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 18.104.22.168.
Proto-Oncogene Proteins p21(ras)
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.
Oncogene Protein p21(ras)
Transforming protein encoded by ras oncogenes. Point mutations in the cellular ras gene (c-ras) can also result in a mutant p21 protein that can transform mammalian cells. Oncogene protein p21(ras) has been directly implicated in human neoplasms, perhaps accounting for as much as 15-20% of all human tumors. This enzyme was formerly listed as EC 22.214.171.124.
ras GTPase-Activating Proteins
ras Guanine Nucleotide Exchange Factors
Proto-Oncogene Proteins c-raf
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)
Alkyl and Aryl Transferases
rap GTP-Binding Proteins
Cell Transformation, Neoplastic
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.-.
ral Guanine Nucleotide Exchange Factor
Amino Acid Sequence
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Harvey murine sarcoma virus
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.
ral GTP-Binding Proteins
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.
Monomeric GTP-Binding Proteins
A class of monomeric, low molecular weight (20-25 kDa) GTP-binding proteins that regulate a variety of intracellular processes. The GTP bound form of the protein is active and limited by its inherent GTPase activity, which is controlled by an array of GTPase activators, GDP dissociation inhibitors, and guanine nucleotide exchange factors. This enzyme was formerly listed as EC 126.96.36.199
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.
Son of Sevenless Proteins
Protein Processing, Post-Translational
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Guanine Nucleotide Exchange Factors
Saccharomyces cerevisiae Proteins
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
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.
Recombinant Fusion Proteins
Calcium-Calmodulin-Dependent Protein Kinases
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
Sarcoma Viruses, Murine
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).
Mitogen-Activated Protein Kinases
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Genes, Neurofibromatosis 1
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.
Cell Line, Transformed
Mitogen-Activated Protein Kinase Kinases
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.
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.
NIH 3T3 Cells
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)
MAP Kinase Signaling System
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.
Mitogen-Activated Protein Kinase 1
GRB2 Adaptor Protein
A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).
Cell Cycle Proteins
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Tumor Cells, Cultured
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).)
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.
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.
Extracellular Signal-Regulated MAP Kinases
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.
rhoB GTP-Binding Protein
Sequence Homology, Amino Acid
Gene Expression Regulation
Mitogen-Activated Protein Kinase 3
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
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.
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.
Epidermal Growth Factor
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 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.
Sequence Homology, Nucleic Acid
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 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).
Proto-Oncogene Proteins c-fos
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.
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.
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)
KRAS Wild-type Metastatic Colorectal Cancer Trial - Full Text View - ClinicalTrials.gov
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 ...
Study of AUY922 and Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal Cancer - Full Text View - ClinicalTrials.gov
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 ...
Phase I study of TS-1+irinotecan+cetuximab as the first-line therapy in patients with KRAS wild-type metastatic colorectal...
This study investigated the efficacy and tolerability of gimeracil/oteracil/tegafur + cetuximab + irinotecan in patients with KRAS wild-type metastatic
Medical News| APN News
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 […]. ...
Downregulation of the Ras-Mitogen-Activated Protein Kinase Pathway by the EphB2 Receptor Tyrosine Kinase Is Required for Ephrin...
Thank you for sharing this Molecular and Cellular Biology article.. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.. ...
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 ...
Homo sapiens v-Ha-ras Harvey rat sarcoma viral oncogene homolog mRNA, - Nucleotide - NCBI
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... ...
FCGR polymorphisms and cetuximab efficacy in chemorefractory metastatic colorectal cancer: an international consortium study |...
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. ...
OriGene - KRAS (NM 004985) Human ORF cDNA Clone
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 subfamily - Wikipedia
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 | World eBook Library - eBooks | Read eBooks online
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.
Glutamate (EAAT) Transporters
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 ...
UK MHRA Drug Safety Update (Volume 7, Issue 7) - Viglya: promoting science, honoring life
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 ...
Gene expression profiling of laterally spreading tumors | BMC Gastroenterology | Full Text
The morphological features of tumors are closely related to their growth patterns . 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 . 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 ...
Sensitivity of wild type and mutant ras alleles to Ras specific exchange factors: Identification of factor specific...
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. ...
Ras-driven cancer cells can scavenge exogenous lipids to support their proliferation | BMC Proceedings | Full Text
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 ...
Thermodynamic and kinetic characterization of the interaction between the Ras binding domain of AF6 and members of the Ras...
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 ...
Deciphering the RAS/ERK pathway in vivo | Biochemical Society Transactions
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. ...
Selective Killing | Science Signaling
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 ...
Genetic and functional characterization of putative Ras/Raf interaction inhibitors in C. elegans and mammalian cells
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 , and Ras is mutationally activated in ~30% of cancers . 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 ...
HRAS Exon 2 Primer Set - FemtoPath | HongJing弘晉
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;. ...
HRAS Exon 4 Primer Set (B) - FemtoPath | HongJing弘晉
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;. ...
SMART: Secondary literature for RAS domain
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 ...
KRAS2 - v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog) - aka: Ki-ras, KRAS - Cancer GeneticsWeb
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 ...
A requirement for wild-type Ras isoforms in mutant KRas-driven signalling and transformation | Biochemical Journal
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 ...
TIBBS » NCI Ras Initiative: Lets get together and drug RAS!
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 ...
Study of Cetuximab + Irinotecan + S-1 as first line therapy in metastatic colorectal cancer with KRAS wild type - AdisInsight
This trial investigated the efficacy and tolerability of cetuximab + irinotecan + S 1 as a first-line treatment in patients with KRAS wild-type metastatic
Compact Sequencing Technology for KRAS Companion Diagnostic Testing | SelectScience
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 Cancer Researchers Identify Irreversible Inhibitor for KRAS Gene Mutation Involved in Lung, Colon, and...
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.
UTSW Cancer Researchers Identify Irreversible Inhibitor for KRAS Gene Mutation
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Application of a MYC degradation screen identifies sensitivity to CDK9 inhibitors in KRAS-mutant pancreatic cancer | Science...
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 ...
Activation of Ras Requires the ERM-Dependent Link of Actin to the Plasma Membrane
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
Blood-based RAS mutation testing: concordance with tissue-based RAS testing and mutational changes on progression
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. ...
An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer | Garvan Institute...
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
Research: Ken Westover Lab - UT Southwestern, Dallas, Texas
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 ...
Buy Dabur Ras-Rasayan with Gold and Pearl - Chaturmukh Ras, Jaimangal Ras, Mahalaxmivilas Ras, Vrihat Purnachandra Ras,...
Buy Dabur Ras-Rasayan with Gold and Pearl - Chaturmukh Ras, Jaimangal Ras, Mahalaxmivilas Ras, Vrihat Purnachandra Ras, Yogendra Ras.
Gab1 and SHP-2 promote Ras/MAPK regulation of epidermal growth and differentiation | JCB
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 ...
Table of Contents - September 01, 2014, 15 (9) | EMBO Reports
More than 30% of all human cancers contain activating mutations of the small G‐protein RAS. As a result of this, RAS has been intensely studied and many efforts have been made to identify pathways that sustain RAS‐driven transformation . Recent studies have indicated that the transcription factor GATA2 is one of these partners in crime, but a mechanistic link between RAS and GATA2 had not been identified . A paper in this issue of EMBO reports closes this gap showing that GATA2 can be activated by p38 in RAS‐transformed cells .. See also: KR Katsumara et al (September 2014) ...
Relationships between KRAS mutation status and baseline radiographic distribution of disease in patients with stage IV...
Purpose KRAS oncogene testing is recommended in all patients with metastatic colorectal cancer due to its impact on treatment selection, but we do not know if KRAS genotype affects extent or pattern...
H ras oncogenes - Definition and misspellings for H ras Oncogenes at Spellorg.com
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 ...
V h ras oncogene - Definition and misspellings for v H ras Oncogene at Spellorg.com
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 ...
Advances in the Development of Cancer Therapeutics Directed against the RAS-Mitogen-Activated Protein Kinase Pathway | Clinical...
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 ...
The prevalent KRAS exon 2 c.35 G|A mutation in metastatic colorectal cancer patients: A biomarker of worse prognosis and...
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. ...
Most recent papers with the keyword Cell free tumour DNA | Read by QxMD
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 ...
RAS proteins | definition of RAS proteins by Medical dictionary
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?
Ras protein | definition of Ras protein by Medical dictionary
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?
Maintenance Therapy for Metastatic Colorectal Cancer - The ASCO Post
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 ...
Prognostic role of KRAS mutations detected by high-sensitivity TAQMELT PCR assay in metastatic colorectal cancer | OncologyPRO
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 ...
Targeting the α4-α5 interface of RAS results in multiple levels of inhibition. - Semantic Scholar
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
Inhibiting ras signaling in the therapy of breast cancer<...
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 ...
Inhibiting ras signaling in the therapy of breast cancer<...
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 ...
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 ...
A conserved, N-terminal tyrosine signal directs Ras for inhibition by Rabex-5 - Ominy Science
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 ...
Amgen drug shrinks tumors in lung cancer patients with KRAS gene mutation - study | Reuters
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.
KEGG PATHWAY: Ras signaling pathway - Homo sapiens (human)
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 ...
Adelaide Research & Scholarship: The relationship between rash, tumour KRAS mutation status and clinical and quality of life...
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 ...
On ras gene function in yeast | PNAS
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.. ...
Interference with endogenous ras function inhibits cellular responses to wounding. | JCB
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. ...
Untangling RAS - Vanderbilt-Ingram Cancer Center
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 ...
Bergen Open Research Archive: KRAS gene amplification and overexpression but not mutation associates with aggressive and...
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 ...
Ras pathway activation can increase cellular glucose uptake without insulin stimulation in human adipose tissue derived stem...
Evidence links KRAS mutations to poor survival in colorectal cancer - ONA
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.
Bromodomain containing protein represses the Ras/Raf/MEK/ERK pathway to attenuate human hepatoma cell proliferation during HCV...
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].
Relationship of radiometabolic biomarkers to KRAS mutation status and ALK rearrangements in cases of lung adenocarcinoma | TJ
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 ...
PLCE1 - Wikipedia
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, ...
Worse prognosis of KRASc.35 G | A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet...
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]. ...
Divergent mechanisms for homologous desensitization of p21ras by insul by Jes K. Klarlund, Andrew D. Cherniack et al.
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
ERMETIC-2 project : Impact of systematic EGFR and KRAS mutation evaluation by alternative testing methods on progression-free ...
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 ...
Intrabodies based on intracellular capture frameworks that bind the RAS protein with high affinity and impair oncogenic...
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
Molecular characterization of transcriptional repressor capicua in GBM - Brain Canada
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 ...
Dosage‐dependent switch from G protein‐coupled to G protein‐independent signaling by a GPCR | The EMBO Journal
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 ...
Checkpoint Kinase | Small-Molecule gdc-0152 SMAC Mimetics as New Cancer Therapeutics
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. ...
EGF Receptor Antibody, anti-human, REAfinity™ - Recombinant antibodies - MACS Antibodies - Products - Miltenyi Biotec - Schweiz
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
kumar kalyan ras baidyanath price | Cough Remedies
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 ...
Ras Attitude, Related | United Reggae
Ras Attitude related on United Reggae Magazine. Read Ras Attitude related, discover Ras Attitude discography, watch some Ras Attitude videos or simply listen to Ras Attitude on United Reggae Magazine
Rabbit polyclonal to IL20. | healthweblognews.info
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 ...
Researchers develop new strategy to target KRAS mutant cancer | Science Codex
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. ...
Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain | Science
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 ...
RAS Pathway v2.0 - National Cancer Institute
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
Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1
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 …
KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib
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.
Rasd1, a small G protein with a big role in the hypothalamic response to neuronal activation | Molecular Brain | Full Text
Rasd1 is becoming somewhat of avant-garde member of the Ras family of GTPases by performing many non-conventional signaling functions. Our identification of Rasd1 in Avp neurons starts a new chapter for this small GTPase. Here we show that Rasd1 is rapidly induced by stress in the PVN, and by elevated plasma osmolality in the PVN and SON of the hypothalamus. We propose that the abundance of RASD1 in MCN and PCNs, based on its inhibitory actions on CREB phosphorylation, is an important mechanism for controlling the transcriptional responses to stressors in both the PVN and SON. In MCN we show, by virally mediated overexpression of Rasd1, that Rasd1 inhibits HS induced stimulation of cAMP inducible genes. When a CAAX box deficient mutant form of Rasd1 is expressed in the SON cAMP inducible genes were further increased by SL. These effects likely occur through modulation of cAMP-PKA-CREB signaling pathway.. Our interest in Rasd1 began following identification increased expression of this gene in ...
Boguski, M. S.; McCormick, F. (1993). "Proteins regulating Ras and its relatives". Nature. 366 (6456): 643-654. doi:10.1038/ ... 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 and 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 Science and a fellow of the American Academy of Arts ...
Platelet-derived growth factor receptor
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: ...
... 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 ...
Christopher Marshall (doctor)
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 ...
Alfred G. Gilman
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 bind 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. CS1 maint: discouraged parameter (link) v t e. ...
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. ... 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 ...
Guanine nucleotide exchange factor
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. CS1 maint: discouraged parameter (link) "Salmonella ...
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. Loss or altered expression of this gene has been associated with the pathogenesis ... "The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1". Oncogene. 21 ( ...
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 ...
Another example of TSAs are abnormal products of mutated oncogenes (e.g. Ras protein) and anti-oncogenes (e.g. p53). Tumor- ... Lake RA, van der Most RG (Jun 2006). "A better way for a cancer cell to die". The New England Journal of Medicine. 354 (23): ... Kroemer G, El-Deiry WS, Golstein P, Peter ME, Vaux D, Vandenabeele P, Zhivotovsky B, Blagosklonny MV, Malorni W, Knight RA, ... Syn NL, Teng MW, Mok TS, Soo RA (December 2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet. ...
Parkes Weber syndrome
"RASA1 gene RAS p21 protein activator 1". "RASA1 RAS p21 protein activator 1". "RASA1 gene RAS p21 protein activator 1". ... RASA1 gene is responsible for making p120-RasGAP protein. This protein regulates the RAS/MAPK signaling pathway. RAS/MAPK ... The p120-RasGAP protein regulates the RAS/MAPK pathway by acting as a negative regulator of the signaling pathway. It turns off ... The protein no longer regulates the RAS/MAPK signaling pathway. However, according to NIH Genetics Home Reference, it is still ...
Ras-related protein Rap-2b is a protein that in humans is encoded by the RAP2B gene. RAP2B belongs to the Ras-related protein ... The proteins encoded by these genes share approximately 50% amino acid identity with the classical RAS proteins and have ... The most striking difference between the RAP and RAS proteins resides in their 61st amino acid: glutamine in RAS is replaced by ... Ohmstede CA, Farrell FX, Reep BR, Clemetson KJ, Lapetina EG (Oct 1990). "RAP2B: a RAS-related GTP-binding protein from ...
Best known for studying the role of Ras superfamily proteins in cancer. Allen Hall (billiards player) World championship ...
Chardin P (1991). "Small GTP-binding proteins of the ras family: a conserved functional mechanism?". Cancer Cells. 3 (4): 117- ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. Bibcode:2005Natur. ... Rnd2 is a small (~21 kDa) signaling G protein (to be specific, a GTPase), and is a member of the Rnd subgroup of the Rho family ... Tanaka H, Fujita H, Katoh H, Mori K, Negishi M (2002). "Vps4-A (vacuolar protein sorting 4-A) is a binding partner for a novel ...
Ras-responsive element-binding protein 1 is a protein that in humans is encoded by the RREB1 gene. Mutations in RREB1 are ... "Entrez Gene: RREB1 ras responsive element binding protein 1". Bonomo, J. A.; Guan, M; Ng, M. C.; Palmer, N. D.; Hicks, P. J.; ... Thiagalingam A, Lengauer C, Baylin SB, Nelkin BD (Jan 1998). "RREB1, a ras responsive element binding protein, maps to human ... 1996). "RREB-1, a novel zinc finger protein, is involved in the differentiation response to Ras in human medullary thyroid ...
... s also mildly inhibit Ras farnesyl-protein transferase. Zaragozic acid D and D2 have been isolated from the ... potent inhibitors of squalene synthase and of Ras farnesyl-protein transferase". J. Nat. Prod. 56 (11): 1923-9. doi:10.1021/ ...
Choroba Alzheimera, wolna encyklopedia
Goedert M, Spillantini MG, Crowther RA. Tau proteins and neurofibrillary degeneration. „Brain Pathol". 1 (4), s. 279-86, 07 ... Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein. „Biochem. Soc. Trans ... a b Ohnishi S, Takano K. Amyloid fibrils from the viewpoint of protein folding. „Cell. Mol. Life Sci.". 61 (5), s. 511-24, 03 ... amyloid precursor protein, prekursorowe białko amyloidu) na chromosomie 21. Informacja ta wiąże się z prawie pewnym ...
Duke BJ, Mouchantat RA, Ketch LL, Winston KR (July 1996). "Transcranial migration of microfixation plates and screws. Case ... that constraint inside the womb is associated with decreased expression of Indian hedgehog protein and noggin. These last two ...
LMNA - 维基百科，自由的百科全书
Markiewicz E, Dechat T, Foisner R, Quinlan RA, Hutchison CJ. Lamin A/C binding protein LAP2alpha is required for nuclear ... endoplasmic reticulum unfolded protein response. · protein localization to nucleus. · sterol regulatory element binding protein ... It stays associated with the membrane through protein-protein interactions of itself and other membrane associated proteins, ... activation of signaling protein activity involved in unfolded protein response. · mitotic nuclear envelope disassembly. · ...
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 ... Mutations in genes encoding these proteins can lead to inactivation of cadherin cell adhesions and elimination of contact ...
الوحدة الفرعية بيتا للفولليتروبين - ويكيبيديا، الموسوعة الحرة
Amoresano A، Orrù S، Siciliano RA، وآخرون. (2002). "Assignment of the complete disulphide bridge pattern in the human ... J Protein Chem. 7 (4): 325-39. PMID 3151250. doi:10.1007/BF01024882. تحقق من التاريخ في: ,date=. (مساعدة) ...
Atromentin and leucomelone possess antibacterial activity, inhibiting the enzyme enoyl-acyl carrier protein reductase, ( ... Block, SL; Harrison, CJ; Hedrick, JA; Tyler, RD; Smith, RA; Keegan, E; Chartrand, SA (1995). "Penicillin-resistant ... and Maclyn McCarty demonstrated that the transforming factor in Griffith's experiment was not protein, as was widely believed ... pneumoniae is associated with increased resistance to oxidative stress and increased expression of the RecA protein, a key ...
Hernandez-Aguilar RA, Moore J, Pickering TR (December 2007). "Savanna chimpanzees use tools to harvest the underground storage ... Large game animals such as deer were an important source of protein in Middle and Upper Paleolithic diets. ...
... protein. PPARα increases the activity of activator protein 1 (AP-1) and NF-κB, thereby leading to the recruitment of ... Farrar MD, Howson KM, Bojar RA, West D, Towler JC, Parry J, et al. (June 2007). "Genome sequence and analysis of a ... These free radicals likely interfere with the bacterium's metabolism and ability to make proteins. Additionally, ... Squalene oxidation activates NF-κB (a protein complex) and consequently increases IL-1α levels. Additionally, squalene ...
The CD20 proteins are sticking out of the cell membrane, and rituximab, the Y-shaped antibody, is binding to the CD20 proteins. ... "Rituximab, RA and PML" (PDF). Archived (PDF) from the original on 2008-09-16. Retrieved 2008-09-14.. ... The antibody binds to the cell surface protein CD20. CD20 is widely expressed on B cells, from early pre-B cells to later in ... In contrast, when the B cell lacked this asymmetric protein cluster, it was killed only 40% of the time. ...
Stinson RA, Spencer MS (1969). "Beta alanine aminotransferase (s) from a plant source". Biochem. Biophys. Res. Commun. 34 (1): ... proteins. In enzymology, a beta-alanine-pyruvate transaminase (EC 188.8.131.52) is an enzyme that catalyzes the chemical reaction ...
Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn GW, Tallini G, Kroll TG, Nikiforov YE (May 2003). "RAS point ... The PAX genes give instructions for making proteins that attach themselves to certain areas of DNA. This nuclear protein is ... These mutations can affect different functions of the protein including DNA biding, gene activation, protein stability, and ... Paired box gene 8, also known as PAX8, is a protein which in humans is encoded by the PAX8 gene. ...
A hexavalent (OspA) protein subunit-based vaccine candidate VLA15 was granted fast track designation by the U.S. Food and Drug ... Jowett N, Gaudin RA, Banks CA, Hadlock TA (June 2017). "Steroid use in Lyme disease-associated facial palsy is associated with ... Within the tick midgut, the Borrelia's outer surface protein A (OspA) binds to the tick receptor for OspA, known as TROSPA. ... Kalish RA, Kaplan RF, Taylor E, Jones-Woodward L, Workman K, Steere AC (February 2001). "Evaluation of study patients with Lyme ...
Bennett NC, Gardiner RA, Hooper JD, Johnson DW, Gobe GC (2010). "Molecular cell biology of androgen receptor signalling". Int. ... "G protein-coupled receptors: extranuclear mediators for the non-genomic actions of steroids". Int J Mol Sci. 15 (9): 15412-25 ...
PB28 - Википедија, слободна енциклопедија
Colabufo NA, Berardi F, Abate C, Contino M, Niso M, Perrone R (2006). „Is the sigma2 receptor a histone binding protein?". ... Abate C, Elenewski J, Niso M, Berardi F, Colabufo NA, Azzariti A, Perrone R, Glennon RA (2010). „Interaction of the sigma(2) ...
88Ra. α→11.4 d. The next element below francium (eka-francium) in the periodic table would be ununennium (Uue), element 119.[37 ... The balance between potassium and sodium is maintained by ion transporter proteins in the cell membrane. The cell membrane ... Empirical (Na-Cs, Mg-Ra) and predicted (Fr-Uhp, Ubn-Uhh) atomic radius of the alkali and alkaline earth metals from the third ... Empirical (Na-Fr, Mg-Ra) and predicted (Uue-Uhp, Ubn-Uhh) ionisation energy of the alkali and alkaline earth metals from the ...
Mutations in the RPS6KA3 disturb the function of the protein, but it is unclear how a lack of this protein causes the signs and ... In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews [Internet]. Seattle, Washington: University of Washington, ... The RPS6KA3 gene makes a protein that is involved with signaling within cells. Researchers believe that this protein helps ... The protein RSK2 which is encoded by the RPS6KA3 gene is a kinase which phosphorylates some substrates like CREB and histone H3 ...
AR NTD antagonists bind covalently to the NTD of the AR and prevent protein-protein interactions subsequent to activation that ... Kaliks RA, Del Giglio A (2008). "Management of advanced prostate cancer" (PDF). Revista Da Associação Médica Brasileira. 54 (2 ... Kavoussi P, Costabile RA, Salonia A (17 October 2012). Clinical Urologic Endocrinology: Principles for Men's Health. Springer ... Bennett NC, Gardiner RA, Hooper JD, Johnson DW, Gobe GC (2010). "Molecular cell biology of androgen receptor signalling". Int. ...
Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 izd.). Wiley- ... PDB 3KLF; Tu X, Das K, Han Q, Bauman JD, Clark AD Jr, Hou X, Frenkel YV, Gaffney BL, Jones RA, Boyer PL, Hughes SH, Sarafianos ... Nicholas C. Price, Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins ( ... Branden C, Tooze J.. Introduction to Protein Structure. New York, NY: Garland Publishing. ISBN: 0-8153-2305-0. http://www. ...
... and forms a complex with protein E. The immature particles are processed in the Golgi apparatus by the host protein furin, ... Auguste AJ, Lemey P, Pybus OG, Suchard MA, Salas RA, Adesiyun AA, Barrett AD, Tesh RB, Weaver SC, Carrington CV (2010). "Yellow ... At first, an immature form of the virus particle is produced inside the ER, whose M-protein is not yet cleaved to its mature ... Receptor binding, as well as membrane fusion, are catalyzed by the protein E, which changes its conformation at low pH, causing ...
Cho DY, Frey RA, Guffy MM, Leipold HW (November 1975). "Hypervitaminosis A in the dog". American Journal of Veterinary Research ... it was thought that the sole important retinoid delivery pathway to tissues involved retinol bound to retinol-binding protein ( ... Rothenberg AB, Berdon WE, Woodard JC, Cowles RA (December 2007). "Hypervitaminosis A-induced premature closure of epiphyses ( ...
Dick RA, Kwak MK, Sutter TR, Kensler TW (2001). "Antioxidative function and substrate specificity of NAD(P)H-dependent alkenal/ ... proteins. In enzymology, a 2-alkenal reductase (EC 184.108.40.206) is an enzyme that catalyzes the chemical reaction ...
Antibody - Simple English Wikipedia, the free encyclopedia
Rhoades RA, Pflanzer RG (2002). Human Physiology (4th ed.). Thomson Learning. ISBN 978-0-534-42174-8. .. ... Antibodies (also called immunoglobulins) are large Y-shaped proteins. They are found in the blood or other body fluids of ... Though the general structure of all antibodies is very similar, a small region at the tip of the protein is extremely variable ... Though the general structure of all antibodies is very similar, that small region at the tip of the protein is extremely ...
Ra. Ac. **. Rf. Db. Sg. Bh. Hs. Mt. Ds. Rg. Cn. Nh. Fl. Mc. Lv. Ts. Og ... Required for many proteins and enzymes, notably hemoglobin to prevent anemia Meat, seafood, nuts, beans, dark chocolate ...
Raw ginger is composed of 79% water, 18% carbohydrates, 2% protein, and 1% fat (table). In 100 grams (a standard amount used to ...
Castenholz RA (1973) "Ecology of blue-green algae in hotsprings". In: The Biology of Blue-green algae. NG Carr and BA Whitton ( ... Cylindrospermopsin is toxic to liver and kidney tissue and is thought to inhibit protein synthesis and to covalently modify DNA ... They have the same chemical structure as proteins, except they are shorter. In a cyclic peptide, the ends link to form a stable ...
Calcium channel, voltage-dependent, L type, alpha 1C subunit (also known as Cav1.2) is a protein that in humans is encoded by ... Pagon RA, Bird TC, Dolan CR, Stephens K, Splawski I, Timothy KW, Priori SG, Napolitano C, Bloise R (1993). "Timothy Syndrome". ... Click on genes, proteins and metabolites below to link to respective Wikipedia articles. [§ 1] ... protein binding. • alpha-actinin binding. • voltage-gated calcium channel activity. • voltage-gated calcium channel activity ...
Garrett RA; Klenk H (2005). Archaea: Evolution, Physiology and Molecular Biology. WileyBlackwell. ISBN 1-4051-4404-1.. ... Proteins related to the cytoskeleton components of other organisms exist in archaea, and filaments form within their cells, ... January 2002). "Introns in protein-coding genes in Archaea". FEBS Lett. 510 (1-2): 27-30. doi:10.1016/S0014-5793(01)03219-7. ... The proteins that archaea, bacteria and eukaryotes share form a common core of cell function, relating mostly to transcription ...
UNKL: encoding protein RING finger protein unkempt-like. *VAT1L: encoding protein Vesicle amine transport protein 1 homolog (T ... Pagon RA, Bird TD, Dolan CR, et al., eds. (1993). GeneReviews™ [Internet]. Seattle WA: University of Washington, Seattle.. ... LINC00273 encoding protein Long intergenic non-protein coding RNA 273. *LOC124220: encoding protein Zymogen granule protein 16 ... SHCBP1: encoding protein SHC SH2 domain-binding protein 1. *SLZ1: encoding protein SLX1 structure-specific endonuclease subunit ...
TATA-binding protein (TBP) can be recruited in two ways, by SAGA, a cofactor for RNA polymerase II, or by TFIID. When ... Takahashi K, Ezekowitz RA (November 2005). "The role of the mannose-binding lectin in innate immunity". Clinical Infectious ... "TATA-binding protein recognition and bending of a consensus promoter are protein species dependent". Biochemistry. 47 (27): ... The TATA-binding protein (TBP) could also be targeted by viruses as a means of viral transcription. ...
Others may not have symptoms and may be picked up on screening or urinalysis as having high amounts of protein loss in the ... Stahl RA, Lambeau G (December 2014). "Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy". The New ...
... who believed that transcription was activated by protein-DNA and protein-protein interactions on largely naked DNA templates, ... de Bruin RA, McDonald WH, Kalashnikova TI, Yates J, Wittenberg C (June 2004). "Cln3 activates G1-specific transcription via ... Nuclear protein Ataxia-Telangiectasia (NPAT), also known as nuclear protein coactivator of histone transcription, is a ... The first step of chromatin structure duplication is the synthesis of histone proteins: H1, H2A, H2B, H3, H4. These proteins ...
CDD Conserved Protein Domain Family: Ras
Conserved Protein Domain Family Ras, Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more ... Ras family. Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin ... They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices. ...
Ras Proteins News, Research
Researchers uncover Ras proteins role in uncontrolled cancer growth Protein systems, such as Ras, make up the complex ... Researchers identify LZTR1 as evolutionarily conserved component of RAS pathway Mutations in RAS proteins initiate many of the ... Of these, the three genes encoding RAS proteins are particularly important, as they are found mutated in over 25% of human ... Study shows how normal RAS interacts with mutated RAS in living cells Many cancer medications fail to effectively target the ...
Proteins regulating Ras and its relatives. - PubMed - NCBI
Proteins regulating Ras and its relatives.. Boguski MS1, McCormick F.. Author information. 1. National Center for Biotechnology ... Numerous proteins affecting the GTPase activity, nucleotide exchange rates and membrane localization of Ras superfamily members ... Many of these proteins are much larger and more complex than their targets, containing multiple domains capable of interacting ... GTPases of the Ras superfamily regulate many aspects of cell growth, differentiation and action. Their functions depend on ...
Ras p21 protein activator 2 - Wikipedia
RAS p21 protein activator 2 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 ...
RAS p21 protein activator 1 - Wikipedia
RAS p21 protein activator 1 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( ...
Ras-related small G protein, RGK family (IPR017358) | InterPro | EMBL-EBI
We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their ... InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... Small GTPase superfamily, Ras-type (IPR020849) *Ras-related small G protein, RGK family (IPR017358) *GTP-binding protein Rad ( ... Ras-related small G protein, RGK family (IPR017358). Short name: RGK Overlapping homologous superfamilies *P-loop containing ...
Ras-related protein Rab-32 - Sus scrofa (Pig)
Protein predictedi ,p>This indicates the type of evidence that supports the existence of the protein. Note that the protein ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ... Ras-related protein Rab-32Imported. ,p>Information which has been imported from another database using automatic procedures.,/p ... Integrated resource of protein families, domains and functional sites. More...InterProi. View protein in InterPro. IPR027417 P- ...
Ras proteins, nitrosylation and homocysteine metabolism.
0/NF-kappa B; 0/Nitrogen Oxides; 2696-92-6/nitrosyl chloride; 454-28-4/Homocysteine; EC 220.127.116.11/ras Proteins ... Nitrosylation of Ras is necessary for maintaining the survival of PC12 cells, while farnesylation of Ras stimulates apoptosis ... Genes, ras / genetics. Homocysteine / metabolism*. Humans. Hyperhomocysteinemia / genetics*, metabolism*. NF-kappa B / genetics ... Besides, our results suggest that in conditions of a low level of nitric oxide PC12 cells with mutated oncogenic Ras produce ...
Are All RAS Proteins Created Equal in Cancer? - National Cancer Institute
Different cancers seem to be preferentially driven by differnt mutations in RAS genes. Channing Der discusses what mechanisms ... The three human RAS genes encode four highly related RAS proteins (82-90% sequence identity), with alternative gene splicing ... distinct anti-RAS strategies will be needed for effective inhibition of each RAS protein. Here we review the mutational ... rather than a requirement for activation of a specific RAS protein, is a basis for RAS isoform preference in cancer induction ...
Ras protein signal transduction Gene Ontology Term (GO:0007265)
The Gene Ontology (GO) project is a collaborative effort to address the need for consistent descriptions of gene products across databases. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated gene data at MGI are provided in Term Detail reports.
KRAS - K-ras - Homo sapiens (Human) - KRAS gene & protein
Protein predictedi ,p>This indicates the type of evidence that supports the existence of the protein. Note that the protein ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ... p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different ... proteins_section target=_top>More...,/a>,/p>Similar proteinsi. *50% Identity ...
Recombinant Human Ras protein (ab61239) References | Abcam
References for Abcams Recombinant Human Ras protein (ab61239). Please let us know if you have used this product in your ... Signal Transduction Signaling Pathway G Protein Signaling Small G Proteins Ras Family ... Proteins and Peptides. Proteomics tools. Agonists, activators, antagonists and inhibitors. Lysates. Multiplex miRNA assays. By ...
Ras Superfamily Small G Proteins: Biology and Mechanisms 2 | SpringerLink
This second of two volumes discusses subfamily proteins involved in nucleo-cytoplasmic and vesicular transport mechanisms ... Arf Proteins and Their Regulators: At the Interface Between Membrane Lipids and the Protein Trafficking Machinery ... G-Protein effector-interactions GTP binding GTPase intracellular transport nucleo-cytoplasmic transport vesicular coats ... Together with Volume 1, this book provides a comprehensive and state-of-the-art work on small G-proteins (GTPases). It was ...
Critical function for the Ras-GTPase activating protein RASA3 in vertebrate erythropoiesis and megakaryopoiesis | PNAS
Here, we identify a missense mutation (G125V) in the scat Rasa3 gene, encoding a Ras GTPase activating protein (RasGAP), and ... Critical function for the Ras-GTPase activating protein RASA3 in vertebrate erythropoiesis and megakaryopoiesis. Lionel Blanc, ... Critical function for the Ras-GTPase activating protein RASA3 in vertebrate erythropoiesis and megakaryopoiesis ... leading to increased GTP-bound Ras. Erythropoiesis is severely blocked in scat crisis mice, and ∼94% succumb during the second ...
RCSB PDB - Protein Feature View - Ras-related protein Rap-1b - P61224 (RAP1B HUMAN)
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... This protein in other organisms (by gene name): P61224 - Homo sapiens 17 * P09526 - Bos taurus no matching PDB entries ... Protein disorder predictions are based on JRONN (Troshin, P. and Barton, G. J. unpublished), a Java implementation of RONN * ... GTP-binding protein that possesses intrinsic GTPase activity. Contributes to the polarizing activity of KRIT1 and CDH5 in the ...
RCSB PDB - Protein Feature View - Ras-related protein Rab-6B - Q9NRW1 (RAB6B HUMAN)
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... This protein in other organisms (by gene name): Q9NRW1 - Homo sapiens 3 * D3DND3 - Homo sapiens no matching PDB entries ... Protein disorder predictions are based on JRONN (Troshin, P. and Barton, G. J. unpublished), a Java implementation of RONN * ... The Protein Feature View requires a browser that supports SVG (Scalable Vector Graphics). Mouse over tracks and labels for more ...
Regulator of G-Protein Signaling 14 (RGS14) Is a Selective H-Ras Effector
Rap1b MGI Mouse Gene Detail - MGI:894315 - RAS related protein 1b
Eph receptor-ephrin bidirectional signals that target Ras and Rho proteins
14-3-3 proteins: potential roles in vesicular transport and Ras signaling in Saccharomyces cerevisiae | PNAS
14-3-3 proteins: potential roles in vesicular transport and Ras signaling in Saccharomyces cerevisiae. D Gelperin, J Weigle, K ... 14-3-3 proteins: potential roles in vesicular transport and Ras signaling in Saccharomyces cerevisiae ... 14-3-3 proteins: potential roles in vesicular transport and Ras signaling in Saccharomyces cerevisiae ... 14-3-3 proteins: potential roles in vesicular transport and Ras signaling in Saccharomyces cerevisiae ...
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... news for Ras Protein - guaranteed. ✓ Click to listen & browse today! ... Looking for Ras Protein info? Audiomack has the latest albums, songs, videos & ... Ras Protein ft Ras Kuuku only one. *Added on: Jun 21st, 2013. by Ras Protein ... RAS PROTEIN Twe Ben Me. *Added on: Jun 21st, 2013. by Ras Protein ...
ras Proteins Summary Report | CureHunter
... monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21 ... The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell ... RAS), plays a role in normal cellular growth, differentiation and development. ... ras Proteins. Subscribe to New Research on ras Proteins Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS ...
Rasip1 (Ras interacting protein 1) - Rat Genome Database
... protein homodimerization activity (ortholog); INVOLVED IN angiogenesis (ortholog); branching morphogenesis of an epithelial ... ENCODES a protein that exhibits GTPase binding (ortholog); ... Ras interacting protein 1. Description:. ENCODES a protein that ... ras-interacting protein 1. Orthologs:. Homo sapiens (human) : RASIP1 (Ras interacting protein 1) HGNC Alliance Mus musculus ( ... RASIP1 (Ras interacting protein 1). NCBI. Ortholog. Mus musculus (house mouse):. Rasip1 (Ras interacting protein 1). Transitive ...
Activated Ras protein, illustration - Stock Image - F021/2798 - Science Photo Library
The activated form of Ras contains a bound GTP (guanosine triphosphate, orange) in its active site. ... Activated Ras protein bound to a cell membrane, illustration. ... Activated Ras protein bound to a cell membrane, illustration. ... The activated form of Ras contains a bound GTP (guanosine triphosphate, orange) in its active site. Ras proteins are involved ... Mutations in ras genes can lead to permanently activated proteins causing cells to subdivide without control, often leading to ...
Activation Of A Ras Protein By A Gef Protein Stock Video & More Clips of Cancer - Illness 973932842 | iStock
ras GTPase-Activating Proteins | Harvard Catalyst Profiles | Harvard Catalyst
... "ras GTPase-Activating Proteins" by people in Harvard Catalyst Profiles by year, and whether "ras GTPase-Activating Proteins" ... "ras GTPase-Activating Proteins" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... Below are the most recent publications written about "ras GTPase-Activating Proteins" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "ras GTPase-Activating Proteins". ...
RAS proteins | definition of RAS proteins by 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 proteins in the Medical Dictionary? ... RAS proteins , definition of RAS proteins by Medical dictionary https://medical-dictionary.thefreedictionary.com/RAS+proteins ... RAS. (redirected from RAS proteins). Also found in: Dictionary, Thesaurus, Encyclopedia. RAS. Abbreviation for reticular ...
Abundant expression of ras proteins in Aplysia neurons. | JCB
Abundant expression of ras proteins in Aplysia neurons.. M E Swanson, A M Elste, S M Greenberg, J H Schwartz, T H Aldrich, M E ... Abundant expression of ras proteins in Aplysia neurons.. M E Swanson, A M Elste, S M Greenberg, J H Schwartz, T H Aldrich, M E ... and which therefore is likely to encode a ras-like Aplysia protein. The cloned locus, designated Apl-ras, is distinct from the ... The prominence of ras protein in neurons, which are terminally differentiated and non-proliferating, indicates that the control ...
Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain | Science
... activity of N-ras protein but does not affect the activity of oncogenic ras mutants has been recently described. This protein ( ... To identify the region of ras p21 with which GAP interacts, 21 H-ras mutant proteins were purified and tested for their ability ... GAP) is shown here to be ubiquitous in higher eukaryotes and to interact with H-ras as well as with N-ras proteins. ... Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain ...
Laboratory of hormonal regulation proteins - IBCh RAS
Proteins, peptides, differentiation, apoptosis, Alzheimers disease, ischemia, myopia ... Laboratory of hormonal regulation proteins Department of Peptide and Protein Technologies Head: Valery Lipkin, corresponding ... in cooperation with the Institute of the Cell Biophysics RAS). In the structure of 45 kDa protein, a lipid-binding domain was ... The Institute of Cell Biophysics RAS, The Institute of Molecular Genetics RAS, The Helmholtz Moscow Research Institute of Eye ...
Signal transductionMutationsPathwayGenePathwaysOncogeneGTPasesMAPKEffectorGenesAbstractAntibodiesNucleotideInhibitionIsoformsMammalianRegulatesSuppressorMember of the Ras familyInhibitorsMembrane localizationSignalsDownstreamExtracellularLocalizationEncodesRegulationRegulateDifferentiationCancersProliferationTumorsMolecular weightOncogenesRolesActivatorEffectorsOncogenic ras mutantsPhosphorylationStimulates2000Increased GTP-boundIntrinsicActivatesFibroblastsReceptorGuanosine triphosphateCellularSignalingFamilySmall GTP-bindingBiochemicalInteractionsAbundantActivitySubfamilyMutantsCellsGTPase RASActivationRegulator
- ras proteins play a key role in transmitting signals from outside the cell through a number of different pathways into the nucleus of the cell, a process called signal transduction. (thefreedictionary.com)
- Much attention has focused on the RAS-RAF-mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) kinase (MEK)-ERK cascade ( Fig. 1 ), hereafter referred to as the RAS-MAPK pathway, as a prototypical signal transduction pathway that is aberrantly activated in many neoplasms. (aacrjournals.org)
- In mammals, several RasGAPs exhibit tumor suppressor activity by preventing excess RAS signal transduction. (uzh.ch)
- The Ras proto-oncogene is a central component of mitogenic signal-transduction pathways, and is essential for cells both to leave a quiescent state (GO) and to pass through the GI/S transition of the cell cycle. (uu.nl)
- H-Ras functions as a 'molecular switch', using nucleotide dependent conformational changes to relay signals in a number of signal transduction pathways. (ncsu.edu)
- The RAB27A gene encodes a protein that in association with the Ras protein controls G protein coupled signal transduction. (moldiag.com)
- The lecture RAS Protein & Signal Transduction - Carcinogenesis by Carlo Raj, MD is from the course Cellular Pathology: Basic Principles. (lecturio.com)
- 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. (ucl.ac.uk)
- Computational scientists, biophysicists and statisticians from Lawrence Livermore National Laboratory and Los Alamos National Laboratory are leading a massive multi-institutional collaboration that has developed a machine learning-based simulation for next-generation supercomputers capable of modeling protein interactions and mutations that play a role in many forms of cancers. (news-medical.net)
- Mutations in RAS proteins initiate many of the most aggressive tumors, and the search for pharmacological inhibitors of these proteins has become a priority in the battle against cancer. (news-medical.net)
- For example, 98 percent of pancreatic cancers show Ras protein mutations. (news-medical.net)
- Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. (wikipedia.org)
- This contrasts with cutaneous melanoma or acute myelogenous leukemia (AML), where NRAS comprises 94% and 59%, respectively, of RAS mutations in these cancers. (cancer.gov)
- Why the frequency of RAS gene mutations varies widely in cancers that arise from different tissues remains largely unresolved. (cancer.gov)
- Mutations in ras genes can lead to permanently activated proteins causing cells to subdivide without control, often leading to cancer. (sciencephoto.com)
- Recently published reports have shown the presence of these ras mutations in plasma samples and therefore the ability to detect the presence of these mutant ras proteins in blood samples may be valuable for the early detection of malignancy. (thefreedictionary.com)
- 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. (sciencemag.org)
- Point mutations in the putative effector region of ras p21 (amino acids 35, 36, and 38) were also insensitive to GAP. (sciencemag.org)
- Mutations in Ras proteins can result in excessive signals for cells to proliferate and cause them to ignore cues for programmed cell death, leading to unchecked growth and tumor formation. (thefreedictionary.com)
- In her dissertation, Anna-Karin Sjogren studied how mutations (activation) of RAS proteins contribute to the formation of many forms of tumors, such as cancer of the large intestine, lungs, blood and pancreas. (thefreedictionary.com)
- We also isolated mutations in five previously uncharacterized genes, one of which, split ends , we have characterized molecularly and have shown to encode a member of the RRM family of RNA-binding proteins. (genetics.org)
- This protein-protein interaction is upregulated by activating-mutations of NRAS and is known to be required for the tumorigenesis, and the maintenance of established tumours. (findaphd.com)
- Thyroid cancer is an example of a tumor with nonoverlapping genetic mutations that up-regulate mitogen-activated protein kinase (MAPK). (aacrjournals.org)
- Gene rearrangements involving the RET proto-oncogene or activating point mutations along the RAS/BRAF pathway account for the majority of these carcinomas ( 3 ). (aacrjournals.org)
- RAS -signaling mutations induce the myelomonocytic differentiation and proliferation of hematopoietic stem and progenitor cells. (haematologica.org)
- Since the majority of endometrial carcinomas do not contain any detectable ras mutations, the precise contribution of aberrant Ras function, if any, to endometerial carcinoma development remains to be determineed. (nii.ac.jp)
- Mutations in codons 12, 13 and 61 creates an oncogenic version of the protein which does not hydrolyze GTP, resulting in the constitutive activation of downstream effector proteins. (ncsu.edu)
- A comprehensive survey of Ras mutations in cancer. (semanticscholar.org)
- Loss of function mutations in RAS could result in all of the following EXCEPT. (lecturio.com)
- What is the incidence of RAS mutations in carcinogenesis? (lecturio.com)
- Michail Steklov, Francesca Baietti, and colleagues from the Anna Sablina lab identified LZTR1 as an evolutionarily conserved component of the RAS pathway. (news-medical.net)
- Activated RIC, a small GTPase, genetically interacts with the Ras pathway and calmodulin during Drosophila development. (springer.com)
- Collectively, these results suggest that the Ras signaling pathway is involved in HIV-1 Tat-induced changes in ZO-1 and NEP, as well as A β deposition in HBEC-5i cells. (hindawi.com)
- While the core RTK/Ras/MAPK signaling cassette has been studied extensively, little is known about the nature of the downstream targets of the pathway or how these effectors regulate the specificity of cellular responses. (genetics.org)
- Drosophila yan is one of a few downstream components identified to date, functioning as an antagonist of the RTK/Ras/MAPK pathway. (genetics.org)
- In an effort to identify new genes functioning downstream in the Ras/MAPK/yan pathway, we have performed a genetic screen to isolate dominant modifiers of the rough eye phenotype associated with eye-specific expression of yan ACT . (genetics.org)
- We suggest that this "unprompted" Ras activity and PI(3,4,5)P 3 accumulation, which are independent of external stimuli, constitute a core regulatory pathway involved in a variety of physiological responses and provide the basis for many ligand- or substrate-mediated processes, such as chemotaxis and phagocytosis. (rupress.org)
- Yang H, Sasaki T, Minoshima S, Shimizu N: Identification of three novel proteins (SGSM1, 2, 3) which modulate small G protein (RAP and RAB)-mediated signaling pathway. (hmdb.ca)
- Bromodomain containing protein represses the Ras/Raf/MEK/ERK pathway to attenuate human hepatoma cell proliferation during HCV infection. (sigmaaldrich.com)
- Activation of Ras/Raf/MEK/ERK pathway is found in more than 30% human cancers. (sigmaaldrich.com)
- HCV promotes hepatoma cell proliferation by activating the Ras/Raf/MEK/ERK pathway, which in turn facilitates HCV replication to further enhance hepatoma cell proliferation. (sigmaaldrich.com)
- After activation, the Ras/Raf/MEK/ERK pathway stimulates BRD7 production, which in turn represses the Ras/Raf/MEK/ERK pathway, leading to the attenuation of hepatoma cell proliferation. (sigmaaldrich.com)
- The Ras/Raf/MEK (mitogen-activated protein kinase/ERK kinase)/ERK (extracellular-signal-regulated kinase) pathway is at the heart of signalling networks that govern proliferation, differentiation and cell survival. (portlandpress.com)
- This review focuses on the role of protein-protein interactions in the regulation of this pathway, and how they contribute to co-ordinate activation steps, subcellular redistribution, substrate phosphorylation and cross-talk with other signalling pathways. (portlandpress.com)
- Co-translational control of protein complex formation: a fundamental pathway of cellular organization? (portlandpress.com)
- Acute application of FPT III was found to act through a novel mechanism to inhibit smooth muscle cell proliferation via a non-ras pathway, which may contribute to the prevention of in-stent restenosis. (strath.ac.uk)
- Experiments with PD98059 (6) and rapamycin (7) suggested that separate intervention of the MAPK pathway or the p70 S6K pathway has little effect on Ki- ras -induced transformation, but simultaneous blockade of the two pathways restores the normal phenotype. (aacrjournals.org)
- Among mammalian mitogen-activated protein kinase (MAPK) signaling cascades, the extracellular signal-related kinase (ERK) pathway has received the most attention in the oncology drug discovery arena. (aacrjournals.org)
- Therefore, the integral role of the RAS-RAF-MEK-ERK pathway in mediating multiple hallmarks of cancer has spurred intense explorations into its amenability for pharmacologic intervention ( 2 - 4 ). (aacrjournals.org)
- The RAS/MAPK signaling pathway. (aacrjournals.org)
- Scaffolding proteins, including kinase suppressor of RAS (KSR) shown here, are important for activation efficiency and spatial regulation of signaling through this pathway. (aacrjournals.org)
- When contemplating how best to cripple this pathway, several key proteins are reasonable candidates for consideration. (aacrjournals.org)
- 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 ). (aacrjournals.org)
- Ras is the activator of the Erk/MAPK kinase pathway, as well as an activator of PI3 Kinase (PI3K). (merckmillipore.com)
- In its oncogenic state, Ras is unable to hydrolyze GTP to GDP, thus staying in an active state and activating numerous pathways including the MAPK pathway through its activation of Raf. (merckmillipore.com)
- All metazoan genomes encode multiple RAS GTPase activating proteins (RasGAPs) that negatively regulate the conserved RAS/MAPK signaling pathway. (uzh.ch)
- The C. elegans RasGAPs have thus undergone partial specialization after gene duplication to allow the differential regulation of the RAS/MAPK signaling pathway in different cell types. (uzh.ch)
- In the C.elegans excretory system, we demonstrated that the EGF-Ras-Erk signaling pathway specified the excretory duct tube versus the pore tube fate. (upenn.edu)
- mls-2 cooperated with the EGF-Ras-Erk pathway to turn on lin-48/Ovo during duct morphogenesis. (upenn.edu)
- Also, other proteins which involved in the same pathway with Rab1 were listed below. (creativebiomart.net)
- In study two, the protein levels in placenta from depressed, SSRI-treated and healthy pregnant women were investigated, focusing on the NGF signaling pathway. (diva-portal.org)
- Heme Deficiency Interferes with the Ras-Mitogen-activated Protein Kinase Signaling Pathway and Expression of a Subset of Neuronal Genes -- Zhu et al. (aacrjournals.org)
- Targeting the mitogen-activated protein kinase pathway: physiological feedback and drug response. (semanticscholar.org)
- Inhibitory regulator of the Ras-cyclic AMP pathway. (sdsc.edu)
- What step in the pathway would directly effected if a patient had mutated farnesyl proteins? (lecturio.com)
- When a RAS gene operates normally, it acts as an on/off switch for cell signaling to control cell proliferation. (news-medical.net)
- You can select a given mouse superfamily member and download (or forward to NCBI BLAST) FASTA formatted protein sequences of that mouse gene and its mouse, human and rat homologs, as defined in the corresponding HomoloGene Class. (jax.org)
- p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence. (uniprot.org)
- RAS p21 protein activator 2 is a protein that in humans is encoded by the RASA2 gene. (wikipedia.org)
- The protein encoded by this gene is member of the GAP1 family of GTPase-activating proteins. (wikipedia.org)
- The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. (wikipedia.org)
- PC12 pheochromocytoma cells expressing a dominant inhibitory mutant of Ha-ras (M-M17-26, PC12 pheochromocytoma cells expressing a mutant v-ras gene (MVR) and PC12 cells transfected with normal c-rasH (M-CR3B) has been used to investigate the role of nitrosylation and farnesylation of Ras on the production of homocysteine and the activities of the redox-sensitive transcription factors NF-kB and c-Fos. (biomedsearch.com)
- The three human RAS genes encode four highly related RAS proteins (82-90% sequence identity), with alternative gene splicing accounting for the expression of the highly related K-RAS4A and K-RAS4B proteins (90% identity). (cancer.gov)
- The frequency of mutation of each RAS gene varies widely in different cancer types. (cancer.gov)
- Another possibility is that the carcinogenic assault and efficiency of DNA repair that each tissue faces will favor the mutational activation of a specific RAS gene. (cancer.gov)
- This possibility was tested in several mouse models of carcinogen-induced RAS gene mutation and cancer induction. (cancer.gov)
- section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. (uniprot.org)
- Here, we identify a missense mutation (G125V) in the scat Rasa3 gene, encoding a Ras GTPase activating protein (RasGAP), and elucidate the mechanism producing crisis episodes. (pnas.org)
- The cloned locus, designated Apl-ras, is distinct from the Aplysia rho (ras-homologue) gene and appears to be more closely related to mammalian ras. (rupress.org)
- In the early 90s, several groups identified in murine brain extracts, a protein of a molecular weight between 100-160 kDa, named Ras-GRF (Ras-Guanine nucleotide Releasing Factor) and Cdc25Mm, based on its ability to induce GDP release in p21ras and on its high homology with the Sacharomyces cerevisiae gene CDC25, whose deficiency it could rescue. (atlasgeneticsoncology.org)
- This gene encodes a ribosomal protein that is a component of the 40S subunit. (antikoerper-online.de)
- As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. (antikoerper-online.de)
- In Saccharomyces cerevisiae, the product of the CDC25 gene controls the RAS-mediated production of adenosine 3',5'-monophosphate (cAMP). (sciencemag.org)
- Partially purified preparations of the carboxy-terminal domain of the SCD25 gene product enhanced the exchange rate of guanosine diphosphate (GDP) to guanosine triphosphate (GTP) of pure RAS2 protein by stimulating the release of GDP. (sciencemag.org)
- Ras-Related Nuclear Protein Ran3B Gene Is Involved in Hormone Responses in the Embryogenic Callus of Dimocarpus longan Lour. (mdpi.com)
- Importantly, we show that infection of mice NAc with lentivirus expressing a short hairpin RNA that targets the H-Ras gene produces a significant reduction of voluntary consumption of 20% alcohol. (jneurosci.org)
- Farrell FX, Ohmstede CA, Reep BR, Lapetina EG: cDNA sequence of a new ras-related gene (rap2b) isolated from human platelets with sequence homology to rap2. (hmdb.ca)
- However, HCV persistent infection attenuates BRD7 gene expression and facilitates the protein degradation to release the Ras/Raf/MEK/ERK signaling, which results in the facilitation of hepatoma cell proliferation. (sigmaaldrich.com)
- It has been proposed that POLGARF evolved approximately 100-200 mln years ago by MIR transposon insertion into POLG gene, which allows alternative reading frame translation and evolution of POLGARF protein coding function. (ibch.ru)
- CAR target gene induction in the tumors was studied at the mRNA and protein levels, and a reverse-phase protein microarray approach was chosen to characterize important signaling cascades. (aspetjournals.org)
- CAR target gene induction was pronounced in B-raf -mutated but not in Ha-ras -mutated tumors. (aspetjournals.org)
- Publications] N. Wake: 'Accumulation of Genetic Events in Endometrial Carcinoma andits Cell Growth Inhibition by Antisense Oligonucleotide Complementary to the Mutated K- ras Gene. (nii.ac.jp)
- In contrast, inactivation of Ras in quiescent cells prevented growth-factor induction of both immediate-early gene transcription and exit from GO in an Rb-independent manner. (uu.nl)
- Protein systems, such as Ras, make up the complex signaling pathways that control whether a cell divides or, in some cases, becomes cancerous and metastasizes into other regions of the body. (news-medical.net)
- These genetic interactions suggest that budding-yeast 14-3-3 proteins are multifunctional and may play a role in both vesicular transport and Ras signaling pathways. (pnas.org)
- Ras proteins control signaling pathways that are believed to be key regulators of both normal cell growth and malignant transformation. (thefreedictionary.com)
- Indeed, the study of the signaling pathways regulated by RAS in yeast cells led to the discovery of properties that were often found interchangeable with RAS proto-oncogenes in human pathways, and vice versa. (mdpi.com)
- In this work, we performed an updated critical literature review on human and yeast RAS pathways, specifically highlighting the similarities and differences between them. (mdpi.com)
- Moreover, we emphasized the contribution of studying yeast RAS pathways for the understanding of human RAS and how this model organism can contribute to unveil the roles of RAS oncoproteins in the regulation of mechanisms important in the tumorigenic process, like autophagy. (mdpi.com)
- Ras proteins have long been the focus of cancer research because of their role as "on/off switch" signaling pathways that control cell division and failure to die like normal, healthy cells do. (technologynetworks.com)
- Although three IL-6 signaling pathways (STAT1, STAT3, and Ras-dependent MAPK cascade) have been reported, cascades mediating IL-6-triggered growth of MM cells and cell lines are not defined. (jimmunol.org)
- The results suggest that normalization of Ki- ras -induced transformed phenotypes by U0126 is a consequence of concurrent inhibition of the MAPK and p70 S6K pathways. (aacrjournals.org)
- RAS plays a central role in mediating both proliferation and survival signaling through the MAPK and PI3K pathways. (aacrjournals.org)
- Ras is a heavily studied protein because of its implications in various pathways and diseases, as well as mutated forms being expressed in many human cancers. (merckmillipore.com)
- These results show that RasGAP can function as an inhibitor of signaling pathways mediated by Ras and receptor tyrosine kinases in vivo. (ucl.ac.uk)
- A recent study has shown that loss of the Erk oncogene can stimulate tumorigenesis in cells where Ras has been eliminated. (news-medical.net)
- The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. (curehunter.com)
- The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). (curehunter.com)
- We have cloned a DNA fragment from the marine mollusc Aplysia californica, which contains sequences homologous to mammalian ras genes, by screening a genomic library with a viral Ha-ras oncogene probe under conditions of low stringency hybridization. (rupress.org)
- The prominence of ras protein in neurons, which are terminally differentiated and non-proliferating, indicates that the control of cell division is not the sole function of this proto-oncogene. (rupress.org)
- 2, ras proteins were detected at high level after addition of Dex, which was used as an inducer of mutated human N-ras oncogene. (thefreedictionary.com)
- Raf has been shown to facilitate the Ras protein function, an oncogene known to be involved in the initiation and progression of some human tumors. (thefreedictionary.com)
- In addition to RAS, which is the most frequently mutated oncogene in human tumors, BRAF and PI3K have been found to be frequently mutated in a wide range of malignancies. (aacrjournals.org)
- Ras, a proto-oncogene, is a small G-protein that has 3 isoforms (H-Ras, N-Ras, and K-Ras) that differ in their 20 C-terminal amino acids. (merckmillipore.com)
- Recombinant Human RAB5A Member RAS Oncogene Family RECOMBINANT & NATURAL PROTEINS Human samples 80 % of the research is conducted on human samples. (antibody-antibodies.com)
- GENTAUR suppliers human normal cells, cell lines, RNA extracts and lots of antibodies and ELISA kits to Human proteins as well as Recombinant Human RAB5A Member RAS Oncogene Family RECOMBINANT & NATURAL PROTEINS. (antibody-antibodies.com)
- They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices. (nih.gov)
- GTPases of the Ras superfamily regulate many aspects of cell growth, differentiation and action. (nih.gov)
- Together with Volume 1, this book provides a comprehensive and state-of-the-art work on small G-proteins (GTPases). (springer.com)
- Recent data have linked Eph receptor-ephrin signaling complexes to the Ras and Rho families of small molecular weight GTPases and also to heterotrimeric G proteins. (nih.gov)
- Rin ( R as-like protein i n n eurons), along with Rit ( R as-like protein i n many t issues) and Drosophila Ric ( R as-related protein which i nteracted with c almodulin), comprise the Rit subfamily of Ras-related small GTPases (Lee et al. (springer.com)
- Colicelli J. Human RAS superfamily proteins and related GTPases. (springer.com)
- Biochemical characterization of the Ras-related GTPases Rit and Rin. (springer.com)
- GTPase-Activating Proteins for the Arf-family Small GTPases: not only for the termination. (indigo.ca)
- Ras-related protein Ral-B (RALB) is a member of a subfamily of Ras-related GTPases. (prospecbio.com)
- The regions essential for inducing GDP/GTP release in Rac and Ras GTPases are underlined. (atlasgeneticsoncology.org)
- Ras-related guanosine triphosphate (GTP)-binding nuclear protein (Ran) GTPases function as molecular switches and regulate diverse cellular events in eukaryotes. (mdpi.com)
- The Ras family of GTPases are important in cell signaling and frequently mutated in human tumors. (elifesciences.org)
- Our study establishes lysine fatty acylation as a previously unknown mechanism that regulates the Ras family of GTPases and provides an important mechanism by which SIRT6 functions as a tumor suppressor. (elifesciences.org)
- Rab17 belongs to the Rab family of small Ras-like GTPases. (creativebiomart.net)
- Accordingly, we next examined downstream IL-6 signaling via the STAT3, STAT1, and Ras-dependent mitogen-activated protein kinase (MAPK) cascades. (jimmunol.org)
- The effects of a Ras farnesyl transferase inhibitor, FPT III on human atherosclerotic vascular smooth muscle (VSM) cells proliferation and p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) activity was measured. (strath.ac.uk)
- FPT III incubation (18 h) inhibited platelet-derived growth factor (PDGF)-stimulated p42/p44 MAPK activation and p21 Ras membrane localization, whereas 15 min incubation had no effect on the activation of p42/p44 MAPK in response to PDGF (added at 18 h) or on membrane p21 Ras localization (measured at 18 h). (strath.ac.uk)
- U0126, a recently introduced mitogen-activated protein kinase kinase (MAPK)/extracellular signal-regulated kinase kinase inhibitor reversed morphology and inhibited anchorage-independent growth of Ki- ras -transformed rat fibroblasts. (aacrjournals.org)
- Another MAPK/extracellular signal-regulated kinase kinase inhibitor, PD98059, showed only marginal effects on p70 S6K phosphorylation and did not effectively block Ki- ras -induced transformation. (aacrjournals.org)
- The RAS/MAPK module is a critical component of a complex signaling network, comprehensively reviewed elsewhere ( 4 ). (aacrjournals.org)
- Most efforts to design small-molecule inhibitors of RAS-MAPK signaling have focused on the major protein players (i.e. (aacrjournals.org)
- We have found that lethal toxin from Clostridium sordellii, which specifically inactivates the low molecular weight G proteins Ras, Rap, and Rac, inhibits the activation of p38 mitogen-activated protein kinase (MAPK) by interleukin-1 (IL-1) in EL4.NOB-1 cells and primary fibroblasts. (tcd.ie)
- The target protein involved appeared to be Ras, because transient transfections with dominant negative RasN17 inhibited p38 MAPK activation by IL-1. (tcd.ie)
- Furthermore, constitutively active Rap1AV12 inhibited p38 MAPK activation by IL-1, consistent with Rap antagonizing Ras function. (tcd.ie)
- Our studies therefore provide clear evidence using multiple approaches for Ras as a signaling component in the activation of p38 MAPK by IL-1, with Rap having an inhibitory effect. (tcd.ie)
- Here, we report that a protein-complex activated by the Ras effector p38γ MAPK is a novel therapeutic target for K-Ras-dependent colon cancer. (elsevier.com)
- The biochemistry, structure, function and G-protein/effector interactions are described in detailed reviews. (springer.com)
- These results indicate that GAP interaction may be essential for ras p21 biological activity and that it may be a ras effector protein. (sciencemag.org)
- A second effector is phosphoinositide 3-OH kinase (PI 3-kinase), which, in turn, activates the small G protein Rac. (asm.org)
- Ras V12S35 and Ras V12G37 , 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. (asm.org)
- All combinations of Rac/Raf and Ras/Raf and Rho/Raf effector mutants that transform cells cooperatively stimulated ERK. (asm.org)
- The major oncogenic signal from Ras utilizes the serine threonine kinase Raf as the effector ( 52 , 54 ). (asm.org)
- Further evidence of the importance of these effectors in Ras signaling comes from new Ras point mutants, known as effector mutants, that bind and activate only subsets of Ras effectors ( 56 ). (asm.org)
- Cytoskeleton, Inc. provides HTS format assays to measure in vivo activities of small G-proteins as well as in vitro drug discovery HTS assays for GEFs, GAPs and G-protein - effector interactions. (cytoskeleton.com)
- MSCS analysis of Ras identifies the known Ras-effector binding domain as a site of protein: protein interaction and predicts a new protein binding site that is located in a large, solvent exposed pocket between Switch II and helix 3. (ncsu.edu)
- Many cancer medications fail to effectively target the most commonly mutated cancer genes in humans, called RAS. (news-medical.net)
- Of these, the three genes encoding RAS proteins are particularly important, as they are found mutated in over 25% of human cancers. (news-medical.net)
- Here we review the mutational frequency of the three RAS genes in human cancers and their ability to induce cancer in specific tissues. (cancer.gov)
- Of the three mammalian RAS genes, only HRAS and KRAS were identified originally as the cellular counterparts of the viral oncogenes of acute transforming Harvey and Kirsten sarcoma retroviruses (Cox and Der, 2010). (cancer.gov)
- Another possible basis for these variations is that the different RAS genes exhibit different potencies in driving cancers from different tissues. (cancer.gov)
- Overexpression of BMH genes also partially suppresses the temperature sensitivity of the cdc25-1 mutant, and high-copy TPK1, encoding a cAMP-dependent protein kinase, restores Bmh- yeast to viability. (pnas.org)
- Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). (curehunter.com)
- Ras proteins are involved in transmitting signals within cells, turning on genes involved in cell growth, differentiation and survival. (sciencephoto.com)
- abstract = "A cancer phenotype is driven by several proteins and targeting a cluster of functionally interdependent molecules should be more effective for therapeutic intervention. (elsevier.com)
- These antibodies are useful in detecting mutant ras proteins which have been shown to be early events in the development of 30-50% of colon cancer cases, approximately 90% of pancreatic cancer cases, and 30% of lung cancer cases. (thefreedictionary.com)
- We used a panel of monoclonal antibodies raised against v-Ha-ras p21 to precipitate an Mr 21,000 protein from extracts of Aplysia nervous tissue, ovotestis, and, to a much lesser degree, buccal muscle. (rupress.org)
- In the HL-60 cell line of human promyelocytic leukemia, a new protein was discovered with molecular mass 19,2 kDa, named haponin (HLDF-alike protein), immunoreactive with polyclonal antibodies to one of HLDF analogs (HLDFβ). (ibch.ru)
- The candidate will evaluate different techniques and processes for the purification of proteins and antibodies from fermentation supernatants. (biospace.com)
- With direction from senior leadership, develop and execute research plans towards developing purification methods of proteins or antibodies. (biospace.com)
- Purify proteins and antibodies from cell cultures or cell lysates using affinity chromatography or other techniques. (biospace.com)
- Proven experience in purification and handling of proteins and/or antibodies. (biospace.com)
- Rapid attachment/spreading of NRK cells on to prepared p52 matrices and inhibition of fibroblast spreading by antibodies to p52 indicated that this protein participates in shape determination or cell-to-substrate adhesion. (biochemj.org)
- The marked down-regulation of p52 expression seen in four different ras-mediated transformation systems, its induction prior to butyrate-induced morphological reorganization in KiMSV-transformed cells, and the morphological consequences of exogenously added p52 or p52 antibodies on NRK fibroblasts suggest that this protein probably functions in cell-shape regulation. (biochemj.org)
- Numerous proteins affecting the GTPase activity, nucleotide exchange rates and membrane localization of Ras superfamily members have now been identified. (nih.gov)
- Similar to other Ras superfamily proteins, RGKs contain a guanine nucleotide binding domain (G-domain). (ebi.ac.uk)
- Nucleotide sequencing revealed a putative exon that encodes amino acids sharing 68% homology with residues 5 to 54 of mammalian p21ras polypeptides, and which therefore is likely to encode a ras-like Aplysia protein. (rupress.org)
- RALB is activated by a unique nucleotide exchange factor, Ral GDS, and deactivated by a distinct GTPase-activating protein. (prospecbio.com)
- The Ras-GEF region, includes the Cdc25 domain which exhibits guanine nucleotide exchange factor (GEF) activity towards the Ras family GTPase and a REM ( R as E xchanger-stabilization M otif) domain, responsible for the stabilization of the core of the Cdc25 domain. (atlasgeneticsoncology.org)
- EDTA is used to sequester magensium ions from the His-H-Ras protein, thereby stimulating nucleotide exchange activity. (cytoskeleton.com)
- BK100 ) is used to monitor the nucleotide exchange in His-H-Ras. (cytoskeleton.com)
- Normally, Ras is activated by growth factor receptors through its guanine nucleotide exchange factors (GEF) ( 12 ). (asm.org)
- RasGRP, a guanyl nucleotide-releasing protein for the small guanosine triphosphatase Ras, was characterized. (elsevier.com)
- There is an emerging perception that the roles and functions of specific RAS proteins in cancer are distinct and, consequently, distinct anti-RAS strategies will be needed for effective inhibition of each RAS protein. (cancer.gov)
- Of most important, pharmacologically inhibition of Hsp90 or p38γ activity disrupts the complex, decreases K-Ras expression, and selectively inhibits the growth of K-Ras MT colon cancer in vitro and in vivo. (elsevier.com)
- These responses correlated with the inhibition of stem cell factor (SCF)-stimulated activation of extracellular signal-regulated kinase (Erk), protein kinase B (PKB) and ribosomal S6 kinase by simvastatin. (nature.com)
- 2014), supporting distinct roles for RAS isoforms in driving cancer from different tissues. (cancer.gov)
- p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. (uniprot.org)
- The 14-3-3 proteins are abundant acidic proteins of approximately 30 kDa with numerous isoforms and a diverse array of reported functions. (pnas.org)
- Although oncogenic lesions occur in a single Ras isoform within individual tumors, it is unclear whether the remaining wild-type isoforms play supporting roles in tumor growth. (semanticscholar.org)
- Here, we show that oncogenic and wild-type Ras isoforms play independent and nonredundant roles within the cell. (semanticscholar.org)
- Oncogenic Ras Isoforms Signaling Specificity at the Membrane. (semanticscholar.org)
- Addgene: Mammalian expression vectors for Ras family proteins: generation and use of expression constructs to analyze Ras family function. (addgene.org)
- The B7-1 Cytoplasmic Tail Enhances Intracellular Transport and Mammalian Cell Surface Display of Chimeric Proteins in the Absence of a Linear ER Export Motif. (creativebiomart.net)
- The HBx protein of hepatitis B virus (HBV) is a small transcriptional transactivator that is essential for infection by the mammalian hepadnaviruses and is thought to be a cofactor in HBV-mediated liver cancer. (semanticscholar.org)
- Like its mammalian homolog, Drosophila RasGAP stimulated the intrinsic GTPase activity of normal mammalian H-Ras but not that of the oncogenic Val12 mutant. (ucl.ac.uk)
- Researchers conduct studies laboratory EIF1AD protein (gaponina) which was opened in the Laboratory and regulates the processes in the body related to oxidative stress (OS). (ibch.ru)
- SMO1 encodes a GTPase-activating protein (GAP), which regulates Ras signalling during infection-related development. (genetics.org)
- Here, we report that a novel posttranslational mechanism, reversible lysine fatty acylation, regulates R-Ras2, a member of the Ras family. (elifesciences.org)
- However, it remains unclear whether SIRT6 regulates other proteins by defatty-acylation. (elifesciences.org)
- Genetic disruption of the scaffolding protein, Kinase Suppressor of Ras 1 (KSR1), differentially regulates GM-CSF-stimulated hyperproliferation in hematopoietic progenitors expressing activating PTPN11 mutants D61Y and E76K. (sigmaaldrich.com)
- The mechanism by which Ras signalling regulates cell-cycle progression is unclear, however. (uu.nl)
- 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. (wikipedia.org)
- Now we report that one of the suppressor loci, BMH2/SCD3, encodes a protein of the 14-3-3 family. (pnas.org)
- SIRT6 is a tumor suppressor protein that has been studied in many different types of cancer. (elifesciences.org)
- We hypothesized that Kinase Suppressor of Ras 1 (KSR1) contributes to activating PTPN11-induced GM-CSF hypersensitivity. (sigmaaldrich.com)
Member of the Ras family1
- RHEB (Ras homolog Enriched in Brain) is an evolutionarily conserved member of the Ras family of small GTP binding proteins originally found to be rapidly induced by synaptic activity in the hippocampus following seizure. (neuromics.com)
- Several drug discovery programs have also been devoted to finding inhibitors of farnesyltransferase as a means to prevent the membrane localization of RAS. (aacrjournals.org)
- Question 2: Which is the best assay format to develop inhibitors of small G-proteins? (cytoskeleton.com)
- The best assay format for developing and screening G-protein inhibitors is Cytoskeleton's G-LISA activation assays (Cat. (cytoskeleton.com)
- Further evidence for Ras involvement came from the observation that IL-1 caused a rapid activation of Ras in the cells and from the inhibitory effects of the Ras inhibitors manumycin A and damnacanthal. (tcd.ie)
- N-terminally myristoylated Ras proteins require palmitoylation or a polybasic domain for plasma membrane localization. (asm.org)
- The drug did not directly affect activation of c-Kit or its localization to lipid rafts, but in addition to its ability to block Ras membrane localization, it selectively downregulated H-Ras protein levels at the post-translational level. (nature.com)
- The specific targeting of Ras to the plasma membrane is therefore critically dependent on signals that are contained in the hypervariable domain but can be supported by N-terminal myristoylation or C-terminal prenylation. (asm.org)
- Interestingly, oncogenic Ras G12V that is localized correctly to the plasma membrane leads to mitogen-activated protein kinase activation irrespective of the combination of targeting signals used for localization, whereas Ras G12V that is mislocalized to the cytosol or to other membranes activates mitogen-activated protein kinase only if the Ras protein is farnesylated. (asm.org)
- Structural alterations in the upstream GTPase RAS occur in ∼25% of human cancers and confer them with the ability to relay mitogenic signals in a ligand-independent manner, thereby obviating the need for ligand activation of growth factor receptors that occurs in normal cells. (aacrjournals.org)
- Signals from Ras through the alternate effectors utilize other small G proteins. (asm.org)
- Subcellular localization influences the nature of Ras/extracellular signal-regulated kinase (ERK) signals by unknown mechanisms. (hud.ac.uk)
- Herein, we demonstrate that the microenvironment from which Ras signals emanate determines which substrates will be preferentially phosphorylated by the activated ERK1/2. (hud.ac.uk)
- We show that the phosphorylation of epidermal growth factor receptor (EGFr) and cytosolic phospholipase A(2) (cPLA(2)) is most prominent when ERK1/2 are activated from lipid rafts, whereas RSK1 is mainly activated by Ras signals from the disordered membrane. (hud.ac.uk)
- Furthermore, we demonstrate that scaffold usage markedly influences the biological outcome of Ras site-specific signals. (hud.ac.uk)
- These results disclose an unprecedented spatial regulation of ERK1/2 substrate specificity, dictated by the microlocalization from which Ras signals originate and by the selection of specific scaffold proteins. (hud.ac.uk)
- Since Ras family proteins transduce receptor tyrosine kinase signals to both the Erk and PI3K signalling cascades, inhibiting their function in SCLC cells may have a negative impact on tumour cell proliferation and survival. (nature.com)
- The emergence of multiple drug candidates targeting these downstream kinases provides us with the means for validating the importance of the RAS-RAF-MEK-ERK signaling cascade in human tumors. (aacrjournals.org)
- Die GTPase RAL aus der Familie der RAS-GTPasen wird als Downstream-Effektor von RAS angesehen, der damit ebenfalls zur Aufrechterhaltung des Tumorzellüberlebens beitragen könnte. (uni-wuerzburg.de)
- Targeting G-proteins, their regulators and their downstream effectors is therefore becoming an important area of drug discovery. (cytoskeleton.com)
- Simultaneous imaging analysis reveals that in the absence of extracellular stimuli, autonomous PI3K and Ras activation occur, concurrently, at the same sites where F-actin projection emerges. (rupress.org)
- We demonstrate that both PI3K and Ras activation occur actively, at the same sites of new pseudopod formation in the absence of extracellular stimuli and without heterotrimeric G protein input. (rupress.org)
- Phosphoproteomic profiling revealed that phosphorylation-activated extracellular signal-regulated kinase (ERK) 1/2 was more abundant in Ha-ras -mutated than in B-raf -mutated tumors. (aspetjournals.org)
- Ras subcellular localization defines extracellular signal-regulated kinase 1 and 2 substrate specificity through distinct utilization of scaffold proteins. (hud.ac.uk)
- We report that g β null cells display PI3K and Ras activation, as well as the reciprocal localization of PI3K and PTEN, which lead to local accumulation of PI(3,4,5)P 3 . (rupress.org)
- Ras encodes a small G protein that binds GTP and GDP and possesses intrinsic GTPase activity. (asm.org)
- Regulation of voltage-dependent calcium channels by RGK proteins. (ebi.ac.uk)
- SMO1 is therefore necessary for regulation of RAS activation required for conidial morphogenesis and septin-mediated plant infection. (genetics.org)
- Cell-shape regulation and matrix protein p52 content in phenotypic variants of ras-transformed rat kidney fibroblasts. (biochemj.org)
- We identified dexamethasone-induced Ras protein 1 (Dexras1) as a negative regulator of protein kinase C (PKC) δ, and the consequences of this regulation have been examined for adenylyl cyclase (EC 18.104.22.168) type 2 (AC2) signaling. (aspetjournals.org)
- These data suggest that Rb is an essential GI-specific mediator that links Ras-dependent mitogenic signalling to cell-cycle regulation. (uu.nl)
- The activity and regulation of small G-proteins has been shown to play an important role in the development and progression of a number of diseases such as cancer, cardiovascular disorders, inflammation and neurological disorders. (cytoskeleton.com)
- Oncogenic and wild-type Ras play divergent roles in the regulation of mitogen-activated protein kinase signaling. (semanticscholar.org)
- Genetic interactions, however, suggested a Ras-independent role for RasGAP in the regulation of growth. (ucl.ac.uk)
- Hoshino M, Yoshimori T, Nakamura S. Small GTPase proteins Rin and Rit Bind to PAR6 GTP-dependently and regulate cell transformation. (springer.com)
- Any of a group of proteins that are found near cell membranes and regulate cell division and proliferation. (thefreedictionary.com)
- In this study, we genetically separate the GPCR heterotrimeric G protein-dependent cellular events that regulate chemotaxis from the basal regulatory signaling loops that control random cell movement and cytokinesis. (rupress.org)
- These proteins are about 50% identical to Ras and regulate the actin cytoskeleton. (asm.org)
- UNLABELLED H-Ras, K-Ras, and N-Ras regulate cellular growth and survival and are often activated by somatic mutation in human tumors. (semanticscholar.org)
- The hepatitis B virus (HBV) HBx protein activates AKT to simultaneously regulate HBV replication and hepatocyte survival. (semanticscholar.org)
- The Laboratory researches the proteins including in transmembrane signaling processes, differentiation and cell apoptosis, and also new proteins and peptides associated with the pathogenesis of social diseases. (ibch.ru)
- Previously, we have shown that ectopic expression of a constitutively active protein (yan ACT ) inhibits the differentiation of multiple cell types. (genetics.org)
- As RKIP loss has recently been described in RAS -mutated myelomonocytic acute myeloid leukemia, we now aimed to analyze its role in myelomonocytic differentiation and RAS -driven leukemogenesis. (haematologica.org)
- Ras plays a key role in regulating cellular proliferation, differentiation, and transformation. (asm.org)
- Products in the GI-4000 series target the mutated Ras protein which occurs in 75-90% of pancreatic cancers, 35-45% of colorectal cancers, and 30-35% of non-small cell lung cancers. (thefreedictionary.com)
- PhD Description: Mutants of the small GTPase RAS are the most common activating lesions found in human cancers, and directly associated with poor response to therapy. (findaphd.com)
- RAS-driven cancers are among the most difficult to treat and often unresponsive to traditional therapies. (findaphd.com)
- Escherichia coli Ras-like protein (ERA) is a member of a conserved family of GTP-binding proteins that are required for proliferation. (clontech.com)
- Ras has a key role in relation to cell proliferation, survival and migration and requires farnesylation for full activity. (strath.ac.uk)
- Downregulation of miR-200a-3p induced by hepatitis B Virus X (HBx) Protein promotes cell proliferation and invasion in HBV-infection-associated hepatocarcinoma. (semanticscholar.org)
- Inhibiting this enzyme causes a reduction in the endogenous production of mevalonate, which in turn triggers a series of reactions resulting in decreased biologic activity of Ras proteins and other oncogenes. (thefreedictionary.com)
- Song C, Satoh T, Edamatsu H, Wu D, Tadano M, Gao X, Kataoka T: Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase C epsilon. (hmdb.ca)
- The human neuroblastoma cell line SH-SY5Y/TrkA differentiates in vitro and acquires a sympathetic phenotype in response to phorbolester (activator of protein kinase C, PKC) in the presence of serum or growth factors, or nerve growth factor (NGF). (diva-portal.org)
- Here, we treated tumor-bearing mice with phenobarbital, an activator of the constitutive androstane receptor (CAR), to analyze the response of chemically induced Ha-ras - and B-raf- mutated mouse liver adenoma to CAR activation in vivo. (aspetjournals.org)
- 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. (asm.org)
- These data suggest that other Ras effectors can collaborate with PI 3-kinase and with each other to activate Pak. (asm.org)
- This is specifically important for Ras-dependent cancer, as mutated (MT) Ras is non-druggable and targeting its interaction with effectors may be essential for therapeutic intervention. (elsevier.com)
Oncogenic ras mutants1
- 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. (sciencemag.org)
- An NGF-inducible, Ras-dependent protein kinase has been identified that catalyzes the phosphorylation of the cyclic AMP response element-binding protein (CREB) at Ser-133. (nih.gov)
- Addgene: Phosphorylation-dependent activation of the Ras-GRF/CDC25Mm exchange factor by muscarinic receptors and G-protein beta gamma subunits. (addgene.org)
- Additional studies demonstrated that this complex is activated by p38γ-induced Hsp90 phosphorylation at S595, which is important for MT K-Ras stability and for K-Ras dependent growth. (elsevier.com)
- We conclude that trophic factor withdrawal stimulates Ras, which apparently through the Rac/NADPH oxidase system induces permanent oxidative stress, modulates the activities of NF-kB and c-Fos, induces production of homocysteine and accelerates apoptosis. (biomedsearch.com)
- Nitrosylation of Ras is necessary for maintaining the survival of PC12 cells, while farnesylation of Ras stimulates apoptosis under withdrawal conditions. (biomedsearch.com)
- 2000). This result suggested that sensitivity to DNA mutagenesis, rather than a requirement for activation of a specific RAS protein, is a basis for RAS isoform preference in cancer induction from a particular tissue. (cancer.gov)
- The mutation causes mislocalization of RASA3 to the cytosol in scat red cells where it is inactive, leading to increased GTP-bound Ras. (pnas.org)
- GTP-binding protein that possesses intrinsic GTPase activity. (rcsb.org)
- Here we show that Ras, but not Raf, activates Pak1 in cotransfection assays of Rat-1 cells but not NIH 3T3 cells. (asm.org)
- GTP-bound Ras binds and activates Raf and simultaneously recruits it to the membrane. (asm.org)
- Ras V12S35 binds and activates Raf, Ras V12G37 binds and activates Ral GDS and Rin 1, and Ras V12C40 binds and activates PI 3-kinase ( 21 , 46 , 56 , 57 ). (asm.org)
- We examined the effects of U0126, a recently introduced MEK inhibitor (5) , on growth properties of Ki- ras - and v- src -transformed rat fibroblasts. (aacrjournals.org)
- 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. (asm.org)
- The 52 kDa transformation-sensitive protein p52 was previously identified as a major substrate-associated component of normal rat kidney (NRK) fibroblasts [Higgins & Ryan (1989) Biochem. (biochemj.org)
- Abrogation of p52 matrix accumulation typically seen in ras transformants may contribute, therefore, to the aberrant cytoarchitecture characteristic of malignant fibroblasts. (biochemj.org)
- RasGRP activated Ras and caused transformation in fibroblasts. (elsevier.com)
- Thus, the presence of mutated K-ras alone, can modulate the growth response of endometrial carcinoma cells to EGF.Finally, we observed that an inhibitor of the EGF receptor tyrosine kinase activity could prevent soft agar colony formation of Ishikawa cells, but not HHUA or mutant K-ras(12V)-transfected Ishikawa cells. (nii.ac.jp)
- Taken together, these results suggest that mutated K-ras causes a loss of responsiveness to EGF stimulation and that EGTF receptor function is now dispensable for the growth of mutant Ras-positive endometrial carcinoma cells. (nii.ac.jp)
- Receptor Protein-Tyrosine Kinases) RN - EC 3.6.1. (ucl.ac.uk)
- The activated form of Ras contains a bound GTP (guanosine triphosphate, orange) in its active site. (sciencephoto.com)
- The loss of PI3K binding to Ras-guanosine triphosphate abolishes this PI3K activation, whereas prevention of PI3K activity suppresses autonomous Ras activation, suggesting that PI3K and Ras form a positive feedback circuit. (rupress.org)
- Many of these proteins are much larger and more complex than their targets, containing multiple domains capable of interacting with an intricate network of cellular enzymes and structures. (nih.gov)
- In the CNS, Ras proteins play a role in cellular mechanisms underlying synaptic plasticity and memory formation via both presynaptic and postsynaptic mechanisms ( Ye and Carew, 2010 ). (jneurosci.org)
- By studying the genetic interaction of gap-3 with the two previously identified RasGAPs gap-1 and gap-2, we find that different combinations of RasGAPs are used to repress LET-60 RAS signaling depending on the cellular context. (uzh.ch)
- Ras superfamily small GTP ( g uanosine t ri p hosphate)-binding proteins function as molecular switches, responding to extra- and intracellular stimuli to control the activity of diverse signaling cascades. (springer.com)
- The aim of the present study was to evaluate the role of Ras signaling in HIV-1 transactivator protein- (Tat-) induced A β accumulation in human cerebral microvascular endothelial cells (HBEC-5i). (hindawi.com)
- The membrane is playing a very critical role in controlling the activity of very complex signaling networks that involve many different protein molecules, Sligar said. (technologynetworks.com)
- RAF kinase inhibitor protein (RKIP) is a negative regulator of RAS -signaling. (haematologica.org)
- In addition, EGF-Ras-Erk signaling influenced the positions that the duct and pore cells adopted within the tubular network. (upenn.edu)
- And finally, after position and fate determination, EGF-Ras-Erk signaling had a continued role in maintaining organ architecture of the duct tube. (upenn.edu)
- Goals for future research will be to determine how EGF-Ras-ERK signaling controls these genetically distinct steps during tube development. (upenn.edu)
- Activation of Src family kinases by hepatitis B virus HBx protein and coupled signaling to Ras. (semanticscholar.org)
- A DAG analog caused sustained activation of Ras-Erk signaling and changes in cell morphology. (elsevier.com)
- Signaling was associated with partitioning of RasGRP protein into the membrane fraction. (elsevier.com)
- The protein belongs to the S8P family of ribosomal proteins. (antikoerper-online.de)
- One example of the high degree of conservation between human and yeast proteins is highlighted by the members of the RAS family. (mdpi.com)
- This protein is part of a large family of oncoproteins. (elifesciences.org)
- SIRT6 (sirtuin 6) belongs to the Sir2 (silencing information regulator 2) family of nicotinamide adenine dinucleotide (NAD + )-dependent protein lysine deacylases. (elifesciences.org)
- FGFs comprise a family of heparin-binding proteins that currently includes 23 members. (aacrjournals.org)
- Rho and two related proteins, Rac and Cdc42, are members of the Rho family of small G proteins. (asm.org)
- Functional interaction between the small GTP-binding protein Rin and the N-terminal of Brn-3a transcription factor. (springer.com)
- Such a distribution can be ascertained by biochemical fractionation, which shows Ras-GRF1 in both soluble and particulate fractions, its proportions vary depending on the cell type. (atlasgeneticsoncology.org)
- A biochemical technique that makes use of synthetic fatty acids, which get incorporated into the mouse cells, showed that SIRT6 removes fatty acyl groups from a protein called R-Ras2. (elifesciences.org)
- Other interacting proteins and the regions involved in such interactions are shown by broken lines. (atlasgeneticsoncology.org)
- 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. (aacrjournals.org)
- Rab17 has direct interactions with proteins and molecules. (creativebiomart.net)
- Ras proteins participate in multiple protein : protein interactions in the cell, making Ras a good candidate protein to extend the Multiple Solvent Crystal Structures method (MSCS) to the analysis and prediction of protein binding surfaces. (ncsu.edu)
- therefore, it is reasonable to speculate that a pharmacological approach that curtails Ras activity may represent a sensible approach to inhibit melanoma growth. (curehunter.com)
- PROTEINS that specifically activate the GTP-phosphohydrolase activity of RAS PROTEINS. (harvard.edu)
- 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. (sciencemag.org)
- EIF1AD localized in the nucleus and controls the transcriptional activity of p53 protein, caused by reactive oxygen species. (ibch.ru)
- Ras-GRF1, along with Ras-GRF2 and Sos, are the only known exchange factors that combine Rho and Ras exchanger activity in the same protein. (atlasgeneticsoncology.org)
- Therefore, we proposed that the balance between BRD7 function and Ras/Raf/MEK/ERK activity is important for determining the outcomes of HCV infection and HCC development. (sigmaaldrich.com)
- The biological activity of His-H-Ras is determined from its ability to catalyze the exchange of GDP for GTP. (cytoskeleton.com)
- In its oncogenic form, Ras acquires a point mutation that inactivates the GTPase activity and causes it to be locked into its activated GTP-bound state. (asm.org)
- Increased K-Ras Protein and Activity in Mouse and Human Lung Epithelial Cells at Confluence -- Kammouni et al. (aacrjournals.org)
- Further experiments showed that this complex requires p38γ and Hsp90 activity to maintain MT, but not WT, K-Ras protein expression. (elsevier.com)
- This second of two volumes discusses subfamily proteins involved in nucleo-cytoplasmic and vesicular transport mechanisms inside the cell. (springer.com)
- Each binds Ras-GTP and can, in some experimental systems, cooperate with partially activated Raf mutants to transform cells (Rin cooperates with Abl). (asm.org)
- Besides, our results suggest that in conditions of a low level of nitric oxide PC12 cells with mutated oncogenic Ras produce more ROS than cells with wild type Ras and switch homocysteine metabolism toward to transsulfuration. (biomedsearch.com)
- The large identified neurons of Aplysia offer the opportunity to examine how ras protein might function in mature nerve cells. (rupress.org)
- Exposure to Tat decreased protein and mRNA levels of zonula occludens- (ZO-) 1 and A β -degrading enzyme neprilysin (NEP) in HBEC-5i cells as determined by western blotting and quantitative real-time polymerase chain reaction. (hindawi.com)
- PI3K and Ras activation also occur at the poles of dividing cells in wild-type strains and in cells lacking functional heterotrimeric G proteins, implying that cell shape changes during cytokinesis are controlled by a similar mechanism. (rupress.org)
- Other proteins, called tumor suppressors, counteract the oncoproteins but are frequently inactive or not present in cancer cells. (elifesciences.org)
- who are part of the research group who performed the 2013 study - have now compared mouse cells that lack SIRT6 with normal mouse cells to find out which proteins SIRT6 removes fatty acyl groups from. (elifesciences.org)
- Eukaryotic cells, when exposed to stress, stopprotein translation and form cytoplasmic granulescalled stress granules (SGs) containing mRNAsand mRNA-binding proteins such as Ras-GAP SH3domain-binding protein (G3BP) 1 and 2. (nii.ac.jp)
- U0126 selectively repressed anchorage-independent growth of Ki- ras transformed cells. (aacrjournals.org)
- GAP-3 is the predominant negative regulator of RAS during meiotic progression of the germ cells, while GAP-1 is the key inhibitor of RAS during vulval induction. (uzh.ch)
- We have now investigated to what extent phorbolester and NGF cause activation of Ras and Raf-1 and the involvement of PKC in this response in differentiating SH-SY5Y/TrkA cells. (diva-portal.org)
- Since there is considerable evidence that Ras-transformation is associated with a decreased requirement growth factors, we compared the growth response of endometrial carcinoma cells harboring wild type (Ishikawa cells)or mutated (HHUA cells)K-ras to epidermal growth factor (EGF). (nii.ac.jp)
- Furthermore, EGF caused an elevation of Ras-GTP levels in Ishikawa, but not HHUA,cells. (nii.ac.jp)
- However, the introduction of mutated, but not normal, K-ras into Ishikawa cells rendered them nonresponsive to EGF growth stimulation. (nii.ac.jp)
- Inactivation of Ras in cycling cells caused a decline in cyclin D1 protein levels, accumulation of the hypophosphorylated, growth-suppressive form of Rb, and Gl arrest. (uu.nl)
- When Rb was disrupted either genetically or biochemically, cells failed to arrest in Gl following Ras inactivation. (uu.nl)
- IL-1 also activated Rap in the cells, but with slower kinetics than Ras. (tcd.ie)
- Unbiased proteomic screening and immune-precipitation analyses identified p38γ interaction with heat shock protein 90 (Hsp90) and K-Ras in K-Ras MT, but not wild-type (WT), colon cancer cells, indicating a role of this complex in Ras-dependent growth. (elsevier.com)
- Together our data demonstrate that inhibiting Ras signalling with simvastatin potently disrupts growth and survival in human SCLC cells. (nature.com)
- Mutationen der GTPase RAS treten bei bis zu 50 % der MM-Patienten auf und tragen zum Überleben von MM-Zellen bei. (uni-wuerzburg.de)
- The DH domain also mediates in Ras-GRF dimerization that ensues upon activation. (atlasgeneticsoncology.org)
- Specifically, acute (15 min) systemic administration of alcohol (2.5 g/kg) leads to the activation of H-Ras in the NAc of mice, which is observed even 24 h later. (jneurosci.org)
- Similarly, rat operant self-administration of alcohol (20%) also results in the activation of H-Ras in the NAc. (jneurosci.org)
- Using the same procedures, we provide evidence suggesting that the exchange factor GRF1 is upstream of H-Ras activation by alcohol. (jneurosci.org)
- However, the mechanistic role(s) of Gβγ and Ras in PI3K activation remains elusive. (rupress.org)
- Shown here is a general program for RAS activation. (aacrjournals.org)
- A dominant negative Rho mutant also inhibited Ras activation of Pak. (asm.org)
- NGF stimulated increased accumulation of Ras-GTP and a threefold activation of Raf-1. (diva-portal.org)
- In contrast, 12-O-tetradecanoylphorbol-13-acetate (TPA) had no effect on the amount of Ras-GTP but led to a smaller activation of Raf-1. (diva-portal.org)
- RasGRP is expressed in the nervous system, where it may couple changes in DAG and possibly calcium concentrations to Ras activation. (elsevier.com)
- Downregulation of either H- or K-Ras by RNA interference (RNAi) did not impair Erk activation by growth factors, whereas an RNAi specific for N-Ras inhibited activation of Erk, PKB and SCLC cell growth. (nature.com)
- Rb), a regulator of GI exit, functionally links Ras to passage through the Gl phase. (uu.nl)
- That Rab plays a role in endocytic recycling, regulating apical recycling of several transmembrane proteins including cystic fibrosis transmembrane conductance regulator/ CFTR , epithelial sodium channel/ENaC, potassium voltage-gated channel, and voltage-dependent L-type calcium channel. (sdsc.edu)