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Rho Guanine Nucleotide Exchange FactorsGuanine Nucleotide Exchange FactorsrhoA GTP-Binding Proteinrho GTP-Binding ProteinsGTP-Binding Protein alpha Subunits, G12-G13A Kinase Anchor Proteinsras Guanine Nucleotide Exchange Factorsrho-Associated KinasesProtein Structure, TertiarySignal TransductionGuanine Nucleotidescdc42 GTP-Binding ProteinProto-Oncogene Proteins c-vavGuanosine Diphosphaterho-Specific Guanine Nucleotide Dissociation InhibitorsProtein BindingGuanine Nucleotide Dissociation InhibitorsMolecular Sequence DataAmino Acid Sequencerac1 GTP-Binding Proteinras-GRF1Guanosine TriphosphateCell Linerho Guanine Nucleotide Dissociation Inhibitor gammarac GTP-Binding ProteinsADP-Ribosylation Factorsrap1 GTP-Binding ProteinsGuanine Nucleotide-Releasing Factor 2rho Guanine Nucleotide Dissociation Inhibitor alphaGTPase-Activating ProteinsSOS1 ProteinGTP-Binding ProteinsADP-Ribosylation Factor 1GTP Phosphohydrolasesral Guanine Nucleotide Exchange FactorSon of Sevenless ProteinsEukaryotic Initiation Factor-2Brab GTP-Binding Proteinsras ProteinsGuanineral GTP-Binding Proteinsrap GTP-Binding ProteinsCOS CellsProteinsrho Guanine Nucleotide Dissociation Inhibitor betaEnzyme ActivationNucleotidesSequence Homology, Amino Acidrab5 GTP-Binding ProteinsCoat Protein Complex IMutationMonomeric GTP-Binding ProteinsAdaptor Proteins, Signal TransducingCell Cycle ProteinsGuanosine 5'-O-(3-Thiotriphosphate)p21-Activated KinasesTwo-Hybrid System TechniquesRecombinant Fusion ProteinsProtein TransportActinsEukaryotic Initiation Factor-23T3 Cellsran GTP-Binding ProteinTransfectionHSP110 Heat-Shock ProteinsProto-Oncogene Proteins p21(ras)Proto-Oncogene ProteinsCell MovementPhosphorylationrab1 GTP-Binding ProteinsSaccharomyces cerevisiae ProteinsHeLa CellsNIH 3T3 CellsBrefeldin ACell MembraneBinding SitesCytoskeletonCarrier ProteinsCloning, MolecularSaccharomyces cerevisiaeOncogene Proteinssrc Homology DomainsKineticsStress FibersModels, BiologicalFungal Proteinscdc42 GTP-Binding Protein, Saccharomyces cerevisiaeBase SequenceRecombinant ProteinsGolgi Apparatusras GTPase-Activating ProteinsGRB2 Adaptor ProteinMicroscopy, FluorescencerhoB GTP-Binding ProteinProtein-Serine-Threonine KinasesCercopithecus aethiopsPhosphoproteinsCells, CulturedSequence AlignmentGTP-Binding Protein alpha Subunits
GEFsGTPaseCdc42Rac1InhibitorsActin cytoskeletonBindsProteinEffectorSignal transductionGTPases RhoRegulationRHOATrioIntracellularActive GTP-bound formDistinctSuperfamilyGenomeMammalianLipidPathwaysMetastaticSubfamiliesEffectorsMutationsInteractionsActivationCellularNeuronalProteins involved in cellCancerSmallRolesProgressionProliferationKinaseCell migrationEpigeneticDomains
GEFs10
GTPase25
  • It serves as a link between dynamin function, Rho GTPase signaling, and actin dynamics. (nih.gov)
  • This process is usually regulated by guanine nucleotide-exchange factors GTPase-activating proteins and guanine nucleotide-dissociation inhibitors (1). (sciencepop.org)
  • There have been limited successes with molecules that disrupt the binding of guanine nucleotide exchange factors to RAC and CDC42 (7-10) as well as with molecules that disrupt GTPase membrane association (11). (sciencepop.org)
  • While efforts continue to develop direct small GTPase inhibitors a PLCG2 promising and more conventional Olmesartan medoxomil therapeutic approach has been to block the activities of RHO GTPase effectors. (sciencepop.org)
  • Growth factor-stimulated mTORC1 activation involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. (abcam.cn)
  • Previous studies have proposed that this polarization process requires a local positive feedback in the leading edge involving Rac small GTPase and actin polymerization with PI3K likely playing a coordinating role. (kaist.ac.kr)
  • In this study we examined the role of βPix, a guanine nucleotide exchange factor for the Rho GTPase and a strong binding partner to Shank2, in NHE3 regulation using integrated molecular and physiological approaches. (elsevierpure.com)
  • Interestingly, the effects of βPix on NHE3 were abolished by cotransfection with dominant-negative Shank2 mutants and by treatment with Clostridium difficile toxin B, a Rho GTPase inhibitor, indicating that Shank2 and Rho GTPases are involved in βPix-mediated NHE3 regulation. (elsevierpure.com)
  • cells the critical NPF underlying lamellipodium formation is the WRC WAVE [WASP (Wiskott-Aldrich syndrome protein)-family verprolin-homologous protein] regulatory complex which is thought to be activated at the plasma membrane by the Rho GTPase Rac1 (Kunda et al. (biodiversityhotspot.org)
  • Mutations in the FGD4 gene encoding the Rho-GTPase guanine-nucleotide-exchange-factor frabin were reported in five families. (uantwerpen.be)
  • Rho2 is a fungal GTPase that plays a role in cell morphogenesis, control of cell wall integrity, control of growth polarity, and maintenance of growth direction. (umbc.edu)
  • GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. (embl-heidelberg.de)
  • The active conformation is promoted by guanine-nucleotide exchange factors, and the inactive state by GTPase-activating proteins (GAPs) which stimulate the intrinsic GTPase activity of small G proteins. (embl-heidelberg.de)
  • This gene is highly expressed in fetal brain and encodes a protein of relative molecular mass 91K, named oligophrenin-1, which contains a domain typical of a Rho-GTPase-activating protein (rhoGAP). (embl-heidelberg.de)
  • By enhancing their GTPase activity, GAP proteins inactivate small Rho and Ras proteins, so inactivation of rhoGAP proteins might cause constitutive activation of their GTPase targets. (embl-heidelberg.de)
  • Structural determinants required for the interaction between Rho GTPase and the GTPase-activating domain of p190. (embl-heidelberg.de)
  • Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)
  • 2007). Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4 . (up.pt)
  • p21-activated kinase 4 (PAK4), a specific effector of the Rho GTPase Cdc42, is activated by HGF, and we have previously shown that activated PAK4 induces a loss of both actin stress fibres and focal adhesions. (silverchair.com)
  • A common theme of these processes is a dynamic reorganization of actin cytoskeleton which has now emerged as a major switch control mainly carried out by Rho and Rac GTPase subfamilies, playing an acknowledged role in adaptation of cell motility to the microenvironment. (biomedcentral.com)
  • Conversely, in amoeboid movement cells have a rounded morphology, the movement is independent from proteases but requires high Rho GTPase to drive elevated levels of actomyosin contractility. (biomedcentral.com)
  • 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)
  • Typically Rho proteins are 190-250 residues long and consist only of the GTPase domain and short terminal C-terminal extensions. (biomedcentral.com)
  • Rho GTPase effectors are a large group of proteins and include actin nucleation promoting molecules, adaptors, as well as kinases. (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)
Cdc4213
  • DyNamin Binding Protein (DNMBP), also called Tuba, is a Cdc42-specific Guanine nucleotide Exchange Factor (GEF) that binds dynamin and various actin regulatory proteins. (nih.gov)
  • 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)
  • The Rho subfamily is divided in three main subgroups - Cdc42, Rac, and Rho - examples of which are represented in all eukaryotes from plants to man. (biomedcentral.com)
  • 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)
  • The messenger RNA expression and methylation of Rho GTPases (RhoA, Rac1, DOCK180, ELMO1, and CDC42) were evaluated in H. pylori -negative (control) human gastric tissues and H. pylori -positive GCs by using real-time reverse transcription-polymerase chain reaction and the quantitative MethyLight assay, respectively. (gutnliver.org)
  • DOCK8 is a Cdc42-specific guanine-nucleotide exchange factor that is essential for development and functions of various subsets of leukocytes in innate and acquired immune responses. (life-science-alliance.org)
  • Although DOCK8 plays a critical role in spatial control of Cdc42 activity during interstitial leukocyte migration, the mechanism remains unclear. (life-science-alliance.org)
  • The encoded protein displays GEF activity toward RAC1 and RAC3 Rho small GTPases but not toward CDC42. (utsouthwestern.edu)
  • Here, we show that the pleckstrin homology and RhoGEF domain containing G3 (PLEKHG3) is a PI3K-regulated Rho guanine nucleotide exchange factor (RhoGEF) for Rac1 and Cdc42 that selectively binds to newly polymerized actin at the leading edge of migrating fibroblasts. (kaist.ac.kr)
  • FGD1 encodes a guanine nucleotide exchange factor (GEF) that specifically activates Cdc42, a member of the Rho (Ras homology) family of the p21 GTPases. (mhmedical.com)
  • 2009). Stage-Specific Control of Neural Crest Stem Cell Proliferation by the Small Rho GTPases Cdc42 and Rac1 . (up.pt)
  • The best-characterized molecules are Rho, which controls the stress fibers and focal adhesion formation, and Rac and Cdc42, which regulate membrane ruffling, and filopodium formation, respectively. (biomedcentral.com)
Rac12
  • Bellanger JM, Lazaro JB, Diriong S, Fernandez A, Lamb N, Debant A. The two guanine nucleotide exchange factor domains of Trio link the Rac1 and the RhoA pathways in vivo. (medecinesciences.org)
  • 2010 suggested that additional unknown factors are required to facilitate WRC-dependent actin polymerisation (Davidson and Insall 2011 We showed that active Rac1 was indeed insufficient for recruitment and activation of the WRC at the membrane in mammalian cell extract (Koronakis et al. (biodiversityhotspot.org)
Inhibitors2
  • 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)
  • Blocking Arf79F activation with guanine nucleotide exchange factor inhibitors impaired WRC localisation to the plasma membrane and concomitant generation of lamellipodia. (biodiversityhotspot.org)
Actin cytoskeleton6
Binds2
  • The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac- specific and rho-specific guanine nucleotide exchange factor domains. (medecinesciences.org)
  • Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac. (embl.de)
Protein16
  • The human ARHGEF10 gene encodes the protein Rho guanine nucleotide exchange factor 10. (wikipedia.org)
  • Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. (wikipedia.org)
  • The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. (wikipedia.org)
  • Rho GTPases play a fundamental role in numerous cellular processes triggered by extracellular stimuli that work through G protein coupled receptors. (antibodies-online.com)
  • 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)
  • This protein is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. (avivasysbio.com)
  • The protein is important in hematopoiesis, playing a role in T-cell and B-cell development and activation. (avivasysbio.com)
  • Coexpression and binding of these partners initiates profound morphological changes, cytoskeletal rearrangements and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication.The protein encoded by this proto-oncogene is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. (avivasysbio.com)
  • This gene encodes a large protein that functions as a GDP to GTP exchange factor. (cancerindex.org)
  • In addition, they play important roles in gene transcription (via activation of mitogen activated protein (MAP) kinase pathways and, in higher eukaryotes, the transcription factor NFκB), generation of reactive oxygen species, apoptosis, and cell-cycle progression. (biomedcentral.com)
  • The DH protein family, exchange factors for Rho-like GTPases. (medecinesciences.org)
  • Seipel K, O'Brien SP, Iannotti E, Medley QG, Streuli M. Tara, a novel F-actin binding protein, associates with the Trio guanine nucleotide exchange factor and regulates actin cytoskeletal organization. (medecinesciences.org)
  • The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that plays a role in axon formation and neuronal polarization. (utsouthwestern.edu)
  • The present study demonstrates that cellular ATP homeostasis ensures proteostasis and revealed that suppressing the high volatility of cellular ATP levels prevented cytotoxic protein aggregation, implying that AMPK and ADK are important factors that prevent proteinopathies, such as neurodegenerative diseases. (waseda.jp)
  • These results indicate that βPix up-regulates NHE3 membrane expression and activity by Shank2-mediated protein-protein interaction and by activating Rho GTPases in the apical regions of epithelial cells. (elsevierpure.com)
  • The domain is named after cellular retinaldehyde-binding protein (CRALBP) and TRIO guanine exchange factor. (embl.de)
Effector1
  • RHO-A has a distinct set of effector kinases including the ROCK CITRON Olmesartan medoxomil and PRK1 all of which regulate cellular processes that contribute to tumorigenesis invasion and metastasis (12). (sciencepop.org)
Signal transduction1
  • Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (embl.de)
GTPases Rho2
  • Ory S, Jurdic P. Microtubules, compartiments cellulaires et GTPases Rho: ménage à trois pour une migration efficace. (medecinesciences.org)
  • Like all other GTPases, Rho proteins act as molecular switches, with an active GTP-bound form and an inactive GDP-bound form. (embl-heidelberg.de)
Regulation5
  • In addition, these two binding sites play different roles in the regulation of Sema4D expression in HUVEC and Caco-2 cells. (jcancer.org)
  • Sec14p-like domains in NF1 and Dbl-like proteins indicate lipid regulation of Ras and Rho signaling. (embl.de)
  • However, the mechanisms underlying receptor-dependent regulation of Rho family members remain incompletely understood. (embl.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.de)
  • However, GEF activity of Dbl toward Rho as measured by in vitro GDP binding assays remained unaffected following Gbetagamma binding, suggesting that additional signals may be required for the regulation of Dbl. (embl.de)
RHOA1
  • The Trio guanine nucleotide exchange factor is a rhoA target : binding of rhoA to the Trio immunoglobulin-like domain. (medecinesciences.org)
Trio2
  • Bateman J, Shu H, Van Vactor D. The guanine nucleotide exchange factor trio mediates axonal development in the Drosophila embryo. (medecinesciences.org)
  • The Dab mutant interacts genetically with mutations in Abl , and with mutations in the Abl accessory factors trio and enabled ( ena ). (biologists.com)
Intracellular1
  • PITP plays an essential role in intracellular vesicle flow and inositol lipid signaling. (embl.de)
Active GTP-bound form1
  • Rho GTPases work as sensitive molecular switches existing either in an inactive, GDP-bound form or an active GTP-bound form. (biomedcentral.com)
Distinct1
  • 2015). Drosophila PS2 and PS3 integrins play distinct roles in retinal photoreceptors-glia interactions . (up.pt)
Superfamily3
Genome1
  • The frequency of SNPs along the genome and estimated genomic inflation factors are illustrated in supplementary data ( Fig. S1 , Fig. S2 ). (biomedcentral.com)
Mammalian2
  • Na + /H + exchanger 3 (NHE3) plays an important role in neutral Na + transport in mammalian epithelial cells. (elsevierpure.com)
  • abstract = "Na+/H+ exchanger 3 (NHE3) plays an important role in neutral Na+ transport in mammalian epithelial cells. (elsevierpure.com)
Lipid2
  • In order to understand the development of adiposity, it is crucial to identify the factors and mechanisms that regulate the recruitment of mesenchymal stem cells (MSCs) of the vascular stromal fraction of the adipose tissue and its transformation into lipid-filled adipocytes. (biomedcentral.com)
  • Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. (umbc.edu)
Pathways3
  • There are many signaling pathways that lead to RHO activation including those initiated by physical stimuli (mechanical stress or cell-cell and cell-substrate adhesion) and chemical factors (growth factors and cytokines) (2). (sciencepop.org)
  • 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)
  • Further analysis via structural equation modeling (SEM) revealed that functional pathways (36% and 31%) explained TN changes better than microbial groups in sediment and water (13% and 11%), suggesting that microbial functional capabilities explain TN better than microbial community composition and other factors (pH, O2, and aquaculture type). (bvsalud.org)
Metastatic2
  • Sema4D is regulated by HIF-1 and plays a role in tumor-associated macrophage-induced metastatic behavior and is clinically significant in colon cancer ( 9 ). (jcancer.org)
  • These proteins may either trigger the metastatic potential of transformed cells or act as factors that contribute to the transforming activity of oncoproteins. (medicineinnovates.com)
Subfamilies1
  • Among other members, we will focus our attention on the Rac and Rho subfamilies, as they are the main effectors of cell motility. (biomedcentral.com)
Effectors1
  • Semaphorin 4D (Sema4D) has been proven to be one of the hypoxia effectors regulated by hypoxia inducible factor (HIF-1) in multiple cells, and play a role in angiogenesis like VEGF. (jcancer.org)
Mutations1
Interactions2
  • These results revealed that species' functional traits and interactions were the intrinsic factors determining community structure and functions. (bvsalud.org)
  • Through their activation of Rho proteins and their interactions with other proteins, the different Kalirin isoforms affect cytoskeletal organization. (biomedcentral.com)
Activation2
  • mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. (solarbio.cc)
  • The whole adipogenic process was driven by a coordinated activation of transcription factors and epigenetic modulators. (biomedcentral.com)
Cellular1
  • Rho-family GTPases orchestrate both of these cellular processes. (silverchair.com)
Neuronal1
Proteins involved in cell1
Cancer3
  • There were three nucleotide variants (T471C/A600G/C862T) frequently detected in cancer cell lines. (jcancer.org)
  • Scientists discovered before that GTP-hydrolases from the Rho/Rha family proteins are involved in the oncogenic events associated with ovarian cancer. (medicineinnovates.com)
  • 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)
Small1
  • The Rho family of small GTPases and the PDZ (PSD-95/discs large/ZO-1) domain-based adaptor Shank2 are known to regulate the membrane expression and activity of NHE3. (elsevierpure.com)
Roles2
  • GTPases play important roles in cell division, the process by which cells mature to carry out specific functions (differentiation), and the self-destruction of cells (apoptosis). (medlineplus.gov)
  • The GTPases play important roles in several cell processes. (medlineplus.gov)
Progression1
  • Hepatocyte growth factor (HGF) is associated with tumour progression and increases the invasiveness of prostate carcinoma cells. (silverchair.com)
Proliferation1
Kinase1
  • c-Jun N-terminal kinase was synergistically activated upon co-expression of Dbl and Gbeta in a dominant-negative Rho-sensitive manner. (embl.de)
Cell migration1
  • Polarized cell migration plays a pivotal role in the development and repair of tissues. (kaist.ac.kr)
Epigenetic1
  • This study aimed to evaluate the changes in epigenetic and genetic expression of multiple Rho GTPases in Helicobacter pylori -related gastric carcinogenesis by comparing H. pylori -positive GCs and negative controls. (gutnliver.org)
Domains1