regulated kinase [ERK]) cascade. (
  • In addition, reduced nicotinamide-adenine dinucleotide phosphate oxidase is known as a Rac effector and p70 S6 kinase (p70S6K) as a Cdc42 effector. (
  • We have found that IQGAP1, an effector of Rac1 and Cdc42, interacts with CLIP-170. (
  • Like other small GTPases, Cdc42 binds effector proteins in its active, GTP-bound state. (
  • For successful infection and replication, many pathogens hijack the cytoskeleton using effector proteins introduced into the host cytosol by specialized secretion systems. (
  • Our laboratory and others have identified protein kinase Cι (PKCι) as an important effector of oncogenic K-ras in vitro and in vivo ( 5 - 11 ). (
  • 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 ). (
  • 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 ). (
  • Selectively, Yersinia enterocolitica strains producing the effector protein Yersinia outer protein P (YopP) hampered NF-κB activation and subsequently conferred apoptosis to J774A.1 macrophages. (
  • A broad range of bacterial pathogens, including the Gram-negative bacterium Yersinia , uses a so-called type III protein secretion machinery to deliver bacterial effector proteins into the host cell for modulation of cellular functions. (
  • The type III protein secretion machinery of Yersinia and a set of six effector Yersinia outer proteins (Yops) 3 (YopE, YopH, YopM, YopO/YpkA, YopP/YopJ, YopT) are encoded by a 70-kb virulence plasmid that is common to the three pathogenic Yersinia species ( 1 ). (
  • In active state binds to a variety of effector proteins to regulate cellular responses. (
  • Using the yeast two hybrid system and overlay assays we identified a putative rholrac effector, citron, which interacts with the GTP-bound forms of rho and rac1, but not with cdc42. (
  • GTP-bound Rac1 activates a large number of effector proteins and promotes various signaling pathways. (
  • During infection, several injected effector proteins promote bacterial internalization, and interfere with multiple host cell responses. (
  • Finally, we showed that S. flexneri effector OspF affected the phosphorylation of several hundred proteins, thereby demonstrating the wide-reaching impact of a single bacterial effector on the host signaling network. (
  • During the infectious process, bacteria use a sophisticated delivery system, the type III secretion apparatus, to inject multiple effector proteins that subvert cellular and immune functions of macrophages and epithelial cells ( 2 ). (
  • The entry of S. flexneri into epithelial cells is a multistep process that requires the secretion of effector proteins into the cytoplasm of target cells via type III secretion. (
  • We propose a role for Mbt as a downstream effector of Cdc42 in photoreceptor cell morphogenesis. (
  • The Ysc TTSS and the Yop effector proteins it exports are encoded by genes located on plasmid pYVe8081. (
  • Additionally, CDC42 can be phosphorylated by diverse kinases which regulate its interaction with RhoGDIs (Forget et al. (
  • Both the Rho family of low-molecular-weight GTP-binding proteins and protein kinases C (PKCs) mediate responses to a variety of extracellular and intracellular signals. (
  • A number of direct targets have been identified, including protein serine/threonine and tyrosine kinases, a protein phosphatase, lipid kinases, and adapter proteins. (
  • Protein kinases C (PKCs) regulate many of the same pathways regulated by Rho family GTP binding proteins. (
  • Multiple downstream effectors of small G proteins, some of them being protein kinases, have been identified. (
  • Activated Cdc42 activates by conformational changes [4] p21-activated kinases PAK1 and PAK2 , which in turn initiate actin reorganization and regulate cell adhesion, migration, and invasion. (
  • Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. (
  • In the case of αPIX, its SH3 domain binds to partner proteins with appropriate polyproline motifs, and particularly to group I p21-activated kinases (PAKs) (PAK1, PAK2 and PAK3). (
  • This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon. (
  • BACKGROUND: Ras-mediated transformation of mammalian cells has been shown to activate multiple signalling pathways, including those involving mitogen-activated protein kinases and the small GTPase Rho. (
  • CELLULAR protein kinases are key mediators of information transfer within eukaryotic cells in response to a variety of signals. (
  • It is demonstrated that, in etiolated pea ( Pisum sativum ) epicotyls, ethylene affects the activation of both monomeric GTP-binding proteins (monomeric G-proteins) and protein kinases. (
  • They involve protein kinases mTORC1, activated by amino acid supplementation, and GCN2, activated by amino acid starvation. (
  • These two kinases play a major role in the control of protein synthesis ( 71 ), transcription, and mRNA turnover of specific genes ( 24 , 46 , 69 ). (
  • PAK2 is a member of a family of p21-activated serine/threonine protein kinases (PAKs) composed of six mammalian isoforms ( 3 ). (
  • p21 protein (Rac1/Rac)-activated kinases 1-3 ( PAK1 , PAK2 , PAK3 ) are known as downstream targets of Rac1 . (
  • This gene encodes a family member of serine/threonine p21-activating kinases, known as PAK proteins. (
  • p21-activated kinases are serine-threonine kinases that serve as targets for the small GTP binding proteins Cdc42 and Rac1 and have been implicated in different morphogenetic processes through remodeling of the actin cytoskeleton such as synapse formation and neuritogenesis. (
  • The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. (
  • Both phosphoinositides and small GTP-binding proteins of the Rho family have been postulated to regulate actin assembly in cells. (
  • These results indicate that Cdc42 and Rac use different pathways to regulate stress fibers. (
  • Vesicle trafficking and cell polarity are two processes Cdc42 is known to regulate. (
  • In metazoan cells, Cdc42 can regulate several steps in the biosynthetic as well as endocytotic and recycling pathways. (
  • The primary signal relay systems studied in the lab involve the mitogen activated protein kinase (MAPK) pathways and how they regulate gene expression, cell growth, development and apoptosis. (
  • The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellular processes. (
  • however, the molecular mechanisms by which integrins and various signaling proteins regulate cell spreading are not fully defined. (
  • This protein could regulate actin polymerization through its direct binding to Neural Wiskott-Aldrich syndrome protein (N-WASP), which subsequently activates Arp2/3 complex. (
  • Rab 3A) and ADP-ribosylation factor 6 (ARF6) subfamilies of G-proteins are known to regulate intracellular vesicle trafficking, and the Ran family participates in the regulation of nuclear transport of macromolecules and plays a crucial role in providing directionality to this trafficking process ( 1 , 2 ). (
  • Fibroblast growth factor receptor 1 ( FGFR1 ) can regulate activity of CDC42 by binding to BCL2/adenovirus E1B 19kDa interacting protein 2 ( NIP2 ) coupled with Rho GTPase activating protein 1 ( RhoGAP1 ) and removing their inhibitory GAP activity from CDC42 [ 27 ]. (
  • VEGFs are a family of proteins that are crucial to regulate vascular development in the embryo and angiogenesis during tissue repair in adults. (
  • Fibroblast growth factor homologous factors and the islet brain-2 scaffold protein regulate activation of a stress-activated protein kinase. (
  • In contrast, mutationally activated Rac1 and Cdc42 GTPases potently activate JNK without affecting MAPK, and oncogenic guanine nucleotide exchange factors for these Rho-like proteins selectively stimulate JNK activity. (
  • Furthermore, expression of inhibitory molecules for Rho-related GTPases and dominant negative mutants of Rac1 and Cdc42 block JNK activation by oncogenic exchange factors or after induction by inflammatory cytokines and growth factors. (
  • Taken together, these findings strongly support a critical role for Rac1 and Cdc42 in controlling the JNK signaling pathway. (
  • Rho family GTP-binding protein family members Rac1 and Cdc42, activated via DHPH RhoGEF domain. (
  • The small GTP binding proteins Rac1 and Cdc42 are also regulators of cell spreading. (
  • In addition, fluorescence recovery after photobleaching results indicate that Rac1 and Cdc42 have different dynamics at the membrane. (
  • Thus, Rac1 and Cdc42, although highly similar to one another, have different roles in C. albicans development. (
  • Altogether, our results indicate that although they are highly similar to one another, Rac1 and Cdc42 have fundamentally different roles in C. albicans development. (
  • Syk tyrosine kinase activity is required for FcgammaR-mediated actin assembly, which is controlled by several GTPases, including Rac1 and CDC42 [6]. (
  • Signaling from the small GTP-binding proteins Rac1 and Cdc42 to the c-Jun N-terminal kinase/stress-activated protein kinase pathway. (
  • Here we show that Ste20 functionally interacts with Cdc42 in a GTP-dependent manner in vivo: Ste20 mutants that can no longer bind Cdc42 were unable to restore growth of ste20 cla4 mutant cells. (
  • PI(4,5)P 2 interacts with several actin binding proteins. (
  • AT 1 interacts with multiple heterotrimetric G proteins, including G q/11 , G i , G 12 , and G 13 , and produces second messengers, such as inositol triphosphate, diacylglycerol, and reactive oxygen species (ROS). (
  • Ack1 was identified as a 120-kDa protein that interacts with activated GTP-bound Cdc42. (
  • Structurally, αPIX assembles as a trimer through its carboxyl-terminal coiled-coil domain, and further interacts with dimers of GIT1 or GIT2 through a nearby GIT-binding domain to form oligomeric GIT-PIX complexes. (
  • αPIX contains an amino-terminal Calponin Homology (CH) domain whose functions remain relatively poorly defined, but interacts with parvin/affixin family proteins. (
  • We report that Cdo also interacts with Bnip-2, a protein that binds the small guanosine triphosphatase (GTPase) Cdc42 and a negative regulator of Cdc42, Cdc42 GTPase-activating protein (GAP). (
  • Interacts specifically with GTP-bound RHOQ. (
  • This serine/threonine kinase interacts with the GTP-bound form of the small GTPase Cdc42 and to a lesser extent with that of Rac. (
  • A structure-function analysis of the Mbt protein in vitro and in vivo revealed that the Mbt kinase domain and the GTPase binding domain, which specifically interacts with GTP-loaded Cdc42, are important for Mbt function. (
  • CDC42 switches between an active GTP-bound state and inactive GDP-bound state. (
  • A small G protein acts as a molecular switch that cycles between inactive GDP-bound and active GTP-bound forms. (
  • Cdc42 cycles between an active GTP-bound state and an inactive GDP-bound state. (
  • Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states. (
  • CDC42 acts as binary switch by cycling between an inactive (GDP-bound) and an active (GTP-bound) conformational state. (
  • Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. (
  • The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. (
  • This proto-oncogene belongs to the RAF subfamily of the Ser/Thr protein kinase family, and maybe involved in cell growth and development. (
  • CC CDC42 subfamily. (
  • The Rho subfamily of G-proteins (e.g. (
  • CDC42 subfamily. (
  • Among these is facio-genital dysplasia-5 (FGD5), a member of a subfamily of Rho GTP-GDP exchange factors. (
  • By using affinity chromatography or yeast two-hybrid selection, many Cdc42 target proteins have been found, including PAK ( 7 ), ACK ( 8 ), Gek ( 9 ), and the Wiskott-Aldrich syndrome protein ( 10 ). (
  • Functional analysis of the interaction between the small GTP binding protein Cdc42 and the Ste20 protein kinase in yeast. (
  • STE20 encodes a protein kinase related to mammalian p65Pak which functions in several signal transduction pathways in yeast, including those involved in pseudohyphal and invasive growth, as well as mating. (
  • Yeast G-proteins mediate directional sensing and polarization behaviors in response to changes in pheromone gradient direction. (
  • 100 small G proteins have been identified in eukaryotes from yeast to humans. (
  • Here we review findings on the interplay between Cdc42 and trafficking in yeast, Caenorhabditis elegans, Drosophila and mammalian cell culture systems, and discuss recent advances in our understanding of the function of Cdc42 and two of its effectors, the WASp-Arp2/3 and Par complexes, in regulating polarized traffic. (
  • Work in yeast suggests that the polarized distribution of Cdc42, which acts here as a key polarity determinant, requires input from multiple processes including endocytosis and recycling. (
  • The rod-shaped fission yeast Schizosaccharomyces pombe has two Cdc42 guanine nucleotide exchange factors (GEFs), Scd1 and Gef1, but little is known about how they are coordinated in polarized growth. (
  • Although the microtubule cytoskeleton is normally not required for polarity maintenance in fission yeast, we show here that when scd1 function is compromised, disruption of microtubules or the polarity landmark proteins Tea1, Tea4 or Pom1 leads to disruption of polarized growth. (
  • Our results suggest a new model of fission yeast cell polarity regulation, involving coordination of 'local' (Scd1) and 'global' (Gef1) Cdc42 GEFs via microtubules and microtubule-dependent polarity landmarks. (
  • However, while Cdc24 is essential for viability, Scd1 is nonessential, as fission yeast has a second Cdc42 GEF, Gef1. (
  • The putative Cdc42p-binding domain of Ste20p, expressed as a fusion protein, binds human and yeast GTP-binding Cdc42p. (
  • This protein is highly similar to Saccharomyces cerevisiae Cdc 42, and is able to complement the yeast cdc42-1 mutant. (
  • In this study we show that overexpression of an apparent Arabidopsis ortholog of Rop1Ps , Rop1At , induces isotropic cell growth in fission yeast ( Schizosaccharomyces pombe ) and that green fluorescence protein-tagged Rop1At displays polar localization to the site of growth in yeast. (
  • To understand the biochemical pathways that link Cdc42 to the actin cytoskeleton, we have reconstituted Cdc42-induced actin polymerization in Xenopus egg extracts. (
  • PKCs and Rho family GTP-binding proteins both have effects on the actin cytoskeleton, the activation of p70 S6 kinase, the JNK pathway, and the fos and NF-κβ promoters ( 44 ). (
  • Cell polarization involves generation of spatial cues (intrinsic or extrinsic) for polarity site selection, recruitment of specific proteins to regions of plasma membrane, and reorganization of the actin and microtubule cytoskeleton and of intracellular trafficking. (
  • Overexpression of p120 catenin in fibroblasts modulates the actin cytoskeleton and promotes cell motility, yet binding to the cytoplasmic domain of coexpresssed cadherins, cell surface adhesion proteins, inhibits this effect. (
  • These small GTP-binding proteins alter the actin cytoskeleton and promote cell motility. (
  • The cytoskeleton is a three-dimensional network of polymeric proteins that provides structural support and assists numerous vital cellular functions. (
  • Rho-type G proteins are required for cytoskeleton organization in virtually all eukaryotic cells ( 13 ). (
  • We have disrupted RAC1 and show here that this G protein is not necessary for viability or actin cytoskeleton organization. (
  • Small GTP-binding proteins of the Rho family (RhoA, Cdc42, Rac1) are key regulators for the organization and turnover of the cytoskeleton, formation of cell-matrix adhesions, transcriptional control of gene expression, cell survival and proliferation. (
  • Although this remains at present a hypothesis and is not easy to define if the de-structuration of the cytoskeleton is a secondary effect of simvastatin treatment or the inhibition of post-translational protein modification have a precise role in the structuration of actin cytoskeleton, we speculate that these signal variations could inhibit the expression of certain stemness genes, which could therefore be considered nucleoskeleton-associated and mechanically regulated genes. (
  • 16 Polarization in response to matrix-bound VEGF 17 involves remodeling of the cell cytoskeleton and endothelial matrix adhesive contacts as tip EC protrude into the surrounding matrix. (
  • It plays an essential role in control of the cell polarity, actin cytoskeleton rearrangements, protein trafficking and directed motility in a vide variety of mammalian cells [ 1 ], [ 2 ]. (
  • These proteins are critical effectors that link RhoGTPases to cytoskeleton reorganization and nuclear signaling, and they serve as targets for the small GTP binding proteins Cdc42 and Rac. (
  • The Drosophila gene mushroom bodies tiny ( mbt ) encodes a putative p21-activated kinase (PAK), a family of proteins that has been implicated in a multitude of cellular processes including regulation of the cytoskeleton, cell polarisation, control of MAPK signalling cascades and apoptosis. (
  • Localisation of PAK proteins to distinct cellular compartments appears to be an important mechanism to control their function in the reorganisation of the cytoskeleton. (
  • Combined with biochemical analysis of the proteins in MAPK signal relay systems, our studies define the role of MAPK pathways in the integrated response of cells to different stimuli and their physiological function in tissues and organs. (
  • A Cdo-Bnip-2-Cdc42 signaling pathway regulates p38alpha/beta MAPK activity and myogenic differentiation. (
  • The p38alpha/beta mitogen-activated protein kinase (MAPK) pathway promotes skeletal myogenesis, but the mechanisms by which it is activated during this process are unclear. (
  • Surprisingly, the ability of Cdc42 to induce p38 MAPK activity in suspended mouse embryonic fibroblast was impaired. (
  • Implicit in the presence of a putative MAPKKK in the transduction sequence is that protein phosphorylation via a mitogen-activated protein kinase (MAPK) cascade(s) is involved in mediating responses to ethylene. (
  • Extracellular signal-regulated protein kinase (ERK, or mitogen-activated protein kinase [MAPK]) regulatory cascades in fungi turn on transcription factors that control developmental processes, stress responses, and cell wall integrity. (
  • A series of studies suggest that Yersinia blocks macrophage TNF-α production by down-regulation of mitogen-activated protein kinase (MAPK) activities ( 3 , 4 , 5 , 6 ). (
  • 10 ) revealed that YopP/YopJ binds and inactivates members of the MAPK kinase superfamily, which function as upstream MAPK activators. (
  • We identified the mitogen-activated protein kinase (MAPK) module MEKK1/MKK7/JNK2 as the pathway responsible for ATF2 phosphorylation on the threonine 69 (Thr69) and Thr71 residues. (
  • Then, we progressed backwards up the signal transduction pathway and showed that the GTPase Rac1/Cdc42 and the protein Gα12 control the MAPK module, ATF2 phosphorylation, and AARE-dependent transcription. (
  • T cell activation following engagement of the TCR involves the coordinated activities of a diverse set of intracellular signaling pathways, including mobilization of calcium, activation of protein kinase C, and activation of Ras and Rho family GTPases, which result in the triggering of the mitogen-activated protein kinase (MAPK) 4 pathway ( 1 ). (
  • Cell division control protein 42 homolog , also known as Cdc42 , is a protein involved in regulation of the cell cycle . (
  • v-akt murine thymoma viral oncogene homolog 3 (protein kinase B gamma) [EC:2.7.1. (
  • A possible target for the subunits is Ste20p, whose structural homolog, the serine/threonine kinase PAK, is activated by GTP-binding p21s Cdc42 and Rac1. (
  • RHOH (Ras Homolog Family Member H) is a Protein Coding gene. (
  • Rac1 can directly bind to Par-6 partitioning defective 6 homolog ( PARD6 ) that activates Protein kinase C, zeta ( PKC-zeta ). (
  • CDC42 acts as a signal transduction convergence point in intracellular signalling networks, and mediates multiple signalling pathways, including tyrosine kinase receptors, heterodimeric G-protein coupled receptors (GPCR), cytokine receptors, integrins, and physical and chemical stress (Etienne-Manneville, 2004). (
  • Rho family GTP-binding proteins also stimulate other signaling pathways that are important in both normal cellular function and transformation, including cell cycle progression, activation of the c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways, and regulation of transcription. (
  • Identification of the proteins that associate with activated Rho family members has been a fruitful approach to understanding their signaling pathways. (
  • In this review, we describe detailed mechanisms of signal transduction pathways of Ang II involving small G proteins in VSMCs together with their functional significances in mediating vascular remodeling. (
  • Human Cdc42 is a small GTPase of the Rho family , which regulates signaling pathways that control diverse cellular functions including cell morphology , cell migration , endocytosis and cell cycle progression. (
  • Cdc42, a highly conserved small GTPase of the Rho family, acts as a molecular switch to modulate a wide range of signaling pathways. (
  • Studies of Endogenous G-Protein-Mediated Pathways in Neurons by Whole-Cell Electrophysiology. (
  • There was evidence that Cdc42 inhibition by AZA197 treatment suppresses proliferative and pro-survival signaling pathways via PAK1-ERK signaling and reduces colon cancer cell migration and invasion. (
  • Extracellular Wnts bind a variety of different receptors, and initiate signaling in several distinct pathways. (
  • The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. (
  • The coordinated activation of Cdc42Hs, RhoG and Rac1, however, elicited a high focus-forming activity, independent of the mitogen-activated ERK and JNK protein kinase pathways. (
  • Phospholipase D (PLD) and heterotrimeric G-proteins are involved in plant signal transduction pathways at the plasma membrane. (
  • Medical nanorobots that have become bound to the extracellular phagocyte surface may attempt to inhibit either or both of these signal transduction pathways. (
  • Please note that proteins can be included in multiple pathways, ie. (
  • The 14-3-3s are a family of regulatory proteins that is present in all eukaryotes and involved in protein interactions mediating signal transduction pathways. (
  • What pathways are this gene/protein implicaed in? (
  • Specific activities of Yop effectors include host cell GTPase activation by YopE ( 1 , 45 ), protein tyrosine phosphatase activity by YopH ( 16 ), serine/threonine kinase activity by YopO (YpkA) ( 14 ), and down-regulation of mitogen-activated protein (MAP) kinase pathways by YopP (YopJ) ( 4 , 27 ). (
  • CDC42 encodes a 21.3 kDa, 191 amino acids small GTPase protein that belongs to the Rho family of Ras GTPases superfamily. (
  • The small G proteins in this superfamily are structurally classified into ≥5 families: the Ras, Rho, Rab, Sar/Arf, and Ran families. (
  • Cdc42/Rac belongs to the superfamily of small GTPases that are structurally linked to the proto-oncogene product p21ras and are important for the control of cell growth and differentiation as well as for intracellular organization. (
  • Superfamily of monomeric GTP-binding proteins in plants: 1. (
  • The protein encoded by this gene is a member of the Ras superfamily of guanosine triphosphate (GTP)-metabolizing enzymes. (
  • The Ras superfamily of G-proteins (e.g. (
  • Cell division cycle 42 ( CDC42 ) is a member of the RAS superfamily of small GTPases. (
  • The effects of junctional protein phosphorylation on endothelial signaling and dysfunction. (
  • GEF activity of Dbl towards CDC42 is enhanced upon Tyrosine kinase, non-receptor, 2 ( ACK1) -dependent phosphorylation [ 15 ], [ 16 ]. (
  • Rho GTPase-activating protein ( p200RhoGAP ) activity is stimulated by FYN oncogene related to SRC, FGR, YES ( Fyn ) phosphorylation [ 24 ]. (
  • Signal-transducing protein phosphorylation cascades mediated by Ras/Rho proteins in the mammalian cell: the potential for multiplex signalling. (
  • The onset of uptake is accompanied by tyrosine phosphorylation of several proteins, which persists for up to 3 minutes, is concentrated at phagocytic cups and nascent phagosomes, and is correlated with the accumulation of actin filaments. (
  • This event requires phosphorylation of activating transcription factor 2 (ATF2), a constitutive AARE-bound factor. (
  • JNK phosphorylation and EGFR protein levels were increased in TIMP-3 −/− cardiomyocytes and heart tissues. (
  • Vascular endothelial growth factor-stimulated Akt phosphorylation and downstream forkhead box protein-O1 inactivation is inhibited by FGD5 loss. (
  • To obtain a systems-level overview of host signaling during infection, we analyzed the global dynamics of protein phosphorylation by liquid chromatography-tandem MS and identified several hundred of proteins undergoing a phosphorylation change during the first hours of infection. (
  • Fuzzy c-means clustering identified six temporal profiles of phosphorylation and a functional module composed of ATM-phosphorylated proteins related to genotoxic stress. (
  • Seventy-two hours after infection, cells were harvested, and recombinant GST-fusion proteins were purified by using glutathione-Sepharose beads (Pharmacia) and were charged with guanosine 5′-[γ-thio]triphosphate (GTPγS) or guanosine 5′-[β-thio]diphosphate (GDPβS) as described ( 13 ). (
  • Here, the role of the small guanosine triphosphate (GTP)-binding protein CDC42Hs in these responses was examined. (
  • However, very little is known with regard to potential regulation by G-protein regulatory factors (e.g., the guanosine diphosphate-dissociation inhibitor [GDI]) of insulin secretion from the islet β-cell. (
  • The monomeric, small molecular mass guanosine triphosphate (GTP)-binding proteins (G-proteins) have been shown to play significant regulatory roles in cell proliferation, survival, and demise ( 1 , 2 ). (
  • In a manner akin to the heterotrimeric G-proteins, small G-proteins cycle between their guanosine diphosphate (GDP)-bound (inactive) and GTP-bound (active) conformations, which appear to be tightly regulated by various G-protein regulatory factors (RGFs). (
  • Blocking of mevalonate synthesis leads to inhibition of the farnesylation and geranylgeranylation of several functional proteins, such as RhoA and other small guanosine triphosphate-binding proteins, that are important in maintaining the undifferentiated status of the cells. (
  • Blocking mevalonate synthesis leads to the inhibition of farnesyl and geranylgeranyl modifications of several functional proteins, such as RhoA, a small guanosine triphosphate (GTP)-binding protein. (
  • This cycle is regulated by its intrinsic GTPase activity and its interaction with three protein families: guanine exchange factors (GEFs), guanine dissociation inhibitors (GDIs) and GTPase activating proteins (GAPs) (Bishop and Hall, 2000). (
  • The GTP/GDP cycle is mainly controlled by GTPase-activating proteins, guanine-nucleotide exchange factors (GEFs), and guanine-nucleotide dissociation inhibitors (GDIs) ( Boguski and McCormick, 1993 ). (
  • Signaling is terminated by GTPase-activating proteins (GAPs), which stimulate GTP hydrolysis and conversion of the proteins to the GDP-bound form. (
  • This process is regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. (
  • Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins. (
  • and the GTPase-activating proteins facilitate conversion of the GTP-bound to the GDP-bound form by activating the intrinsic GTPase function of candidate G-proteins. (
  • A group of proteins called GTPase-activating proteins (GAPs) inactivates CDC42 by catalyzing the hydrolysis of GTP to GDP. (
  • Rho GTPase-activating proteins are also GAPs for CDC42 . (
  • genes encoding mG-proteins were found. (
  • At a molecular level, most of the results have been obtained by studying the transcriptional regulation of the activating transcription factor 3 ( ATF3 ), C/EBP homologous protein ( CHOP ), and asparagine synthetase ( ASNS ) genes. (
  • Although several genes are considered to contribute to maintaining hyperproliferative status, we have focused on three representative stemness-related genes, Oct4, Sox2 and Nanog ( 7 - 9 ), with the aim of investigating whether simvastatin is able to modify, directly or indirectly, the expression equilibrium of these genes or influence the translation process of the respective proteins. (
  • Strikingly, the human orthologs of these three genes, activated CDC42-associated kinase (TNK2), Wiskott-Aldrich syndrome protein (WASP), and noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) are part of a known signaling pathway in mammals. (
  • The Ysa TTSS is encoded by a set of genes located on the chromosome and exports Ysp proteins. (
  • Protein-protein interaction network and module analysis suggested that some apoptosis related genes, such as PRKCA, CDC42 and BCL2 may play critical roles in striatal neurons growth. (
  • Small GTP-binding proteins (G proteins) are monomeric G proteins with a low molecular weight of 20 to 40 kDa. (
  • 5-8 Importantly, recent accumulating evidence highlighted the significance of these small G proteins as essential molecular switches that trigger many of the signal transduction and functions of Ang II. (
  • The small molecular inhibitor AZA197 has been used to inhibit Cdc42 in the treatment of KRAS mutant colorectal cancers. (
  • They are the principal components in an interconnected intracellular "highway" by which all manner cellular cargo may be shuttled via a bustling network of molecular motor proteins. (
  • Heat shock protein 90 (Hsp90) is a molecular chaperone involved in maintaining the correct conformation and stability of its client proteins. (
  • Molecular chaperones, such as heat shock protein 90 (Hsp90), enable the correct folding, maturation, and subcellular localization of their client proteins, particularly under the stress conditions induced by hypoxia and nutrient deprivation frequently found in cancers ( 11 ). (
  • With the development of imaging technologies, particularly green fluorescent protein (GFP) and its derivative fluorescent proteins (FPs), it is now convenient to visualize molecular signals at subcellular levels in live cells. (
  • 1997 ). Inhibition of oncogenic and activated wild-type ras-p21 protein-induced oocyte maturation by peptides from the ras-binding domain of the raf-p74 protein, identified from molecular dynamics calculations. (
  • The Rho small GTP-binding proteins are versatile, conserved molecular switches in eukaryotic signal transduction. (
  • 14-3-3 proteins function as molecular scaffolds by modulating the conformation of their binding partners. (
  • A series of molecular signals within the cell that are mediated by the Cdc42 protein switching to a GTP-bound active state. (
  • We and others have recently shown involvement of activated Cdc42-associated tyrosine kinase Ack1 in advanced human prostate cancer. (
  • In 8 of 18 primary androgen-independent prostate tumor samples, tyrosine-phosphorylated AR protein was detected and correlated with the detection of tyrosine-phosphorylated Ack1. (
  • 1996 ). The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, andhas separate rac-specific and rho-specific guanine nucleotide exchange factor domains. (
  • YopH tyrosine dephosphorylates host cell proteins, such as p130Cas and focal adhesion kinase FAK ( 2 ). (
  • In the first case, during actin assembly, engagement of particle-bound immunoglobulin IgG ligands by receptors for the Fc portion of IgG results in receptor aggregation and recruitment of cytosolic tyrosine kinase, especially Syk [6]. (
  • Following chemical mutagenesis, two Viro ( v irus i nduced r eporter o ff) mutants that failed to express GFP were mapped to sid-3 , a nonreceptor tyrosine kinase, and B0280.13 (renamed viro-2 ), an ortholog of human Wiskott-Aldrich syndrome protein (WASP). (
  • Due to the exchange of GDP to GTP by CDC42 itself occurs very slowly, GEFs promote such exchange from GDP- to GTP-bound state. (
  • To date over 70 Rho-GEFs, 60 Rho-GAPs and 3 Rho-GDIs have been identified in mammals, reflecting the complexity of regulation of these classes of proteins. (
  • The first step in their activation is the catalysis of GTP exchange for GDP by guanine nucleotide exchange factors (GEFs). (
  • Like other GEFs, αPIX can promote both release of GDP from an inactive small GTP-binding protein and binding of GTP to promote its activation. (
  • Activation of Rho proteins through release of bound GDP and subsequent binding of GTP, is catalysed by guanine nucleotide exchange factors (GEFs) in the Dbl family. (
  • Although most Cdc42 GEFs are membrane associated, we find that Gef1 is a broadly distributed cytosolic protein rather than a membrane-associated protein at cell tips like Scd1. (
  • Guanine nucleotide exchange factors (GEFs) are essential for CDC42 activation. (
  • 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. (
  • Proteomic analysis demonstrated differentially expressed proteins in DNMC that are involved in cellular metabolism, detoxification, and cytoskeletal organization processes, such as GTP-binding Rho-like protein CDC42, glutathione-S-transferase omega-1 and prolyl 4-hydroxylase. (
  • Collectively these results point to deregulation of cellular processes, such as metabolism and protein synthesis, consistent with the observed elevated oxidative stress levels in DNMC potentially resulting in oxidative DNA damage in these cells. (
  • To understand the mechanism by which Cdc42 regulates actin polymerization in these processes, an enormous effort has been focused on the identification of proteins that interact with Cdc42. (
  • MLK3 regulates bone development downstream of the faciogenital dysplasia protein FGD1 in mice. (
  • It has not been clear how the cytoplasmic protein p120 catenin regulates cell motility. (
  • Das M, Wiley DJ, Chen X, Shah K, Verde F. The conserved NDR kinase Orb6 controls polarized cell growth by spatial regulation of the small GTPase Cdc42. (
  • In almost all cases, this regulation is posttranslational and the locus of this posttranslational control is not on actin, but rather on actin binding proteins that control actin dynamics in the cell. (
  • The recent discovery that the Par polarity complex co-operates with Cdc42 in the regulation of endocytosis and recycling opens exciting possibilities for the integration of polarity protein function and endocytotic machinery. (
  • Expression and Characterization of Rat Brain Phospholipase D. G-Protein-Coupled Receptor Regulation of Phospholipase D. Analysis and Quantitation of Ceramide. (
  • The encoded protein contains a high mobility group-box DNA binding domain and participates in the regulation of cell. (
  • Structural studies have revealed sites of Cdc42 and Ack1 interaction and an autoinhibitory mode of kinase regulation ( 7 ). (
  • For monomeric G-proteins, the effect may be a rapid (2 min) and bimodal up-regulation, a transiently unimodal activation, or a transient down-regulation. (
  • Cloning and direct G-protein regulation of phospholipase D from tobacco. (
  • These results provide a first indication for a direct regulation of PLDalpha by a heterotrimeric G-protein alpha-subunit in plants. (
  • Negative regulation of mixed lineage kinase 3 by protein kinase B/AKT leads to cell survival. (
  • Besides regulation of kinase activity, another important function of Cdc42 is to recruit Mbt to adherens junctions. (
  • This gene encodes a protein that is a member of the dickkopf family. (
  • This gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. (
  • The protein encoded by this gene is a member of the keratin gene family. (
  • This gene encodes the microtubule-associated protein tau (MAPT) whose transcript undergoes complex, regulated alternative splicing, giving rise to several mRNA species. (
  • More recently, we have made gene knockins to inactivate the kinase activity of specific MEKKs but the kinase-inactive protein is still expressed. (
  • Rho guanine nucleotide exchange factor 6 is a protein that, in humans, is encoded by the ARHGEF6 gene. (
  • Because the ARHGEF6 gene is located on the X chromosome so that males have only one copy, mutations in this gene in humans can cause X-chromosome-linked non-specific intellectual disability, as can mutations affecting its binding partner PAK3 whose gene is also located on the X chromosome. (
  • The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. (
  • The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. (
  • The protein encoded by this gene is a member of the serine/threonine kinase family. (
  • The product of this gene is a member of the CDC42-binding protein family. (
  • TRIP10 (Thyroid Hormone Receptor Interactor 10) is a Protein Coding gene. (
  • GO annotations related to this gene include identical protein binding and lipid binding . (
  • GO annotations related to this gene include GTP binding and GTPase inhibitor activity . (
  • An important paralog of this gene is CDC42 . (
  • Gene 33/Mig-6, a transcriptionally inducible adapter protein that binds GTP-Cdc42 and activates SAPK/JNK. (
  • has shown that, in tomato ( Lycopersicon esculentum ) fruit, the transcription of a gene, which showed high homology to a monomeric G-protein from pea, is rapidly but transiently up-regulated by ethylene. (
  • What does this gene/protein do? (
  • The protein encoded by this gene is a GTPase activating protein that binds to focal adhesion kinase and mediates the activity of the GTP binding proteins RhoA and Cdc42. (
  • cdc42 GTP-Binding Protein, Saccharomyces cerevisiae" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • This graph shows the total number of publications written about "cdc42 GTP-Binding Protein, Saccharomyces cerevisiae" by people in Harvard Catalyst Profiles by year, and whether "cdc42 GTP-Binding Protein, Saccharomyces cerevisiae" was a major or minor topic of these publication. (
  • Below are the most recent publications written about "cdc42 GTP-Binding Protein, Saccharomyces cerevisiae" by people in Profiles. (
  • Pheromone signalling in Saccharomyces cerevisiae requires the small GTP-binding protein Cdc42p and its activator CDC24. (
  • Pheromone signalling in Saccharomyces cerevisiae is mediated by the STE4-STE18 G-protein beta gamma subunits. (
  • Prototypically, the growth factor receptor on activation recruits a Ras guanine nucleotide exchange factor (GEF), Sos, via adaptor proteins Shc and Grb2. (
  • ARHGEF6 is commonly known as the p21-activated protein kinase exchange factor alpha (alpha-PIX or αPIX), because it was identified by binding to p21-activated kinase (PAK) and also contains a guanine nucleotide exchange factor domain. (
  • αPIX contains a central DH/PH RhoGEF domain that functions as a guanine nucleotide exchange factor (GEF) for small GTPases of the Rho family, and specifically Rac and Cdc42. (
  • 1993 ). Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2. (
  • 1997 ). Huntingtin-associated protein 1 (HAP1) binds to a Trio-like polypeptide, with a rac1 guanine nucleotide exchange factor domain. (
  • now report that, when in the cytoplasm, p120 catenin binds to Vav2, an exchange factor that activates Cdc42 and Rac1. (
  • Also promotes CDC42-induced actin polymerization by recruiting WASL/N-WASP which in turn activates the Arp2/3 complex. (
  • Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. (
  • it has been shown that ethylene at physiological concentrations activates monomeric G-proteins. (
  • The small GTP-binding protein Cdc42 is thought to induce filopodium formation by regulating actin polymerization at the cell cortex. (
  • Although several Cdc42-binding proteins have been identified and some of them have been implicated in filopodium formation, the precise role of Cdc42 in modulating actin polymerization has not been defined. (
  • One component is purified to homogeneity and is identified as the Arp2/3 complex, a protein complex that has been shown to nucleate actin polymerization. (
  • We propose that activation of the Arp2/3 complex by Cdc42 and other signaling molecules plays a central role in stimulating actin polymerization at the cell surface. (
  • A family of signaling molecules, the Rho-like small GTP-binding proteins, have been implicated in controlling actin polymerization because they are involved in many actin-dependent processes ( 1 ). (
  • Although some of these proteins have been shown to modulate Cdc42-induced cellular responses ( 11 ), the precise role of Cdc42 in regulating actin polymerization has not been defined. (
  • To examine these complex processes biochemically, several groups, including ours, have reconstituted Cdc42-induced actin polymerization in cell-free systems ( 12 , 13 ). (
  • By conventional protein purification, we identified one component as the Arp2/3 complex, a protein complex that nucleates actin polymerization ( 14 ). (
  • Because recent studies have implicated that the nucleation activity of the Arp2/3 complex might be regulated in cells ( 14 , 15 ), our findings suggest a role for Cdc42 in the recruitment and activation of the complex and the subsequent stimulation of actin polymerization at the cell surface. (
  • The Rho family of small GTP-binding proteins plays a central role in regulating actin polymerization, the formation of cellular structures dependent on actin, and transformation by some oncogenes ( 21 ). (
  • Atkins BD, Yoshida S, Pellman D. Symmetry breaking: scaffold plays matchmaker for polarity signaling proteins. (
  • The conserved Rho-family GTPase Cdc42 plays a central role in eukaryotic cell polarity. (
  • Cdc42--the centre of polarity. (
  • These results reveal a previously unknown linkage between a cell surface receptor and downstream modulation of Cdc42 activity. (
  • They promote the exchange of GDP for GTP to generate the activated form of CDC42 capable of recognizing downstream targets [ 4 ]. (
  • There is evidence suggesting that PLD acts downstream from G-proteins, but a direct interaction of specific members has not been shown. (
  • To identify novel effectors downstream of the TCR, we designed a retroviral-based functional genetic screen to select for proteins that inhibit receptor-mediated T cell activation. (
  • Dystrophia myotonica-protein kinase ( DMPK ) and Phospholipase D1, phosphatidylcholine-specific ( PLD1 ) are also downstream targets of the Rac1 [ 26 ], [ 27 ]. (
  • a second component that binds Cdc42 directly and mediates the interaction between Cdc42 and the complex also is required. (
  • Signaling scaffolds bind to specific partners to promote efficient signal transduction by arranging sequential elements of a pathway near each other to facilitate interaction/information transfer, and also by holding these partner protein complexes in specific locations within the cell to promote local or regional signaling. (
  • Major interacting proteins include: Itself, or the highly-related ARHGEF7/βPIX via a trimeric coiled-coil interaction. (
  • Gain- and loss-of-function experiments with myoblasts indicate that the Cdo-Bnip-2 interaction stimulates Cdc42 activity, which in turn promotes p38alpha/beta activity and cell differentiation. (
  • Furthermore, interaction with multiple scaffold-type proteins is a distinctive mode of cell surface receptor signaling and provides one mechanism for specificity of p38alpha/beta activation during cell differentiation. (
  • As it is ECM bound, TIMP-3 may have more influential biological effects compared with the other TIMPs that are soluble and able to diffuse away from the interaction site. (
  • Protein-protein interaction network was constructed to find out the modules with close interactions. (
  • Baculorviruses containing coding regions of Cdc42, Rac1, or RhoA fused with glutathione S -transferase (GST) at their N termini (kindly provided by Kimberly Tolias and Christopher Carpenter, Beth Israel Hospital, Boston) were used to infect Sf9 cells at a density of 1 × 10 6 cells/ml. (
  • Wild-type Ste20 protein was visualized as a crescent at emerging buds during vegetative growth and at shmoo tips in cells arrested with alpha-factor. (
  • p16 Stimulates CDC42-dependent migration of hepatocellular carcinoma cells. (
  • Though lipid binding has been studied extensively in individual actin binding proteins, it is not clear which phosphoinositides are able to modulate actin assembly in cells. (
  • Kinase-dead PKCλ and -ζ constructs acted as dominant negatives and restored stress fibers in cells expressing the activated V12 Cdc42 mutant, indicating that Cdc42-dependent loss of stress fibers requires aPKCs. (
  • In addition, expression of activated forms of Rac or Cdc42 causes cells to lose stress fibers ( 48 ). (
  • [9] Cdc42 expression was gradually increased showing significant difference and was significantly higher in HeLa cells than in regular cells. (
  • The migration ability of HeLa cells transfected with Cdc42 was higher than that of non-transfected cells. (
  • [9] It was proposed that the overexpression of Cdc42 can promote filopodia formation in HeLa cells. (
  • Cdc42 overexpression significantly improved the ability of cervical cancer cells to migrate, possibly due to improved pseudopodia formation. (
  • [10] Levels of β1 integrin were reduced in Cdc42-deficient cells. (
  • Knocking down β1 integrin inhibited cancer cell migration, whereas overexpressing the integrin in Cdc42-deficient cells restored endothelial invasion. (
  • A continually active form of the transcription factor was also capable of restoring endothelial insertion to cancer cells lacking Cdc42. (
  • Normal cancer cells and Cdc42-deficient cancer cells have also been compared in vivo. (
  • When both types of cells were injected into mouse tail veins, control cells spread out more on the vessel endothelium within minutes, suggesting that Cdc42 assists in cell migration. (
  • [10] After six weeks, the control cells had generated more metastases than the Cdc42-deficient cells. (
  • In the absence of Cdc42, cancer cells failed to spread out on the basement membrane, and Cdc42-deficient cells showed reduced adhesion to extracellular matrix-coated coverslips. (
  • Cdc42 therefore promotes the attachment of cancer cells to both endothelial cells and the underlying basement membrane during transendothelial migration. (
  • The metastatic phenotype can be modulated by dysregulating the synthesis of different structural and functional proteins of tumor cells. (
  • The principal attention is paid to Rop mG-proteins, unique small GTPases of eukaryotic cells functioning during various developmental stages of plants, from pollen tube and root hair growth to plant responses to biotic and abiotic stresses. (
  • Both PS and anti-PSR antibodies stimulated membrane ruffling, vesicle formation, and "bystander" uptake of cells bound to the surface of the phagocyte. (
  • Expression of a dominant interfering mutant of CDC42 (CDC42HsN17) prevented S. typhimurium -induced cytoskeletal reorganization and subsequent macropinocytosis and bacterial internalization into host cells. (
  • Cells expressing constitutively active CDC42 (CDC42HsV12) internalized an S. typhimurium mutant unable to trigger host cell responses. (
  • These results indicate that CDC42 is required for bacterial invasion and induction of nuclear responses in host cells. (
  • In order to examine the cross-talk between Ras and Rho proteins, we investigated the effects on focus-forming activity and cell growth of the Rho-family members Cdc42Hs, Rac1 and RhoG by expressing constitutively active or dominant-negative forms in NIH3T3 cells. (
  • 1989 ). The mammalian G protein rhoC is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilaments in Vero cells. (
  • Rhodamine-phalloidin, which selectively binds to polymerized actin, was detected in perikarya and proximal dendrites of CA1 pyramidal cells that received low-frequency afferent activity but was essentially absent in spines and fine dendritic processes. (
  • Each of these activated signaling proteins was able to restore cell spreading as assayed by an increase in the area of cells expressing tac-β1. (
  • The encoded protein is expressed in hematopoietic cells, where it functions as a negative regulator of cell growth and survival. (
  • Protein kinase Cι (PKCι) is required for the oncogenic Ras-mediated transformed growth of lung cancer and intestinal epithelial cells. (
  • PKCι promotes the transformed growth of pancreatic cancer cells through activation of the proliferative Rac1-mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK1/2 signaling pathway. (
  • We identified and disrupted RAC1 and show here that, in contrast to CDC42 , it is not necessary for viability or serum-induced hyphal growth but is essential for filamentous growth when cells are embedded in a matrix. (
  • Rac1 is essential for filamentous growth when cells are embedded in an agar matrix yet is not required for serum-induced hyphal growth, in contrast to Cdc42. (
  • The ligands of EGFR consist of a family of structurally and functionally related integral membrane proteins that can be proteolytically cleaved and shed from cells ( 18 , 32 ). (
  • The 14-3-3 proteins are a family of conserved adaptor and scaffolding proteins expressed in all eukaryotic cells. (
  • 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. (
  • PKR (Protein Kinase-R) is a 68-kDa serine-threonine kinase that appears to play a primary role in mediating the antiviral activities of infected cells. (
  • Studies focusing on the functions of the Ysc TTSS have demonstrated that Yop proteins are secreted in a contact-dependent manner during infection of cultured mammalian cells, with many of the Yops being translocated directly into the cytosol of the cells ( 33 , 43 , 44 ). (
  • In contrast, a Ste20 mutant protein unable to bind Cdc42 was found diffusely throughout the cytoplasm, suggesting that Cdc42 is required to localize Ste20 properly in vivo. (
  • Thus, RhoGDIs sequester CDC42-GDP in the cytoplasm through a transfer of geranylgeranyl moiety from membrane to GDI and inhibit its spontaneous GDP/GTP exchange activity. (
  • Expression of activated Cdc42 results in the translocation of PKCλ from the nucleus into the cytosol, and Cdc42 and PKCλ colocalize at the plasma membrane and in the cytoplasm. (
  • Expression, Purification, and Assay of Cytosolic (Catalytic) Domains of Membrane-Bound Mammalian Adenylyl Cyclases. (
  • R-Ras and Rac1 rescued cell spreading in a GTP-dependent manner, whereas PKCε required an intact kinase domain. (
  • We show that this construct binds directly to the kinase domain of PAK2 and inhibits anti-TCR-stimulated T cell activation. (
  • All PAK proteins share a C-terminal kinase domain and a N-terminal binding domain for proteins of the Rho family of small GTPases (p21-binding domain, PBD). (
  • The contribution of CDC42 to cancer progression seems to be tissue specific due to it has been found to have pro-oncogenic and anti-oncogenic properties depending on cellular context. (
  • My laboratory defines the "signal relay" systems initiated by various cellular stimuli including cytokines, growth factors, antigens, and drugs used to treat human disease.The unifying hypothesis directing the work in my laboratory is that the differential expression and spatial organization of signal relay proteins controls the responsiveness of different cell types to specific stimuli. (
  • This study investigated the effects of Hsp90 inhibitors on client protein expression and key cellular functions required for tumor angiogenesis. (
  • 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 ). (
  • Under normal cellular physiological conditions, the concentration of GTP is higher than that of GDP, favoring the replacement of GDP by GTP in association with the GTPase. (
  • since αPIX can activate the "p21'' small GTPases Rac1 or Cdc42 through its GEF activity, this αPIX/PAK/Rac complex exemplifies a scaffolding function. (
  • It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. (
  • This protein has been shown to bind both CDC42 and TC10 GTPases in a GTP-dependent manner. (
  • These two proteins interact with the GTP-bound forms of the small GTPases Rho and Rac but not with Cdc42. (
  • Rop1Ps belongs to the Rho family of small GTPases, which has become an important group of conserved signaling proteins in eukaryotes. (
  • The presence of such a large number of regulatory proteins makes it very difficult to study the physiological mechanisms controlling actin functions. (
  • Several common GTPase families like Rac and Rho promote microtubule assembly indirectly by facilitating GDP/GTP exchange on regulatory members that effect assembly and disassembly of tubulin dimers. (
  • Activation of the MKKK by GTP binding regulatory proteins (i.e. (
  • of regulatory proteins with mol wts of 20-30 kD. (
  • 14-3-3 proteins are a family of acidic regulatory molecules found in all eukaryotes. (
  • Activation of the oxidase is controlled by the recruitment to the Cytochrome b-558 of such cytosolic regulatory proteins as Neutrophil cytosolic factors 1 and 2 ( p47-phox and p67-phox ) [ 11 ]. (
  • NCK Interacting Kinase (NIK), a serine/threonine protein kinase. (
  • PKC (Protein Kinase-C) is a cyclic nucleotide-independent enzyme that phosphorylates serine and threonine residues in many target proteins. (
  • Cdc42 cluster formation depends on spontaneous symmetry-breaking via multiple converging positive feedback loops involving active Cdc42, Cdc42 effectors and the Cdc42 GEF, Cdc24. (
  • A subset of effectors contains eukaryotic-like motifs that mimic host proteins to exploit signaling and modify specific cytoskeletal components such as actin and microtubules. (
  • We recently identified three others putative rho effectors characterized by a common rho binding motif. (
  • Upon contact between the tip complex of the type III apparatus and host cell receptors, including α5β1-integrins and CD44, the secreted proteins IpaB and IpaC insert into the plasma membrane and form a pore into the host membrane through which several effectors translocate ( 10 ⇓ ⇓ ⇓ - 14 ). (
  • Assay of Cdc42, Rac, and Rho GTPase Activation by Affinity Methods. (
  • Nonisotopic Methods for Detecting Activation of Small G Proteins. (
  • LIF, secreted from the endometrial glands (GEs), binds to the LIFR, activating the Janus kinase-signal transducer and activation of transcription (STAT) 3 (Jak-Stat3) signaling pathway in the LE. (
  • Their activation is controlled by guanine exchange factors (GEF) that catalyze their binding to GTP. (
  • 1997 ). Minimal Ras-binding domain of Raf1 can be used as an activation-specific probe for Ras. (
  • Cdc42p is required for alpha-factor-induced activation of FUS1.cdc24ts strains defective for Cdc42p GDP/GTP exchange show no pheromone induction at restrictive temperatures but are partially rescued by overexpression of Cdc42p, which is potentiated by Cdc42p12V mutants. (
  • Mediates VEGF-induced CDC42 activation. (
  • However, in anchorage free conditions, whereas activation of either Cdc42 or Ras results in cyclin A transcription and cell cycle progression, Cdc42 is not required for Ras-mediated cyclin A induction, and the two proteins act in a synergistic manner in this process. (
  • Protein kinase activity is rapidly up-regulated by ethylene, the effect is inhibited by 1-methylcyclopropene, and the activation is bimodal. (
  • In Part I of this paper [2], we described the initial antiphagocytic strategy for medical nanorobots which is to avoid phagocyte contact, recognition, binding and activation. (
  • These foci can be detected underneath bound CO particles within 30 seconds of cell activation, and their formation requires active protein kinase C. Complement receptor-mediated internalization requires intact microtubules and is accompanied by the accumulation of vesicles beneath the forming phagosome [4]. (
  • Activated WASF1(WAVE1) stimulates Actin related protein 2/3 complex ( Arp2/3 ) that mediates Actin cytoskeletal polymerization [ 16 ]. (
  • Immunoprecipitation studies indicate that some of the monomeric G-proteins affected may be of the Rab class. (
  • Other candidates that have emerged as possible components of the ethylene signal transduction pathway are monomeric GTP-binding proteins (monomeric G-proteins). (
  • We have found that GTPγS stimulates actin assembly in the presence of endogenous membrane vesicles in low speed extracts. (
  • In cultured VSMCs, Ang II stimulates the formation of Ras-GTP and Ras-Raf association. (
  • 1991). A comparison of the RhoA-GDP and [Val14]RhoA-GTP[S] crystal structures, reveals that the conformational differences between the GTP and GDP-bound forms are restricted primarily to two surface loops, named switch regions I and II that correspond to CDC42 amino acids 26 and 59 (Bishop and Hall, 2000). (
  • Construction of Soluble Adenylyl Cyclase from Human Membrane-Bound Type 7 Adenylyl Cyclase. (
  • Determination of Strength and Specificity of Membrane-Bound G Protein-Phospholipase C Association Using Fluorescence Spectroscopy. (
  • Western Blotting refers to the electrophoretic transfer of proteins from sodium dodecyl sulfate polyacrylamide gels to sheets of PVDF or nitrocellullose membrane, followed by immunodetection of prote. (
  • Binds to lipids such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine and promotes membrane invagination and the formation of tubules. (
  • Rac1 is localized to the plasma membrane, yet its distribution is more homogenous than that of Cdc42, with no enrichment at the tips of either buds or hyphae. (
  • We also show that Rac1 is localized to the plasma membrane with different dynamics from those of Cdc42. (
  • In contrast to the wealth of knowledge regarding PAR proteins and interacting components, the involvement of lipid plasma membrane components in these processes is less understood, in particular in developing systems. (
  • Identification of novel membrane-bound phospholipase D from Streptoverticillium cinnamoneum, possessing only hydrolytic activity. (
  • A membrane-bound phospholipase D (PLD) has been identified and isolated in a soluble form from an actinomycete, Streptoverticillium cinnamoneum. (
  • Together with the absence of immunochemical cross-reactivity, these enzymatic properties demonstrate that the membrane-bound enzyme is distinct from the extracellular enzyme recently characterized and cloned from the same bacterial strain [C. Ogino et al. (
  • ABC (ATP Binding Cassette Transporters) comprise a large family of membrane-spanning proteins that are responsible for transporting a variety of substrates in prokaryotes and eukaryotes. (
  • RhoGDI, a guanine-nucleotide dissociation inhibitor for the Rho family, inhibits phosphoinositide-induced actin assembly, suggesting the involvement of the Rho family small G proteins. (
  • 1,2 Recently, small G proteins have been noted as novel therapeutic targets in cardiovascular medicine. (
  • At least three types of RGFs have been described for small G-proteins ( 1 , 2 ). (
  • Several earlier studies, including our own, suggested critical involvement of small G-proteins, such as Rac1, Cdc42, and ARF6, in GSIS from normal rat islets, human islets, and clonal β-cell preparations ( 3 - 5 , 19 - 31 ). (
  • GTP binding increases the activity, and the hydrolysis of GTP to GDP renders the protein inactive. (
  • Vesicles containing phosphatidylinositol (4,5) bisphosphate or phosphatidylinositol (3,4,5) trisphosphate can induce actin assembly even in the absence of GTPγS. (
  • Hence, both phosphoinositides and Cdc42 are required to induce actin assembly in this cell-free system. (
  • Recent data also suggest that constitutive active forms of Cdc42 can induce apoptosis through a mechanism requiring signaling through SAPK/JNK. (
  • When overexpressed in fibroblasts, this protein was able to induce pseudopodia formation, which suggested a role in inducing actin filament assembly and cell shape control. (
  • Finally, we demonstrate that SLPR overexpression can induce ectopic JNK signaling and that the SLPR protein is enriched at the epithelial cell cortex. (
  • The product of oncogene Dbl was reported to specifically catalyze the dissociation of GDP from this protein. (
  • The first one involves the ability of the GDI to prevent dissociation of GDP from Rho G-proteins. (
  • Rho GDP dissociation inhibitors (GDI) alpha, beta and gamma ( RhoGDI alpha , LyGDI , RhoGDI gamma ) are inhibitors of CDC42 activity [ 28 ], [ 29 ]. (
  • Furthermore, CDC42 is able to interact with membranes via post-translational C-terminal geranylgeranyl lipid modification, however it can be found as a soluble complex association with RhoGDI. (
  • There are ∼50 actin binding proteins identified so far that directly interact with actin and modulate its assembly properties ( Kreis and Vale, 1993 ). (
  • CLASPs, such as CLASP1, are nonmotor microtubule-associated proteins that interact with CLIPs (e.g. (
  • In addition, it has been shown that superoxide can interact directly with protein kinase C (PKC), resulting in a persistent increase in autonomous PKC activity ( Knapp and Klann, 2000 ). (
  • αPIX has been reported to interact with over 40 proteins. (
  • This has led to current initiation of clinical trials in inflammatory disease states evaluating small molecule inhibitors of MAP kinase proteins and encouraging results have been obtained. (
  • The structural and functional integrity of the ECM is ensured through a balance between matrix metalloproteinases (MMPs), which cleave ECM proteins, and their endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs) ( 37 ). (