Constitutively activeProteinInhibitionAssayKinaseGTPasesProteinsActivatesRhoAActinPhenotypesDownstreamGTPaseInteractorAntibodyPathwayEndogenousCdc42InhibitorInhibitsGeneLysatesPhosphorylationVivoGEFsDistinctEnhancesContributesGlucoseImportantlyMiceFunctionalSkeletalActivityCellularMetastasisActiveActivationTissueLevelsMarker
Constitutively active3
- 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)
- This phenotype could be phenocopied by inhibition of RAC1 or rescued by the introduction of constitutively active RAC1 into cells . (bvsalud.org)
Protein12
- Rac1, also known as Ras-related C3 botulinum toxin substrate 1, is a protein found in human cells. (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)
- 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)
- 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)
- 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)
- A small molecular weight G-protein essential for Nox2 activation, Rac1, is also transcriptionally activated via active DNA methylation-hydroxymethylation. (nature.com)
- The multi-component Nox2 has both trans-membrane and cytosolic proteins, and the small G-protein, Ras-related C3 botulinum toxin substrate 1 (Rac1), is an integral cytosolic component for its activation 8 . (nature.com)
- 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)
- Transgenic rac1 protein was expressed at levels comparable to endogenous rac levels, with activation of the rac1 signaling pathway resulting in two distinct cardiomyopathic phenotypes: a lethal dilated phenotype associated with neonatal activation of the transgene and a transient cardiac hypertrophy seen among juvenile mice that resolved with age. (jci.org)
- His-tagged Rac1 protein (Cat. (cytoskeleton.com)
- A model of Rac1 GTPase dynamics has been previously developed using reaction-diffusion equations in one dimension, which indicated that patterns are formed due to dynamic instabilities originating from non-linear protein interactions. (unizg.hr)
- This ideas at a potential function of GEFs as scaffolding protein not merely for Rac1 also for Rac1 effectors. (cancer-ecosystem.com)
Inhibition7
- 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)
- 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)
- The immune suppressive mechanism of thiopurines, by the active thiopurine metabolite 6-thioguanine triphosphate, is primarily based on blocking the Ras-related C3 botulinum toxin substrate 1 (Rac1) causing T-cell apoptosis by inhibition of the phosphorylated downstream transcription factor signal transducer and activator of transcription 3 (pSTAT3) ( Figure 1 ). (ecco-ibd.eu)
- We therefore studied the ability of contraction and exercise to stimulate glucose transport in isolated muscles with AMPK loss-of-function combined with either pharmacological inhibition or genetic deletion of Rac1.Muscle-specific knockout (mKO) of Rac1, a kinase dead α2 AMPK (α2KD), and double KO of β1 and β2 AMPK subunits (β1β2 KO), each partially decreased contraction-stimulated glucose transport in mouse soleus and EDL muscle. (ku.dk)
- Interestingly, when pharmacological Rac1 inhibition was combined with either AMPK β1β2 KO or α2KD, contraction-stimulated glucose transport was almost completely inhibited. (ku.dk)
- Glucocorticoid therapy regulates podocyte motility by inhibition of Rac1. (ox.ac.uk)
- Furthermore, Rac1 inhibition had a direct, protective effect on podocyte barrier function. (ox.ac.uk)
Assay9
- Transcreener GDP Assay directly measures GDP produced by Rac1 (Ras-related C3 botulinum toxin substrate 1). (bellbrooklabs.com)
- The assay provides a powerful tool to screen compound libraries for Rac1 modulators to help find new therapies for disease. (bellbrooklabs.com)
- Rac1 enzyme is not included in the inhibitor screening assay kit. (bellbrooklabs.com)
- How Does This Rac1 Assay Work? (bellbrooklabs.com)
- The Transcreener Rac1 Assay determines Rac1 enzyme activity by directly measuring the GDP formed by the enzyme using the Transcreener GDP Assay. (bellbrooklabs.com)
- Transcreener Rac1 Assay technology uses a simple but highly effective method that consists of an antibody selective to GDP and a far-red fluorescent tracer. (bellbrooklabs.com)
- The Rac1 assay is available with FP, FI, and TR-FRET. (bellbrooklabs.com)
- The Rac1 assay is compatible with 96, 384, and 1536-well formats. (bellbrooklabs.com)
- Proximity Ligation Assay (PLA) utilized to imagine the endogenous connections between Rac1 and TMOD3 (Fig.?6C D). Used together this means that that TMOD3 is normally a Rac1 interactor that displays improved Rac1 binding within a P-Rex1-reliant way. (cancer-ecosystem.com)
Kinase1
- The rac1 target p21-activated kinase translocated from a cytosolic to a cytoskeletal distribution, suggesting that rac1 activation was inducing focal adhesion reorganization. (jci.org)
GTPases3
- In this approach, we performed FRET time-lapse imaging of Rac1 and Cdc42, members of Rho GTPases which are responsible for cell motility and quantitatively identified the response functions that describe the conversion from the molecular activities to the morphological changes. (nature.com)
- In spite of such accumulating knowledge of Rac1 and Cdc42 downstream pathways, little is known about the functional differences between Rac1 and Cdc42, in particular, how these Rho GTPases participate in cell migration. (nature.com)
- 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)
Proteins9
- Detection of compounds and proteins that enhance Rac1 activity. (cytoskeleton.com)
- The following endoplasmic reticulum proteins have been identified as putative RAC1 effectors in the high throughput screen by Bagci et al. (reactome.org)
- A) Venn diagram looking at proteins that present elevated Rac1 binding under P-Rex1 Crazy Type (WT) and P-Rex1 GEF-dead mutant (GEF*) as well as decreased … Intriguingly based on the SILAC SF-TAP displays appearance of both P-Rex1 WT and P-Rex1 GEF* was connected with elevated Rac1-TMOD3 binding (Fig.?supplementary and 6A Document 1 highlighted in Desk?S.2). (cancer-ecosystem.com)
- In addition to TMOD3 the SILAC SF-TAP screens also highlighted a number of additional proteins that exhibited GEF-specific changes in Rac1 binding upon manifestation of Tiam1 GEF* and P-Rex1 GEF* further supporting a role of GEFs as scaffolding proteins irrespective of Rac1 activation. (cancer-ecosystem.com)
- Practical analysis of these proteins using Ingenuity IPA analysis suggests that Rhein-8-O-beta-D-glucopyranoside in addition to modulating Rac1-effector binding GEFs might also mediate Rac1 connection with regulatory proteins potentially influencing Rac1 levels subcellular localization and Rhein-8-O-beta-D-glucopyranoside post-translational changes (Fig.?7 and Fig.?8). (cancer-ecosystem.com)
- Consequently analysis of these proteins might also shed light on additional modes by which GEFs modulate Rac1 signaling through spatial and temporal rules. (cancer-ecosystem.com)
- Functional classification of proteins with Tiam1 GEF*-specific changes in Rac1 binding. (cancer-ecosystem.com)
- A) Venn diagram comparing proteins with increased Rac1 binding in ≥ 2 SILAC SF-TAP experiments upon manifestation of indicated GEF constructs. (cancer-ecosystem.com)
- Functional classification of proteins with P-Rex1 GEF*-specific changes in Rac1 binding. (cancer-ecosystem.com)
Activates1
- In its GTP bound active form, endoplasmic reticulum membrane associated RAC1 binds to and activates KTN1 (Hotta et al. (reactome.org)
RhoA1
- Vav3 GTP Exchange Factor (GEF) of Rac1, RhoA and Cdc42. (cytoskeleton.com)
Actin2
- 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)
- Furthermore, Rac1-induced actin assembly and subsequent AJ formation critically depends on FMNL2. (rupress.org)
Phenotypes1
- This shows that activation of Rac1 isn't very important to this connections that occurs and means that TMOD3 might not directly donate to the noticed P-Rex1-Rac1-driven mobile phenotypes. (cancer-ecosystem.com)
Downstream2
- These data uncover FMNL2 as a driver for human epithelial AJ formation downstream of Rac1. (rupress.org)
- P-Rex1 GEF-dead … Conclusions Due to the difficulty of Rac1 signaling under normal and pathological conditions it is Tmem5 crucial to identify factors that contribute to its downstream specificity. (cancer-ecosystem.com)
GTPase1
- We demonstrated that treatment with Gc reduced the activity of the pro-migratory small GTPase regulator Rac1. (ox.ac.uk)
Interactor1
- TMOD3 is normally a book P-Rex1-enriched Rac1 interactor that binds to FLII within a P-Rex1-reliant way. (cancer-ecosystem.com)
Antibody6
- Western Blot: Rac1 Antibody [NB100-91266] - WB on tissue lysates. (novusbio.com)
- Immunocytochemistry/ Immunofluorescence: Rac1 Antibody [NB100-91266] - Mouse Brain (cerebral cortex). (novusbio.com)
- Immunohistochemistry: Rac1 Antibody [NB100-91266] - Rat spinal cord using Rabbit antibody to RAC1, RAC2 (100-150) at 1:1000 dilution. (novusbio.com)
- This Rac1 antibody is validated for ICC/IF from a verified customer review. (novusbio.com)
- Control and racET heart lysates were separated by SDS-PAGE, blotted, and the region corresponding to the molecular mass of rac1 (21 kDa) was excised for antibody labeling. (jci.org)
- Rac1 monoclonal antibody (Cat. (cytoskeleton.com)
Pathway1
- ARHGAP15 promotes metastatic colonization in gastric cancer by suppressing RAC1-ROS pathway. (bvsalud.org)
Endogenous3
- The lower band of the doublet corresponds to endogenous rac1, and the upper band is myc-tagged transgene. (jci.org)
- Arrows indicate position of transgenic (tg) or endogenous (wt) rac1. (jci.org)
- Variable but persistent transgene expression is evident in racET lysates, whereas only endogenous rac1 is observed in control samples. (jci.org)
Cdc423
- Based on the identified response functions, we clarified the profiles of how the morphology spatiotemporally changes in response to local and transient activation of Rac1 and Cdc42 and found that Rac1 and Cdc42 activation triggers laterally propagating membrane protrusion. (nature.com)
- Interestingly, we discovered distinct predictive performance of Rac1 and Cdc42 depending on the migration modes, indicating that Rac1 and Cdc42 contribute to persistent and random migration, respectively. (nature.com)
- In those studies, our cross-correlation analysis revealed that local membrane elongation preceded the Rac1 and Cdc42 activation by 30-60 seconds, which was then found to be consistent with another study 16 . (nature.com)
Inhibitor1
- The Rac1 inhibitor can ameliorate neuropathic pain only when administrated in the maintenance phase. (iasp-pain.org)
Inhibits1
- However, given Rac1's role in glucose transport, drugs that inhibits Rac1 could potentially be harmful to glucose homeostasis. (wikipedia.org)
Gene2
- It is encoded by the RAC1 gene. (wikipedia.org)
- Detects both RAC1 (Gene ID: 5879, UniProt: P63000) and RAC2 (Gene ID: 5880, UniProt: P15153). (novusbio.com)
Lysates1
- Expression level of rac1 and V12rac1 transgene in heart lysates by immunoblot. (jci.org)
Phosphorylation1
- We showed that knockdown of DNp63a in HaCaT and A431 cell lines lead to a decrease in miR-320a levels and a corresponding increase in the phosphorylation of Rac1 at Ser71, while overexpression of DNp63a in SW480 and Caco2 cells led to a decrease in the S71 phosphorylation of Rac1. (wright.edu)
Vivo4
- This study, the first examination of rac1-mediated cardiac effects in vivo, demonstrates that dilation and hypertrophy can share a common molecular origin and presents evidence that both timing and concurrent signaling from multiple pathways can influence cardiac remodeling. (jci.org)
- Analysis of in vivo Rac1 activation levels. (cytoskeleton.com)
- Importantly, α2KD+Rac1 mKO double-transgenic mice also displayed severely impaired contraction-stimulated glucose transport, while exercise-stimulated glucose uptake in vivo was only partially reduced by Rac1 mKO with no additive effect of α2KD. (ku.dk)
- It is concluded that Rac1 and α2AMPK together account for almost the entire ex vivo contraction-response in muscle glucose transport, while only Rac1, but not α2AMPK, regulates muscle glucose uptake during submaximal exercise in vivo. (ku.dk)
GEFs1
- Through conducting a comparative analysis of Rac1-driven cellular functions upon activation by 2 Rac-specific GEFs Tiam1 and P-Rex1 we provide clear evidence highlighting their part in dictating differential Rac1-dependent cellular processes. (cancer-ecosystem.com)
Distinct1
- Distinct roles of srGAP3-Rac1 in the initiation and maintenance phases of neuropathic pain induced by paclitaxel. (iasp-pain.org)
Enhances1
- Decreased srGAP3 in the maintenance phase enhances Rac1 activity facilitating maturation of dendritic spines and the persistence of neuropathic pain. (iasp-pain.org)
Contributes1
- 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)
Glucose4
- Here Rac1 regulated the translocation of glucose transporting GLUT4 vesicles from intracellular compartments to the plasma membrane. (wikipedia.org)
- Using human retinal endothelial cells in 20 mM D-glucose, H3K9me3 at Rac1 promoter was quantified by chromatin-Immunoprecipitation technique. (nature.com)
- Compared to cells in normal glucose, high glucose increased H3K9me3 and Suv39H1 binding at Rac1 promoter, and Suv39H1 -siRNA prevented glucose-induced increase 5 hydroxy methyl cytosine (5hmC) and Rac1 mRNA. (nature.com)
- Both Rac1 and AMPK have been shown to partly regulate contraction-stimulated muscle glucose uptake but whether those two signaling pathways jointly account for the entire signal to glucose transport is unknown. (ku.dk)
Importantly1
- Importantly we link these differential effects to the ability of each GEF to induce specific changes to the Rac1. (cancer-ecosystem.com)
Mice2
- Similarly, in diabetic mice, Suv39H1 -siRNA attenuated increase in 5hmC and Rac1 mRNA. (nature.com)
- To examine the effect of rac1 activation upon cardiac structure and function, transgenic mice were created that express constitutively activated rac1 specifically in the myocardium. (jci.org)
Functional1
- Here we present the full list of recognized Rac1 interactors together with functional annotation of the differentially controlled Rac1 binding partners. (cancer-ecosystem.com)
Skeletal2
- Rac1 is expressed in significant amounts in insulin sensitive tissues, such as adipose tissue and skeletal muscle. (wikipedia.org)
- An ARHGAP25 variant links aberrant Rac1 function to early-onset skeletal fragility. (scilifelab.se)
Activity6
- However, Rac1 activity which can be reduced by srGAP3, decreased in the initiation phase and increased in the maintenance phase. (iasp-pain.org)
- These GDP measurements allow researchers to effectively determine the activity of the Rac1 enzyme. (bellbrooklabs.com)
- FMNL2 associates with components of the AJ complex involving Rac1 activity and the FMNL2 C terminus. (rupress.org)
- We hypothesize that DNp63a decreases cell invasion through down-regulation the activity of Rac1 via miR-320a. (wright.edu)
- We also showed that DNp63a effect the GTP activity of Rac1. (wright.edu)
- Knockdown of DNp63a showed significant increase in Rac1 GTP levels and subsequent increase the activity of its effector PAK1. (wright.edu)
Cellular1
- In light of Rhein-8-O-beta-D-glucopyranoside this data we also Rhein-8-O-beta-D-glucopyranoside provide additional insights into known and novel signaling cascades that might account for the GEF-mediated Rac1-driven cellular effects. (cancer-ecosystem.com)
Metastasis2
- Previous studies have shown that miR-320a is downregulated in colorectal cancer and targets Ras-related C3 botulinum toxin substrate 1 (RAC1), leading to a decrease in non- canonical WNT signaling and EMT and thereby a corresponding decrease in tumor metastasis and invasion. (wright.edu)
- Taken together, these findings suggested a novel role of ARHGAP15 in promoting gastric cancer metastasis by quenching ROS through inhibiting RAC1 and its potential value for prognosis estimation and targeted therapy . (bvsalud.org)
Active3
- Thus, H3K9me3 at Rac1 promoter assists in active DNA methylation-hydroxymethylation, activating Rac1 transcription. (nature.com)
- To assess feasibility, T-cell Rac1 and pSTAT3 expression was evaluated in six parallel IBD groups: patients with active disease (1) and patients in remission on AZA/MP (2), TG (3), infliximab (IFX) (4), thiopurine and IFX (5) or without medication (6). (ecco-ibd.eu)
- Rac1-corrected pSTAT3 expression in T-cells was significantly decreased in IBD patients in remission on thiopurine monotherapy compared to IBD patients with active disease, resulting in comparable values to healthy subjects. (ecco-ibd.eu)
Activation2
- Our aim is to investigate the role of histone methylation (H3K9me3) of Rac1 promoter in dynamic DNA methylation- transcriptional activation. (nature.com)
- changes in the Rac1 Rhein-8-O-beta-D-glucopyranoside interactome following activation by either GEF indicating that these Rhein-8-O-beta-D-glucopyranoside opposing effects are mediated through GEF modulation of the Rac1 interactome. (cancer-ecosystem.com)
Tissue1
- Rac1 has ubiquitous tissue expression, and drives cell motility by formation of lamellipodia. (wikipedia.org)
Levels1
- Accordingly, the expression levels of PDGF (3-folds), Rac1 (1.6-folds), NF-κB (7-folds) and AngII (12-folds) significantly increased in the TAC group compared to the SHAM group, and these levels were also reduced by 25% to 64% with following drug intervention. (medsci.org)
Marker3
- P464 Rac1/pSTAT3 expression in T lymphocytes: A potential pharmacodynamic marker for thiopurines in the treatment of Inflammatory Bowel Disease patients? (ecco-ibd.eu)
- The aim of this study was to explore whether expression of Rac1 and pSTAT3 in T-cells may be used as a pharmacodynamic marker for the therapeutic effect of thiopurine therapy in IBD patients. (ecco-ibd.eu)
- Rac1/pSTAT3 expression may serve as a potential, class specific pharmacodynamic marker to assess therapeutic efficacy of thiopurine monotherapy or as a marker to explain thiopurine resistance. (ecco-ibd.eu)