Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.
Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC 3.6.1.47.
Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.
Transforming protein encoded by ras oncogenes. Point mutations in the cellular ras gene (c-ras) can also result in a mutant p21 protein that can transform mammalian cells. Oncogene protein p21(ras) has been directly implicated in human neoplasms, perhaps accounting for as much as 15-20% of all human tumors. This enzyme was formerly listed as EC 3.6.1.47.
PROTEINS that specifically activate the GTP-phosphohydrolase activity of RAS PROTEINS.
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.
Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.
A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.
A family of GUANINE NUCLEOTIDE EXCHANGE FACTORS that are specific for RAS PROTEINS.
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.
A ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.
A colorless liquid extracted from oils of plants such as citronella, neroli, cyclamen, and tuberose. It is an intermediate step in the biological synthesis of cholesterol from mevalonic acid in vertebrates. It has a delicate odor and is used in perfumery. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
A somewhat heterogeneous class of enzymes that catalyze the transfer of alkyl or related groups (excluding methyl groups). EC 2.5.
A family of MONOMERIC GTP-BINDING PROTEINS that are related to RAS PROTEINS.This enzyme was formerly listed as EC 3.6.1.47.
Proteins that activate the GTPase of specific GTP-BINDING PROTEINS.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
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.
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.-.
A guanine nucleotide exchange factor that stimulates the dissociation of GDP from RAL GTP-BINDING PROTEINS. It also has GDP exchange activity towards other MONOMERIC GTP-BINDING PROTEINS.
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.
Proteins found in any species of fungus.
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.
Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.
An enzyme that catalyzes the synthesis of geranylgeranyl diphosphate from trans, trans-farnesyl diphosphate and isopentenyl diphosphate.
A replication-defective mouse sarcoma virus (SARCOMA VIRUSES, MURINE) first described by J.J. Harvey in 1964.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Cell 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.
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.
A family of ubiquitously expressed MONOMERIC GTP-BINDING PROTEINS that are involved in intracellular signal transduction. This enzyme was formerly listed as EC 3.6.1.47.
A protein found most abundantly in the nervous system. Defects or deficiencies in this protein are associated with NEUROFIBROMATOSIS 1, Watson syndrome, and LEOPARD syndrome. Mutations in the gene (GENE, NEUROFIBROMATOSIS 1) affect two known functions: regulation of ras-GTPase and tumor suppression.
Covalent attachment of LIPIDS and FATTY ACIDS to other compounds and PROTEINS.
A class of monomeric, low molecular weight (20-25 kDa) GTP-binding proteins that regulate a variety of intracellular processes. The GTP bound form of the protein is active and limited by its inherent GTPase activity, which is controlled by an array of GTPase activators, GDP dissociation inhibitors, and guanine nucleotide exchange factors. This enzyme was formerly listed as EC 3.6.1.47
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A mammalian homolog of the DROSOPHILA SON OF SEVENLESS PROTEIN. It is a guanine nucleotide exchange factor for RAS PROTEINS.
Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2.
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.
A class of RAS GUANINE NUCLEOTIDE EXCHANGE FACTORS that are genetically related to the Son of Sevenless gene from DROSOPHILA. Sevenless refers to genetic mutations in DROSOPHILA that cause loss of the R7 photoreceptor which is required to see UV light.
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.
Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.
Established cell cultures that have the potential to propagate indefinitely.
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.
Phosphoric or pyrophosphoric acid esters of polyisoprenoids.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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.
An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.
Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.
The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.
The functional hereditary units of FUNGI.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
The 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.
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.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A group of 16-carbon fatty acids that contain no double bonds.
A group of replication-defective viruses, in the genus GAMMARETROVIRUS, which are capable of transforming cells, but which replicate and produce tumors only in the presence of Murine leukemia viruses (LEUKEMIA VIRUS, MURINE).
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The rate dynamics in chemical or physical systems.
Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).
Proteins prepared by recombinant DNA technology.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Tumor suppressor genes located on the long arm of human chromosome 17 in the region 17q11.2. Mutation of these genes is thought to cause NEUROFIBROMATOSIS 1, Watson syndrome, and LEOPARD syndrome.
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.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
The salts or esters of salicylic acids, or salicylate esters of an organic acid. Some of these have analgesic, antipyretic, and anti-inflammatory activities by inhibiting prostaglandin synthesis.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.
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.
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Enzymes that catalyze the methylation of amino acids after their incorporation into a polypeptide chain. S-Adenosyl-L-methionine acts as the methylating agent. EC 2.1.1.
A genus of protozoa, formerly also considered a fungus. Its natural habitat is decaying forest leaves, where it feeds on bacteria. D. discoideum is the best-known species and is widely used in biomedical research.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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.
A partitioning within cells due to the selectively permeable membranes which enclose each of the separate parts, e.g., mitochondria, lysosomes, etc.
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).)
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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
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.
Chemical substances, excreted by an organism into the environment, that elicit behavioral or physiological responses from other organisms of the same species. Perception of these chemical signals may be olfactory or by contact.
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 mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
A GTP-BINDING PROTEIN involved in regulating a signal transduction pathway that controls assembly of focal adhesions and actin stress fibers. This enzyme was formerly listed as EC 3.6.1.47.
Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
A family of closely-related serine-threonine kinases that were originally identified as the cellular homologs of the retrovirus-derived V-RAF KINASES. They are MAP kinase kinase kinases that play important roles in SIGNAL TRANSDUCTION.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
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 CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
The phylum of sponges which are sessile, suspension-feeding, multicellular animals that utilize flagellated cells called choanocytes to circulate water. Most are hermaphroditic. They are probably an early evolutionary side branch that gave rise to no other group of animals. Except for about 150 freshwater species, sponges are marine animals. They are a source of ALKALOIDS; STEROLS; and other complex molecules useful in medicine and biological research.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
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 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.
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.
Peptides composed of between two and twelve amino acids.
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.
The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
A class of compounds composed of repeating 5-carbon units of HEMITERPENES.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
An enzyme found mostly in plant tissue. It hydrolyzes glycerophosphatidates with the formation of a phosphatidic acid and a nitrogenous base such as choline. This enzyme also catalyzes transphosphatidylation reactions. EC 3.1.4.4.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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).
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
A cell line derived from cultured tumor cells.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
Biochemical identification of mutational changes in a nucleotide sequence.
The sum of the weight of all the atoms in a molecule.
Cellular DNA-binding proteins encoded by the c-fos genes (GENES, FOS). They are involved in growth-related transcriptional control. c-fos combines with c-jun (PROTO-ONCOGENE PROTEINS C-JUN) to form a c-fos/c-jun heterodimer (TRANSCRIPTION FACTOR AP-1) that binds to the TRE (TPA-responsive element) in promoters of certain genes.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
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.
A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)

Plasma membrane recruitment of RalGDS is critical for Ras-dependent Ral activation. (1/4833)

In COS cells, Ral GDP dissociation stimulator (RalGDS)-induced Ral activation was stimulated by RasG12V or a Rap1/Ras chimera in which the N-terminal region of Rap1 was ligated to the C-terminal region of Ras but not by Rap1G12V or a Ras/Rap1 chimera in which the N-terminal region of Ras was ligated to the C-terminal region of Rap1, although RalGDS interacted with these small GTP-binding proteins. When RasG12V, Ral and the Rap1/Ras chimera were individually expressed in NIH3T3 cells, they localized to the plasma membrane. Rap1Q63E and the Ras/Rap1 chimera were detected in the perinuclear region. When RalGDS was expressed alone, it was abundant in the cytoplasm. When coexpressed with RasG12V or the Rap1/Ras chimera, RalGDS was detected at the plasma membrane, whereas when coexpressed with Rap1Q63E or the Ras/Rap1 chimera, RalGDS was observed in the perinuclear region. RalGDS which was targeted to the plasma membrane by the addition of Ras farnesylation site (RalGDS-CAAX) activated Ral in the absence of RasG12V. Although RalGDS did not stimulate the dissociation of GDP from Ral in the absence of the GTP-bound form of Ras in a reconstitution assay using the liposomes, RalGDS-CAAX could stimulate it without Ras. RasG12V activated Raf-1 when they were coexpressed in Sf9 cells, whereas RasG12V did not affect the RalGDS activity. These results indicate that Ras recruits RalGDS to the plasma membrane and that the translocated RalGDS induces the activation of Ral, but that Rap1 does not activate Ral due to distinct subcellular localization.  (+info)

Ral-specific guanine nucleotide exchange factor activity opposes other Ras effectors in PC12 cells by inhibiting neurite outgrowth. (2/4833)

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

Cell growth inhibition by farnesyltransferase inhibitors is mediated by gain of geranylgeranylated RhoB. (3/4833)

Recent results have shown that the ability of farnesyltransferase inhibitors (FTIs) to inhibit malignant cell transformation and Ras prenylation can be separated. We proposed previously that farnesylated Rho proteins are important targets for alternation by FTIs, based on studies of RhoB (the FTI-Rho hypothesis). Cells treated with FTIs exhibit a loss of farnesylated RhoB but a gain of geranylgeranylated RhoB (RhoB-GG), which is associated with loss of growth-promoting activity. In this study, we tested whether the gain of RhoB-GG elicited by FTI treatment was sufficient to mediate FTI-induced cell growth inhibition. In support of this hypothesis, when expressed in Ras-transformed cells RhoB-GG induced phenotypic reversion, cell growth inhibition, and activation of the cell cycle kinase inhibitor p21WAF1. RhoB-GG did not affect the phenotype or growth of normal cells. These effects were similar to FTI treatment insofar as they were all induced in transformed cells but not in normal cells. RhoB-GG did not promote anoikis of Ras-transformed cells, implying that this response to FTIs involves loss-of-function effects. Our findings corroborate the FTI-Rho hypothesis and demonstrate that gain-of-function effects on Rho are part of the drug mechanism. Gain of RhoB-GG may explain how FTIs inhibit the growth of human tumor cells that lack Ras mutations.  (+info)

Telomerase activity is sufficient to allow transformed cells to escape from crisis. (4/4833)

The introduction of simian virus 40 large T antigen (SVLT) into human primary cells enables them to proliferate beyond their normal replicative life span. In most cases, this temporary escape from senescence eventually ends in a second proliferative block known as "crisis," during which the cells cease growing or die. Rare immortalization events in which cells escape crisis are frequently correlated with the presence of telomerase activity. We tested the hypothesis that telomerase activation is the critical step in the immortalization process by studying the effects of telomerase activity in two mortal SVLT-Rasval12-transformed human pancreatic cell lines, TRM-6 and betalox5. The telomerase catalytic subunit, hTRT, was introduced into late-passage cells via retroviral gene transfer. Telomerase activity was successfully induced in infected cells, as demonstrated by a telomerase repeat amplification protocol assay. In each of nine independent infections, telomerase-positive cells formed rapidly dividing cell lines while control cells entered crisis. Telomere lengths initially increased, but telomeres were then maintained at their new lengths for at least 20 population doublings. These results demonstrate that telomerase activity is sufficient to enable transformed cells to escape crisis and that telomere elongation in these cells occurs in a tightly regulated manner.  (+info)

Signals from the Ras, Rac, and Rho GTPases converge on the Pak protein kinase in Rat-1 fibroblasts. (5/4833)

Ras plays a key role in regulating cellular proliferation, differentiation, and transformation. Raf is the major effector of Ras in the Ras > Raf > Mek > extracellular signal-activated kinase (ERK) cascade. A second effector is phosphoinositide 3-OH kinase (PI 3-kinase), which, in turn, activates the small G protein Rac. Rac also has multiple effectors, one of which is the serine threonine kinase Pak (p65(Pak)). Here we show that Ras, but not Raf, activates Pak1 in cotransfection assays of Rat-1 cells but not NIH 3T3 cells. We tested agents that activate or block specific components downstream of Ras and demonstrate a Ras > PI 3-kinase > Rac/Cdc42 > Pak signal. Although these studies suggest that the signal from Ras through PI 3-kinase is sufficient to activate Pak, additional studies suggested that other effectors contribute to Pak activation. RasV12S35 and RasV12G37, two effector mutant proteins which fail to activate PI 3-kinase, did not activate Pak when tested alone but activated Pak when they were cotransfected. Similarly, RacV12H40, an effector mutant that does not bind Pak, and Rho both cooperated with Raf to activate Pak. A dominant negative Rho mutant also inhibited Ras activation of Pak. All combinations of Rac/Raf and Ras/Raf and Rho/Raf effector mutants that transform cells cooperatively stimulated ERK. Cooperation was Pak dependent, since all combinations were inhibited by kinase-deficient Pak mutants in both transformation assays and ERK activation assays. These data suggest that other Ras effectors can collaborate with PI 3-kinase and with each other to activate Pak. Furthermore, the strong correlation between Pak activation and cooperative transformation suggests that Pak activation is necessary, although not sufficient, for cooperative transformation of Rat-1 fibroblasts by Ras, Rac, and Rho.  (+info)

Control of growth and differentiation by Drosophila RasGAP, a homolog of p120 Ras-GTPase-activating protein. (6/4833)

Mammalian Ras GTPase-activating protein (GAP), p120 Ras-GAP, has been implicated as both a downregulator and effector of Ras proteins, but its precise role in Ras-mediated signal transduction pathways is unclear. To begin a genetic analysis of the role of p120 Ras-GAP we identified a homolog from the fruit fly Drosophila melanogaster through its ability to complement the sterility of a Schizosaccharomyces pombe (fission yeast) gap1 mutant strain. Like its mammalian homolog, Drosophila RasGAP stimulated the intrinsic GTPase activity of normal mammalian H-Ras but not that of the oncogenic Val12 mutant. RasGAP was tyrosine phosphorylated in embryos and its Src homology 2 (SH2) domains could bind in vitro to a small number of tyrosine-phosphorylated proteins expressed at various developmental stages. Ectopic expression of RasGAP in the wing imaginal disc reduced the size of the adult wing by up to 45% and suppressed ectopic wing vein formation caused by expression of activated forms of Breathless and Heartless, two Drosophila receptor tyrosine kinases of the fibroblast growth factor receptor family. The in vivo effects of RasGAP overexpression required intact SH2 domains, indicating that intracellular localization of RasGAP through SH2-phosphotyrosine interactions is important for its activity. These results show that RasGAP can function as an inhibitor of signaling pathways mediated by Ras and receptor tyrosine kinases in vivo. Genetic interactions, however, suggested a Ras-independent role for RasGAP in the regulation of growth. The system described here should enable genetic screens to be performed to identify regulators and effectors of p120 Ras-GAP.  (+info)

BLNK required for coupling Syk to PLC gamma 2 and Rac1-JNK in B cells. (7/4833)

Signaling through the B cell receptor (BCR) is essential for B cell function and development. Despite the key role of Syk in BCR signaling, little is known about the mechanism by which Syk transmits downstream effectors. BLNK (B cell LiNKer protein), a substrate for Syk, is now shown to be essential in activating phospholipase C (PLC)gamma 2 and JNK. The BCR-induced PLC gamma 2 activation, but not the JNK activation, was restored by introduction of PLC gamma 2 membrane-associated form into BLNK-deficient B cells. As JNK activation requires both Rac1 and PLC gamma 2, our results suggest that BLNK regulates the Rac1-JNK pathway, in addition to modulating PLC gamma 2 localization.  (+info)

A2B adenosine and P2Y2 receptors stimulate mitogen-activated protein kinase in human embryonic kidney-293 cells. cross-talk between cyclic AMP and protein kinase c pathways. (8/4833)

Mitogen-activated protein kinase (MAPK) cascades underlie long-term mitogenic, morphogenic, and secretory activities of purinergic receptors. In HEK-293 cells, N-ethylcarboxamidoadenosine (NECA) activates endogenous A2BARs that signal through Gs and Gq/11. UTP activates P2Y2 receptors and signals only through Gq/11. The MAPK isoforms, extracellular-signal regulated kinase 1/2 (ERK), are activated by NECA and UTP. H-89 blocks ERK activation by forskolin, but weakly affects the response to NECA or UTP. ERK activation by NECA or UTP is unaffected by a tyrosine kinase inhibitor (genistein), attenuated by a phospholipase C inhibitor (U73122), and is abolished by a MEK inhibitor (PD098059) or dominant negative Ras. Inhibition of protein kinase C (PKC) by GF 109203X failed to block ERK activation by NECA or UTP, however, another PKC inhibitor, Ro 31-8220, which unlike GF 109203X, can block the zeta-isoform, and prevents UTP- but not NECA-induced ERK activation. In the presence of forskolin, Ro 31-8220 loses its ability to block UTP-stimulated ERK activation. PKA has opposing effects on B-Raf and c-Raf-1, both of which are found in HEK-293 cells. The data are explained by a model in which ERK activity is modulated by differential effects of PKC zeta and PKA on Raf isoforms.  (+info)

Vectibix® (panitumumab) is a FDA approved drug (BLA-125147) indicated as a single agent for the treatment of EGFR-expressing metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy regimens. Approval is based on progression-free survival; no data demonstrate an improvement in disease-related symptoms or increased survival.. DRUG DESCRIPTION Vectibix® (panitumumab) is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). Panitumumab has an approximate molecular weight of 147 kDa. Panitumumab is produced in genetically engineered mammalian (Chinese Hamster Ovary) cells.. Panitumumab will be given on this study at 6 mg/kg, IV over 1 hr ...
Any continuous-dosing (i.e. daily dosing, every-other-day dosing, Monday-Wednesday-Friday dosing, weekly etc.) of systemic anti-cancer treatment for which the recover period is not known, or investigational drugs (i.e. targeted agents) within a duration of ≤ 5 half lives of the agent and their active metabolites (if any ...
Purpose: Although cetuximab, an anti-EGF receptor (EGFR) monoclonal antibody, is an effective treatment for patients with KRAS wild-type metastatic colorectal cancer (mCRC), its clinical use is limited by onset of resistance.. Experimental Design: We characterized two colorectal cancer models to study the mechanisms of acquired resistance to cetuximab.. Results: Following chronic treatment of nude mice bearing cetuximab-sensitive human GEO colon xenografts, cetuximab-resistant GEO (GEO-CR) cells were obtained. In GEO-CR cells, proliferation and survival signals were constitutively active despite EGFR inhibition by cetuximab treatment. Whole gene expression profiling identified a series of genes involved in the hepatocyte growth factor (HGF)-MET-dependent pathways, which were upregulated in GEO-CR cells. Furthermore, activated, phosphorylated MET was detected in GEO-CR cells. A second colorectal cancer cell line with acquired resistance to cetuximab was obtained (SW48-CR). Inhibition of MET ...
This study investigated the efficacy and tolerability of gimeracil/oteracil/tegafur + cetuximab + irinotecan in patients with KRAS wild-type metastatic
Merck Serono, a division of Merck KGaA,Darmstadt,Germany has announced that new data presented today at the 35th Congressof the European Society for Medical Oncology (ESMO) have shown that patients with KRAS wild-type metastatic colorectal cancer (mCRC) who experienced early tumor shrinkage (within 8 weeks) during 1st line Erbitux® (cetuximab) based treatment lived a median of […]. ...
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Somatic genetic mutation in the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene has been linked to poor prognosis and resistance to various targeted therapeutics in Non Small Cell Lung Cancer (NSCLC). Therapeutic strategies that target tumors harboring these mutations represent an unmet medical need. In this study, we investigated the relationship between antifolate sensitivity and KRAS mutation/amplification status in NSCLC.. Human NSCLC cell lines (KRAS wild type, KRAS mutant non-amplified and KRAS mutant amplified) were treated with Methotrexate (MTX) or Pemetrexed (PEM) and assayed for proliferation after 72h. In these studies, 5 out of 7 KRASwt (wildtype) cells and all KRASmut (mutant) amplified cells showed resistance to MTX treatment (IC50 ,10μM). In contrast, growth of all KRASmut non-amplified cell lines studied was inhibited with MTX treatment (IC50 ,100nM). Similar effects were observed for PEM in this study. Interrogation of the NCI Developmental Therapeutics ...
Opens the Highlight Feature Bar and highlights feature annotations from the FEATURES table of the record. The Highlight Feature Bar can be used to navigate to and highlight other features and provides links to display the highlighted region separately. Links in the FEATURES table will also highlight the corresponding region of the sequence. More... ...
Design To show a HR advantage of 0.6 in progression-free survival (PFS) for FCGR2A-HH versus the rest and FCGR3A-VV versus the rest, with an 80% power, 80 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type (KRAS-WT) and 52 KRAS-WT patients are required, respectively. This leads to a total sample size of 952 and 619 patients, respectively. Samples were collected from 1123 mCRC patients from 15 European centres treated with cetuximab alone or in combination with chemotherapy. Fc gamma receptor (FCGR) status was centrally genotyped. Two additional externally genotyped series were included. ...
KRAS - KRAS mutant (Q61R), Myc-DDK-tagged ORF clone of Homo sapiens v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), transcript variant b as transfection-ready DNA available for purchase from OriGene - Your Gene Company.
Ras is a family of related proteins which is expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells (cellular signal transduction). Ras is the prototypical member of the Ras superfamily of proteins, which are all related in 3D structure and regulate diverse cell behaviours. When Ras is switched on by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation and survival. Mutations in ras genes can lead to the production of permanently activated Ras proteins. As a result, this can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals. Because these signals result in cell growth and division, overactive Ras signaling can ultimately lead to cancer. The 3 Ras genes in humans (HRas, KRas, and NRas) are the most common oncogenes in human cancer; ...
Kras: | |GTPase KRas| also known as |V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog| a... World Heritage Encyclopedia, the aggregation of the largest online encyclopedias available, and the most definitive collection ever assembled.
Colon cancer accounts for a large proportion of all the cancer-associated morbidities worldwide. tumor stage and location, and genetic status of mismatch repair (MMR), Kirsten rat sarcoma viral oncogene homolog (KRAS), B-Raf proto-oncogene lorcaserin HCl novel inhibtior serine/threonine kinase (BRAF) and tumor protein p53 (TP53). In the present study, the mRNA expression levels of TAZ, AXL and CTGF were evaluated, and the TAZ-AXL-CTGF signature was correlated with the available pathological parameters and survival data. Overexpression of TAZ, AXL and CTGF was observed to be associated with severe pathological stage, deficiency in MMR, colon lorcaserin HCl novel inhibtior cancer subtype C4 and mutations in the BRAF gene. In addition, overexpression of lorcaserin HCl novel inhibtior TAZ-AXL-CTGF was associated with short overall survival in patients with mutations in the TP53 gene, colon cancer subtype C6, proficient MMR and wild-type status of the KRAS and BRAF genes. Furthermore, the prognostic ...
Drug safety update. Cetuximab: importance of establishing wild type RAS (KRASand NRAS) status before treatment of metastatic colorectal cancer. In the treatment of metastatic colorectal cancer, inferior overall survival, progression-free survival, and objective response rates have been shown in people with RAS mutations (at exons 2, 3, and 4 ofKRAS and NRAS) who received cetuximab in combination with FOLFOX4 (oxaliplatin-containing) chemotherapy versus FOLFOX4 alone. Cetuximab is now indicated for the treatment of people with epidermal growth factor receptor (EGFR)-expressing, RAS wild-type metastatic colorectal cancer in combination with irinotecan or oxaliplatin based chemotherapy or as a single agent.. Combined hormonal contraceptives and venous thromboembolism: review confirms risk is small-consider risk factors and remain vigilant for signs and symptoms. A review of the latest evidence on the risk of thromboembolism in association with combined hormonal contraceptives (CHCs) has concluded ...
The morphological features of tumors are closely related to their growth patterns [8]. Polypoid tumors are believed to exhibit a predominantly vertical growth pattern, rather than a horizontal growth pattern, while non-polypoid tumors are believed to exhibit the opposite pattern, resulting in horizontal growth. Although there are some reports that LSTs have distinct biological characteristics compared to polypoid tumors [9, 10], the mechanism by which the LST conformation is generated remains unknown.. LSTs are believed to have distinct characteristics in terms of histological and genetic features [11]. Several molecular characteristics of LSTs have been described, including alteration of the adenomatous polyposis coli (APC) gene or β-catenin [12-14] affecting the WNT/APC/β-catenin signaling pathway, mutation of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) [12, 15-20]. However, the molecular background of LSTs has remained largely unknown [19, 21]. Most of these studies have ...
TY - JOUR. T1 - Sensitivity of wild type and mutant ras alleles to Ras specific exchange factors. T2 - Identification of factor specific requirements. AU - Nielsen, Klaus Hvid. AU - Gredsted, Lars. AU - Broach, James R.. AU - Willumsen, Berthe Marie. PY - 2001/4/19. Y1 - 2001/4/19. N2 - We have investigated the productive interaction between the four mammalian Ras proteins (H-, N-, KA- and KB-Ras) and their activators, the mammalian exchange factors mSos1, GRF1 and GRP, by using a modified Saccharomyces cerevisiae whose growth is dependent on activation of a mammalian Ras protein by its activator. All four mammalian Ras proteins were activated with similar efficiencies by the individual exchange factors. The H-Ras mutant V103E, which is competent for membrane localization, nucleotide binding, intrinsic and stimulated GTPase activity as well as intrinsic exchange, was defective for activation by all factors tested, suggesting that the integrity of this residue is necessary for catalyzed exchange. ...
Determination of fatty acid acquisition routes in an isogenic model with either Akt or Ras pathway activation demonstrated that Akt induces de novo fatty acid synthesis, whereas Ras decreases it. This was most evident for the mono-unsaturated fatty acid oleate (C18:1), of which 96% was produced de novo in Akt-driven cells but only 57% in Ras-driven cells. We confirmed that Akt pathway activation leads to elevated levels of stearoyl-CoA desaturase 1 (SCD1), a key enzyme in the synthesis of oleate, and that Ras pathway activation leads to increased uptake of exogenous lipids. We hypothesized that SCD1 inhibition would therefore be particularly toxic to the Akt-driven cells. We confirmed that Akt activated cells were significantly more sensitive to SCD1 inhibition than those with Ras activation. Growth of Ras-driven cells was unaffected by SCD1 inhibition for multiple doublings, after which the cells stopped growing. We found that growth inhibition coincided with depletion of lysolipids in the ...
Cellular signaling downstream of Ras is highly diversified and may involve many different effector molecules. A potential candidate is AF6 which was originally identified as a fusion to ALL-1 in acute myeloid leukemia. In the present work the interaction between Ras and AF6 is characterized and compared with other effectors. The binding characteristics are quite similar to Raf and RalGEF, i.e. nucleotide dissociation as well as GTPase-activating protein activity are inhibited, whereas the intrinsic GTPase activity of Ras is unperturbed by AF6 binding. Particularly, the dynamics of interaction are similar to Raf and RalGEF with a lifetime of the Ras. AF6 complex in the millisecond range. As probed by 31P NMR spectroscopy one of two major conformational states of Ras is stabilized by the interaction with AF6. Looking at the affinities of AF6 to a number of Ras mutants in the effector region, a specificity profile emerges distinct from that of other effector molecules. This finding may be useful in ...
The RAS/ERK pathway has been intensely studied for about three decades, not least because of its role in human pathologies. ERK activation is observed in the majority of human cancers; in about one-third of them, it is driven by mutational activation of pathway components. The pathway is arguably one of the best targets for molecule-based pharmacological intervention, and several small-molecule inhibitors are in clinical use. Genetically engineered mouse models have greatly contributed to our understanding of signaling pathways in development, tissue homeostasis, and disease. In the specific case of the RAS/ERK pathway, they have revealed unique biological roles of structurally and functionally similar proteins, new kinase-independent effectors, and unsuspected relationships with other cascades. This short review summarizes the contribution of mouse models to our current understanding of the pathway. ...
One of the main goals when developing anticancer therapies is to find a compound that will target a tumor cell but not adversely affect a normal cell. Yagoda et al. discovered one such compound, erastin, in a screen of 24,000 compounds. The compounds were screened for the ability to cause cell death (as determined by Trypan blue exclusion) in an engineered human tumor cell line with oncogenic v-Ha-ras Harvey rat sarcoma viral oncogene homolog (H-Ras)V12 but not in a nontumorigenic cell line that did not contain oncogenic Ras. Ras is a small guanosine triphosphatase that activates the mitogen-activated protein kinase (MAPK) pathway in response to signaling of receptor tyrosine kinases. Three mammalian ras genes are oncogenic: H-ras, K-ras, and N-ras. Light and electron microscopic analyses showed that treatment with erastin did not result in changes in the nucleus that are characteristic of apoptotic cell death, but instead resulted in loss of the structural integrity of mitochondria. The authors ...
Over the past two decades, there have been many attempts to isolate and characterize pharmacological inhibitors targeting Ras-dependent signaling pathways. The small GTPase Ras normally transmits signals downstream of diverse inputs and is a critical signaling node for many cellular activities. Aberrant Ras activity leads to the deregulation of numerous cellular processes including proliferation, survival, cell adhesion and migration, that in turn can contribute to cellular transformation, invasion and metastasis [1], and Ras is mutationally activated in ~30% of cancers [2]. Among the downstream effectors of Ras, the most well-characterized is the Ras-Raf-MAPK signaling pathway, in which Ras interaction with the serine/threonine kinase Raf causes a cascade of kinase activation, with Raf activating the mitogen-activated protein kinase kinases (MAPKK, or MEK) and MEK activating the ERK MAPK, which then translocates to the nucleus to phosphorylate and activate transcription factors to carry out the ...
Alternative Name. HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog; HRAS1; GTPase HRas; p21ras; H-Ras- 1; p19 H-RasIDX protein; c-has/bas p21 protein; transforming protein p21; Ha-Ras1 proto-oncoprotein; c-ras-Ki-2 activated oncogene; GTP- and GDP-binding peptide B; transformation gene: oncogene HAMSV; Ras family small GTP binding protein H-Ras; CTLO; HAMSV; K-RAS; N-RAS; RASH1; C-HRAS; H-RASIDX; C-BAS/HAS; C-HA-RAS1;. ...
Alternative Name. HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog; HRAS1; GTPase HRas; p21ras; H-Ras- 1; p19 H-RasIDX protein; c-has/bas p21 protein; transforming protein p21; Ha-Ras1 proto-oncoprotein; c-ras-Ki-2 activated oncogene; GTP- and GDP-binding peptide B; transformation gene: oncogene HAMSV; Ras family small GTP binding protein H-Ras; CTLO; HAMSV; K-RAS; N-RAS; RASH1; C-HRAS; H-RASIDX; C-BAS/HAS; C-HA-RAS1;. ...
Ras proteins are members of a superfamily of small GTPases that are involved in many aspects of cell growth control. The ras p21 protooncogene products, H-ras, K-ras, and N-ras, transmit signals from growth factor receptors to a cascade of protein kinases that begins with the Raf protooncogene product, and leads to alterations in transcription factors and cell cycle proteins in the nucleus. This cascade is controlled at several points: Ras p21 proteins are regulated by GAPs and by exchange factors, whose activities are altered by growth factor receptor activation (Boguski and McCormick, 1993: Nature 366:643-654). Transmission of signals from Ras to Raf is regulated by the Ras-related protein Rap1 (a protein capable of reverting cell transformation) and by cAMP. Other aspects of Ras p21 regulation will be discussed, including the existence of RasGDl proteins that inhibit GDP dissociation from Ras, and may thus regulate the level of active Ras in the cell. The role of Ras in activation of Raf ...
Standard faecal occult blood testing for colorectal cancer has the benefit of being non-invasive, however, there are problems with sensitivity (tumours may bleed intermittently or not at all) and specificity. Since DNA is continuously released into the faecal stream there is potential for developing new screening tests to detect mutations in tumour DNA. KRAS mutations in tumours can be detected in stools some patients with colorectal cancer. Detection of KRAS mutations alone may be limited as theses occur in less than half of all colorectal cancers and may occur in pancreatic hyperplasia and other non-malignant conditions. However, research into developing tests for multiple DNA alterations, including KRAS, may offer great potential for new non-invasive screening for colorectal cancer with high levels of sensitivity and specificity ...
The mutant forms of KRas, NRas and HRas drive the initiation and progression of a number of human cancers, but less is known about the role of WT (wild-type) Ras alleles and isoforms in cancer. We used zinc-finger nucleases targeting HRas and NRas to modify both alleles of these genes in the mutant KRas-driven Hec1A endometrial cancer cell line, which normally expresses WT copies of these genes. The disruption of either WT isoform of Ras compromised growth-factor-dependent signalling through the ERK (extracellular-signal-regulated kinase) pathway. In addition, the disruption of HRas hindered the activation of Akt and subsequent downstream signalling. This was associated with decreased proliferation, increased apoptosis and decreased anchorage-independent growth in the HRas-disrupted cells. However, xenograft tumour growth was not significantly affected by the disruption of either NRas or HRas. As expected, deleting the mutant allele of KRas abolished tumour growth, whereas deletion of the ...
Why is it so difficult to design a drug for RAS? Well, RAS proteins are small GTPases that cycle between an on state when bound to a small intracellular molecule called GTP, and an off state when GTP is hydrolyzed to GDP. When RAS is on, it is communicating with a multitude of downstream proteins that drive cellular proliferation and survival - two key functions that are necessary for normal cell growth, but must be tightly regulated. However, when RAS is mutated, it is chronically bound to GTP and in the on state. This hyperactive mutant RAS signaling promotes tumor initiation and maintenance, and it allows these corrupted cells to continue proliferating under conditions of DNA damage and metabolic stress. Researchers have attempted to design small molecules that disrupt GTP binding and inhibit activation of RAS, but because the affinity of RAS for GTP is so strong, so far, it has been impossible to generate a compound that can inhibit GTP-binding and RAS signaling.. To circumvent the ...
This trial investigated the efficacy and tolerability of cetuximab + irinotecan + S 1 as a first-line treatment in patients with KRAS wild-type metastatic
Certain KRAS gene mutations are often present in patients with colon, lung and pancreas cancer. Therapeutic antibodies Erbitux® and Vectibix ® are only effective treatment options in patients without KRAS gene mutations. This poster describes how compact sequencing technology can be used as a fast and cost effective alternative to established PCR methods.
UT Southwestern Medical Center cancer researchers have found a molecule that selectively and irreversibly interferes with the activity of a mutated cancer gene common in 30 percent of tumors.
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Although RAS and MYC are well-validated cancer drivers implicated in the growth of a diverse spectrum of cancers, both have largely been considered undruggable cancer targets (17). Renewed efforts have identified promising directions for inhibiting RAS (6), but the development of selective anti-MYC therapies remains a formidable challenge (44, 45). One promising but relatively underexplored strategy to target MYC involves disruption of the signaling mechanisms that promote MYC protein stability (27). For example, we previously found that mutant KRAS prevents MYC degradation in PDAC through both ERK-dependent and ERK-independent signaling mechanisms (14). These findings prompted us to identify additional protein kinase-dependent mechanisms that regulate MYC protein stability in KRAS-mutant PDAC. Targeting of these kinases to promote MYC degradation may then serve as an indirect therapeutic strategy in KRAS-driven cancers. In this study, we applied a MYC degradation screen in the KRAS-mutant ...
Background Receptor tyrosine kinases (RTKs) participate in a multitude of signaling pathways, some of them via the small G-protein Ras. An important component in the activation of Ras is Son of sevenless (SOS), which catalyzes the nucleotide exchange on Ras. Principal Findings We can now demonstrate that the activation of Ras requires, in addition, the essential participation of ezrin, radixin and/or moesin (ERM), a family of actin-binding proteins, and of actin. Disrupting either the interaction of the ERM proteins with co-receptors, down-regulation of ERM proteins by siRNA, expression of dominant-negative mutants of the ERM proteins or disruption of F-actin, abolishes growth factor-induced Ras activation. Ezrin/actin catalyzes the formation of a multiprotein complex consisting of RTK, co-receptor, Grb2, SOS and Ras. We also identify binding sites for both Ras and SOS on ezrin; mutations of these binding sites destroy the interactions and inhibit Ras activation. Finally, we show that the formation of
Aim: To determine the concordance between plasma and tissue RAS mutation status in metastatic colorectal cancer patients to gauge whether blood-based testing is a viable alternative. We also evaluated the change in mutation status on progression. Materials/methods: RAS testing was performed on plasma from patients commencing first-line therapy (OncoBEAM™ RAS CEIVD kit). Results were then compared with formalin-fixed paraffin embedded tumor samples. Results: The overall percentage agreement (concordance) was 86.0% (86/100), which demonstrates that blood-based testing is an alternative to tissue-based testing. Reproducibility was 100% between three laboratories and 20% showed changes in their RAS mutational status on progression. Conclusion: These results show good concordance between tissue and plasma samples and suggest the need for longitudinal plasma testing during treatment to guide management decisions. Keywords: BEAMing; RAS; circulating-free DNA; colon cancer; ctDNA; mCRC. ...
KRAS mutated tumours represent a large fraction of human cancers, but the vast majority remains refractory to current clinical therapies. Thus, a deeper understanding of the molecular mechanisms triggered by KRAS oncogene may yield alternative therapeutic strategies. Here we report the identification of a common transcriptional signature across mutant KRAS cancers of distinct tissue origin that includes the transcription factor FOSL1. High FOSL1 expression identifies mutant KRAS lung and pancreatic cancer patients with the worst survival outcome. Furthermore, FOSL1 genetic inhibition is detrimental to both KRAS-driven tumour types. Mechanistically, FOSL1 links the KRAS oncogene to components of the mitotic machinery, a pathway previously postulated to function orthogonally to oncogenic KRAS. FOSL1 targets include AURKA, whose inhibition impairs viability of mutant KRAS cells. Lastly, combination of AURKA and MEK inhibitors induces a deleterious effect on mutant KRAS cells. Our findings unveil KRAS
Large-scale tumor DNA sequencing campaigns have shown that activating RAS mutations are among the most common drivers of cancer. It is, therefore, not surprising that RAS sits at the epicenter of multiple signal transduction pathways that control cell survival and growth. A primary working hypothesis in our lab is that not all RAS mutations function in the same way and that mutation-specific tailored strategies will be required. To this end we are determined to characterize and understand the unique properties of specific mutant RAS isoforms. So far our work has shed new light on how KRAS G13D, a major cause of colorectal cancer, becomes activated and provided rationalle for new treatment strategies to address other RAS mutations (MCR, 2015). In a related effort we are developing small molecule inhibitors for KRAS G12C, the most common RAS mutation in lung cancer. RAS signaling is contingent upon RAS binding to GTP. Designing small-molecules that compete for the GTP-binding site may seem like an ...
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Buy Dabur Ras-Rasayan with Gold and Pearl - Chaturmukh Ras, Jaimangal Ras, Mahalaxmivilas Ras, Vrihat Purnachandra Ras, Yogendra Ras.
concept that Ras protein may work as oligomers was initially described almost three decades ago when Santos et al. More recently two groups using molecular-dynamic modeling and a variety of biophysical methods have reported dimerization of the G domains of N-Ras (6) and H-Ras (7) when tethered via C-terminal lipid modifications to artificial phospholipid bilayers. Finally Nussinov and colleagues (8) using comparable techniques very recently reported two different modes of dimerization of bacterially expressed and therefore unprocessed K-Ras4B in answer one including α-helices 3 and 4 and the other involving β-sheet interactions of Huperzine A the effector binding region. Importantly both modes of dimerization were dependent on GTP binding. This flurry of activity was fueled in part by the recent discovery that Raf kinases the Ras effectors that transmission down the mitogen-activated protein kinase pathway function as dimers (9-11). In PNAS Nan et al. (12) lend another voice to the growing ...
Here, we have shown that altering the function of Gab1 and SHP-2 modulates the levels of active Ras/MAPK in epidermal cells in association with changes in growth and differentiation. Differentiation induced by dominant-negative Gab1 and SHP-2 mutants is abolished by active Ras, indicating that Gab1/SHP-2 actions in this process may reside upstream of Ras, consistent with prior biochemical data (Itoh et al., 2000; Shi et al., 2000; Cunnick et al., 2002). Duration of MAPK signaling is important in generating different biologic outcomes, but major cell type differences exist in signaling by Ras and its effectors (Shields et al., 2000). We observed that Gab1 and SHP-2 overexpression prolong the persistence of active epidermal MAPK in response to EGF stimulation, consonant with prior observations in fibroblasts and transformed cell lines. However, dominant-negative Gab1 and SHP-2 fail to block MAPK induction in response to strong EGF stimulation, underscoring the contribution of other elements such ...
g ras oncogenes, b ras oncogenes, n ras oncogenes, j ras oncogenes, u ras oncogenes, y ras oncogenes, h eas oncogenes, h das oncogenes, h fas oncogenes, h tas oncogenes, h 5as oncogenes, h 4as oncogenes, h rzs oncogenes, h rss oncogenes, h rws oncogenes, h rqs oncogenes, h raa oncogenes, h raz oncogenes, h rax oncogenes, h rad oncogenes, h rae oncogenes, h raw oncogenes, h ras incogenes, h ras kncogenes, h ras lncogenes, h ras pncogenes, h ras 0ncogenes, h ras 9ncogenes, h ras obcogenes, h ras omcogenes, h ras ojcogenes, h ras ohcogenes, h ras onxogenes, h ras onvogenes, h ras onfogenes, h ras ondogenes, h ras oncigenes, h ras onckgenes, h ras onclgenes, h ras oncpgenes, h ras onc0genes, h ras onc9genes, h ras oncofenes, h ras oncovenes, h ras oncobenes, h ras oncohenes, h ras oncoyenes, h ras oncotenes, h ras oncogwnes, h ras oncogsnes, h ras oncogdnes, h ras oncogrnes, h ras oncog4nes, h ras oncog3nes, h ras oncogebes, h ras oncogemes, h ras oncogejes, h ras oncogehes, h ras oncogenws, h ras ...
c h ras oncogene, b h ras oncogene, g h ras oncogene, f h ras oncogene, v g ras oncogene, v b ras oncogene, v n ras oncogene, v j ras oncogene, v u ras oncogene, v y ras oncogene, v h eas oncogene, v h das oncogene, v h fas oncogene, v h tas oncogene, v h 5as oncogene, v h 4as oncogene, v h rzs oncogene, v h rss oncogene, v h rws oncogene, v h rqs oncogene, v h raa oncogene, v h raz oncogene, v h rax oncogene, v h rad oncogene, v h rae oncogene, v h raw oncogene, v h ras incogene, v h ras kncogene, v h ras lncogene, v h ras pncogene, v h ras 0ncogene, v h ras 9ncogene, v h ras obcogene, v h ras omcogene, v h ras ojcogene, v h ras ohcogene, v h ras onxogene, v h ras onvogene, v h ras onfogene, v h ras ondogene, v h ras oncigene, v h ras onckgene, v h ras onclgene, v h ras oncpgene, v h ras onc0gene, v h ras onc9gene, v h ras oncofene, v h ras oncovene, v h ras oncobene, v h ras oncohene, v h ras oncoyene, v h ras oncotene, v h ras oncogwne, v h ras oncogsne, v h ras oncogdne, v h ras oncogrne, v ...
When contemplating how best to cripple this pathway, several key proteins are reasonable candidates for consideration. Most efforts to design small-molecule inhibitors of RAS-MAPK signaling have focused on the major protein players (i.e., RAS, RAF, MEK, and ERK). We may see more attention devoted in the future, however, to several scaffolding proteins and endogenous inhibitors that also come into play with respect to pathway dynamics (5). Recent advances in the development of genome-wide RNA interference libraries have enabled screening that may potentially identify other novel regulators of MAP signaling amenable to pharmacologic intervention (6, 7).. Is RAS druggable? Attempts to target RAS by perturbing its interaction with either SOS or GRB2 have not yielded viable drug development candidates largely because of the inherent difficulties of disrupting protein-protein interactions with drug-like molecules. Several drug discovery programs have also been devoted to finding inhibitors of ...
TY - JOUR. T1 - The prevalent KRAS exon 2 c.35 G,A mutation in metastatic colorectal cancer patients: A biomarker of worse prognosis and potential benefit of bevacizumab-containing intensive regimens?. AU - Russo, Antonio. AU - Tessitore, Alessandra. AU - Bruera, Gemma. AU - Cannita, Katia. AU - Ricevuto, Enrico. AU - Ficorella, Corrado. AU - Alesse, Edoardo. PY - 2015. Y1 - 2015. N2 - Bevacizumab-containing chemotherapy differently predict increased efficacy in KRAS exon 2 mutant and wild-type metastatic colorectal cancer (MCRC) patients. Mutant compared to wild-type status did not significantly affect progression-free survival (PFS) and overall survival (OS) in patients fit for first line bevacizumab-containing FIr-B/FOx regimen, and after progression. In patients unfit for intensive regimens, mutant status significantly affected PFS, while not OS. Codon 12 KRAS mutations differentially affect GTPase function, and confer worse clinical behaviour. Prognostic relevance of the prevalent c.35 G. ...
BACKGROUND: In lung adenocarcinoma, molecular profiling of actionable genes has become essential to set up targeted therapies. However, the feasibility and the relevance of molecular profiling from the cerebrospinal fluid (CSF) in the context of meningeal metastasis have been poorly assessed. METHODS: We selected patients with stage IV lung adenocarcinoma harbouring metastatic cells in the CSF after cytological analysis. Seven samples from six patients were eligible for molecular testing of epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS), v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) and human epidermal growth factor receptor 2 (HER2) mutations using quantitative polymerase chain reaction (PCR) high-resolution melting curve analysis and Sanger sequencing after DNA extraction from the cell pellets of the CSF ...
Looking for online definition of RAS proteins in the Medical Dictionary? RAS proteins explanation free. What is RAS proteins? Meaning of RAS proteins medical term. What does RAS proteins mean?
Looking for online definition of Ras protein in the Medical Dictionary? Ras protein explanation free. What is Ras protein? Meaning of Ras protein medical term. What does Ras protein mean?
About two-thirds of patients were male, with a median age of 62 years. About half of patients (53%-58%) had a single metastatic site, the majority (62%-64%) had undergone primary tumor resection, and between 14% and 18% had received previous adjuvant treatment. The tumor location was primarily on the left side (80%-84%), and most patients (95%-97%) had BRAF wild-type metastatic colorectal cancer.. After a median follow-up of 13.8 months, the 10-month progression-free survival rate favored the 5-FU/LV plus panitumumab group: 62.8% vs 52.8% with panitumumab alone, with a median progression-free survival of 13 months and 10.2 months, respectively (P = .011).. You can see that 5-FU, the old workhorse drug, seems to be important here. By not giving 5-FU with panitumumab, you had a worse outcome, he observed. You also got about 3 months of progression-free survival benefit. If we had a new drug that gave 3 months of benefit, it would likely be approved. Thats something to consider.. Panitumumab ...
Background KRAS mutation is present in approximately 35-40% of patients with metastatic colorectal cancer (mCRC) and has been established as a predictive marker of resistance to anti-EGFR therapy, but its role as prognostic factor is not yet clear. This study is aimed to analyze the prevalence and the impact in prognosis of expanded number of KRAS mutations in caucasian mCRC population and the sensitivity of the TaqMelt PCR assay cobas KRAS Mutation Test.. Methods A single institution retrospective cohort of 669 consecutive mCRC patients between 2000-9 with clinical follow-up was studied for frequent 7 mutations in codons 12/13 by ARMS-scorpion real-time PCR (Therascreen, Qiagen) and TaqMelt PCR assay cobas KRAS Mutation Test (Roche), which are designed to detect 19 mutations in KRAS codons 12, 13 and 61. DNA was obtained by cobas DNA preparation kit (Roche) from one single 5um FFPE tissue section and by QIAamp DNA FFPE Tissue Kit (Qiagen) from 50um of tissue.. Results KRAS mutation was detected ...
Generation of RAS-targeted therapeutics has long been considered a holy grail in cancer research. However, a lack of binding pockets on the surface of RAS and its picomolar affinity for guanine nucleotides have made isolation of inhibitors particularly challenging. We recently described a monobody, termed NS1, that blocks RAS signaling and oncogenic transformation. NS1 binds to the α4-β6-α5 interface of H-RAS and K-RAS thus preventing RAS dimerization and nanoclustering, which in turn prevents RAS-stimulated dimerization and activation of RAF. Interestingly, NS1 reduces interaction of oncogenic K-RAS, but not H-RAS, with RAF and reduces K-RAS plasma membrane localization. Here, we show that these isoform specific effects of NS1 on RAS:RAF are due to the distinct hypervariable regions of RAS isoforms. NS1 inhibited wild type RAS function by reducing RAS GTP levels. These findings reveal that NS1 disrupts RAS signaling through a mechanism that is more complex than simply inhibiting RAS dimerization
TY - JOUR. T1 - Inhibiting ras signaling in the therapy of breast cancer. AU - Li, Tianhong. AU - Sparano, Joseph A.. PY - 2003/2. Y1 - 2003/2. N2 - Ras is a small guanosine triphosphate-binding protein that plays an important role in signal transduction pathways that influence cellular proliferation, apoptosis, cytoskeletal organization, and other important biological processes. Prenylation of Ras proteins by the enzyme farnesyltransferase renders the protein hydrophobic, causing localization to the inner surface of the cell membrane, where it exerts its biological effects. Ras mutations that result in constitutive activation of the Ras pathway are common in certain human cancers, and transfection of cell lines with mutant Ras renders them tumorigenic. Farnesyltransferase inhibitors (FTIs) were initially developed to inhibit growth of cancers harboring Ras mutations, but preclinical data suggests that they also have antiproliferative effects in cell lines with wild-type Ras. Preclinical data ...
TY - JOUR. T1 - Inhibiting ras signaling in the therapy of breast cancer. AU - Li, Tianhong. AU - Sparano, Joseph A.. PY - 2003. Y1 - 2003. N2 - Ras is a small guanosine triphosphate-binding protein that plays an important role in signal transduction pathways that influence cellular proliferation, apoptosis, cytoskeletal organization, and other important biological processes. Prenylation of Ras proteins by the enzyme farnesyltransferase renders the protein hydrophobic, causing localization to the inner surface of the cell membrane, where it exerts its biological effects. Ras mutations that result in constitutive activation of the Ras pathway are common in certain human cancers, and transfection of cell lines with mutant Ras renders them tumorigenic. Farnesyltransferase inhibitors (FTIs) were initially developed to inhibit growth of cancers harboring Ras mutations, but preclinical data suggests that they also have antiproliferative effects in cell lines with wild-type Ras. Preclinical data ...
Definition : Molecular assay reagents intended to identify mutations in the Harvey rat sarcoma viral oncogene homologue (HRAS) gene, located at chromosome 11p15.5, an oncogene that encodes for a protein involved in cell division. Mutations at this locus have been identified in patients with solid tumor cancers, including bladder cancer, invasive breast cancer, and differentiated liposarcoma; they are also associated with Costello syndrome.. Related Terms : IVD Panels, Human Genetics, Cancer, Somatic Mutation, Bladder , IVD Panels, Human Genetics, Cancer, Somatic Mutation, Myeloid Neoplasm. Entry Terms : Solid Tumor Cancer Gene Mutation Detection Reagents , HRAS Gene Mutation Detection Reagents , Reagents, Molecular Assay, Gene Anomaly, Mutation, HRAS. UMDC code : 24475 ...
by Chalita Washington, Rachel Chernet, Rewatee H. Gokhale, Yesenia Martino-Cortez, Hsiu-Yu Liu, Ashley M. Rosenberg, Sivan Shahar, Cathie M. Pfleger. Dysregulation of the Ras oncogene in development causes developmental disorders, Rasopathies, whereas mutational activation or amplification of Ras in differentiated tissues causes cancer. Rabex-5 (also called RabGEF1) inhibits Ras by promoting Ras mono- and di-ubiquitination. We report here that Rabex-5-mediated Ras ubiquitination requires Ras Tyrosine 4 (Y4), a site of known phosphorylation. Ras substitution mutants insensitive to Y4 phosphorylation did not undergo Rabex-5-mediated ubiquitination in cells and exhibited Ras gain-of-function phenotypes in vivo. Ras Y4 phosphomimic substitution increased Rabex-5-mediated ubiquitination in cells. Y4 phosphomimic substitution in oncogenic Ras blocked the morphological phenotypes associated with oncogenic Ras in vivo dependent on the presence of Rabex-5. We developed polyclonal antibodies raised ...
An experimental Amgen Inc drug that targets a specific genetic mutation shrank tumors in 32% of advanced lung cancer patients and 7% of those with colon cancer, according to data from an early-stage trial presented on Sunday.
The Ras proteins are GTPases that function as molecular switches for signaling pathways regulating cell proliferation, survival, growth, migration, differentiation or cytoskeletal dynamism. Ras proteins transduce signals from extracellular growth factors by cycling between inactive GDP-bound and active GTP-bound states. The exchange of GTP for GDP on RAS is regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Activated RAS (RAS-GTP) regulates multiple cellular functions through effectors including Raf, phosphatidylinositol 3-kinase (PI3K) and Ral guanine nucleotide-dissociation stimulator (RALGDS ...
BACKGROUND: The NCIC CTG/AGITG CO.17 trial demonstrated that cetuximab monotherapy improved overall and progression-free survival (OS and PFS) in patients previously treated for advanced colorectal cancer. A strong relationship was observed between benefit from cetuximab and development of rash. In this analysis, the association of rash and benefit from cetuximab is explored and presented by KRAS mutation status. MATERIAL AND METHODS: Rash was graded by NCI CTC 2.0 criteria. Landmark analysis was performed by excluding patients who died or dropped out within 28 days and then grouping by worst grade of rash experienced by day 28. Multivariate Cox models were conducted separately for patients with KRAS wild-type (WT) tumours and KRAS mutated (MUT) tumours. CO.17 primary outcome was OS. RESULTS: Development of grade 2 + rash on cetuximab was associated with a trend towards increased OS (HR 0.61 with 95% CI 0.36-1.02 and p = 0.06) and PFS (HR 0.68 with 95% CI 0.45-1.03 and p = 0.07) as compared to ...
Saccharomyces cerevisiae contains two RAS genes, RAS1 and RAS2. An insertion mutation in RAS2 (ras2::LEU2) does not affect growth on glucose based media but it does prevent growth on media with pyruvate or other noncarbohydrate carbon sources. This defect is pH sensitive and is most severe at pH 7 and above. The ras2::LEU2 mutation also causes markedly higher levels of glycogen in the derepressed phase of growth after glucose exhaustion. Selection for restoration of growth on pyruvate yields unlinked suppressor mutations. Some of the suppressors also reduce glycogen as well as trehalose (the other reserve carbohydrate in yeast) to levels much lower than those of wild-type strains. These suppressor mutations do not suppress the lethality of ras1 ras2 double mutants. The results indirectly accord with yeast RAS2 governing a G protein activity of adenylate cyclase.. ...
Wounding of tissue induces cellular responses that ultimately result in wound repair. Studies in tissue culture model systems indicate that these responses include induction of AP-1 regulated genes, cell migration and mitogenesis which are also characteristic of cellular responses to growth factors. Investigations have identified cellular ras proteins as critical components of growth factor-stimulated signal transduction pathways, however their role in the wounding response is less clear. Investigation of the potential involvement of c-Ras in this process utilized quiescent living bovine corneal endothelium cells (BCE) which were microinjected with ras dominant interfering mutant protein (N17) and subsequently stimulated by mechanical wounding. Analysis of these cells demonstrated that microinjection of dominant-interfering ras protein, but not control proteins, inhibited the wounding response as evidenced by diminished Fos expression, lack of cell migration and a block in DNA synthesis. ...
In fact, up to one-third of all human cancers have a mutation in one of the RAS genes (there are three of them), making RAS family members the most common cancer-causing genes. Activating RAS mutations are found in up to 90 percent of pancreatic cancers, 50 percent of colon cancers and 30 percent of lung cancers-three of the four deadliest cancers in the United States.. It has been three decades since mutations in RAS genes were first linked to human cancers. Studies since then have shown that turning off activated Ras reverses cancerous characteristics in cells and shrinks tumors in animal models-making Ras an attractive target for cancer therapy. Yet despite intensive investigation, there are no therapies directed at the faulty switch.. Perhaps the time is nigh.. A new national initiative-the Ras Project-aims to bring together the resources and expertise to finally crack the Ras riddle and discover drugs that block its cancer-causing ways.. Increasing technology and increasing knowledge ...
BACKGROUND: Three quarter of endometrial carcinomas are treated at early stage. Still, 15 to 20% of these patients experience recurrence, with little effect from systemic therapies. Homo sapiens v-Ki-ras2 Kirsten rat sarcoma viral oncogenes homologue (KRAS) mutations have been reported to have an important role in tumorigenesis for human cancers, but there is limited knowledge regarding clinical relevance of KRAS status in endometrial carcinomas. METHODS: We have performed a comprehensive and integrated characterisation of genome-wide expression related to KRAS mutations and copy-number alterations in primary- and metastatic endometrial carcinoma lesions in relation to clinical and histopathological data. A primary investigation set and clinical validation set was applied, consisting of 414 primary tumours and 61 metastatic lesions totally. RESULTS: Amplification and gain of KRAS present in 3% of the primary lesions and 18% of metastatic lesions correlated significantly with poor outcome, high ...
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KRAS gene mutations are strong predictors of reduced overall and progression-free survival and greater treatment failure in patients with advanced colorectal cancer undergoing anti-EGFR therapy.
Sigma-Aldrich offers abstracts and full-text articles by [Qi Zhang, Liang Wei, Hongchuan Yang, Wanqi Yang, Qingyu Yang, Zhuofan Zhang, Kailang Wu, Jianguo Wu].
A total of 218 patients with lung adenocarcinoma (EGFR analyzed) who were seen at our clinic between 2012 and 2014 were included in the study. The results of the 18 F-FDG-PET scans for each patient were retrospectively recorded with the associated medical documents. ALK rearrangements were analyzed in 166 of the 218 patients, while 50 of the 218 patients were analyzed for KRAS mutational status. SPSS 15.0 for Windows was used for statistical analysis.. ...
Bardelli A, Corso S, Bertotti A, Hobor S, Valtorta E, Siravegna G, et al. Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer. Cancer Discov 2013;3:658-73.. Patients with metastatic colorectal cancer whose tumors initially respond to EGFR-targeted antibodies develop acquired resistance early on in therapy. Resistance in this setting is primarily driven by secondary mutations in the KRAS oncogene, a downstream component of the EGFR signaling pathway. Interestingly, KRAS mutational status is also a key predictor of primary resistance to anti-EGFR therapy in patients with metastatic colorectal cancer. To identify novel mechanisms of resistance, Bardelli and colleagues performed exome sequencing from three cases obtained before and after anti-EGFR treatment and identified high-level amplification of the MET oncogene mutually exclusive from KRAS mutations in the posttreatment specimens. The MET gene is constitutively activated in other human cancers, and ...
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase epsilon-1 is an enzyme that in humans is encoded by the PLCE1 gene. PLCE1 belongs to the phospholipase family that catalyzes the hydrolysis of polyphosphoinositides such as phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) to generate the second messengers Ins(1,4,5)P3 and diacylglycerol. These products initiate a cascade of intracellular responses that result in cell growth and differentiation and gene expression.[supplied by OMIM] GRCh38: Ensembl release 89: ENSG00000138193 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000024998 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Lopez I, Mak EC, Ding J, Hamm HE, Lomasney JW (May 2001). A novel bifunctional phospholipase c that is regulated by Galpha 12 and stimulates the Ras/mitogen-activated protein kinase pathway. J Biol Chem. 276 (4): 2758-65. doi:10.1074/jbc.M008119200. PMID 11022047. Song C, Hu CD, Masago M, Kariyai K, Yamawaki-Kataoka Y, ...
The prognostic relevance of KRAS status, wild-type or mutant, is not significantly different in MCRC pts treated with BEV-containing chemotherapy. Reported median OS ranges from 29.9 to 38 months in KRAS wild-type and 19.9 to 21 months in KRAS mutant pts [4, 5, 8, 13]. The addition of anti-EGFR or anti-VEGF molecules to doublet chemotherapy predicts a favorable clinical outcome in KRAS wild-type pts [2, 5]. BEV addition to IFL compared to IFL significantly predicts prolonged PFS up to 9.3 months, but not increased OS and activity, in KRAS mutant pts [5, 14]. BEV addition to triplet chemotherapy, according to FIr-B/FOx or FOLFOXIRI/BEV schedules, resulted in high activity and efficacy in KRAS wild-type and mutant MCRC pts [8, 13]. In particular, KRAS mutant pts had an ORR of 67% and 71%, median PFS of 11 and 12.6 months, and median OS 20 months, respectively [8, 13]. We recently reported a significantly favorable prognosis (PFS and OS) in KRAS wild-type L-L compared to O/MM pts [11, 13]. ...
Previous work suggested that desensitization of p21ras in response to growth factors such as epidermal growth factor (EGF) results from receptor down-regulation. Here we show that p21ras is desensitized by insulin in 3T3-L1 adipocytes in the continued presence of activated insulin receptors, while loss of epidermal growth factor and platelet-derived growth factor (PDGF) receptors in response to their ligands correlates with p21ras desensitization. Furthermore, elevated amounts of Grb2/Shc complexes persisted throughout p21ras desensitization by insulin. However, immunoblotting of anti-Son-of-sevenless (Sos) 1 and 2 immunoprecipitates with anti-Grb2 antisera revealed that p21ras desensitization in response to insulin and PDGF, but not EGF, is associated with a marked decrease in cellular complexes containing Sos and Grb2 proteins. Nonetheless, the desensitization of p21ras in response to these stimuli was homologous, in that each peptide could reactivate [32P]GTP loading of p21ras after desensitization
Population included 59% of adenocarcinoma, 37% of women and 19% of non-smokers. Overall mutation rate is 46%: 31 EGFR mutations (13%) and 78 KRAS mutations (33%); 40 new mutations compared to previous study were found: 9 EGFR and 31 KRAS. In the ERMETIC 2 cohort, OS and PFS remained significantly (global test p < 0.01) better for EGFR mutated (hazard ration [HR] 0.57 [95%CI: 0.33-1.00] and 0.47 [0.28-0.78] respectively) and worse for KRAS mutated (HR 1.35 [0.97-1.88] and 1.16 respectively [0.85-1.59]) compared to wild-type (WT) NSCLC. No prognostic significant difference was found in the 177 pts common to both cohorts between pts with KRAS mutation in both cohorts (n= 28) and those with new (n = 31) mutations. In the 228 pts with several techniques, KRAS mutations detected by less sensitive technique (n = 42) have a lower OS compared to WT than those detected only by the best sensitive technique (n = 34), but are not significantly different: 1.63 (1.09-2.44) and 1.08 (0.69-1.69); results between ...
We have applied in vivo intracellular antibody capture (IAC) technology to isolate human intrabodies which bind to the oncogenic RAS protein. IAC facilitates the capture of antibody fragments, in this case single-chain Fvs (scFvs), which tolerate reducing environments, such as the cytoplasm of cancer cells. Three anti-RAS scFvs with different affinity, solubility and intracellular binding activity were characterized. The anti-RAS scFvs with highest affinity were expressed relatively poorly in mammalian cells, and greater soluble expression was achieved by mutating the antibody framework to canonical consensus scaffolds, previously derived from IAC, without losing antigen specificity. Mutagenesis experiments showed that the consensus scaffolds are functional as intrabody fragments without an intra-domain disulfide bond. Furthermore, we could convert an intrabody which does not bind RAS in mammalian cells into a high-affinity reagent capable of inhibiting RAS-mediated NIH 3T3 transformation by exchanging
Malignant gliomas, including oligodendrogliomas (OD) and glioblastomas (GBM), are currently incurable brain tumours with few effective treatment options. A better understanding of the molecular underpinnings of glioma is required to find new and better treatments. The goal of this study is to investigate the function of a protein that turns off gene activity called Capicua (CIC) as an important component of a cell signalling pathway that is often abnormal in cancer, called the Ras/ERK pathway. CIC is mutated in most OD tumours and lost in GBM tumours. In this project, Dr. Gelareh Zadeh and her team aim to understand how the loss of CIC contributes to malignant gliomas and to determine whether its loss impacts the efficacy of drugs that are routinely used to block the Ras/ERK pathway that have shown disappointing results in the clinic so far.. In this project, the team will examine how CIC becomes abnormally regulated, along with how the Ras/ERK pathway is activated in GBM, with the intent to ...
Our new finding of the dose‐dependent shift of signaling modes by a GPCR has several implications. G‐protein‐dependent signaling and G‐protein‐independent signaling are related by their different sensitivity to concentrations of the same agonist. The G‐protein‐dependent signaling of GPCRs is similar to receptor tyrosine kinase signaling through the small GTPase Ras. The G protein‐independent signaling of GPCRs can be compared to cytokine JAK-STAT signaling, in which non‐receptor tyrosine kinases are directly coupled to membrane receptors. Also, it is interesting to note that some seven‐transmembrane receptors, such as Smoothened in Hedgehog gradient signaling, mainly use their C‐terminal tails to directly interact with downstream signaling molecules without the participation of G proteins (Lum and Beachy, 2004). Both the JAK-STAT and the Smoothened pathways result in activation of latent cytoplasmic transcription factors. Src could mediate GPCR‐responsive changes in gene ...
In this new work, Fang and his colleagues instead used fragment-based lead discovery. They screened highly soluble fragments of small molecules at high concentrations and used nuclear magnetic resonance spectroscopy to identify fragments that bind with RAS. We use this approach to probe the RAS protein structure for a binding pocket, said Fang. RAS has a smooth surface topology, so its hard to find a pocket.. Of 3,300 screened fragment compounds, 25 bound to RAS. These 25 fragment compounds all bound in the same pocket, a site very close to the place where RAS binds with SOS, a co-factor that switches RAS from off to on. Our compounds interrupt the RAS-SOS interaction and block the nucleotide exchange reaction that activates RAS, says Fang. Further, when Fang and colleagues applied these compounds to a cellular model, RAS activity dropped by 50%.. The team confirmed that their compounds bind with K-Ras and H-Ras, 2 of the 3 Ras isoforms. The 3 isoforms are very similar in structure, so I ...
Supplementary Materialsba026054-suppl1. proteins-9 nuclease (Cas9) negative-selection testing and discovered a requirement of the catalytic Jumonji (JmjC) area and zinc finger area for leukemia cell success in vitro and in vivo. Furthermore, we discovered that histone H3 lysine 36 methylation (H3K36me) is certainly a marker for JMJD1C activity at gene loci. Furthermore, we performed one cell transcriptome evaluation of mouse leukemia cells harboring an individual information RNA (sgRNA) against the JmjC area and identified elevated activation of RAS/MAPK as well as the JAK-STAT pathway in cells harboring the JmjC sgRNA. We found that upregulation of interleukin 3 (IL-3) receptor genes mediates elevated activation of IL-3 signaling upon JMJD1C reduction or mutation. Along these relative lines, Indoramin D5 we observed level of resistance to JMJD1C reduction in MLLr AML bearing activating RAS mutations, recommending that RAS pathway activation confers level of resistance to JMJD1C reduction. ...
Clone RE688 recognizes the human epidermal growth factor receptor (EGFR) antigen. EGFR is a single-pass type I membrane protein which is also known as receptor tyrosine-protein kinase ErbB-1 or HER1. It is a critical regulator of many normal cellular processes, including cell growth, differentiation, survival, and migration. The EGFR also is implicated in pathological processes of cellular transformation and oncogenesis due to its overexpression in many types of cancers and its ability to induce morphological transformation of cultured cells and tumor formation in nude mice. Many different signaling pathways have been discovered to mediate the effects of EGF, the most notable being Ras-mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3-kinase pathways. In these pathways EGF binds to the EGFR to induce dimerization, catalytic activation, and autophosphorylation of tyrosines in the C-terminal tail of the EGFR. These phosphorylated tyrosines provide docking sites for adapter proteins
Kumarkalyan Ras is a special Ayurvedic medicament that could be extraordinarily healthful for our existence. Ancient scholars have made Kumarkalyan Ras in a way that is beneficial for all sorts of health inclinations especially the ailments which occur in infant and adolescence. Ayurveda believes that all the diseases are directly associated with Vatta, Pitta, and Kapha and Kumarkalyan Ras is increasingly fruitful for alleviating the issues related to what I have mentioned above (Vatta, Pitta, and Kapha). Kumarkalyan Ras holds the benefits of Swarna Bhasma. Swarna Bhasma is highly beneficial for obliterating innumerable health issues especially when it comes to eradicating the digestive issues, Asthma and Fever.. Kumarkalyan Ras does allow us to obliterate the issues associated with the brain. It is because it holds the comprehensive amount of antioxidants in it that allow our body to scavenge the free radical and prevent the extensive damage of the healthy cells. Having the significant amount ...
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Development aspect induced signaling cascades are fundamental regulatory components in tissues advancement regeneration and maintenance. type II cells. Constitutive appearance of B-RAF V600E triggered abnormalities in alveolar epithelium development that resulted in airspace enlargements. These lung lesions demonstrated signs of tissues remodeling and had been often connected with chronic irritation and low occurrence of lung tumors. The inflammatory cell infiltration didnt precede the forming of the lung lesions but was rather followed with past due tumor advancement. These data support a model where in fact the continuous regenerative procedure Posaconazole initiated by oncogenic B-RAF-driven alveolar disruption offers a tumor-promoting environment connected with persistent irritation. Launch The Ras-mitogen-activated proteins kinase (MAPK) pathway is certainly an integral signaling pathway thats mixed up in regulation of regular cell proliferation success development differentiation and ...
Although KRAS is one of the major oncogenes associated with aggressive cancers, drugs designed to block KRAS function have not been able to halt cancer progression in a clinical setting. Until now, KRAS has remained infamously undruggable.. In a new study, published this month in Cancer Discovery, University of California San Diego School of Medicine researchers report that approximately half of lung and pancreatic cancers that originate with a KRAS mutation become addicted to the gene as they progress. By understanding the mechanism that causes these cancers to remain dependent on KRAS for survival, they were able to identify a drug capable of targeting it.. Certain tumors use mutant KRAS to boost their survival by helping them take up nutrients and process toxins, causing them to become addicted to KRAS, said David Cheresh, PhD, UC San Diego School of Medicine Distinguished Professor of Pathology and senior author of the paper. Other tumors that do not use KRAS in this way can do without ...
NewEast Biosciences Ras Activation Assay Kit bases on the configuration-specific anti-Ras-GTP monoclonal antibody to measure the active Ras-GTP levels, either from cell extracts or from in vitro GTP?S loading Ras activation assays. Briefly, anti-active Ras mouse monoclonal antibody will be incubated with cell lysates containing Ras-GTP. The bound active Ras will then be pulled down by protein A/G agarose. The precipitated active Ras will be detected by immunoblot analysis using anti-Ras mouse monoclonal antibody. ...
A cytoplasmic protein that greatly enhances the guanosine triphosphatase (GTPase) activity of N-ras protein but does not affect the activity of oncogenic ras mutants has been recently described. This protein (GAP) is shown here to be ubiquitous in higher eukaryotes and to interact with H-ras as well as with N-ras proteins. To identify the region of ras p21 with which GAP interacts, 21 H-ras mutant proteins were purified and tested for their ability to undergo stimulation of GTPase activity by GAP. Mutations in nonessential regions of H-ras p21 as well as mutations in its carboxyl-terminal domain (residues 165-185) and purine binding region (residues 117 and 119) did not decrease the ability of the protein to respond to GAP. In addition, an antibody against the carboxyl-terminal domain did not block GAP activity, supporting the conclusion that GAP does not interact with this region. Transforming mutations at positions 12, 59, and 61 (the phosphoryl binding region) abolished GTPase stimulation by ...
Frank McCormick, scientific lead of the RAS Initiative, incorporates over 30 suggestions from the RAS community to formulate an updated version of the RAS pathway, v2.0
In higher eukaryotes, the Ras and Raf-1 proto-oncoproteins transduce growth and differentiation signals initiated by tyrosine kinases. The Ras polypeptide and the amino-terminal regulatory domain of Raf-1 (residues 1-257) are shown to interact, directly in vitro and in a yeast expression system. Raf …
Mutational analysis of the KRAS gene in lung cancer patients treated with two different kinase inhibitors suggests that tumors with KRAS mutations do not respond to these drugs.
... is a protein that in humans is encoded by the RASA2 gene. The protein encoded by this gene is ... Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in ... "Identification of the ras GTPase-activating protein GAP1(m) as a phosphatidylinositol-3,4,5-trisphosphate-binding protein in ... "Entrez Gene: RAS p21 protein activator 2". Retrieved 2018-09-14. Lockyer PJ, Wennström S, Kupzig S, Venkateswarlu K, Downward J ...
... or RasGAP (Ras GTPase activating protein), also known as RASA1, is a 120-kDa cytosolic human ... Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in ... "Entrez Gene: RASA1 RAS p21 protein activator (GTPase activating protein) 1". Chow A, Gawler D (October 1999). "Mapping the site ... 1997). "Ras-GTPase activating protein (GAP): a putative effector for Ras". Cell. Signal. 9 (2): 153-8. doi:10.1016/S0898-6568( ...
... is a family of evolutionarily related proteins. Ras proteins are membrane- ... Protein pages needing a picture, Protein domains, Protein families, Membrane proteins, All stub articles, Membrane protein ... As it is the GTP bound form of ras which is active, these proteins are said to be down-regulators of ras. The Ras GTPase- ... Note: There are distinctly different GAPs for the rap and rho/rac subfamilies of ras-like proteins (reviewed in reference) that ...
An important target is the ras protein signal-transduction chain. Tyrosine kinases recruited to a receptor following hormone ... Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and ... Eukaryotic protein kinases are enzymes that belong to a very extensive family of proteins that share a conserved catalytic core ... A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation ...
Activating mutations of the Ras protein and upstream elements of the Ras protein may play a role in more than two-thirds of all ... RRAS2 Mutations in the Ras family of proto-oncogenes (comprising H-Ras, N-Ras and K-Ras) are very common, being found in 20% to ... All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals ... Mutations in Ras genes can lead to the production of permanently activated Ras proteins, which can cause unintended and ...
Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP. The balance ... Protein families, Peripheral membrane proteins, All stub articles, Membrane protein stubs). ... McCormick F, Boguski MS (1993). "Proteins regulating Ras and its relatives". Nature. 366 (6456): 643-654. Bibcode:1993Natur.366 ... Boguski, MS; McCormick, F (1993). "Proteins regulating Ras and its relatives". Nature. 366 (6456): 643-54. Bibcode:1993Natur. ...
Boguski, M. S.; McCormick, F. (1993). "Proteins regulating Ras and its relatives". Nature. 366 (6456): 643-654. doi:10.1038/ ... v t e (Protein domains, Peripheral membrane proteins, All stub articles, Membrane protein stubs). ... RhoGAP domain is an evolutionary conserved protein domain of GTPase activating proteins towards Rho/Rac/Cdc42-like small ... "Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP". Nature. 388 (6643): 693-697. doi: ...
He also published many papers on the structures of protein molecules including human Ras, human cyclin dependent kinase 2 and ... Tong, L.; Milburn, MV; de Vos, AM; Kim, S.-H. (1989). "Structure of Ras Protein". Science. 245 (244): 244. Bibcode:1989Sci... ... small heat shock protein. He is a member of the U.S. National Academy of Sciences and a fellow of the American Academy of Arts ...
Once activated, Ras interacts with several proteins, namely Raf. Activated Raf stimulates MAPK-kinase (MAPKK or MEK) by ... Examination of the different signaling cascades induced by RTKs established Ras/mitogen-activated protein kinase (MAPK), PI-3 ... thereby allowing interaction with Ras and the exchange of GDP for GTP on Ras. Whereas the interaction between Grb2 and PDGFR ... The adaptor protein Grb2 forms a complex with Sos by the Grb2 SH3 domain. Grb2 (or the Grb2/Sos complex) is recruited to the ...
Bosgraaf L, Van Haastert PJ (Dec 2003). "Roc, a Ras/GTPase domain in complex proteins" (PDF). Biochim Biophys Acta. 1643 (1-3 ... 2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi: ... 2006). "LRRK1 protein kinase activity is stimulated upon binding of GTP to its Roc domain". Cell. Signal. 18 (6): 910-20. doi: ... The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 8 (2): 85-95. doi: ...
These Ras genes have GTP/GDP binding and GTPase activity, and their normal function may be as G-like regulatory proteins ... The N-ras proto-oncogene is a member of the Ras gene family. It is mapped on chromosome 1, and it is activated in HL60, a ... Yuasa Y, Gol RA, Chang A, et al. (1984). "Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells". ... The mammalian Ras gene family consists of the Harvey and Kirsten Ras genes (HRAS and KRAS), an inactive pseudogene of each (c- ...
... is a small G protein in the Ras subfamily of the Ras superfamily of small GTPases. Once bound to Guanosine triphosphate, H ... HRAS is in the Ras family, which also includes two other proto-oncogenes: KRAS and NRAS. These proteins all are regulated in ... McCormick F (Dec 1995). "Ras-related proteins in signal transduction and growth control". Molecular Reproduction and ... The rate of conversion is usually slow but can be sped up dramatically by an accessory protein of the GTPase activating protein ...
Ras homolog gene family, member B, also known as RHOB, is a protein which in humans is encoded by the RHOB gene. RHOB is a ... Robertson D, Paterson HF, Adamson P, Hall A, Monaghan P (May 1995). "Ultrastructural localization of ras-related proteins using ... Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG". The Journal of ... Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG". The Journal of ...
His track record includes the discovery of the N-Ras oncogene , the identification of farnesylation of Ras proteins, and the ... His work in the field of cell signalling showed how RAS and other signalling proteins are involved in transmitting signals from ... Hancock, JF; Magee, AI; Childs, JE; Marshall, CJ (June 1989). "All ras proteins are polyisoprenylated but only some are ... Hall, A; Marshall, CJ; Spurr, NK; Weiss, RA (1983). "Identification of transforming gene in two human sarcoma cell lines as a ...
Hurley, JB; Simon, MI; Teplow, DB; Robishaw, JD; Gilman, AG (1984). "Homologies between signal transducing G proteins and ras ... G proteins are a vital intermediary between the extracellular activation of receptors (G protein-coupled receptors) on the cell ... This was due to loss of proteins in these cancer cells. When he introduced the missing protein from normal cells into the ... In 1980, he succeeded in identifying and isolating the new protein, which he named G protein, as it specifically binds to GTP ...
RAS p21 protein activator 4B is a protein that in humans is encoded by the RASA4B gene. GRCh38: Ensembl release 89: ... "Entrez Gene: RAS p21 protein activator 4B". Retrieved 2016-10-15. v t e (Genes on human chromosome 7, All stub articles, Human ...
RAS guanyl releasing protein 4 is a protein in humans that is encoded by the RASGRP4 gene in chromosome 19. The protein encoded ... This protein was shown to activate H-Ras in a cation-dependent manner in vitro. Expression of this protein in myeloid cell ... provided by RefSeq, Apr 2009]. "Entrez Gene: RAS guanyl releasing protein 4". Retrieved 2013-01-31. v t e (Articles with short ... lines was found to be correlated with elevated level of activated RAS protein, and the RAS activation can be greatly enhanced ...
... (Ras-proximate-1 or Ras-related protein 1) is a small GTPase, which are small cytosolic proteins that act like cellular ... These proteins are divided into families depending on their protein structure, and the most well studied is the Ras superfamily ... RIAM (Rap1-GTP-interacting adapter molecule) is a broadly expressed adaptor protein that contains an RA (Ras association)-like ... Rap1 belongs to Ras-related protein family. GTPases are inactive when in their GDP-bound form, and become active when they bind ...
SOS1 activates the small G protein Ras. eIF-2b is a eukaryotic initiation factor necessary to initiate protein translation. eIF ... GEFs are multi-domain proteins and interact with other proteins inside the cell through these domains. Adaptor proteins can ... For example, SOS1, the Ras GEF in the MAPK/ERK pathway, is recruited by the adaptor protein GRB2 in response to EGF receptor ... Ras-GRF1 Kalirin PLEKHG2 Ephexin5 is a RhoA GEF involved in neuronal synapse development. G proteins Guanine Nucleotide ...
RAS protein activator like 3 is a protein that in humans is encoded by the RASAL3 gene. GRCh38: Ensembl release 89: ... "Entrez Gene: RAS protein activator like 3". Retrieved 2016-07-16. Saito S, Kawamura T, Higuchi M, Kobayashi T, Yoshita- ... a novel hematopoietic RasGAP protein, regulates the number and functions of NKT cells". Eur. J. Immunol. 45 (5): 1512-23. doi: ...
Ras suppressor protein 1 is a protein that in humans is encoded by the RSU1 gene. This gene encodes a protein that is involved ... "Entrez Gene: RSU1 Ras suppressor protein 1". Cutler ML, Bassin RH, Zanoni L, Talbot N (1992). "Isolation of rsp-1, a novel cDNA ... Dougherty GW, Chopp T, Qi SM, Cutler ML (2005). "The Ras suppressor Rsu-1 binds to the LIM 5 domain of the adaptor protein ... In mouse, the encoded protein was initially isolated based on its ability to inhibit v-Ras transformation. Multiple ...
Fenwick C, Na SY, Voll RE, Zhong H, Im SY, Lee JW, Ghosh S (2000). "A subclass of Ras proteins that regulate the degradation of ... NF-kappa-B inhibitor beta is a protein that in humans is encoded by the NFKBIB gene. NFKB1 (MIM 164011) or NFKB2 (MIM 164012) ... Chen Y, Wu J, Ghosh G (June 2003). "KappaB-Ras binds to the unique insert within the ankyrin repeat domain of IkappaBbeta and ... Lee JW, Choi HS, Gyuris J, Brent R, Moore DD (1995). "Two classes of proteins dependent on either the presence or absence of ...
There are more than a hundred proteins in the Ras superfamily. Based on structure, sequence and function, the Ras superfamily ... The best-known members are the Ras GTPases and hence they are sometimes called Ras subfamily GTPases. A typical G-protein is ... 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 ...
... functions differently compared to other proteins in the Ras superfamily. Similar to those in the Ras superfamily, the ... The protein is a lipid-anchored, cell-membrane protein with five repeats of the RAS-related GTP-binding region. Also present ... "The Ras-related protein Rheb is farnesylated and antagonizes Ras signaling and transformation". The Journal of Biological ... RHEB also known as Ras homolog enriched in brain (RHEB) is a GTP-binding protein that is ubiquitously expressed in humans and ...
Fenwick C, Na SY, Voll RE, Zhong H, Im SY, Lee JW, Ghosh S (Feb 2000). "A subclass of Ras proteins that regulate the ... NF-κB inhibitor interacting Ras-like 2 is a protein that in humans is encoded by the NKIRAS2 gene. Model organisms have been ... Tago K, Funakoshi-Tago M, Sakinawa M, Mizuno N, Itoh H (Oct 2010). "KappaB-Ras is a nuclear-cytoplasmic small GTPase that ... "Entrez Gene: NFKB inhibitor interacting Ras-like 2". Retrieved 2011-08-30. "Salmonella infection data for Nkiras2". Wellcome ...
Ras association domain-containing protein 1 is a protein that in humans is encoded by the RASSF1 gene. This gene encodes a ... The encoded protein was found to interact with DNA repair protein XPA. The protein was also shown to inhibit the accumulation ... protein similar to the RAS effector proteins. The RASSF1 gene has eight isoforms, of which RASSF1A and RASSF1C are the most ... "The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1". Oncogene. 21 ( ...
Ras and EF-hand domain-containing protein also known as Ras-related protein Rab-45 is a protein that in humans is encoded by ... "RCSB PDB - Protein Feature View - Ras and EF-hand domain-containing protein - Q8IZ41 (RASEF_HUMAN)". Branden C, Tooze J (1999 ... The basic members of this group of proteins are Ras oncogens. It's divided into five major families (Ras, Rho, Arf/Sar, Ran and ... This could provoke a malignant tumor if combined with a separate mutation in a protein's RAS group. RASEF or Rab 45 is ...
This gene encodes a member of the GAP1 family of GTPase-activating proteins that suppresses the Ras/mitogen-activated protein ... "Entrez Gene: RASA4 RAS p21 protein activator 4". Nagase T, Ishikawa K, Miyajima N, et al. (1998). "Prediction of the coding ... Ras GTPase-activating protein 4 is an enzyme that in humans is encoded by the RASA4 gene. ... Consequently, Ras is converted from the active GTP-bound state to the inactive GDP-bound state and no longer activates ...
Ras-related protein Rab-5C is a protein that in humans is encoded by the RAB5C gene. RAB5C belongs to the Ras-related protein ... 2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi: ... encoding a small GTP-binding protein homologous to the Ras-related RAB gene". Cytogenet Cell Genet. 73 (1-2): 137-9. doi: ... "Entrez Gene: RAB5C RAB5C, member RAS oncogene family". Albertsen HM, Smith SA, Mazoyer S, et al. (1994). "A physical map and ...
Ras GTPase-activating protein nGAP is an enzyme that in humans is encoded by the RASAL2 gene. This gene encodes a protein that ... "Entrez Gene: RASAL2 RAS protein activator like 2". Maekawa M, Nakamura S, Hattori S (1993). "Purification of a novel ras GTPase ... GAPs function as activators of Ras superfamily of small GTPases. The protein encoded by this gene is able to complement the ... 2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation ...
Deng L, Garrett RA, Shah SA, Peng X, She Q (March 2013). "A novel interference mechanism by a type IIIB CRISPR-Cmr module in ... Class 2 systems use a single large Cas protein for the same purpose. Class 1 is divided into types I, III, and IV; class 2 is ... Class 1 systems use a complex of multiple Cas proteins to degrade foreign nucleic acids. ...
... is a laboratory technique for the study of protein-protein, protein-peptide, and protein-DNA interactions that ... Gao C, Mao S, Lo CH, Wirsching P, Lerner RA, Janda KD (May 1999). "Making artificial antibodies: a format for phage display of ... a gene encoding a protein of interest is inserted into a phage coat protein gene, causing the phage to "display" the protein on ... characterize small molecules-protein interactions and map protein-protein interactions. Users can use three dimensional ...
Picot D, Loll PJ, Garavito RM (January 1994). "The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1 ... Koki AT, Khan NK, Woerner BM, Seibert K, Harmon JL, Dannenberg AJ, Soslow RA, Masferrer JL (January 2002). "Characterization of ... PTGS (COX, which can be confused with "cytochrome oxidase") enzymes are monotopic membrane proteins; the membrane-binding ... of the protein. The catalytic domain is homologous to mammalian peroxidases such as myeloperoxidase. It has been found that ...
... a major structural protein (VP1) of about 58~60 kDa and a minor capsid protein (VP2). The most variable region of the viral ... Tu ET, Bull RA, Greening GE, Hewitt J, Lyon MJ, Marshall JA, McIver CJ, Rawlinson WD, White PA (2008). "Epidemics of ... The protein MDA-5 may be the primary immune sensor that detects the presence of noroviruses in the body. Some people have ... The vaccine relies on using a virus-like particle that is made of the norovirus capsid proteins in order to mimic the external ...
PI3K Akt IKK NFkB Caspase 9 STAT3 p38 MAPK VEGF IL-8 Shc Grb2/SOS Ras Raf MEK1 / MEK2 Erk1/2 FAK p190Rho/GAP Paxillin p130CAS ... c-Src can be activated by many transmembrane proteins that include: adhesion receptors, receptor tyrosine kinases, G-protein ... Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src (cellular Src; pronounced "sarc ... Nada S, Okada M, MacAuley A, Cooper JA, Nakagawa H (May 1991). "Cloning of a complementary DNA for a protein-tyrosine kinase ...
Floyd T, Nelson RA (1990). "Bone Metabolism in Black Bears". Bears: Their Biology and Management. 8: 135-137. doi:10.2307/ ... Lundberg, D. A.; Nelson, R. A.; Wahner, H. W.; Jones, J. D. (1976). "Protein metabolism in the black bear before and during ... Hibernating bears are able to recycle their proteins and urine, allowing them to stop urinating for months and to avoid muscle ... Nelson, R. A. (1980). "Protein and fat metabolism in hibernating bears". FASEB J. 39 (12): 2955-2958. PMID 6998737. Lohuis, T. ...
Thomas SH, Wagner RD, Arakaki AK, Skolnick J, Kirby JR, Shimkets LJ, Sanford RA, Löffler FE (May 2008). "The mosaic genome of ... Myxobacteria are also known to produce gephyronic acid, an inhibitor of eukaryotic protein synthesis and a potential agent for ... Sasse F, Steinmetz H, Höfle G, Reichenbach H (January 1995). "Gephyronic acid, a novel inhibitor of eukaryotic protein ...
Perlman R, Schiemann WP, Brooks MW, Lodish HF, Weinberg RA (2001). "TGF-beta-induced apoptosis is mediated by the adapter ... Death-associated protein 6 also known as Daxx is a protein that in humans is encoded by the DAXX gene. Daxx, a Death domain- ... This protein also associates with centromeres in G2 phase. In the cytoplasm, the encoded protein may function to regulate ... It interacts with a wide variety of proteins, such as apoptosis antigen Fas, centromere protein C, and transcription factor ...
Gruters RA, Neefjes JJ, Tersmette M, de Goede RE, Tulp A, Huisman HG, Miedema F, Ploegh HL (1987). "Interference with HIV- ... Murphy CI, Lennick M, Lehar SM, Beltz GA, Young E (Oct 1990). "Temporal expression of HIV-1 envelope proteins in baculovirus- ... Montefiori DC, Robinson WE, Mitchell WM (Dec 1988). "Role of protein N-glycosylation in pathogenesis of human immunodeficiency ... v t e (Genes on human chromosome 15, All stub articles, Protein stubs). ...
"The eps8 Family of Proteins Links Growth Factor Stimulation to Actin Reorganization Generating Functional Redundancy in the Ras ... Epidermal growth factor receptor kinase substrate 8-like protein 1 is an enzyme that in humans is encoded by the EPS8L1 gene. ... This gene encodes a protein that is related to epidermal growth factor receptor pathway substrate 8 (EPS8), a substrate for the ... The function of this protein is unknown. Several alternatively spliced transcript variants encoding different isoforms exist. ...
This family consists of 9 proteins although most of them are known to have one or more isoforms. These proteins are: chemokine- ... "A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLE". Journal of Immunology Research. 2018: ... Li H, Guo X, Shao L, Plate M, Mo X, Wang Y, Han W (March 2010). "CMTM5-v1, a four-transmembrane protein, presents a secreted ... That is, the methylation of a cluster(s) regulates its nearby gene by blocking it from making mRNAs and thereby the proteins ...
Gilman S, Koeppe RA, Chervin RD, Consens FB, Little R, An H, et al. (July 2003). "REM sleep behavior disorder is related to ... Tau proteins have been found in some glial cytoplasmic inclusion bodies. Clinical diagnostic criteria were defined in 1998 and ... A modified form of the alpha-synuclein protein within affected neurons may cause MSA. About 55% of MSA cases occur in men, with ... In 2020, researchers at The University of Texas Health Science Center at Houston concluded that protein misfolding cyclic ...
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 is a protein that in humans is encoded by the GNG4 gene. GNG4 ... Cuello F, Schulze RA, Heemeyer F, Meyer HE, Lutz S, Jakobs KH, Niroomand F, Wieland T (2003). "Activation of heterotrimeric G ... "Entrez Gene: GNG4 guanine nucleotide binding protein (G protein), gamma 4". Yan K, Kalyanaraman V, Gautam N (Mar 1996). " ... "A direct interaction between G-protein beta gamma subunits and the Raf-1 protein kinase". J. Biol. Chem. 270 (24): 14251-4. doi ...
Proteins are made of amino acids arranged in a linear chain joined by peptide bonds. Many proteins are enzymes that catalyze ... Capaldi RA, Aggeler R (March 2002). "Mechanism of the F(1)F(0)-type ATP synthase, a biological rotary motor". Trends in ... In prokaryotes, these proteins are found in the cell's inner membrane. These proteins use the energy from reduced molecules ... Amino acids are made into proteins by being joined in a chain of peptide bonds. Each different protein has a unique sequence of ...
The plasma protein binding of threohydrobupropion is 42%. Threohydrobupropion is formed from bupropion via reduction of the ... Bondarev ML, Bondareva TS, Young R, Glennon RA (August 2003). "Behavioral and biochemical investigations of bupropion ...
Martienssen RA, Colot V (August 2001). "DNA methylation and epigenetic inheritance in plants and filamentous fungi". Science. ... of breast and ovarian cancers the protein encoded by DIRAS3 is not expressed, suggesting that it functions as a tumor ... Bjornsson HT, Albert TJ, Ladd-Acosta CM, Green RD, Rongione MA, Middle CM, Irizarry RA, Broman KW, Feinberg AP (May 2008). "SNP ... "DNA sequence polymorphisms within the bovine guanine nucleotide-binding protein Gs subunit alpha (Gsα)-encoding (GNAS) genomic ...
To recognize protein as designated substrate, 19S complex has subunits that are capable to recognize proteins with a special ... Simon JH, Gaddis NC, Fouchier RA, Malim MH (Dec 1998). "Evidence for a newly discovered cellular anti-HIV-1 phenotype". Nature ... Accordingly, misfolded proteins and damaged protein need to be continuously removed to recycle amino acids for new synthesis; ... The 19S regulatory particles can recognize ubiquitin-labeled protein as degradation substrate, unfold the protein to linear, ...
They exhibit a high degree of protein dynamics, alone or in complex. Several types of catenins work with N-cadherins to play an ... One possible way to achieve this, which has been successful in mouse models, is to use inhibitors of Ras activation in order to ... Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells. The first two ... Nam JS, Ino Y, Sakamoto M, Hirohashi S (September 2002). "Ras farnesylation inhibitor FTI-277 restores the E-cadherin/catenin ...
As tendons develop they lay down collagen, which is the main structural protein of connective tissue. As tendons pass near bony ... RA (2016). "Chapter 5: Diseases and surgery of the globe and orbit". In Gilger, BC (ed.). Equine Ophthalmology (3rd ed.). John ... Pepsin allows for the further breakdown of proteins into amino acid chains. Other enzymes include resin and lipase. ... Most food is digested and absorbed into the bloodstream from the small intestine, including proteins, simple carbohydrate, fats ...
The protein encoded by this gene belongs to the CD28 and CTLA-4 cell-surface receptor family. It forms homodimers and plays an ... Shilling RA, Bandukwala HS, Sperling AI (Oct 2006). "Regulation of T:B cell interactions by the inducible costimulator molecule ... ICOS+protein at the US National Library of Medicine Medical Subject Headings (MeSH) Human ICOS genome location and ICOS gene ... Beier KC, Hutloff A, Dittrich AM, Heuck C, Rauch A, Büchner K, Ludewig B, Ochs HD, Mages HW, Kroczek RA (Dec 2000). "Induction ...
Mucin and cadherin-like protein is a protein that in humans is encoded by the MUPCDH gene. This gene is a novel mucin-like gene ... Paris MJ, Williams BR (Jan 2001). "Characterization of a 500-kb contig spanning the region between c-Ha-Ras and MUC2 on ... 2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and ... The role of the hybrid extracellular region and the specific function of this protein have not yet been determined. Alternative ...
... proteins are of interest for biotechnology and industrial use due to their thermostable nature. One application is ... Chen, L; Brügger, K; Skovgaard, M; Redder, P; She, Q; Torarinsson, E; Greve, B; Awayez, M; Zibat, A; Klenk, HP; Garrett, RA ( ... Intracellular proteins are not necessarily stable at low pH however, as Sulfolobus species maintain a significant pH gradient ... They are also unique in the sense that the genes encoding the structural proteins of the virus are constantly transcribed and ...
By suppressing Jarid1b protein level, miR-137 is believed to play a role in modulating the differentiated state of mouse ESCs. ... Langevin SM, Stone RA, Bunker CH, Grandis JR, Sobol RW, Taioli E (May 2010). "MicroRNA-137 promoter methylation in oral rinses ... miR-137 is located on chromosome 1p22 within the non-protein-coding RNA gene AK094607. It is transcribed as a non-coding ... This binding in turn results in an inhibition of translation of the target protein or degradation of the target messenger RNA. ...
FLS that are present in the synovium during RA display altered phenotype compared to the cells present in normal tissues. They ... Specific for fibroblast-like synoviocytes is also the expression of CD55; this protein is often used to identify this cell type ... These hallmark features of FLS in RA are divided into 7 cell-intrinsic hallmarks and 4 cell-extrinsic hallmarks. The cell- ... These include especially lubricin, a protein crucial for the joint lubrication. Furthermore these cells express a number of ...
Wen ST, Van Etten RA (October 1997). "The PAG gene product, a stress-induced protein with antioxidant properties, is an Abl SH3 ... Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL ... Welch PJ, Wang JY (November 1993). "A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl ... Yamanashi Y, Baltimore D (January 1997). "Identification of the Abl- and rasGAP-associated 62 kDa protein as a docking protein ...
In Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A (1993). Pagon RA, Bird TD, Dolan CR, et ... a consensus significant loss of betasheet structure of the Notch3 protein has been predicted using in silico analysis. MRIs ... Deficiencies of intracellular signaling peptides and proteins, Cerebrovascular diseases, Skin conditions resulting from errors ...
Free radicals can damage proteins, lipids or DNA. Glycation mainly damages proteins. Damaged proteins and lipids accumulate in ... Miller RA (April 2001). "Biomarkers of aging: prediction of longevity by using age-sensitive T-cell subset determinations in a ... Chemical damage to structural proteins can lead to loss of function; for example, damage to collagen of blood vessel walls can ... These adducts can further rearrange to form reactive species, which can then cross-link the structural proteins or DNA to ...
Pinto LH, Holsinger LJ, Lamb RA (May 1992). "Influenza virus M2 protein has ion channel activity". Cell. 69 (3): 517-28. doi: ... which can modulate protein trafficking of viral proteins or protect the proteins from the low pH they would otherwise encounter ... Holins, small pore-forming transmembrane proteins produced by dsDNA bacteriophages Thomaston JL, Alfonso-Prieto M, Woldeyes RA ... The human papillomavirus 16 E5 protein, the least well-studied of the three known oncogenic HPV proteins, was reported in 2012 ...
Lin J, Lin L, Thomas DG, Greenson JK, Giordano TJ, Robinson GS, Barve RA, Weishaar FA, Taylor JM, Orringer MB, Beer DG (2004 ... The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the ... MAGEA10 (MAGE family member A10) is a protein-coding gene in humans clustered at chromosomal location Xq28. This gene is a ... "MAGE-A10 is a nuclear protein frequently expressed in high percentages of tumor cells in lung, skin and urothelial malignancies ...
ras GTPase-activating protein 2. Names. GTPase-activating protein 1m. GTPase-activating protein of RAS. ... Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in ... RasGAP_RASA2; Ras-GTPase Activating Domain of RASA2. smart00323. Location:301 → 642. RasGAP; GTPase-activator protein for Ras- ... RasGAP_RASA2; Ras-GTPase Activating Domain of RASA2. smart00323. Location:301 → 642. RasGAP; GTPase-activator protein for Ras- ...
Previous symbols and names : Synaptic Ras GTPase activating protein 1 homolog (rat), synaptic Ras GTPase activating protein 1 ... SYNGAP1 - synaptic Ras GTPase activating protein 1. *Synonym(s) : KIAA1938, RASA5, SYNGAP ...
ProSpecs Member RAS Oncogene Family include: Recombinant Human RAB27A, Recombinant Human RAB11A. ... Member RAS Oncogene Family Function. RAN is a GTP binding protein that is small in size and is part of the RAS superfamily that ... About Member RAS Oncogene Family:. Member RAS Oncogene Family consists of RAN, which is a Protein Coding gene. Diseases that ... The RAN protein also plays a role in the progression of the cell cycle and in controlling DNA synthesis. For the RAN to be ...
Protein (GST tag). Spezies: Human. Quelle: Wheat germ. Jetzt Produkt ABIN1317037 bestellen. ... RAB13, Member RAS Oncogene Family (RAB13) (AA 1-200) protein (His tag) RAB13 Spezies: Rind (Kuh) Wirt: Hefe Recombinant > 90 % ... RAB13, Member RAS Oncogene Family (RAB13) (AA 1-200) protein (His tag) RAB13 Spezies: Ratte Wirt: Hefe Recombinant > 90 % ELISA ... RAB13 Protein (RAB13, Member RAS Oncogene Family) (AA 1-203) (GST tag). RAB13 Spezies: Human Wirt: Wheat germ Recombinant AP, ...
The mRNA and protein expressions of RhoC, ROCK1, and ROCK2 were detected by quantitative reverse transcription-polymerase chain ... the mRNA and protein expressions of RhoC, ROCK1, and ROCK2 in RPMI8226 and U266 cells were significantly decreased with single ... We found that 5-Aza-Dc and TSA can effectively decrease the mRNA and protein expressions of RhoC, ROCK1, and ROCK2. Furthermore ... The aim of this study was to explore the impact of Ras homolog C/Rho-associated coiled-protein kinase (Rho/ROCK) signaling ...
Title: Mevalonate-Ras Homology (Rho)/Rho-Associated Coiled-Coil-Forming Protein Kinase (ROCK)-Mediated Signaling Pathway as a ... Activation of the Ras homology (Rho)/Rho-associated coiled-coil-forming protein kinase (ROCK)-mediated signaling pathway with ... Activation of the Ras homology (Rho)/Rho-associated coiled-coil-forming protein kinase (ROCK)-mediated signaling pathway with ... Mevalonate-Ras Homology (Rho)/Rho-Associated Coiled-Coil-Forming Protein Kinase (ROCK)-Mediated Signaling Pathway as a ...
The expression of Jun proteins is not significantly altered in v-ras(Ha) keratinocytes. Transduction of cells with v-ras(Ha) ... The expression of Jun proteins is not significantly altered in v-ras(Ha) keratinocytes. Transduction of cells with v-ras(Ha) ... The expression of Jun proteins is not significantly altered in v-ras(Ha) keratinocytes. Transduction of cells with v-ras(Ha) ... The expression of Jun proteins is not significantly altered in v-ras(Ha) keratinocytes. Transduction of cells with v-ras(Ha) ...
Overexpression of mitogen-activated protein kinase superfamily proteins unrelated to Ras and AF-1 of estrogen receptor α ... Ras is the prototypical member of a class of low molecular weight GTP binding proteins involved in the regulation of many ... Establishment of Ras Effector-Loop LNCaP Stable Cell Lines.. LNCaP cells were transfected with 5 μg of Ras vector {N-[1-(2,3- ... MAPK Activation in Ras Effector-Loop Stable Cell Lines.. Ras is a common downstream focal point of many growth factor signaling ...
Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs (Homo sapiens) * mutant RAS:GTP:p-RAF:MAP2Ks:MAPKs:scaffold proteins [plasma ... Mutant RAS:p-RAF complexes phosphorylate MAP2Ks (Homo sapiens) * mutant RAS:GTP:p-RAF:MAP2Ks:MAPKs:scaffold proteins [plasma ... mutant RAS:GTP:p-RAF:MAP2Ks:MAPKs:scaffold proteins [plasma membrane] Stable Identifier ... Signaling by RAS mutants (Homo sapiens) * Signaling downstream of RAS mutants (Homo sapiens) * ...
A Ras GTPase activating protein tumor suppressor (RasGAP), DAB2 interacting protein (DAB2IP), was discovered as an miR-431 ... Overexpression of DAB2IPs rat homolog, but not its mutant defective in Ras GTPase activating protein activity, reverses miR- ... Taken together, miR-431 silences DAB2IP to active Ras/Erk and promote metastasis of PNETs. miR-431 may be targeted to manage ... Herein, we show that miR-431 overexpression activates Ras/extracellular signal-regulated kinase (Erk) signaling and promotes ...
SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras ... SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras ... revealed that the SPN domain is an unexpected Ras-association domain with high affinity for GTP-bound Ras and Rap G-proteins. ... SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras. Nature Cell Biology, 19 (4). 292 - 305. ...
The structure of Ras protein: a model for a universal molecular switch. scientific article published on October 1, 1991 ... The cytoplasmic protein GAP is implicated as the target for regulation by the ras gene product. ... The structure of Ras protein: a model for a universal molecular switch (English) ... Crystal structures at 2.2 A resolution of the catalytic domains of normal ras protein and an oncogenic mutant complexed with ...
The Raf-MEKK-MAP kinase pathway is triggered by activation of Ras and thought to be important in Ras transformation of rodent ... The pathways downstream of Ras that are required for transformation are an active topic of research. ... These results suggest that c-Raf-1 is not required for Ras transformation in this system. ... were transfected with H-ras and myc(v). The resulting cell line derived from the knock out cells grew slower both in tissue ...
Recombinant Human Ras-related protein Rab-5B(RAB5B) ... Recombinant Human Ras-related protein Rab-5B(RAB5B). CSB- ... Relevance: Protein transport. Probably involved in vesicular traffic .. Reference: "Lys-N and trypsin cover complementary parts ... storage temperature and the stability of the protein itself. Generally, the shelf life of liquid form is 6 months at -20℃/-80 ...
Researchers discover alternative mechanism for Ras protein activation The protein Ras plays an important role in cellular ... SUMO1 protein may treat and/or prevent heart failure A promising new drug target for the treatment and prevention of heart ... Researchers have focused on the protein because mutations in its gene are found in more than 30 percent of all cancers, making ... Scientists affiliated with VIB and UGent have discovered a mechanism used by the protein A20 to combat inflammation. This could ...
Plasma proteins. Potential drug targets. RAS pathway related proteins. Predicted locationi All transcripts of all genes have ... Protein evidencei Evidence score for genes based on UniProt protein existence (UniProt evidence); a Human Protein Atlas ... Protein classi Assigned HPA protein class(es) for the encoded protein(s). ... HUMAN PROTEIN ATLAS INFORMATIONi Summary of RNA expression and protein localization based on data generated within the Human ...
K-Ras must localize to the plasma membrane (PM) for biological activity. We show here that multiple acid sphingomyelinase (ASM ... ras Proteins Grant support * K99 CA188593/CA/NCI NIH HHS/United States ... Sphingomyelin Metabolism Is a Regulator of K-Ras Function Mol Cell Biol. 2018 Jan 16;38(3):e00373-17. doi: 10.1128/MCB.00373-17 ... K-Ras must localize to the plasma membrane (PM) for biological activity. We show here that multiple acid sphingomyelinase (ASM ...
Ras-Associated protein Rab7. 3q21. CMT2B. Severe sensory loss, ulcerations. 602298. TRPV4 Transient Receptor Potential ... Peripheral myelin protein 22. 17p11.2. CMT1A. HNPP (deletion). 601097. MPZ Myelin Protein Zero. 1q22. CMT1B, CMT1E. Late onset ... Peripheral Myelin Protein 22. 17p11.2. HNPP. CMT1A (duplication). 162500. aGene highlighted in this review.. ALS11, amyotrophic ... Gap Junction associated protein B1. Xq13.1. CMTX1. More severe phenotype in males (demyelinating). 304040. ...
... which moves proteins and other molecules within cells in sac-like structures called vesicles. Learn about this gene and related ... The RAB27A gene provides instructions for making a protein that is involved in a process called vesicle trafficking, ... ras-related protein Rab-27A. *RB27A_HUMAN. Additional Information & Resources. Tests Listed in the Genetic Testing Registry. * ... of any Rab27a protein or lead to the production of an abnormal or unstable protein that cannot form a complex with the proteins ...
Endomembrane Trafficking of Ras: The CAAX Motif Targets Proteins to the ER and Golgi. ...
CURCUMIN INHIBITS CARCINOGEN INDUCED C-HA-RAS AND C-FOS PROTO-ONCOGENES EXPRESSION, AND PROTEIN KINASE C ACTIVITY IN MOUSE SKIN ... c-Ha-ras) proteins in tumorous skin. This was compared with the non-tumorous skin isolated from the same mouse. Dot blot ... The enhanced expression of ras and fos proto-oncogenes in skin tumors in DMBA and TPA-treated animals was decreased by dietary ... Also, it was found that the curcumin inhibited protein kinase C (PKC) activities in mouse epidermal extracts in a dose ...
RAB17 may also be known by the following names: ras-related protein Rab-17. Orthologs of the gene, including human and mouse ... The protein encoded by RAB17 has a predicted amino acid length of 212 and a mass of 23.5 kDa. There are currently 2 reported ... The ELISA kits listed below target RAB17, the symbol for the human gene, RAB17, member RAS oncogene family, and a member of the ...
Pertumbuhan Kompensasi Ayam Betina Hasil Persilangan Antara Ayam Kampung Jantan Dengan Ayam Ras Petelur Betina Yang Mendapat ... dietary protein, P3 type with 16,58% dietary protein, and P4 type with 14,79% dietary protein. At 9 weeks of age, each ... There was also no significant difference of the protein and energy consumption among the treatment groups. Protein efficiency ... Pengaruh Level Protein dengan Koreksi Asam Amino Esensial dalam Pakan terhadap Penampilan dan Nitrogen Ekskreta Ayam Kampung. ...
... expression of type I interferon-induced proteins and proteins involved in extracellular matrix repulation in SLE versus RA and ... expression of type I interferon-induced proteins and proteins involved in extracellular matrix repulation in SLE versus RA and ...
RAS GTPASE-ACTIVATING PROTEINS PROTEINAS ACTIVADORAS DE RAS GTPASA PROTEÍNAS COM DOMÍNIO T T-BOX DOMAIN PROTEINS PROTEINAS DE ... RAS-GRF1 RAS-GRF1 RAS-GRF1 RECEPTOR DO FATOR DE CRESCIMENTO NEURAL RECEPTOR, NERVE GROWTH FACTOR RECEPTOR DE FACTOR DE ... RAN GTP-BINDING PROTEIN PROTEINA DE ENLACE-GTP RAN PROTEÍNA RHO3 DE LIGAÇÃO A GTP RHOB GTP-BINDING PROTEIN PROTEINA DE ENLACE- ... RAB2 GTP-BINDING PROTEIN PROTEINA DE ENLACE-GTP RAB2 PROTEÍNA RAB3A DE LIGAÇÃO A GTP RAB3A GTP-BINDING PROTEIN PROTEINA DE ...
RA is characterized by the proliferation of synoviocytes in inflamed synovia, as well as by their expression of inflammatory ... RA is characterized by the proliferation of synoviocytes in inflamed synovia, as well as by their expression of inflammatory ... Together, our results thus confirm that kirenol has po-tent therapeutic efficacy in RA owing to its ability to suppress ... In the present study, we found that Kirenol inhibited the migration, invasion, and proinflammatory of IL-6 secretion of RA- ...
ras GTPase-Activating Proteins. 1. 2015. 99. 0.140. Why? Dysentery, Bacillary. 1. 2015. 82. 0.140. Why? ...
Our neuropathology data reveals a loss of MATR3 S85C protein in the cell bodies of Purkinje cells and motor neurons, suggesting ... RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature 498, 325-331 (2013). ... Many disease-causing proteins have been identified and studied to understand how these proteins render certain neurons more ... ALS associated mutations in Matrin 3 alter protein-protein interactions and impede mRNA nuclear export. Sci. Rep. 7, 14529 ( ...
Down-regulation of Ras-related Protein Rab 5C-dependent Endocytosis and Glycolysis in Cisplatin-resistant Ovarian Cancer Cell ... A Pipeline for Determining Protein-Protein Interactions and Proximities in the Cellular Milieu*. *Roman I. Subbotin, ... A Novel Immuno-Competitive Capture Mass Spectrometry Strategy for Protein-Protein Interaction Profiling Reveals That LATS ... Determining Protein Complex Structures Based on a Bayesian Model of in Vivo Förster Resonance Energy Transfer (FRET) Data*. * ...
  • A ras oncogene-amplified recombinant BHK-21 cell line (ras-rBHK-IgG) has been established, and was shown to hyperproduce the recombinant IgG chimeric human monoclonal antibody (hMAb) AE6F4, which recognizes lung cancer cells. (elsevier.com)
  • Transfection of primary cells with mutated oncogenic ras plus a cooperating oncogene such as myc results in the acquisition of the transformed cell phenotype. (ox.ac.uk)
  • Researchers have focused on the protein because mutations in its gene are found in more than 30 percent of all cancers, making it the most prevalent human oncogene. (news-medical.net)
  • Using the enhanced chemiluminescence Western blotting detection system (Amersham), we found a relative increase in the cellular oncogene of FBJ murine osteogenic sarcoma virus (c-fos) and cellular oncogene of Harvey rat sarcoma virus (c-Ha-ras) proteins in tumorous skin. (who.int)
  • The ELISA kits listed below target RAB17, the symbol for the human gene, RAB17, member RAS oncogene family, and a member of the Small GTPase superfamily, Rab family. (biocompare.com)
  • Only the ras oncogene (p21) protein was significantly elevated. (cdc.gov)
  • The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. (bvsalud.org)
  • The oncogene-derived protein ONCOGENE PROTEIN P21(RAS) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). (bvsalud.org)
  • The protein encoded by this gene is member of the GAP1 family of GTPase-activating proteins. (nih.gov)
  • The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. (nih.gov)
  • Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. (nih.gov)
  • Identification of the ras GTPase-activating protein GAP1(m) as a phosphatidylinositol-3,4,5-trisphosphate-binding protein in vivo. (nih.gov)
  • cDNA cloning and chromosomal mapping of a novel human GAP (GAP1M), a GTPase-activating protein of Ras. (nih.gov)
  • A Ras GTPase activating protein tumor suppressor (RasGAP), DAB2 interacting protein (DAB2IP), was discovered as an miR-431 target. (ox.ac.uk)
  • Overexpression of DAB2IP's rat homolog, but not its mutant defective in Ras GTPase activating protein activity, reverses miR-431's effect on promoting invasion, Erk phosphorylation, and epithelial-mesenchymal transition of PNETs. (ox.ac.uk)
  • We found that the increased Gankyrin present following Ras activation increased the interaction between the RhoA GTPase and its GDP dissociation inhibitor RhoGDI, which resulted in inhibition of the RhoA effector kinase Rho-associated coiled coil-containing protein kinase (ROCK). (jci.org)
  • PLD1 has also been shown to be associated with the small GTPase RalA, which functions downstream from Ras in a Ras-RalA GTPase cascade that facilitates intracellular signal transduction. (embl.de)
  • These data implicate Arf in the transduction of intracellular signals activated by v-Src and mediated by the Ras-RalA GTPase cascade. (embl.de)
  • Ras proteins are of interest because they contain a C-terminal motif that targets the GTPase to the membrane, and relationships between homologs of TOR and Ras-GTPases have been found in other model organisms. (berkeley.edu)
  • Activation of the Ras homology (Rho)/Rho-associated coiled-coil-forming protein kinase (ROCK)-mediated signaling pathway with simultaneously enhanced myofibroblastic differentiation is involved in this mechanism. (eurekaselect.com)
  • Many of these growth factor receptors engage the Ras/mitogen-activated protein (MAP) kinase pathway as part of their signaling activities. (aacrjournals.org)
  • Here we demonstrate that stable expression of Ras effector-loop mutants that activate the Ras/MAP kinase pathway is sufficient to reduce the androgen requirement of LNCaP prostate cancer cells for growth, prostate-specific antigen expression, and tumorigenicity. (aacrjournals.org)
  • The Raf-MEKK-MAP kinase pathway is triggered by activation of Ras and thought to be important in Ras transformation of rodent fibroblasts. (ox.ac.uk)
  • Our findings suggest that Gankyrin is a key regulator of Ras-mediated activation of Akt through inhibition of the downstream RhoA/ROCK pathway and thus plays an essential role in Ras-induced tumorigenesis. (jci.org)
  • The SHOC2-MRAS-PP1C complex is made up of three proteins that regulate the RAS signaling pathway and help cancer cells with RAS mutations survive. (broadinstitute.org)
  • Scientists have solved the structure of an important complex of RAS-pathway proteins, explaining how known mutations lead to disease and suggesting potential new binding sites for cancer drugs. (broadinstitute.org)
  • Scientists at the Broad Institute of MIT and Harvard and the Dana-Farber Cancer Institute have determined the molecular structure of a RAS-pathway protein called SHOC2 and two other proteins it binds to. (broadinstitute.org)
  • This three-protein assembly, called the SHOC2-MRAS-PP1C ("SMP") complex, regulates the RAS signaling pathway and helps cancer cells with RAS mutations survive. (broadinstitute.org)
  • The high-resolution structure of this complex, revealed through X-ray crystallography and cryogenic electron microscopy, suggests possible ways that drugs can bind to it to inhibit the RAS pathway and block cancer growth. (broadinstitute.org)
  • However, further analyses revealed the structural details of how SHOC2 brings together and binds to two key proteins, PP1C and MRAS, which are also part of the RAS signaling pathway. (broadinstitute.org)
  • RAS/ERK pathway transcriptional regulation through ETS/AP-1 binding sites. (iu.edu)
  • Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis. (bvsalud.org)
  • Considered part of RASopathies, which are caused by dysregulation of the RAS/mitogen-activated protein kinase (MAPK) signaling pathway, which also include ☞ Noonans , ☞ Costello , and Legius Syndromes . (mhmedical.com)
  • FRS2 plays an important role in linking FGF and NGF with the Ras/MAPK signaling pathway, thus relaying information from the cell surface to the nucleus. (novusbio.com)
  • BRAFTOVI® (encorafenib) is an oral small-molecule BRAF kinase inhibitor that targets a key enzyme in the MAPK signalling pathway (RAS-RAF-MEK-ERK). (bjmo.be)
  • Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, including melanoma, colorectal cancer and others. (bjmo.be)
  • The most frequently hyperactivated pathways in this form of cancer are the mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3-kinase (PI3K) pathway . (medscape.com)
  • RAS-RAF pathway alterations are often seen in cutaneous melanoma, with approximately half harboring oncogenic driver mutations in BRAF , nearly 30% harboring NRAS mutations, and about 15% harboring mutations in NF1 . (medscape.com)
  • Rab27a interacts with proteins produced from the MLPH and MYO5A genes to form a complex that transports melanosomes to the outer edges of melanocytes. (medlineplus.gov)
  • The known mutations either prevent the production of any Rab27a protein or lead to the production of an abnormal or unstable protein that cannot form a complex with the proteins produced from the MLPH and MYO5A genes. (medlineplus.gov)
  • Transgenic ALS models usually contain multiple copies of exogenous disease-linked genes and express high levels of proteins under a constitutively active promoter. (nature.com)
  • Some of the most infamous drivers of cancer are mutations in RAS genes, which lead to tumor growth in about a quarter of all cancer patients. (broadinstitute.org)
  • They and their colleagues with Broad's Cancer Dependency Map project were studying essential genes in cancers with mutations in RAS proteins. (broadinstitute.org)
  • In their 2019 study , the team used CRISPR-Cas9 to knock out genes one-by-one across the entire genome to see which ones might be causing RAS-mutated cancer cells to resist the effects of MEK inhibitors. (broadinstitute.org)
  • Proteínas monoméricas de unión al GTP codificadas por GENES RAS. (bvsalud.org)
  • Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). (bvsalud.org)
  • Polymorphisms of cytochrome P450 1A1, glutathione S-transferase class mu, and tumour protein p53 genes and the risk of developing gallbladder cancer in Japanese. (cdc.gov)
  • Integrated transcriptome and protein-protein interaction studies revealed an enrichment of genes implicated in RAS signaling and showed that PRMT6 interacted with CRAF on arginine 100, which decreased its RAS binding potential and altered its downstream MEK/ERK signaling. (mdrresearch.nl)
  • Activating mutations in Ras proteins are present in about 30% of human cancers. (jci.org)
  • At the time, cancer drugs called MEK inhibitors had been developed to target mutations in RAS proteins, but they were effective in only a fraction of cancer patients. (broadinstitute.org)
  • Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells. (iu.edu)
  • We could demonstrate that the treatment with nicotine resulted in increased surface molecules expression, enhanced hu-imDCs-mediated PBMC proliferation, upregulated release of IL-12 in the supernatant of cocultured DCs-PBMC, and augmented phosphorylation of Akt and ribosomal protein S6. (hindawi.com)
  • The productivity of recombinant hMAb from the cells cultured in dishes at high cell densities was higher in protein-free medium than in serum-containing medium.True high density culture of the ras-rBHK-IgG cells was done in protein-free medium using the Tecnomouse, which is a novel hollow fiber bioreactor system. (elsevier.com)
  • After culture for 30 days in protein-free culture, a total amount of about 14 mg of the recombinant hMAb AE6F4 was obtained, and was shown to be reactive against lung cancer cells in tissues. (elsevier.com)
  • Recombinant small G-proteins and human platelet extract were separated by SDS-PAGE and transferred to a PVDF membrane according to the method given in this datasheet. (cytoskeleton.com)
  • Researchers at the Tabriz University of Medical Science found pain and sleep affect inflammatory markers in rheumatoid arthritis (RA) patients. (yuniquemedical.com)
  • Rheumatoid Arthritis (RA) is a chronic inflammatory disease with a slow onset. (yuniquemedical.com)
  • Rheumatoid Arthritis (RA) is a tricky disease. (medlineplus.gov)
  • IJDs include rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and other forms of spondyloarthritis (SpA). (bvsalud.org)
  • MAIN RESULTS: We included two studies with 57 smokers with a diagnosis of rheumatoid arthritis (RA). (bvsalud.org)
  • OBJECTIVE: Carotid plaques (CP) are predictive of acute coronary syndrome in patients with rheumatoid arthritis (RA), suggesting that atherosclerotic plaques in these patients are vulnerable. (bvsalud.org)
  • Endothelial Scaffolding Protein ENH (Enigma Homolog Protein) Promotes PHLPP2 (Pleckstrin Homology Domain and Leucine-Rich Repeat Protein Phosphatase 2)-Mediated Dephosphorylation of AKT1 and eNOS (Endothelial NO Synthase) Promoting Vascular Remodeling. (nih.gov)
  • Here, we show that SHANK1 and SHANK3 act as integrin activation inhibitors by sequestering active Rap1 and R-Ras via the SPN domain and thus limiting their bioavailability at the plasma membrane. (liverpool.ac.uk)
  • We show here that multiple acid sphingomyelinase (ASM) inhibitors, including tricyclic antidepressants, mislocalized phosphatidylserine (PtdSer) and K-RasG12V from the PM, resulting in abrogation of K-RasG12V signaling and potent, selective growth inhibition of mutant K-Ras-transformed cancer cells. (nih.gov)
  • ASM inhibitors also inhibited activated LET-60 (a K-Ras ortholog) signaling in Caenorhabditis elegans , as evidenced by suppression of the induced multivulva phenotype. (nih.gov)
  • Selected compounds, including sphingosine kinase inhibitors, potently inhibited the proliferation of oncogenic K-Ras-expressing pancreatic cancer cells. (nih.gov)
  • Although once considered undruggable, this blog looks at recent advances in RAS inhibitors and emerging therapies. (cas.org)
  • The team wondered whether another protein was enabling mutated RAS proteins to bypass these inhibitors. (broadinstitute.org)
  • In addition, NIAMS researchers are collaborating with investigators outside of NIH to explore whether people with RA who are in remission (no symptoms of the disease) while taking TNF inhibitors are at risk of having symptoms come back if they stop taking the medicine. (medlineplus.gov)
  • SHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function. (liverpool.ac.uk)
  • infected bisecting proteins re-enter endosomal body chains to promote with the SAMM50 regulator and extracellular plasma metazoans to have with the TIMM22 superpathway. (erik-mill.de)
  • Because activator protein 1 (AP-1) proteins are likely targets of Ras activation, we have examined the role of AP-1 factors in v-ras(Ha) keratinocytes. (elsevier.com)
  • Genome-Wide Analysis of RAS/ERK Signaling Targets. (iu.edu)
  • The RA drug tofacitinib, approved for the treatment of RA in 2012, targets a protein that was discovered in the early 1990s by O'Shea and his colleagues. (medlineplus.gov)
  • The aim of this study was to explore the impact of Ras homolog C/Rho-associated coiled-protein kinase (Rho/ROCK) signaling pathways intervention on biological characteristics of the human multiple myeloma cell lines RPMI-8226 and U266 cells, and to investigate the expression of RhoC, ROCK1, and ROCK2 in RPMI-8226 and U266 cells. (medscimonit.com)
  • The pathways downstream of Ras that are required for transformation are an active topic of research. (ox.ac.uk)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. (ox.ac.uk)
  • Cloning of bovine GAP and its interaction with oncogenic ras p21. (wikidata.org)
  • These include genotoxicity, DNA damage, lipid peroxidation, activation of transcription factors activator protein-1 (AP-1) or nuclear factor kappa B (NF-kappaB), and p53 or k-ras gene alterations. (cdc.gov)
  • Membrane thinning in combination with curvature changes may also lead to the lateral transfer of the small lipid-anchored GTPases Ras1 and H-Ras out of lipid rafts for clustering and signaling. (frontiersin.org)
  • Through this project, my main aim is to understand more about the potential relationship between TORC2 and Ras-GTPases of Saccharomyces cerevisiae by analyzing the role of Ras proteins in the complexs localization. (berkeley.edu)
  • In v-ras(Ha) keratinocytes, the A-FOS virus reversed the suppression of keratins 1 and 10 transcripts and protein, which is characteristically seen in tumors and v-ras(Ha) keratinocytes. (elsevier.com)
  • Concordantly, in nude mice, the ASM inhibitor fendiline decreased the rate of growth of oncogenic K-Ras-expressing MiaPaCa-2 tumors but had no effect on the growth of the wild-type K-Ras-expressing BxPC-3 tumors. (nih.gov)
  • The enhanced expression of ras and fos proto-oncogenes in skin tumors in DMBA and TPA-treated animals was decreased by dietary curcumin. (who.int)
  • Hypercalcemia secondary to gastrointestinal stromal tumors: parathyroid hormone-related protein independent mechanism? (medscape.com)
  • In conclusion, these results show that normal SM metabolism is critical for K-Ras function, which may present therapeutic options for the treatment of K-Ras-driven cancers. (nih.gov)
  • In addition, we found that Gankyrin is highly expressed in human lung cancers that have Ras mutations and that increased Gankyrin expression is required for the constitutive activation of Akt and tumorigenesis in these lung cancers. (jci.org)
  • It is estimated that one in five human cancers involve RAS mutations. (cas.org)
  • Prostate cancer ETS rearrangements switch a cell migration gene expression program from RAS/ERK to PI3K/AKT regulation. (iu.edu)
  • The mRNA and protein expressions of RhoC, ROCK1, and ROCK2 were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot, respectively. (medscimonit.com)
  • Pathogenicity in mammalian models was generally correlated with Lys at residue 627 of polymerase basic protein 2. (cdc.gov)
  • Similarly, initiation of mouse keratinocytes with a retrovirus encoding the v-ras(Ha) gene (v-ras(Ha) keratinocytes) causes characteristic alterations of epidermal gene expression (A. A. Dlugosz et al. (elsevier.com)
  • Beta-agonist-induced alterations in organ weights and protein content: comparison of racemic clenbuterol and its enantiomers. (msm.edu)
  • However, increasing evidence has also indicated that the phospholipid bilayer itself by altering various physical parameters serves as a sensor that regulate membrane proteins in a specific manner. (frontiersin.org)
  • This finding has firmly established the importance of local thinning effects on the functioning of membrane proteins ( Andersen and Koeppe, 2007 ). (frontiersin.org)
  • Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain. (wikidata.org)
  • ETS1 is a genome-wide effector of RAS/ERK signaling in epithelial cells. (iu.edu)
  • A-FOS replaces endogenous Fos proteins in the formation of heterodimers with Jun family members and thus prevents the AP-1 transcription factor from binding to DNA. (elsevier.com)
  • We propose that chronic activation of endogenous c-Ras by autocrine and paracrine growth factor stimulation sensitizes the androgen receptor transcriptional complex to subphysiological levels of androgen. (aacrjournals.org)
  • A family of endogenous regulatory proteins that associate with RETINOBLASTOMA PROTEIN via a specific high-affinity binding domain. (musc.edu)
  • They used X-ray crystallography and cryogenic electron microscopy to solve high-resolution structures of SHOC2 and the proteins it interacts with. (broadinstitute.org)
  • ADP interacts P2Y1 and P2Y12, which have via both the download Финансовый анализ and stress: immune characteristics of the inactive G-protein( Hirsch et al. (erik-mill.de)
  • Herein, we show that miR-431 overexpression activates Ras/extracellular signal-regulated kinase (Erk) signaling and promotes epithelial-mesenchymal transition, migration/invasion in vitro, and metastasis in both xenograft and spontaneous mouse models of PNET. (ox.ac.uk)
  • Differential synovial expression of type I interferon-induced proteins and proteins involved in extracellular matrix repulation in SLE versus RA and OA arthritis. (ox.ac.uk)
  • Despite tremendous progress in the study of Ras oncogenes, many aspects of the molecular mechanisms underlying Ras-induced tumorigenesis remain unknown. (jci.org)
  • Shi and Nuttall [9] reported loud sound activated expression of adhesion molecular protein and leukocyte migration. (noiseandhealth.org)
  • It has been shown that FRS2 proteins are tyrosine phos phorylated in response to activation of the RET receptor, a tyrosine kinase that functions as the signal transducing receptor for the GDNF. (novusbio.com)
  • ABSTRACT The study aimed to determine whether serum C-reactive protein (CRP) levels can be used to identify when antibiotics can safely be discontinued in cases of suspected neonatal septicaemia. (who.int)
  • K-Ras must localize to the plasma membrane (PM) for biological activity. (nih.gov)
  • Ras homologues involved in vesicular transport. (embl.de)
  • These findings indicate that AP-1 proteins are involved in the changes in gene expression that define the v-ras(Ha) phenotype in mouse keratinocytes. (elsevier.com)
  • microRNAs are small non-protein-coding RNA molecules that regulate gene expression, and have a potential epigenetic role in disease progression and survival of colorectal cancer. (biomedcentral.com)
  • Members of this family of proteins are often found associated with histone-modifying enzymes and protein complexes that regulate gene expression. (musc.edu)
  • Decrease of interleukin (IL)17a gene expression in leucocytes and in the amount of IL-17a protein in CD4+ T cells in children with Down syndrome. (edu.pl)
  • Introduction of v-ras(Ha) into keratinocytes up-regulates c-Fos, ΔFos B, and Fra-1 transcripts and protein levels in nuclear extracts. (elsevier.com)
  • XIII" YMR047C 3 13 3 YMR047C "Nuclear pore complex protein that is member of GLFG repeat-containing family of nucleoporins and is,XIII" YMR049C 3 13 4 YMR049C "Ymr049cp,XIII" YMR051C 3 13 5 YMR051C "TyA Gag protein. (davidson.edu)
  • An Interaction with Ewing's Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer. (iu.edu)
  • The ARFs are a family of 21,000 M(r) proteins with biological roles in constitutive secretion and activation of phospholipase D. The structure of ARF-1 complexed to GDP determined from two crystal forms reveals a topology that is similar to that of the protein p21 ras with two differences: an additional amino-terminal helix and an extra beta-strand. (embl.de)
  • Cow's milk protein allergy requires changes in family habits to maintain children's health. (bvsalud.org)
  • The diagnosis of allergy to cow's milk protein imposes a series of changes in the family lifestyle2,6,10 related to the prevention of the occurrence of allergic responses10, and to the development of conducts to be performed when these responses occur. (bvsalud.org)
  • Myers MW, Lazzarini RA, Lee VM, Schlaepfer WW, Nelson DL: The human mid-size neurofilament subunit: a repeated protein sequence and the relationship of its gene to the intermediate filament gene family. (t3db.ca)
  • Retinoblastoma Binding Proteins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (musc.edu)
  • This graph shows the total number of publications written about "Retinoblastoma Binding Proteins" by people in this website by year, and whether "Retinoblastoma Binding Proteins" was a major or minor topic of these publications. (musc.edu)
  • Below are the most recent publications written about "Retinoblastoma Binding Proteins" by people in Profiles. (musc.edu)
  • Inhibition of HMG-CoA reductase by statin in effect prevents the synthesis of mevalonic acid, a precursor of nonsteroidal isoprenoids, lipid attachment molecules for small G proteins, such as Ras, Rho, and Rac. (cdc.gov)
  • FRS functions as a lipid-anchored docking protein that is tyrosine phosphorylated and recruited to FGFR upon FGF stimulation. (novusbio.com)
  • Transduction of cells with v-ras(Ha) results in increased AP-1-dependent transcriptional activity, which is also simulated by transfection of keratinocytes with either c-Fos or ΔFos B but not Fra-1, suggesting that the up-regulation of c-Fos and ΔFos B contributes to this effect. (elsevier.com)
  • The cytoplasmic protein GAP is implicated as the target for regulation by the ras gene product. (wikidata.org)
  • The protein Ras plays an important role in cellular growth control. (news-medical.net)
  • Autophosphorylation sites located within the catalytic domain are crucial for stimulation of kinase activity, while autophosphorylation sites located in other regions are usually involved in the recruitment of cellular target proteins. (novusbio.com)
  • Overexpression of wild-type and mutant proteins show similar degrees of phenotypic severity, suggesting that toxicity arises mostly from overexpression rather than from the mutation itself. (nature.com)
  • To explore the role of AP-1 proteins in regulating keratinocyte markers in v-ras(Ha) keratinocytes, we blocked the binding of AP-1 proteins to DNA by infecting keratinocytes with an adenovirus encoding a dominant-negative Fos mutant (A-FOS). (elsevier.com)
  • Determining the factors that increase these markers can help limit the severity of RA. (yuniquemedical.com)
  • Using the celiac assays we are evaluating if there is any correlation between seropositivity for celiac disease and markers for plasma protein abnormalities. (cdc.gov)
  • Autism-related mutations within the SHANK3 SPN domain (R12C and L68P) disrupt G-protein interaction and fail to counteract integrin activation along the Rap1-RIAM-talin axis in cancer cells and neurons. (liverpool.ac.uk)
  • We use a wide variety of approaches ranging from biochemistry to genomics to study the interaction of ETS proteins with the genome and to determine the role these mechanisms play in carcinogenesis. (iu.edu)
  • Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2. (iu.edu)