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Guanine NucleotidesGuanine Nucleotide Exchange FactorsGuaninerac GTP-Binding ProteinsRho Guanine Nucleotide Exchange FactorsGuanosine TriphosphateNucleotidesGuanosine Diphosphateras Guanine Nucleotide Exchange FactorsGTP-Binding ProteinsGuanylyl ImidodiphosphateMolecular Sequence DataGuanosine 5'-O-(3-Thiotriphosphate)Guanine Nucleotide Dissociation Inhibitorscdc42 GTP-Binding ProteinAmino Acid SequenceGTP PhosphohydrolasesProto-Oncogene Proteins c-vavrho GTP-Binding Proteinsras-GRF1ThionucleotidesADP-Ribosylation FactorsAdenine NucleotidesrhoA GTP-Binding ProteinKineticsGTPase-Activating ProteinsBase SequenceAdenylate Cyclaserac1 GTP-Binding ProteinProtein BindingPurine Nucleotidesrho-Specific Guanine Nucleotide Dissociation Inhibitorsral Guanine Nucleotide Exchange FactorIMP DehydrogenaseGuanine Nucleotide-Releasing Factor 2Cloning, MolecularMutationPolymorphism, Single NucleotideGuanosine MonophosphateSignal TransductionVirulence Factors, BordetellaPertussis Toxinrap1 GTP-Binding ProteinsGuanine DeaminaseCell MembraneADP-Ribosylation Factor 1Protein Structure, TertiarySOS1 ProteinEnzyme ActivationCell LineBinding SitesSequence Homology, Amino Acidrap GTP-Binding ProteinsDNAAdenosine Diphosphate RiboseEscherichia coliras ProteinsProto-Oncogene Proteins p21(ras)ProteinsEukaryotic Initiation Factor-2BAdenylate Cyclase Toxinral GTP-Binding ProteinsSodium Fluoriderab GTP-Binding ProteinsCOS Cellsrho Guanine Nucleotide Dissociation Inhibitor alphap21-Activated KinasesCholera ToxinRecombinant ProteinsTransfectionGuanosineAdenosine TriphosphateMagnesiumMonomeric GTP-Binding ProteinsNucleic Acid ConformationSon of Sevenless ProteinsSequence AlignmentRecombinant Fusion ProteinsActinsCattlePlasmidsras GTPase-Activating ProteinsModels, MolecularCyclic AMPCells, Culturedrab5 GTP-Binding ProteinsPhosphorylationDeoxyguanine NucleotidesSequence Homology, Nucleic AcidAdaptor Proteins, Signal Transducingrab1 GTP-Binding ProteinsSaccharomyces cerevisiaeHydrolysisTransducinSequence Analysis, DNAGTP-Binding Protein alpha Subunits, G12-G13Cell Cycle ProteinsFluoridesNucleotides, CyclicPyrimidine Nucleotides
Catalysed by guanine nucleotGTPasesGEFsRhoAExchange factorsConstitutively activeInhibitorsARHGEF7Gain-of-function mutatiGTPase RAC1Tiam1RegulatesActinRAC2Bound GDP for freeGeneCytoskeletalProteinProteinsSkeletal musclePathwayMembraneDissociationPhenotypesPI3KInhibitsActivityActivateFocalAxonalAffinityMechanismSiRNADependentInsulin1998DependsDominant negativeInvasionExpressionTherapeuticMutant
Catalysed by guanine nucleot1
GTPases13
  • Rac1 is a small (~21 kDa) signalling G protein (more specifically a GTPase), and is a member of the Rac subfamily of the family Rho family of GTPases. (wikipedia.org)
  • Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. (embl-heidelberg.de)
  • Vav3 is a member of the Vav family (the others being Vav1 and Vav2) of guanine nucleotide exchange factors (GEFs) for Rho-family GTPases such as Rac1, RhoA, and RhoG. (cytoskeleton.com)
  • 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)
  • A novel group of bacterial virulence factors termed the WXXXE family has emerged as guanine nucleotide exchange factors (GEFs) for these GTPases. (helmholtz-hzi.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)
  • The Rac1 and Rac2 GTPases play important roles in many processes including cytoskeletal reorganization, proliferation, and survival, and are required for B-cell development. (northwestern.edu)
  • Acts as guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. (antibodies-online.cn)
  • 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)
  • The encoded protein displays GEF activity toward RAC1 and RAC3 Rho small GTPases but not toward CDC42. (utsouthwestern.edu)
  • 2011 This led to our discovery that Arf family GTPases directly recruit and activate the WRC which is enhanced when Arf and Rac1 work together to trigger actin polymerisation. (biodiversityhotspot.org)
  • 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)
GEFs3
RhoA7
  • Vav3 GTP Exchange Factor (GEF) of Rac1, RhoA and Cdc42. (cytoskeleton.com)
  • Structure of Shigella IpgB2 in complex with human RhoA: implications for the mechanism of bacterial guanine nucleotide exchange factor mimicry. (helmholtz-hzi.de)
  • 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)
  • The Trio guanine nucleotide exchange factor is a rhoA target : binding of rhoA to the Trio immunoglobulin-like domain. (medecinesciences.org)
  • Regulates cell migration and adhesion assembly and disassembly through a RAC1, PI3K, RHOA and AKT1-dependent mechanism. (antibodies-online.cn)
  • Increases both RAC1 and CDC42 activity, but decreases the amount of active RHOA (By similarity). (antibodies-online.cn)
  • Cell migration Neural crest Directionality Persistence Syndecan-4 Non-canonical Wnt signaling PCP RhoA Rac1 Considerable progress has been made recently in understanding cell. (silverchair.com)
Exchange factors3
Constitutively active5
  • Overexpression of a constitutively active Rac1 V12 in mice caused a tumour that is phenotypically indistinguishable from human Kaposi's sarcoma. (wikipedia.org)
  • Dominant negative or constitutively active germline RAC1 mutations cause diverse phenotypes that have been grouped together as Mental Retardation Type 48. (wikipedia.org)
  • Lamellipodium formation in Arf79F-silenced cells was restored by expressing mammalian Arf1 but not by constitutively active Rac1 showing that Arf79F does not act via Rac1. (biodiversityhotspot.org)
  • We transfected cells with Rap1 targeting or scrambled siRNA and then done protein Retroperitoneal lymph node dissection transfection of the GST fused constitutively active type of Rac1. (survivinpathway.com)
  • Epistasis analyses with constitutively active and dominant-negative versions of the small GTPase Rac1 suggest that HA acts by Rac1 activation, rather than. (silverchair.com)
Inhibitors1
  • Blocking Arf79F activation with guanine nucleotide exchange factor inhibitors impaired WRC localisation to the plasma membrane and concomitant generation of lamellipodia. (biodiversityhotspot.org)
ARHGEF71
  • Here, we identify ßPix (Arhgef7), the guanine nucleotide exchange factor for Rac1 GTPase, as a regulator of axonal regeneration. (bvsalud.org)
Gain-of-function mutati2
  • Activating or gain-of-function mutations of Rac1 are shown to play active roles in promoting mesenchymal-type of cell movement assisted by NEDD9 and DOCK3 protein complex. (wikipedia.org)
  • More recently, cancer-associated gain-of-function mutations in Rac1 have been identified which contribute to tumor phenotypes and confer resistance to targeted therapies. (silverchair.com)
GTPase RAC13
  • We used data generated from genome-scale CRISPR-Cas9 Project Achilles screens to discover vulnerabilities in KRAS-mutant cancer cell lines, and identified the Rho GTPase RAC1 as a key signaling node supporting proliferation and survival of KRAS-mutant cancers. (broadinstitute.org)
  • 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)
  • Here, we report a novel role for ELMO-DOCK1, which is a bipartite guanine nucleotide exchange factor complex for the small GTPase Rac1 , and for the membrane-cytoskeletal linker Ezrin, in regulating centriole/basal body migration, docking and spacing. (silverchair.com)
Tiam14
  • cancer guanine nucleotide exchange factor molecular basis of health and disease Rac Tiam1/STEF T. (silverchair.com)
  • Immunoblotting from OxPAPC-treated ECs revealed OxPAPC-mediated rapid recruitment (5 minutes) to CEMs of the sphingosine 1-phosphate receptor (S1P 1 ), the serine/threonine kinase Akt, and the Rac1 guanine nucleotide exchange factor Tiam1 and phosphorylation of caveolin-1, indicative of signaling activation in CEMs. (arizona.edu)
  • Silencing (small interfering RNA) Akt expression blocked OxPAPC-mediated S1P 1 activation (threonine phosphorylation), whereas silencing S1P 1 receptor expression blocked OxPAPC-mediated Tiam1 recruitment to CEMs, Rac1 activation, and EC barrier enhancement. (arizona.edu)
  • In this study, we show that the Rac-specific guanine nucleotide exchange factor Tiam1 (T-lymphoma invasion and metastasis) controls the cell polarity of epidermal keratinocytes. (rupress.org)
Regulates1
  • 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)
Actin4
  • Rac1 is a pleiotropic regulator of many cellular processes, including the cell cycle, cell-cell adhesion, motility (through the actin network), and of epithelial differentiation (proposed to be necessary for maintaining epidermal stem cells). (wikipedia.org)
  • Bellanger JM, Astier C, Sardet C, Ohta Y, Stossel TP, Debant A. The Rac1- and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin. (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)
  • Mbc, active Rac1 and F-actin foci are highly enriched in the FCMs, where they localize to the Sns:Kirre junction. (silverchair.com)
RAC24
  • Immunohistochemistry: Rac1 Antibody [NB100-91266] - Rat spinal cord using Rabbit antibody to RAC1, RAC2 (100-150) at 1:1000 dilution. (novusbio.com)
  • Detects both RAC1 (Gene ID: 5879, UniProt: P63000) and RAC2 (Gene ID: 5880, UniProt: P15153). (novusbio.com)
  • Previous studies had shown that deficiency in Rac2 did not affect T-cell development, whereas the function of Rac1 in this process has not been investigated. (northwestern.edu)
  • Unexpectedly, deficiency of Rac1 and Rac2 also resulted in the aberrant survival of thymocytes lacking expression of TCRβ, showing hallmarks of hyperactive Notch signaling. (northwestern.edu)
Bound GDP for free1
  • It has been shown to bind to and activate RAC1 by exchanging bound GDP for free GTP. (utsouthwestern.edu)
Gene5
  • It is encoded by the RAC1 gene. (wikipedia.org)
  • This gene can produce a variety of alternatively spliced versions of the Rac1 protein, which appear to carry out different functions. (wikipedia.org)
  • The protein encoded by this gene acts as a guanine nucleotide exchange factor for the RHO family of small GTP-binding proteins (RACs). (utsouthwestern.edu)
  • 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)
  • We study two early onset, childhood forms of HSP due to mutations in the Kinase D-interacting substrate of 220 kDa (KIDINS220) gene that codes for Kidins220, a membrane protein implicated in the neurotrophic pathways controlling neural cell survival and maturation, and in the Alsin Rho Guanine Nucleotide Exchange Factor (ALS2) gene, coding for Alsin, an endosome- associated Rac1 and Rab5 activator. (academicgates.com)
Cytoskeletal2
  • Abolishing CEM formation (methyl-β-cyclodextrin) blocked OxPAPC-mediated Rac1 activation, cytoskeletal reorganization, and EC barrier enhancement. (arizona.edu)
  • We show that loss of Piezo1 promotes focal adhesion turnover and cytoskeletal dynamics by controlling Rac1 activity. (silverchair.com)
Protein6
  • Rac1, also known as Ras-related C3 botulinum toxin substrate 1, is a protein found in human cells. (wikipedia.org)
  • Rac1 protein is also necessary for glucose uptake in skeletal muscle activated by exercise and muscle stretching Activating mutations in Rac1 have been recently discovered in large-scale genomic studies involving melanoma and non-small cell lung cancer. (wikipedia.org)
  • This Rac1 antibody was developed against a synthetic peptide from amino acid region 100-150 as a part of human Rac1 conjugated to blue carrier protein. (novusbio.com)
  • It forms a complex with the small GTP binding protein Rac1 and recruits Rac1 to membrane ruffles and to focal adhesions. (antibodies-online.com)
  • 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)
  • To understand the signal transduction required, we focused primarily on IL-6 induction by measuring mitogen-activated protein kinase activity and analyzing the effects of mutant or dominant negative forms of Vav, Rac1, and c-Jun N-terminal kinase-1 (JNK1). (aai.org)
Proteins2
Skeletal muscle2
  • Rac1 is expressed in significant amounts in insulin sensitive tissues, such as adipose tissue and skeletal muscle. (wikipedia.org)
  • In conditions of obesity and type 2 diabetes, Rac1 signalling in skeletal muscle is dysfunctional, suggesting that Rac1 contributes to the progression of the disease. (wikipedia.org)
Pathway4
  • For example, Rac1-dependent pathway inhibition resulted in the reversal of tumour cell phenotypes, suggesting Rac1 as a predictive marker and therapeutic target for trastuzumab-resistant breast cancer. (wikipedia.org)
  • Gauthier-Rouviere C, Vignal E, Meriane M, Roux P, Montcourier P, Fort P. RhoG GTPase controls a pathway that independently activates Rac1 and Cdc42Hs. (medecinesciences.org)
  • both Rap1 and Rac1 positively influence spreading of v Abl 3T3 wtCbl cells, it was appropriate to ascertain whether or not Rap1 functions upstream of Rac1 in the pathway that links c Cbl to cell spreading in our program. (survivinpathway.com)
  • This finding is consistent with the idea that Rac1 is situated downstream of Rap1 in the signaling pathway that induces scattering of v Abl/3T3/wtCbl cells. (survivinpathway.com)
Membrane3
  • Here Rac1 regulated the translocation of glucose transporting GLUT4 vesicles from intracellular compartments to the plasma membrane. (wikipedia.org)
  • In the presence of either pY/GβGγ or pY/Rac1(GTP), PI3Kβ activity is dramatically enhanced beyond what can be explained by the increase in membrane avidity for these complexes. (elifesciences.org)
  • Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. (nih.gov)
Dissociation2
  • We also show that dissociation of the GDP.Mg(2+) complex is preceded by the displacement of the metal ion to the alpha-phosphate of the nucleotide, diminishing its affinity to the GTPase. (helmholtz-hzi.de)
  • The molecule, Rho guanine nucleotide dissociation inhibitor α (RhoGDIα), slowed down muscle glucose uptake and hindered insulin's effect. (growkudos.com)
Phenotypes1
  • These phenotypes are dependent on Rac1, PI3 kinase and GPCR signalling and can be stimulated by growth factor mediated accumulation of PIP3. (gla.ac.uk)
PI3K2
  • We find that auto-inhibited PI3Kβ must first cooperatively engage a single RTK-derived tyrosine phosphorylated (pY) peptide before it can engage either GβGγ or Rac1(GTP). (elifesciences.org)
  • Instead, PI3Kβ is synergistically activated by pY/GβGγ and pY/Rac1(GTP) through a mechanism of allosteric regulation. (elifesciences.org)
Inhibits1
  • However, given Rac1's role in glucose transport, drugs that inhibits Rac1 could potentially be harmful to glucose homeostasis. (wikipedia.org)
Activity5
  • A few recent studies have also exploited targeted therapy to suppress tumour growth by pharmacological inhibition of Rac1 activity in metastatic melanoma and liver cancer as well as in human breast cancer. (wikipedia.org)
  • This study investigates whether the guanine nucleotide exchange activity of Vav is linked to cytokine production in mast cells. (aai.org)
  • Through detailed studies, the researchers found that RhoGDIα inhibited the activity of another molecule essential for muscle glucose uptake, called Rac1. (growkudos.com)
  • By reducing RhoGDIα levels through siRNA technology, they increased Rac1 activity and improved glucose uptake. (growkudos.com)
  • Deregulated expression/activity of Rac guanine nucleotide exchange. (silverchair.com)
Activate2
  • To activate Rap1, we utilized CPT, a cAMP analogue, which doesn't activate PKA, but specifically stimulates EPAC, a guanine nucleotide exchange factor definitely controlling Rap1. (survivinpathway.com)
  • guanine nucleotide exchange factor (GEF) Mbc plays a fundamental role in the FCMs, where it functions to activate Rac1 , but is not required in the founder cells for fusion. (silverchair.com)
Focal1
  • Promotes targeting of RAC1 to focal adhesions (By similarity). (nih.gov)
Axonal1
  • Bateman J, Shu H, Van Vactor D. The guanine nucleotide exchange factor trio mediates axonal development in the Drosophila embryo. (medecinesciences.org)
Affinity1
Mechanism1
  • The precise mechanism of nucleotide exchange, however, has remained unclear. (helmholtz-hzi.de)
SiRNA2
  • v Abl/3T3/wtCbl cells were transfected with scrambled or Rac1 specific Ganetespib chemical structure siRNA to deplete Rac1, and their scattering was reviewed in the presence or in the absence of CPT, which activated Rap1, however not Rac1. (survivinpathway.com)
  • Consistent with our previous data, CA Rac1 dramatically increased distribution of scrambled siRNA transfected cells. (survivinpathway.com)
Dependent3
  • We evaluated cell lines that were predicted by CRISPR-Cas9 screening to be preferentially dependent on RAC1 as well as lines that did not show this dependency. (broadinstitute.org)
  • This was dependent on Vav-mediated activation of Rac1 as a Dbl domain-mutated Vav, inactive Rac N17, and inactive JNK1 down-regulated the Vav-induced JNK1 or IL-6 responses. (aai.org)
  • Take-n together, these results suggest that the effect of Rap1 depends o-n Rac1, while the effect of Rac1 is in-dependent of Rap1, hence arguing that Rac1 is located downstream of Rap1 in the spreading inducing signaling in v Abl/3T3/wtCbl cells. (survivinpathway.com)
Insulin1
  • Under the influence of insulin, RhoGDIα was phosphorylated and Rac1 released, which allowed the uptake of glucose into muscle cells. (growkudos.com)
19981
  • 1998 Purified mammalian WRC is inactive but can be activated in buffer by high concentrations of Rac1 (Ismail et al. (biodiversityhotspot.org)
Depends1
  • In addition it depends on Rac1-mediated cell polarization and lamellipodia formation. (biomedcentral.com)
Dominant negative1
  • In addition, the expression of dominant-negative Rac1 inhibited neurite extension and blocked agrin-mediated. (silverchair.com)
Invasion1
  • P-Rex1, a Rac guanine nucleotide exchange factor (GEF), was previously identified in this lab in a transcriptional screen for mediators of cell invasion. (gla.ac.uk)
Expression1
  • Rac1 has ubiquitous tissue expression, and drives cell motility by formation of lamellipodia. (wikipedia.org)
Therapeutic1
  • As a result, Rac1 is considered a therapeutic target for many of these diseases. (wikipedia.org)
Mutant2
  • In this project, we validated RAC1 dependency in KRAS-mutant lines. (broadinstitute.org)
  • We present data supporting RAC1 dependency in KRAS mutant cell lines and demonstrate synergistic interactions with MEK inhibition. (broadinstitute.org)