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ras ProteinsGenes, rasMonomeric GTP-Binding Proteinsras Guanine Nucleotide Exchange FactorsSignal Transductionrho GTP-Binding ProteinsAmino Acid SequenceMolecular Sequence DataProto-Oncogene Proteins p21(ras)GTP Phosphohydrolasescdc42 GTP-Binding ProteinOncogene Protein p21(ras)rac1 GTP-Binding Proteinrac GTP-Binding Proteinsras GTPase-Activating Proteinsrab GTP-Binding ProteinsrhoA GTP-Binding ProteinGuanine Nucleotide Exchange FactorsGTPase-Activating Proteinsral GTP-Binding ProteinsGuanosine TriphosphateGTP-Binding ProteinsGuanosine DiphosphateGuanine Nucleotide Dissociation Inhibitorsrap GTP-Binding Proteinsrab5 GTP-Binding Proteinsp21-Activated KinasesProto-Oncogene Proteins c-rafCytoskeletonEnzyme ActivationActinsADP-Ribosylation FactorsProtein BindingProtein PrenylationMutationrho-Specific Guanine Nucleotide Dissociation Inhibitorsrap1 GTP-Binding Proteins3T3 CellsRho Guanine Nucleotide Exchange FactorsProtein Structure, TertiaryCell LineProtein Transportrab4 GTP-Binding ProteinsCell MovementTransfectionRecombinant Fusion ProteinsCOS CellsProtein-Serine-Threonine KinasesProto-Oncogene Proteins c-vavrhoB GTP-Binding Proteinral Guanine Nucleotide Exchange FactorPrenylationras-GRF1rho Guanine Nucleotide Dissociation Inhibitor alphaCell Transformation, Neoplasticcdc42 GTP-Binding Protein, Saccharomyces cerevisiaeADP-Ribosylation Factor 1PseudopodiaCell Membranerab1 GTP-Binding ProteinsCell PolarityProteinsPhosphorylationMitogen-Activated Protein KinasesModels, BiologicalProto-Oncogene ProteinsSequence Homology, Amino AcidCell AdhesionPhosphatidylinositol 3-KinasesEndosomesCells, CulturedMembrane ProteinsNIH 3T3 CellsGolgi ApparatusHeLa CellsCell Cycle ProteinsVesicular Transport Proteinsrho-Associated KinasesMAP Kinase Signaling SystemTwo-Hybrid System TechniquesEndocytosisMicroscopy, Fluorescencerab3 GTP-Binding ProteinsCalcium-Calmodulin-Dependent Protein KinasesRecombinant ProteinsSon of Sevenless Proteinsp120 GTPase Activating ProteinBacterial ToxinsFungal ProteinsFarnesolraf KinasesADP Ribose TransferasesSaccharomyces cerevisiae ProteinsSaccharomyces cerevisiaeFibroblastsGTP Phosphohydrolase ActivatorsStress FibersBase SequenceNeuropeptidesSequence Alignment
Superfamily of smallBelong to the Ras superfamilyRegulateEffectorsSubfamilyCdc42DownstreamRegulatorsMembraneMoleculesGTPaseNRasKinaseExtracellular signalsMutationsGuanineSmall GTP-bindingSignal transductionInteractGuanosineCytoskeletonMolecularKRASInhibitorsBelongsHomologyRac1CellularMembersSignalsInterestinglyAminoTargetsTumorigenesisNeuronalUndruggablePathwaysMammalsYeastEncodeMemberVulnerabilitiesSignalingCancerLaboratory
Superfamily of small5
  • Rho and rac, two members of the ras-related superfamily of small GTPases, regulate the polymerization of actin to produce stress fibers and lamellipodia, respectively. (nih.gov)
  • RAB18, a member of Ras-related small GTPases family, belongs to members of the Ras oncogene superfamily of small guanosine triphosphatases [ 15 ]. (hindawi.com)
  • RHO GTPases members of the RAS superfamily of small GTPases are adhesion and growth-factor activated molecular switches that play important roles in tumor development and progression. (sciencepop.org)
  • Rho GTPases belong to the Ras superfamily of small GTPases and are highly conserved throughout eukaryotes. (spandidos-publications.com)
  • RAS proteins are members of the superfamily of small GTPases comprising over 150 members. (tocris.com)
Belong to the Ras superfamily2
Regulate8
  • The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants. (wikipedia.org)
  • The rab family of small, ras-like GTPases regulate membrane trafficking events in the secretory and endocytic pathways. (bl.uk)
  • These approaches closely align with the National Cancer Institute (NCI) RAS Initiative to identify druggable candidates that regulate KRAS signaling and that could develop as new therapeutic targets for the treatment of pancreatic cancer. (pancan.org)
  • The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellular processes. (embl-heidelberg.de)
  • Upon activation GTP-bound RHO-GTPases interact with a wide spectrum of effectors to regulate various cellular pathways including cytoskeletal dynamics motility cytokinesis cell growth apoptosis and transcriptional activity. (sciencepop.org)
  • GEFs regulate the activity of members of the Ras superfamily of GTPases. (medscape.com)
  • RAS proteins function as GDP-GTP regulated binary on-off switches, which regulate a diverse set of cytoplasmic signaling networks. (tocris.com)
  • The Rat sarcoma (Ras) family of small membrane-associated GTPases are essential molecules involved in a signal transduction cascade that regulate, among other cellular properties, survival and proliferation. (illinois.edu)
Effectors7
  • In an effort to understand the fundamental signaling elements, or 'core machinery', required for the function of these GTPases, we describe here the conservation and functional similarities of Cdc42 and Rac effectors in five different species: plant, yeast, fruit fly, roundworm and human. (biomedcentral.com)
  • We focus on six 'core' effectors that operate in almost all these species - members of the Pak, WASP/WAVE, formin, lipid-kinase, IQGAP and NADPH oxidase families. (biomedcentral.com)
  • Pharmacological modulators of RAS function are discussed in depth, including those that inhibit RAS directly, RAS membrane association and RAS effectors. (tocris.com)
  • Ras-GTPases act as molecular switches that bind to downstream effectors, such as the protein kinase c-Raf , and localizes them to the membrane resulting in their activation. (bionity.com)
  • When GTP is bound, for instance, Ras proteins can interact with effectors and other molecules to affect cell proliferation, differentiation and apoptosis. (justia.com)
  • In turn, GTP-bound active GTPases can interact with a plethora of different effectors which mediate the different cellular functions of this family of proteins. (biomedcentral.com)
  • Two factors concur to determine specific Rho GTPase function: tissue specificity of GTPase effectors and distinct intracellular localizations of closely related Rho GTPases, due to different lipid modifications [ 1 ]. (biomedcentral.com)
Subfamily3
  • The Rho family of GTPases is a family of small (~21 kDa) signaling G proteins, and is a subfamily of the Ras superfamily. (wikipedia.org)
  • Ras-like protein belongs to the Rac subfamily of the Rho family of GTPases. (prospecbio.com)
  • All NSP proteins contain an NH 2 -terminal SH2 (Src homology domain 2) domain, a central proline/serine-rich domain, and a COOH-terminal domain with modest homology to Ras subfamily GDP-exchange factors (GEFs). (molvis.org)
Cdc4213
  • Transforming activity of the Rho family GTPase, Wrch-1, a Wnt-regulated Cdc42 homolog, is dependent on a novel carboxyl-terminal palmitoylation motif. (xenbase.org)
  • Three members of the family have been studied in detail: Cdc42, Rac1, and RhoA. (wikipedia.org)
  • Almost all research involves the three most common members of the Rho family: Cdc42, Rac1 and RhoA. (wikipedia.org)
  • We report here that cdc42, another member of the rho family, triggers the formation of a third type of actin-based structure found at the cell periphery, filopodia. (nih.gov)
  • Activation of cdc42 in Swiss 3T3 cells leads to the sequential activation of rac and then rho, suggesting a molecular model for the coordinated control of cell motility by members of the rho family of GTPases. (nih.gov)
  • Cdc42 and Rac - ancient, highly conserved, small GTPases - mediate extracellular signals, triggering changes in transcription and in the actin cytoskeleton. (biomedcentral.com)
  • Although dozens of proteins act downstream of these GTPases, a comparison of effector proteins from evolutionarily diverse organisms suggests that six groups of proteins serve as the core machinery for signaling from Cdc42 and Rac. (biomedcentral.com)
  • The basic signaling properties of two major subgroups of Rho GTPases - the Cdc42 and Rac subfamilies - are highly conserved amongst all eukaryotes, but the means by which they act are not well understood. (biomedcentral.com)
  • This broad distribution across widely divergent eukaryotic species suggests that Cdc42 and Rac GTPases have an ancient origin, perhaps even predating that of their cousin Ras. (biomedcentral.com)
  • Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. (embl-heidelberg.de)
  • Background The RHO family proteins RAC1 CDC42 and RHOA are small GTP-binding proteins that act as molecular switches shifting between an inactive GDP-bound form and an active GTP-bound form that define functions of RHO GTPases. (sciencepop.org)
  • The three best studied members of the RHO family - RAC1 CDC42 and RHOA - are essential for transformation by activated RAS (3 4 and in the case of RAC1 and RAC2 themselves can be oncogenic drivers in human malignancies (5 6 As with RAS the RHO GTPases have proven difficult to Olmesartan medoxomil target directly with small molecule inhibitors. (sciencepop.org)
  • Another common effector of CDC42 and RAC the mixed-lineage kinases (MLKs) are a family of serine/threonine kinases that translate signals from cell surface receptors to MAPKs. (sciencepop.org)
Downstream4
  • Although inhibitors of RHO GTPases and their downstream signaling kinases have not yet been widely adopted for clinical use their potential value as cancer therapeutics continues to facilitate Olmesartan medoxomil pharmaceutical research and development and is a promising therapeutic strategy. (sciencepop.org)
  • Although a report has shown that RhoB, a small GTPase involved in cytoskeletal actin rearrangement, lies downstream of Slug ( 11 ), another member of the Snail super-family, there is no evidence to support a link between Snail and Rho GTPases. (spandidos-publications.com)
  • Central to Ras-mediated signal transduction is proper transport from the endoplasmic reticulum and subsequent stable association with the lipid bilayer of the plasma membrane where, once activated, Ras recruits downstream effector proteins leading to their subsequent activation. (illinois.edu)
  • The exchange of GDP to GTP and thus the activation of Rho GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), which act downstream of numerous growth factor receptors, integrins, cytokine receptors, and cadherins. (biomedcentral.com)
Regulators4
  • These findings give a comprehensive view of the evolutionary canvas of the Rho family and provide guides for future structure and evolution studies of other components of Rho signaling pathways, in particular regulators of the RhoGEF family. (xenbase.org)
  • On identification of novel regulators of RAS GTPases from the proposed study, Dr. Adhikari aims to identify novel therapeutic vulnerabilities in pancreatic cancer. (pancan.org)
  • Dr. Adrienne Cox is Associate Professor of Radiation Oncology and Pharmacology, whose laboratory studies RAS with a focus on RAS isoform and mutation-selective functions and regulators of RAS subcellular localization. (tocris.com)
  • A common feature of these genes is that their products have all been strongly implicated as positive regulators of the Ras/ MAP kinase signal transduction pathway. (bionity.com)
Membrane3
  • Members of the Rab family of GTPases are non-transforming, membrane-bound, geranylgeranylated members of the Ras superfamily that are involved in the fusion and trafficking of cellular vesicles. (bdbiosciences.com)
  • Fukuda M. Versatile role of Rab17 in membrane trafficking: Focus on the Rab27 effector families. (bdbiosciences.com)
  • RAB14 belongs to the large RAB family of low molecular mass GTPases that are involved in intracellular membrane trafficking. (novusbio.com)
Molecules3
  • Thomas Turbyville heads the RAS Initiative's Imaging Research Team, which develops and applies new optical microscopy techniques to understand how RAS molecules move and interact both in living cells and on synthetic membranes. (cancer.gov)
  • The N-Ras protein acts like a switch, and it is turned on and off by the GTP and GDP molecules. (medlineplus.gov)
  • Rho GTPases are key integrating molecules from different extracellular signals, as they can be activated by different GEFs. (biomedcentral.com)
GTPase9
  • These modes of regulation add to the complexity of the Rho GTPase signaling network and allow precise spatiotemporal control of individual Rho GTPases. (wikipedia.org)
  • The N-Ras protein is a GTPase, which means it converts a molecule called GTP into another molecule called GDP. (medlineplus.gov)
  • Thus, upon binding to GTP, the duration of Ras-GTPase activity is limited by the rate at which it hydrolyzes its bound GTP to GDP. (bionity.com)
  • Once released from SOS, the Ras-GTPase quickly binds fresh guanine nucleotide from the cytosol. (bionity.com)
  • The normal rate of Ras catalytic GTPase (GTP hydrolysis) activity can be increased by proteins of the RasGAP family, which bind to Ras and increase its catalytic rate by a factor of one thousand - in effect, increasing the rate at which Ras is inactivated. (bionity.com)
  • This may be explained because the SOS1 protein adopts an auto-inhibited conformation dependent on multiple domain-to-domain interactions that cooperate to block access of the SOS1 catalytic core to its Ras-GTPase targets [7] . (bionity.com)
  • This phosphorylation occurs in the active site of the plexin GTPase-activating protein (GAP) domain, which in turn inhibits endogenous GAP activity toward Ras/Rap family small GTP-binding proteins by recruiting the phospho-serine/threonine-binding protein 14-3-3ε. (stanford.edu)
  • A structural feature that distinguishes the Rho proteins from other small GTPases is the so-called Rho insert domain located between a β strand and an α helix within the small GTPase domain [ 1 - 3 ]. (biomedcentral.com)
  • Within their GTPase domains, they share approximately 30% amino acid identity with the Ras proteins and 40-95% identity within the family. (biomedcentral.com)
NRas3
  • The NRAS gene provides instructions for making a protein called N-Ras that is involved primarily in regulating cell division. (medlineplus.gov)
  • Interestingly, the other RAS family members, HRAS and NRAS, are absent from pancreatic cancer cells. (pancan.org)
  • Three human RAS genes ( HRAS , KRAS and NRAS ) encode four highly related RAS small GTPases (HRAS, KRAS4A, KRAS4B and NRAS). (tocris.com)
Kinase1
  • The class 1A phosphoinositide 3-kinase (PI3K) beta (PI3Kβ) is functionally unique in the ability to integrate signals derived from receptor tyrosine kinases (RTKs), heterotrimeric guanine nucleotide-binding protein (G-protein)-coupled receptors (GPCRs), and Rho-family GTPases. (elifesciences.org)
Extracellular signals1
  • Small GTPases function as binary molecular switches, transmitting extracellular signals to an intracellular environment [ 4 ]. (oncotarget.com)
Mutations5
  • The mutations that cause this condition affect a single protein building block (amino acid) in the N-Ras protein. (medlineplus.gov)
  • These mutations lead to production of an N-Ras protein that is constantly turned on (constitutively active). (medlineplus.gov)
  • These mutations lead to an N-Ras protein that is constitutively active and can direct cells to grow and divide without control. (medlineplus.gov)
  • Again, Dr. Adhikari will zero in her efforts on proteins that interact with these mutations of KRAS, and not with other cancer-causing KRAS mutations or other RAS family members. (pancan.org)
  • Biochemically, these mutations have been shown to similarly effect aberrant activation of the catalytic domain towards Ras-GTPases. (bionity.com)
Guanine5
  • Activation of Rho proteins through release of bound GDP and subsequent binding of GTP, is catalysed by guanine nucleotide exchange factors (GEFs) in the Dbl family. (embl-heidelberg.de)
  • The guanine nucleotide exchange factor (GEF) Dbl targets Rho family proteins thereby stimulating their GDP/GTP exchange, and thus is believed to be involved in receptor-mediated regulation of the proteins. (embl-heidelberg.de)
  • Small G-proteins, monomeric GTPases, or the RAS (Rat sarcoma) superfamily are a large family of small guanine nucleotide-binding proteins with molecular weights ranging from 20 to 30 kDa [ 1 , 2 ]. (oncotarget.com)
  • In cell signalling , Son of Sevenless , or SOS , is a gene encoding a guanine nucleotide exchange factor that acts on Ras - GTPases . (bionity.com)
  • SOS (and other guanine nucleotide exchange factors) act by binding Ras-GTPases and forcing them to release of their bound nucleotide (usually GDP). (bionity.com)
Small GTP-binding1
  • This gene encodes a small GTP-binding protein that belongs to the largest family within the Ras superfamily. (nih.gov)
Signal transduction1
Interact1
  • It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. (embl-heidelberg.de)
Guanosine2
Cytoskeleton4
Molecular2
  • GTPases of the Rho family are molecular switches that play important roles in converting and amplifying external signals into cellular effects. (xenbase.org)
  • Rho GTPases work as sensitive molecular switches existing either in an inactive, GDP-bound form or an active GTP-bound form. (biomedcentral.com)
KRAS3
  • Megan Rigby works in the RAS Initiative's Drug Screening and Preclinical Research group where she contributes to the search for novel KRAS mutant-specific covalent and non-covalent inhibitors, and aids in efforts to further understand fundamental RAS biology. (cancer.gov)
  • A RAS family member, KRAS is the most frequently mutated protein in pancreatic cancer. (pancan.org)
  • Despite decades of extensive effort, researchers have not devised a way to inhibit the activity of KRAS or other RAS protein family members as a cancer treatment. (pancan.org)
Inhibitors1
  • This review focuses on the vulnerabilities of RAS that have been targeted by RAS pharmacologic inhibitors, with a focus on RAS-dependent metabolic processes. (tocris.com)
Belongs2
  • The encoded protein belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. (antibodies-online.com)
  • Runx2 belongs to the Run family and is an essential upstream transcription factor during osteoblast differentiation. (frontiersin.org)
Homology1
  • The proteins encoded by members of the Dbl family share a common domain, presented in this entry, of about 200 residues (designated the Dbl homology or DH domain) that has been shown to encode a GEF activity specific for a number of Rho family members. (embl-heidelberg.de)
Rac12
  • Improved methods and pharmaceutical compositions are provided herein for mobilizing hematopoietic progenitor cells from bone marrow into peripheral blood, comprising the administration of an effective amount of an inhibitor of GTPases, such as Rac1 and Rac2 alone or in combination. (justia.com)
  • In particular, embodiments of the method involve inhibition of both Rac1 and Rac2 GTPases to increase the numbers of hematopoietic stem cells into a subject's peripheral blood of a subject. (justia.com)
Cellular2
Members9
  • Our data establish that the 20 mammalian Rho members are structured into 8 subfamilies, among which Rac is the founder of the whole family. (xenbase.org)
  • Eight additional mammalian Rho members were identified from biological screenings until the late 1990s, a turning point in biology where availability of complete genome sequences allowed full identification of gene families. (wikipedia.org)
  • Rho proteins sometimes denote some members of the Rho family (RhoA, RhoB, and RhoC), and sometimes refers to all members of the family. (wikipedia.org)
  • In mammals, the Rho family contains 20 members. (wikipedia.org)
  • Accumulating evidences have elucidated connection between the expression of GTPases members and several diseases, including colorectal cancer, lung cancer, and prostate cancer [ 16 - 18 ]. (hindawi.com)
  • Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states. (embl-heidelberg.de)
  • However, the mechanisms underlying receptor-dependent regulation of Rho family members remain incompletely understood. (embl-heidelberg.de)
  • 150 human members) encompasses Ras GTPases involved in cell proliferation, Rho GTPases involved in regulating the. (vietbooks.info)
  • Sar1p-like members of the Ras-family of small GTPases. (umbc.edu)
Signals1
  • To transmit signals, the N-Ras protein must be turned on by attaching (binding) to a molecule of GTP. (medlineplus.gov)
Interestingly1
  • Interestingly, small GTPases related to Rac are found even in organisms that lack Ras, such as plants. (biomedcentral.com)
Amino3
  • An amino-terminal portion conserved among a subset of Dbl family proteins is sufficient for the binding of Gbetagamma. (embl-heidelberg.de)
  • RAS mutant cancer cells are characterized by increased macropinocytosis and uptake of albumin, leading to lysosomal degradation and release of amino acids. (tocris.com)
  • RAS mutant cancer cells also exhibit altered autophagy , leading to degradation of organelles and proteins, and production of amino acids and other components to support metabolism . (tocris.com)
Targets1
  • Over 60 targets of the three common Rho GTPases have been found. (wikipedia.org)
Tumorigenesis1
  • Dr. Adhikari expanded her postdoctoral research in cancer biology in the Duke University laboratory of Dr. Christopher Counter, a leader in RAS tumorigenesis research. (pancan.org)
Neuronal1
Undruggable2
  • Kevan, what made you throw your hat in the ring to target RAS initially back when it was deemed undruggable? (cancer.gov)
  • Long-termed the "undruggable target", RAS has recently recaptured the attention of cancer researchers. (tocris.com)
Pathways1
Mammals1
  • To elucidate the evolutionary history of the Rho family, we have analyzed over 20 species covering major eukaryotic clades from unicellular organisms to mammals, including platypus and opossum, and have reconstructed the ontogeny and the chronology of emergence of the different subfamilies. (xenbase.org)
Yeast1
Encode1
  • Trio and its homologue UNC-73 are unique within the Dbl family insomuch as they encode two distinct DH/PH domain modules. (embl-heidelberg.de)
Member1
  • This family member can be activated by the GAP protein RN-Tre, and it is localized to the Golgi complex. (nih.gov)
Vulnerabilities1
  • We learn from RAS biology how each of the mutants have their own personalities, and their own vulnerabilities. (cancer.gov)
Signaling3
  • Serving a critical role in cell signaling, the class I family of phosphoinositide 3-kinases (PI3Ks) catalyze the phosphorylation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] to generate PI(3,4,5) P 3 . (elifesciences.org)
  • Dr. Channing Der is Sarah Graham Kenan Professor of Pharmacology whose studies centre on drugging RAS effector signaling networks. (tocris.com)
  • Van Aelst L, D'Souza-Schorey C. Rho GTPases and signaling networks. (medecinesciences.org)
Cancer3
  • Dr. Adhikari's work focuses on deciphering and studying the unique regulatory network of proteins that associate with RAS GTPases and its implication on pancreatic cancer. (pancan.org)
  • This review will focus on the role of Rac and Rho small GTPases in cell motility and in the complex relationship driving the reciprocal control between Rac and Rho granting for the opportunistic motile behaviour of aggressive cancer cells. (biomedcentral.com)
  • In addition we analyse the role of these GTPases in cancer progression and metastatic dissemination. (biomedcentral.com)
Laboratory1
  • Dr. Kirsten Bryant is a Postdoctoral Fellow in Dr. Der's laboratory whose studies focus on exploiting the metabolic dependencies of RAS mutant cancers. (tocris.com)