Effectors guanine nucleotide exchange factors. Medical search. Frequent questions

In this active, GTP-bound conformation, Rho can bind to and activate specific effector proteins and enzymes to regulate cellular functions. (wikipedia.org)
GPCR-regulated RhoGEF12 (and these related GEF proteins) acts as an effector for G12 and G13 G proteins. (wikipedia.org)
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)
Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) accelerate GTP loading and hydrolysis, respectively. (nih.gov)
These accessory proteins play a fundamental role in regulating activities of RAS superfamily small GTPase via a conserved guanine binding (G)-domain, which consists of five G motifs. (nih.gov)
The role of Mg2+ cofactor in the guanine nucleotide exchange and GTP hydrolysis reactions of Rho family GTP-binding proteins. (helmholtz-hzi.de)
This process is usually regulated by guanine nucleotide-exchange factors GTPase-activating proteins and guanine nucleotide-dissociation inhibitors (1). (sciencepop.org)
p21 activated kinases (PAKs) the most extensively studied CDC42 and RAC effector proteins consist of two subgroups made up of three members each: group I (PAK1-3) and group II (PAK4-6). (sciencepop.org)
The Consortium is an initiative whose goals include gaining a deep understanding of the functions in mammalian cells of each of the ~30 ARF family GTPases, their GAPs (GTPase Activating Proteins), their GEFs (Guanine nucleotide Exchange Factors), and their effectors. (emory.edu)
Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS. (ouhsc.edu)
Like other members of the RAS superfamily, ARF family proteins can be activated by guanine-nucleotide exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs) [ 9 ]. (biomedcentral.com)
When ARF family proteins are activated, they bind to effector molecules, which in turn mediate downstream functions. (biomedcentral.com)
Often starting as a phagosome in the endocytic compartment, these bacteria-occupied vacuoles transition into organelles with novel molecular features via remodeling of host proteins and lipids through the highly coordinated actions of bacterial factors [3] [5] . (microbialcell.com)
Guanine nucleotide exchange factors ("GEFs") stimulate the dissociation of the GTP hydrolytic product, GDP, from small GTP-binding proteins, to promote the binding of a new GTP molecule. (justia.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)
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)
Signaling proteins that promote morphological adjustments required for invasion and metastasis of cancer cells, either stimulated by chemotactic factors from the tumor microenvironment or as effectors of oncogenic proteins, are potential therapeutic targets. (cinvestav.mx)
We study RhoGEFs as possible effectors of oncogenic proteins that drive cancer cell dissemination and activation of tumor stromal cells. (cinvestav.mx)
RhoGEFs (guanine nucleotide exchange factors for Rho family GTPases) are controlled by dynamic interaction with other signaling proteins, post-translational modifications, and second messengers. (cinvestav.mx)
This cyclic conformation allows cyclic nucleotides to bind to proteins to which other nucleotides cannot. (pancreapedia.org)
They are recruited from the cytosol onto cell membranes in the inactive form, are activated by guanine nucleotide exchange factors and then bind a large number of Rab effector proteins. (sputnic-group.ru)
Rab effector proteins are functionally diverse, which allows Rabs to co-ordinate multiple aspects of membrane trafficking, including transport vesicle formation, motility, docking and fusion. (sputnic-group.ru)
These various functions are controlled through distinct effector proteins and mediated through a GTP-binding/GTPase cycle involving three classes of regulating proteins: GAPs (GTPase-activating proteins), GEFs (guanine nucleotide exchange factors), and GDIs (guanine nucleotide dissociation inhibitors). (umbc.edu)
This gene encodes a transcription factor belonging to a family of proteins that share homology with the high mobility group protein-1. (cancer-genetics.org)
Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. (icr.ac.uk)
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)
Rho GTPase effectors are a large group of proteins and include actin nucleation promoting molecules, adaptors, as well as kinases. (biomedcentral.com)
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)
In active state binds to a variety of effector proteins to regulate cellular responses, such as secretory processes, phagocytose of apoptotic cells and epithelial cell polarization. (lu.se)
Regulated by guanine nucleotide exchange factors (GEFS) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (gaps) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. (lu.se)
Programmable DNA binding proteins have emerged as an exciting platform for engineering synthetic transcription factors for modulating endogenous gene expression 5 - 11 . (cdc.gov)
Among the established custom DNA binding domains, Cas9 is most easily scaled to facilitate genome-scale perturbations 3 , 4 due to its simplicity of programming relative to zinc finger proteins and transcription activator-like effectors (TALEs). (cdc.gov)

They play an important role in the recognition of regulatory factors (GEFs and GAPs) and effectors. (nih.gov)
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)
In tumors, RAC1 is usually hyper-activated and RAC1 inhibitors such as EHop-016 aim at blocking the interaction of RAC1 with several of its known guanine nucleotide exchange factors (GEFs). (broadinstitute.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)
As a proangiogenic response effecter, the interaction of Sema4D with plexin-B1 is dependent on the COOH-terminal PDZ-binding motif of plexin-B1, which binds two guanine nucleotide exchange factors (GEFs) for Rho and is mediated by the activation of Rho-initiated (Ras homolog gene family) pathways ( 4 - 8 ). (jcancer.org)

Rho guanine nucleotide exchange factor 12 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. (wikipedia.org)
Rho is a small GTPase protein that is inactive when bound to the guanine nucleotide GDP. (wikipedia.org)
Guanine nucleotide exchange factor (GEF) for Ral-A. Potential effector of GTPase HRas and Ras-related proteinM-Ras. (novusbio.com)
Many, but not all, of these effectors contain a conserved 18 amino-acid binding motif that has been termed CRIB (Cdc42-Rac interactive binding), PBD (p21-binding domain) or GBD (GTPase-binding domain) [ 4 ]. (biomedcentral.com)
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)
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)
Once released from SOS, the Ras-GTPase quickly binds fresh guanine nucleotide from the cytosol. (bionity.com)
The cytoskeletal effector protein, Vav3, which is the guanine nucleotide exchange factor for the small GTPase, Rac, is also necessary for sealing zone formation. (wustl.edu)
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)

Guanine nucleotide dissociation stimulators (GDSs, or exchange factors), such as RALGDS, are effectors of Ras-related GTPases (see MIM 190020) that participate in signaling for a variety of cellular processes. (cancerindex.org)
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)
Strikingly, once phosphorylated, Rab GTPases switch their preference and bind to new sets of phospho-specific protein effectors. (elifesciences.org)
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)
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)
In cell signalling , Son of Sevenless , or SOS , is a gene encoding a guanine nucleotide exchange factor that acts on Ras - GTPases . (bionity.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)
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)

However, it is unclear how the activity of plexin-B1 and its downstream effectors is regulated by its ligand Sema4D. (rupress.org)
As an alternative, current work aims at targeting crucial KRAS downstream effectors. (broadinstitute.org)

After a ligand binds to the GPCR, it activates a heterotrimeric G-protein, which is composed of three subunits: a guanine nucleotide binding α-subunit, and a βγ-heterodimer (98). (pancreapedia.org)
Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac. (embl.de)

Plexin-B1 has recently been shown to mediate activation of RhoA through a stable interaction with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. (rupress.org)
The interaction of Ran with the guanine nucleotide exchange factor protein RCC1 was also studied by (31)P NMR spectroscopy. (mpg.de)
The observed behavior indicates conformational exchange between bound and free states upon protein-micelle interaction. (embl-heidelberg.de)

Through a variety of effector and signaling pathways, plants achieve survival under salinity stress by maintaining high cytosolic potassium/sodium ion (K/Na) ratios, preventing Na cytotoxicity, and retaining osmotic balance. (ncbs.res.in)

Following inactivation by GTP hydrolysis, Rabs release their effectors and become available for the next round of activation and effector binding. (sputnic-group.ru)

Rab10 expression can up-regulate LPS-induced production of TNF-α, IL-6, and IFN-β, as well as potentiate LPS-induced activation of multiple intracellular signaling pathways, including MAPK, NF-κB, and IFN regulatory factor 3 (IRF3) signaling pathways. (sputnic-group.ru)
Studies in the past decade have demonstrated the essential roles of several AJC protein, including underlying actinomyosin components, actin isoforms, and intracellular signal transducer and activator of transcription (STAT) transcription factors, and nuclear factor-κB (NF-κB) in the maintenance and remission of IBD progression ( 5 ). (frontiersin.org)

In this article, we focus on the signaling mechanisms of two of these three subgroups, Cdc42 and Rac, as they are often linked in their physiological functions and have several effectors in common. (biomedcentral.com)
For example RAC and CDC42 share two protein serine-threonine kinase effectors in common - PAK and MLK - and inhibitors for both these kinases have been developed. (sciencepop.org)
CDC42 also has distinct kinase effectors such as MRCK and the tyrosine kinase ACK and these kinases too might provide suitable drug targets in cancer. (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)
Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. (icr.ac.uk)

Among these effectors are several protein kinases that either are or might be amenable to small molecule inhibition. (sciencepop.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)
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)

Structure of Shigella IpgB2 in complex with human RhoA: implications for the mechanism of bacterial guanine nucleotide exchange factor mimicry. (helmholtz-hzi.de)

This protein is also called RhoGEF12 or Leukemia-associated Rho guanine nucleotide exchange factor (LARG). (wikipedia.org)

Previous studies of beta-cells focused on protein kinase A (PKA) as a downstream effector of cAMP action. (nih.gov)
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)
their downstream protein kinase effectors. (sciencepop.org)

Mutant K-RAS has been shown to have both tumor-promoting and -suppressing functions, and growing evidence suggests that the RASSF family of tumor suppressors can act as RAS apoptosis and senescence effectors. (cancerindex.org)
Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. (icr.ac.uk)

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)

Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. (icr.ac.uk)

In doing so, this GEF-facilitated exchange of GDP for GTP is associated with structural changes in the GTP-binding protein which influence the degree to which the GTP-binding protein can interact with other molecules. (justia.com)

and have poor effector function, express multiple inhibitory receptors, possess low proliferative capacity, and cannot persist without antigen. (gsea-msigdb.org)
The mammalian homologue similarly functions downstream of many growth factor and adhesion receptors. (bionity.com)

Rabex-5 is a Rab22 effector and mediates a Rab22-Rab5 signaling cascade in endocytosis. (ouhsc.edu)

Metformin Enhances the Effect of Regorafenib and Inhibits Recurrence and Metastasis of Hepatic Carcinoma After Liver Resection via Regulating Expression of Hypoxia Inducible Factors 2α (HIF-2α) and 30 kDa HIV Tat-Interacting Protein (TIP30). (cancerindex.org)
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)

Rho guanine nucleotide exchange factor 12 is a protein that in humans is encoded by the ARHGEF12 gene. (wikipedia.org)

As the Drosophila homologue of mammalian DENN/MADD and Caenorhabditis elegans AEX-3, Rab3-GEF is a guanine nucleotide exchange factor (GEF) for Rab3 that stimulates GDP to GTP exchange. (eneuro.org)

In this way, Rabs co-ordinate the assembly of effector complexes and generate functional membrane domains. (sputnic-group.ru)
We propose that the phosphorylation and membrane dissociation of GBF1 and the consequent reduction in ARF-GTP levels in mitosis are important for changes in Golgi dynamics and possibly other mitotic events mediated through effectors other than the COPI vesicle coat. (aston.ac.uk)

Cyclic nucleotides form when the phosphate group of the molecule of nucleotide triphosphate (ATP or GTP) is attacked by the 3' hydroxyl group of the ribose, forming a cyclic 3',5'-phosphate ester with release of pyrophosphate. (pancreapedia.org)

Ras effector protein, which may serve as an inhibitory modulator of neuronal plasticity in aversive memory formation. (novusbio.com)

A restricted set of 28 RAB18 interactions were dependent on the binary RAB3GAP1-RAB3GAP2 RAB18-guanine nucleotide exchange factor complex. (bvsalud.org)
In the presence of nucleotide, the ternary complex of Ran.nucleotide.RCC1, an intermediate in the guanine nucleotide exchange reaction, could be observed. (mpg.de)
Recent data demonstrate that IBD arises from the complex interplay of genetic and environmental factor caused by a change in the intestinal microbiota ( 1 ). (frontiersin.org)

If its negative charge is not reduced, the nucleotide triphosphate cannot be approached by a nucleophile, which is, in this reaction, the 3' hydroxyl group of the ribose (183). (pancreapedia.org)
The end products of this catalytic reaction are a cyclic nucleotide (cyclic AMP or cyclic GMP) and a pyrophosphate group. (pancreapedia.org)

The Igf 1 receptor signaling pathway is a cellular signaling pathway that is activated by the binding of insulin-like growth factor 1 (IGF-1) to its receptor on the cell surface. (ebiwinner.com)

Although one effector of Epac is the Ras-related G protein Rap1, it is not fully understood what the functional consequences of Epac-mediated signal transduction are at the cellular level. (nih.gov)
Cyclic nucleotides, like other nucleotides, are composed of three functional groups: a ribose sugar, a nitrogenous base, and a single phosphate group. (pancreapedia.org)

Guanine Nucleotide Exchange Factors" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (ouhsc.edu)

Transduces extracellular signals to cytosolic and nuclear effectors. (icr.ac.uk)

The precise mechanism of nucleotide exchange, however, has remained unclear. (helmholtz-hzi.de)

Genes down-regulated in CD8 T cells: na ve versus effectors at day 8 after acute infection with LCMV-Armstrong. (gsea-msigdb.org)
During acute viral infections, na ve CD8+ T cells differentiate into effector CD8+ T cells and, after viral control, into memory CD8+ T cells. (gsea-msigdb.org)

ETS variant transcription factor 3 [Sou. (gsea-msigdb.org)
This transcription factor is involved in the Wnt signaling pathway, and it may function in hair cell differentiation and follicle morphogenesis. (cancer-genetics.org)

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)
Additionally, Akt promotes cell survival by inhibiting pro-apoptotic factors and activating anti-apoptotic factors. (ebiwinner.com)
There were three nucleotide variants (T471C/A600G/C862T) frequently detected in cancer cell lines. (jcancer.org)

We report here the identification of the ARF exchange factor GBF1 as a Golgi phosphoprotein. (aston.ac.uk)

Our data demonstrate that guanine nucleotide exchange factor-dependent Rab interactions are highly amenable to interrogation by proximity biotinylation and may suggest that Micro syndrome is a cholesterol biosynthesis disorder. (bvsalud.org)

Age and the high mRNA expression of ARL9 were independent risk factors for a poor prognosis in patients with colon adenocarcinoma. (biomedcentral.com)

Here, we review the diverse, and still expanding, collection of stimuli and processes now known to harness the noncanonical autophagy pathway, including engulfment processes, drug treatments, TRPML1 and STING signaling, viral infection, and other pathogenic factors. (babraham.ac.uk)

This pathway is activated by the binding of insulin-like growth factor 1 (IGF-1) to its receptor, leading to the activation of downstream signaling cascades. (ebiwinner.com)

Anatomy30

Organisms7

Diseases1

Chemicals and Drugs138

Analytical, Diagnostic and Therapeutic Techniques and Equipment18

Phenomena and Processes58

Information Science4

Health Care1

Proteins32

GEFs5

GTPase10

GTPases8

Downstream effectors2

Binds2

Interaction3

Variety of effector1

Hydrolysis1

Intracellular2

Cdc425

Protein kinases1

Pathways2

RhoA1

LARG1

Kinase3

Tumor2

Kinases1

Epidermal growth f1

Molecules1

Receptors2

Mediates1

Hypoxia2

Gene1

Stimulates1

Membrane2

Molecule1

Inhibitory1

Complex3

Reaction2

Receptor signali1

Functional2

Mesh1

Nuclear1

Unclear1

Acute2

Transcription factor2

Cell3

Identification1

Dependent1

Expression1

Viral1

Activation1