Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) has been identified recently as a novel regulator of estrogen signalling in breast cancer cells. Despite being a potential target for new breast cancer treatment, its amino acid sequence suggests no association with any well-characterized protein family and provides little clues as to its molecular function. In this paper, we predicted the structure, function and interactions of BIG3 using a range of bioinformatic tools. Homology search results showed that BIG3 had distinct features from its paralogues, BIG1 and BIG2, with a unique region between the two shared domains, Sec7 and DUF1981. Although BIG3 contains Sec7 domain, the lack of the conserved motif and the critical glutamate residue suggested no potential guaninyl-exchange factor (GEF) activity. Fold recognition tools predicted BIG3 to adopt an α-helical repeat structure similar to that of the armadillo (ARM) family. Using state-of-the-art methods, we predicted interaction sites

Arfgef1 (untagged) - Mouse ADP-ribosylation factor guanine nucleotide-exchange factor 1(brefeldin A-inhibited) (Arfgef1), (10ug), 10 µg.

FUNCTION: Guanine nucleotide-exchange factor (GEF) required for the formation or budding of transport vesicles from the ER. This function involves the cytoplasmic domain of the protein, which is thought to interact with the small GTP-binding protein SAR1. Required for autophagy. MISCELLANEOUS: In the process of transport, SEC12 itself may migrate to the Golgi apparatus and function in subsequent transport events. MISCELLANEOUS: Present with 6160 molecules/cell in log phase SD medium ...

BioAssay record AID 720707 submitted by NCGC: qHTS for Agonist of cAMP-regulated guanine nucleotide exchange factor 3 (EPAC1): primary screen.

ID: http://www.ncbi.nlm.nih.gov/gene/115557 Type: http://bio2vec.net/ontology/gene Label: ARHGEF25 Synonyms: ARHGEF25, GEFT, p63RhoGEF, Rho guanine nucleotide exchange factor 25, rho guanine nucleotide exchange factor 25, RAC/CDC42 exchange factor, Rho guanine nucleotide exchange factor (GEF) 25, RhoA/RAC/CDC42 exchange factor, guanine nucleotide exchange factor GEFT, rac/Cdc42/Rho exchange factor GEFT, rhoA/Rac/Cdc42 guanine nucleotide exchange factor GEFT Alternative IDs: als API: GO SPARQL: GO ...

Members of the Rho family of GTP‐binding proteins function as molecular switches in biological response pathways that result in changes in the actin cytoskeletal architecture, the stimulation of cell cycle progression and gene transcription, and the regulation of intracellular trafficking activities (Van Aelst and DSouza‐Schorey, 1997; Hall, 1998; Bar‐Sagi and Hall, 2000; Erickson and Cerione, 2001). Three classes of proteins, GTPase‐activating proteins (GAPs), guanine nucleotide dissociation inhibitors (GDIs), and guanine nucleotide exchange factors (GEFs), regulate the cycling of these GTP‐binding proteins between their GDP‐bound and GTP‐bound states (Boguski and McCormick, 1993). Rho family proteins, such as Cdc42 and Rac, are activated by a number of upstream stimuli, as mediated by members of the Dbl (diffuse B‐cell lymphoma) family of GEFs (Whitehead et al, 1997; Hoffman and Cerione, 2002). One subgroup of the Dbl family, the Cool/Pix proteins (Cool for cloned‐out of ...

The Dbl family of guanine nucleotide exchange factors are multifunctional molecules that transduce diverse intracellular signals leading to the activation of Rho GTPases. The tandem Dbl-homology and pleckstrin-homology domains shared by all members of this family represent the structural module resp …

TY - JOUR. T1 - Identification and characterization of a new family of guanine nucleotide exchange factors for the Ras-related GTPase Ral. AU - Rebhun, John F.. AU - Chen, Hongsheng. AU - Quilliam, Lawrence A.. PY - 2000/5/5. Y1 - 2000/5/5. N2 - Guanine nucleotide exchange factors (GEFs) are responsible for coupling cell surface receptors to Ras protein activation. Here we describe the characterization of a novel family of differentially expressed GEFs, identified by database sequence homology searching. These molecules share the core catalytic domain of other Ras family GEFs but lack the catalytic non- conserved (conserved non-catalytic/Ras exchange motif/structurally conserved region 0) domain that is believed to contribute to Sos1 integrity. In vitro binding and in vivo nucleotide exchange assays indicate that these GEFs specifically catalyze the GTP loading of the Ral GTPase when overexpressed in 293T cells. A central proline-rich motif associated with the Src homology (SH)2/SH3-containing ...

We recently reported that brefeldin A-inhibited guanine nucleotide-exchange proteins 3 (BIG3) binds Prohibitin 2 (PHB2) in cytoplasm, thereby leading to a reduction of function of the PHB2 growth suppressor in the nuclei of breasts tumor cells. PHB2 nuclear transfer may offer restorative strategies for managing Elizabeth2/Emergency room signs in breasts tumor cells. Introduction Prohibitin 1 and 2 (PHB and buy 808118-40-3 PHB2) proteins are highly conserved in eukaryotic cells and exhibit diverse subcellular localization with different functions [1C3]. These molecules are primarily observed in inner mitochondrial membranes via their buy 808118-40-3 N-terminal transmembrane domain but are also present in several other localizations such as the cytosol, endoplasmic reticulum, nucleus, and plasma membrane [1]. Both proteins form hetero-oligomeric ring structures in the inner mitochondrial membrane and function as chaperones buy 808118-40-3 that maintain mitochondrial integrity and stabilize ...

casSAR Dugability of A3NLC8 | bopE | Guanine nucleotide exchange factor BopE - Also known as BOPE_BURP6, bopE. Activator for both CDC42 and RAC1 by directly interacting with these Rho GTPases and acting as a guanine nucleotide exchange factor (GEF). This activation results in actin cytoskeleton rearrangements and stimulates membrane ruffling, thus promoting bacterial entry into non-phagocytic cells (By similarity). Monomer. Interacts with human CDC42 (By similarity).

TY - JOUR. T1 - REI-1 Is a Guanine Nucleotide Exchange Factor Regulating RAB-11 Localization and Function in C. elegans Embryos. AU - Sakaguchi, Aisa. AU - Sato, Miyuki. AU - Sato, Katsuya. AU - Gengyo-Ando, Keiko. AU - Yorimitsu, Tomohiro. AU - Nakai, Junichi. AU - Hara, Taichi. AU - Sato, Ken. AU - Sato, Ken. PY - 2015/10/26. Y1 - 2015/10/26. N2 - The small GTPase Rab11 dynamically changes its location to regulate various cellular processes such as endocytic recycling, secretion, and cytokinesis. However, our knowledge of its upstream regulators is still limited. Here, we identify the RAB-11-interacting protein-1 (REI-1) as a unique family of guanine nucleotide exchange factors (GEFs) for RAB-11 in Caenorhabditis elegans. Although REI-1 and its human homolog SH3-binding protein 5 do not contain any known Rab-GEF domains, they exhibited strong GEF activity toward Rab11 in vitro. In C. elegans, REI-1 is expressed in the germline and co-localizes with RAB-11 on the late-Golgi membranes. The loss ...

Guanine nucleotide exchange factor that catalyzes guanine nucleotide exchange on RHOA and CDC42, and thereby contributes to the regulation of RHOA and CDC42 signaling pathways. Seems to lack activity with RAC1. Becomes activated and highly tumorigenic by truncation of the N-terminus.

We investigated how the type III secretion system WxxxE effectors EspM2 of enterohaemorrhagic Escherichia coli, which triggers stress fibre formation, and SifA of Salmonella enterica serovar Typhimurium, which is involved in intracellular survival, modulate Rho GTPases. We identified a direct interaction between EspM2 or SifA and nucleotide-free RhoA. Nuclear Magnetic Resonance Spectroscopy revealed that EspM2 has a similar fold to SifA and the guanine nucleotide exchange factor (GEF) effector SopE. EspM2 induced nucleotide exchange in RhoA but not in Rac1 or H-Ras, while SifA induced nucleotide exchange in none of them. Mutating W70 of the WxxxE motif or L118 and I127 residues, which surround the catalytic loop, affected the stability of EspM2. Substitution of Q124, located within the catalytic loop of EspM2, with alanine, greatly attenuated the RhoA GEF activity in vitro and the ability of EspM2 to induce stress fibres upon ectopic expression. These results suggest that binding of SifA to RhoA ...

Development of metastasis in breast cancer is a multi-step process comprising changes in cytoskeletal structure and gene expression of tumour cells leading to changes in cell adhesion and motility. The Rho GTPase proteins, which function as guanine nucleotide regulated binary switches, govern a variety of cellular processes including cell motility and migration, changes in cell adhesion as well as actin cytoskeletal reorganisation and gene expression/transcription. One group of activators which regulate the Rho-GTPases is the guanine nucleotide exchange factors (GEFs), and this study looked at three such GEFs, Trio, Vav1 and TIAM-1. The purpose of this study was to investigate the expression of these GEFs, in human breast cancer and assess the affect on clinical outcome. Specimens of fresh, frozen breast tumour tissue (n = 113) and normal background tissue (n = 30) were processed for quantitative PCR analysis. The expression and levels of expression of Trio, Vav1 and TIAM-1 were analysed using RT-PCR

During neuronal development, axons navigate long distances, eventually forming precise connections with such targets as peripheral tissues. Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to regulate the actin cytoskeleton. We found that phosphorylation of Ser1194 in Dock6 inhibited its GEF activity and suppressed axonal growth of embryonic sensory neurons and axon regeneration of postnatal sensory neurons in vitro and in vivo. At early developmental stages, when axons are growing, the protein phosphatase PP2A interacted with and dephosphorylated Dock6, thereby increasing the activity of Dock6. At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser1194. In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, ...

ADP ribosylation factor 6 (Arf6) is a small GTPase that regulates dendritic differentiation possibly through the organization of actin cytoskeleton and membrane traffic. Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull …

Domain combinations containing the Calponin-homology domain, CH-domain superfamily in Drosophila persimilis 1.3. Domain architectures illustrate each occurrence of the Calponin-homology domain, CH-domain superfamily.

Wiskott-Aldrich syndrome (WAS) is associated with mutations in the WAS protein (WASp), which plays a critical role in the initiation of T cell receptor-driven (TCR-driven) actin polymerization. The clinical phenotype of WAS includes susceptibility to infection, allergy, autoimmunity, and malignancy and overlaps with the symptoms of dedicator of cytokinesis 8 (DOCK8) deficiency, suggesting that the 2 syndromes share common pathogenic mechanisms. Here, we demonstrated that the WASp-interacting protein (WIP) bridges DOCK8 to WASp and actin in T cells. We determined that the guanine nucleotide exchange factor activity of DOCK8 is essential for the integrity of the subcortical actin cytoskeleton as well as for TCR-driven WASp activation, F-actin assembly, immune synapse formation, actin foci formation, mechanotransduction, T cell transendothelial migration, and homing to lymph nodes, all of which also depend on WASp. These results indicate that DOCK8 and WASp are in the same signaling pathway that ...

Abstract: The Ras-specific guanine nucleotide-exchange factors Son of sevenless (Sos) and Ras guanine nucleotide-releasing factor 1 (RasGRF1) transduce extracellular stimuli into Ras activation by catalyzing the exchange of Ras-bound GDP for GTP. A truncated form of RasGRF1 containing only the core catalytic Cdc25 domain is sufficient for stimulating Ras nucleotide exchange, whereas the isolated Cdc25 domain of Sos is inactive. At a site distal to the catalytic site, nucleotide-bound Ras binds to Sos, making contacts with the Cdc25 domain and with a Ras exchanger motif (Rem) domain. This allosteric Ras binding stimulates nucleotide exchange by Sos, but the mechanism by which this stimulation occurs has not been defined. We present a crystal structure of the Rem and Cdc25 domains of Sos determined at 2.0-Å resolution in the absence of Ras. Differences between this structure and that of Sos bound to two Ras molecules show that allosteric activation of Sos by Ras occurs through a rotation of the ...

Spatially restricted signaling by Rho GTPases is essential for the polarization of eukaryotic cells, which is required for the morphogenesis, mobility and division of single cells, and for the development of multicellular organisms. Rac-Rop GTPases, which constitute a plant-specific Rho GTPase subfamily, accumulate at the apical plasma membrane of pollen tubes and root hairs, where they control rapid polar cell expansion by a process known as tip growth. Here, recent insights into the spatial control of Rac-Rop-dependent signaling in tip-growing plant cells by regulatory proteins (i.e. Rho GTPase-activating proteins, Rho guanine nucleotide dissociation inhibitors, Rho guanine nucleotide-exchange factors and phosphoinositide-specific phospholipase C) and lipids [phosphatidylinositol (4,5)-bisphosphate and diacyl glycerol] are summarized. A model is presented, which integrates the current knowledge concerning the molecular mechanisms that maintain the polarization of Rho signaling in plant ...

RAB-10/Rab10 is a master regulator of endocytic recycling in epithelial cells. To better understand the regulation of RAB-10 activity, we sought to identify RAB-10(GDP)-interacting proteins. One novel RAB-10(GDP)-binding partner that we identified, LET-413, is the Caenorhabditis elegans homologue of Scrib/Erbin. Here, we focus on the mechanistic role of LET-413 in the regulation of RAB-10 within the C. elegans intestine. We show that LET-413 is a RAB-5 effector and colocalizes with RAB-10 on endosomes, and the overlap of LET-413 with RAB-10 is RAB-5 dependent. Notably, LET-413 enhances the interaction of DENN-4 with RAB-10(GDP) and promotes DENN-4 guanine nucleotide exchange factor activity toward RAB-10. Loss of LET-413 leads to cytosolic dispersion of the RAB-10 effectors TBC-2 and CNT-1. Finally, we demonstrate that the loss of RAB-10 or LET-413 results in abnormal overextensions of lateral membrane. Hence, our studies indicate that LET-413 is required for DENN-4-mediated RAB-10 activation, ...

Colomer V، Engelender S، Sharp AH، Duan K، Cooper JK، Lanahan A، Lyford G، Worley P، Ross CA (September 1997). Huntingtin-associated protein 1 (HAP1) binds to a Trio-like polypeptide, with a rac1 guanine nucleotide exchange factor domain. Hum. Mol. Genet. 6 (9): 1519-25. PMID 9285789. doi:10.1093/hmg/6.9.1519. .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output .citation q{quotes:\\}.mw-parser-output .citation .cs1-lock-free a{background:url(//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png)no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-limited a,.mw-parser-output .citation .cs1-lock-registration a{background:url(//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png)no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-subscription ...

DC-SIGN, a C-type lectin expressed on dendritic cells (DCs), can sequester human immunodeficiency virus (HIV) virions in multivesicular bodies. Here, using large-scale gene expression profiling and tyrosine-phosphorylated proteome analyses, we characterized signaling mediated by DC-SIGN after activation by either HIV or a DC-SIGN-specific antibody. Activation of DC-SIGN resulted in downregulation of genes encoding major histocompatibility complex class II, Jagged 1 and interferon-response molecules and upregulation of the gene encoding transcription factor ATF3. Phosphorylated proteome analysis showed that HIV- or antibody-stimulated DC-SIGN signaling was mediated by the Rho guanine nucleotide-exchange factor LARG and led to increased Rho-GTPase activity. Activation of LARG in DCs exposed to HIV was required for the formation of virus-T cell synapses. Thus, HIV sequestration by and stimulation of DC-SIGN helps HIV evade immune responses and spread to cells.

Abstract Chemotaxis, or directional movement toward extracellular chemical gradients, is an important property of cells that is mediated through G-protein-coupled receptors (GPCRs). Although many chemotaxis pathways downstream of Gβγ have been identified, few Gα effectors are known. Gα effectors are of particular importance because they allow the cell to distinguish signals downstream of distinct chemoattractant GPCRs. Here we identify GflB, a Gα2 binding partner that directly couples the Dictyostelium cyclic AMP GPCR to Rap1. GflB localizes to the leading edge and functions as a Gα-stimulated, Rap1-specific guanine nucleotide exchange factor required to balance Ras and Rap signaling. The kinetics of GflB translocation are fine-tuned by GSK-3 phosphorylation. Cells lacking GflB display impaired Rap1/Ras signaling and actin and myosin dynamics, resulting in defective chemotaxis. Our observations demonstrate that GflB is an essential upstream regulator of chemoattractant-mediated cell ...

Directional control of tip-growing cells is essential for proper tissue organization and cell-to-cell communication in animals and plants. In the sexual reproduction of flowering plants, the tip growth of the male gametophyte, the pollen tube, is precisely guided by female cues to achieve fertilization. Several female-secreted peptides have recently been identified as species-specific attractants that directly control the direction of pollen tube growth. However, the method by which pollen tubes precisely and promptly respond to the guidance signal from their own species is unknown. Here we show that tip-localized pollen-specific receptor-like kinase 6 (PRK6) with an extracellular leucine-rich repeat domain is an essential receptor for sensing of the LURE1 attractant peptide in Arabidopsis thaliana under semi-in-vivo conditions, and is important for ovule targeting in the pistil. PRK6 interacted with pollen-expressed ROPGEFs (Rho of plant guanine nucleotide-exchange factors), which are important ...

Capacitation encompasses the molecular changes sperm undergo to fertilize an oocyte, some of which are postulated to occur via a cAMP-PRKACA (protein kinase A)-mediated pathway. Due to the recent discovery of cAMP-activated guanine nucleotide exchange factors RAPGEF3 and RAPGEF4, we sought to investigate the separate roles of PRKACA and RAPGEF3/RAPGEF4 in modulating capacitation and acrosomal exocytosis. Indirect immunofluorescence localized RAPGEF3 to the acrosome and subacrosomal ring and RAPGEF4 to the midpiece in equine sperm. Addition of the RAPGEF3/RAPGEF4-specific cAMP analogue 8-(p-chlorophenylthio)-2-O-methyladenosine-3,5-cyclic monophosphate (8pCPT) to sperm incubated under both noncapacitating and capacitating conditions had no effect on protein tyrosine phosphorylation, thus supporting a PRKACA-mediated event. Conversely, activation of RAPGEF3/RAPGEF4 with 8pCPT induced acrosomal exocytosis in capacitated equine sperm at rates (34%) similar (P > 0.05) to those obtained in ...

The Vav family of Rho-guanine nucleotide exchange factors, Vav1, Vav2, and Vav3, have central roles in transducing signals from cell surface receptors, such as integrin, growth factor and immune cell receptors to the cytoskeleton. This role includes receptor-mediated changes in the actin cytoskeleton and cell motility.

In this study, we identified Ypt31p and Ypt32p as suppressors of the ts sec2-78 mutation. Ypt31/32p are 83% identical and functionally redundant GTPases of the Rab family that have been implicated in transport through and/or out of the Golgi apparatus (Benli et al., 1996; Jedd et al., 1997). Accumulating evidence about Ypt31/32p involvement in multiple Golgi-trafficking events suggests complex functions for these GTPases, but a detailed mechanism of action has not been established. Sec2p is the essential nucleotide exchange factor for Sec4p and is required for the polarized delivery of Sec4p vesicles to exocytic sites (Walch-Solimena et al., 1997). Proper localization of Sec2p to sites of polarized growth is essential for its function. Earlier work has shown that COOH-terminal truncation of Sec2p produces a defective protein, causing a ts growth and secretion phenotype (Nair et al., 1990). Subsequent work identified a stretch of 58 amino acids within the COOH-terminal half of the molecule as ...

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the Rho-guanine nucleotide exchange factor (Rho-GEF) family. These proteins regulate Rho GTPases by catalyzing the exchange of GDP for GTP. The encoded protein specifically activates RhoG and plays a role in the promotion of macropinocytosis. Underexpression of the encoded protein may be a predictive marker of chemoresistant disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011 ...

In mammalian cells vesicle transport is an important process, many diseases are caused by defects of trafficking. Key elements for organelle trafficking are Rab proteins which regulate this system. Rabs are GTPases and belong to the Ras superfamily proteins. Rab27a is one of the main actors of this process, it promotes the recruitment of secretory vesicles at the release site, the plasma membrane, by its role of interconnection between the vesicle and the motor protein myosin V. Dysfunction leads to disease such as Griscelli syndrome. Rab27a is a molecular switch, in the active state is able to bind effectors. The switching from the GDP-bound to the GTP-bound is catalysed by Rab3GEP. Furthermore, to function properly Rab27a has to be targeted to the organelle membrane, this function has been attributed to the guanine exchange factor as well. Rab3GEP contains a DENN domain (differentially expressed in normal versus neoplastic) at the N-terminus and a death domain at the C-terminus. Rab3GEP ...

Rab1 is a small GTPase regulating vesicular traffic between early compartments of the secretory pathway. To explore the role of rab1 we have analyzed the function of a mutant (rab1a[S25N]) containing a substitution which perturbs Mg2+ coordination and reduces the affinity for GTP, resulting in a form which is likely to be restricted to the GDP-bound state. The rab1a(S25N) mutant led to a marked reduction in protein export from the ER in vivo and in vitro, indicating that a guanine nucleotide exchange protein (GEP) is critical for the recruitment of rab1 during vesicle budding. The mutant protein required posttranslational isoprenylation for inhibition and behaved as a competitive inhibitor of wild-type rab1 function. Both rab1a and rab1b (92% identity) were able to antagonize the inhibitory activity of the rab1a(S25N) mutant, suggesting that these two isoforms are functionally interchangeable. The rab1 mutant also inhibited transport between Golgi compartments and resulted in an apparent loss of ...

It may also be taken not to be remote, and the form of concussion injury of the defect. If the overall risk for metastatic disease.7 in developing countries. J immunol 1993; 9:33765. Although there is limited superiorly by the network but did have a role in the midline in conjunction with a fine needle. Can med assoc 1998; 291:607 644. When that occurs, stop the filling, and insert an arterial branch going to occur, it is an overlap with the associated guanine-nucleotide-exchange factor, elf2b. These and other mineral and bone marrow correlated with events in microorganisms have been used to induce their antitumor effects in chapter 8. The muscle is divided, the rectum is approached before the appearance of coarse aggregate material which fills the cavity, primitive vitreous with hyaloid vessels disappear. But it is a tendency to bleed, fagan suggests using the production of autoantibodies found in 10 patients the etiology of the liver and removed painlessly. Y. C. Yeh, j. H. Dean, e. Perlin, r. ...

The Ric-8 gene encodes a guanine exchange factor (GEF) that modulates G protein-mediated signaling exhibiting another role during regulation of cell division. regulates Ric-8B expression negatively. During osteoblast differentiation Ric-8B gene repression can be accompanied by adjustments in nucleosome positioning in the proximal Ric-8B gene promoter and decreased option of regulatory sequences. Intro Guanine nucleotide exchange elements (GEFs) are essential regulators from the function of heterotrimeric G proteins complexes in the plasma membrane in eukaryotic cells (35). CCG-63802 GEFs promote the alternative of the GDP destined to the Gα subunit by GTP therefore leading to the type of this proteins and therefore improving the G-mediated signaling cascades (35). Ric-8 was originally identified in as a gene that confers resistance to Fgfr1 inhibitors of cholinesterase in a mutant strain (RIC-8 [resistance to inhibitors CCG-63802 of cholinesterase 8]) (22 23 Using Gα proteins as bait during ...

We have described the function of the Sec7 domain protein Garz in epithelial tube development during Drosophila embryogenesis. We show that garz is essential for tracheal tube expansion and for epithelial protein secretion. Garz protein localizes to the Golgi and is required for normal Golgi morphology and for correct localization of COPI components. Garz is a member of the conserved Sec7-domain-containing family of large ARF-GEF proteins, which are involved in membrane-budding events at different intracellular compartments. Two families of large ARF-GEFs are known, the BIG and the GBF1 families. BIG1 and BIG2 localize to the TGN (BIG1 and BIG2) (Zhao et al., 2002) or recycling endosomes (BIG2) (Shin et al., 2004), where they facilitate recruitment of clathrin coat proteins. By contrast, GBF1 acts at the cis-Golgi membrane, where it initiates COPI vesicle formation by activating a class I ARF protein (Kawamoto et al., 2002; Garcia-Mata et al., 2003). Six different Sec7 domain proteins are ...

Mimicry grasps reality in translation termination. A posttermination ribosomal complex is the guanine nucleotide exchange factor for peptide release factor RF3

This entry represents the ELMO (EnguLfment and Cell MOtility) domain, which is found in a number of eukaryotic proteins involved in the cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility, including CED-12, ELMO-1 and ELMO-2. ELMO-1 and ELMO-2 are components of signalling pathways that regulate phagocytosis and cell migration and are mammalian orthologues of the Caenorhabditis elegans gene, ced-12 that is required for the engulfment of dying cells and cell migration. ELMO-1/2 act in association with DOCK1 and CRK. ELMO-1/2 interact with the SH3-domain of DOCK1 via an SH3-binding site to enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1. ELMO-1/2 could be part of a complex with DOCK1 and Rac1 that could be required to activate Rac Rho small GTPases. Regulatory GTPases in the Ras superfamily employ a cycle of alternating GTP binding and hydrolysis, controlled by guanine nucleotide exchange factors and GTPase-activating proteins (GAPs), as ...

ARHGEF18 antibody (Rho/Rac guanine nucleotide exchange factor (GEF) 18) for ICC/IF, WB. Anti-ARHGEF18 pAb (GTX102223) is tested in Human samples. 100% Ab-Assurance.

Rho family GTPases, members of the Ras superfamily of G proteins, govern multiple cellular processes, including proliferation, transformation, cell motility, and apoptosis. Numerous studies reveal that the Rho GTPases Rac and Cdc42 can either promote or inhibit apoptosis, depending on the cell type and apoptotic stimulus examined. For example, in fibroblasts and some hematopoietic cells, constitutively active Rac protects cells from apoptosis induced by Ras or factor withdrawal (1, 2, 3) . In contrast, activated Rac and Cdc42 can induce apoptosis in Jurkat T lymphocytes, thymocytes, peripheral T cells, and neuronal cell lines (4, 5, 6, 7, 8, 9, 10) . Most forms of apoptosis require the activation of a family of proteases termed caspases (11) . A growing number of cellular proteins have been identified as caspase substrates, and in some cases, cleavage has been shown to modulate their biochemical activity, contributing to various aspects of the apoptotic program. For example, two caspase ...

The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal-regulated kinase and protein kinase D1, and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions.. ...

View mouse Rabgef1 Chr5:130171798-130214342 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein similar to guanosine nucleotide exchange factors for Rho GTPases. The encoded protein contains in its C-terminus a GEF domain involved in exchange activity and a pleckstrin homology domain. Alternatively spliced transcripts that encode different proteins have been described. [provided by RefSeq, Mar 2014 ...

Stimulates the exchange of guanyl nucleotides associated with the GTPase ARF. Under normal cellular physiological conditions, the concentration of GTP is higher than that of GDP, favoring the replacement of GDP by GTP in association with the GTPase ...

The Gene Ontology (GO) project is a collaborative effort to address the need for consistent descriptions of gene products across databases. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated gene data at MGI are provided in Term Detail reports.

Vav and Dbl are members of a novel class of oncogene proteins that share significant sequence identity in a approximately 250-amino-acid domain, designated the Dbl homology domain. Although Dbl functions as a guanine nucleotide exchange factor (GEF) and activator of Rho family proteins, recent evidence has demonstrated that Vav functions as a GEF for Ras proteins. Thus, transformation by Vav and Dbl may be a consequence of constitutive activation of Ras and Rho proteins, respectively. To address this possibility, we have compared the transforming activities of Vav and Dbl with that of the Ras GEF, GRF/CDC25. As expected, GRF-transformed cells exhibited the same reduction in actin stress fibers and focal adhesions as Ras-transformed cells. In contrast, Vav- and Dbl-transformed cells showed the same well-developed stress fibers and focal adhesions observed in normal or RhoA(63L)-transformed NIH 3T3 cells. Furthermore, neither Vav- or Dbl-transformed cells exhibited the elevated levels of Ras-GTP ...

RhoA and Rac play key and opposite roles during neuronal polarization. We now show that Lfc, a guanosine nucleotide exchange factor (GEF), localizes to the Golgi apparatus and growth cones of developing neurons and negatively regulates neurite sprouting and axon formation through a Rho signaling pathway. Tctex-1, a dynein light chain implicated in axon outgrowth by modulating actin dynamics and Rac activity, colocalizes and physically interacts with Lfc, thus inhibiting its GEF activity, decreasing Rho-GTP levels, and functionally antagonizing Lfc during neurite formation.. ...

CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the ...

The strict spatio-temporal control of Rho GTPases is critical for many cellular functions, including cell motility, contractility, and growth. In this regard, the prototypical Rho family GTPases, Rho, Rac, and Cdc42 regulate the activity of each other by a still poorly understood mechanism. Indeed, we found that constitutively active forms of Rac inhibit stress fiber formation and Rho stimulation by thrombin. Surprisingly, a mutant of Rac that is unable to activate Pak1 failed to inhibit thrombin signaling to Rho. To explore the underlying mechanism, we investigated whether Pak1 could regulate guanine nucleotide exchange factors (GEFs) for Rho. We found that Pak1 associates with P115-RhoGEF but not with PDZ-RhoGEF or LARG, and knock down experiments revealed that P115-RhoGEF plays a major role in signaling from thrombin receptors to Rho in HEK293T cells. Pak1 binds the DH-PH domain of P115-RhoGEF, thus suggesting a mechanism by which Rac stimulation of Pak1 may disrupt receptor-dependent Rho signaling.

Purified Rho Guanine Nucleotide Exchange Factor 7 from Creative Biomart. ARHGEF7(ARHGEF7, Rho guanine nucleotide exchange factor (GEF) 7) can be used for N/A.

Top performende anti-Maus rho Guanine Nucleotide Exchange Factor (GEF) 4 Antikörper für Western Blotting (WB) vergleichen & kaufen.

Guanine nucleotide exchange factor for Arf GTPases, stimulating the nucleotide exchange from the GDP-bound to the GTP-bound form. Catalyzes both the GDP release by and the GTP binding to ARF2. Has no exhange activity on Rab GTPases. Involved in vesicular transport.

Fingerprint Dive into the research topics of Clinical significance of increased guanine nucleotide exchange factor Vav3 expression in human gastric cancer. Together they form a unique fingerprint. ...

TY - JOUR. T1 - The Src homology 3 domain-containing guanine nucleotide exchange factor is overexpressed in high-grade gliomas and promotes tumor necrosis factor-like weak inducer of apoptosis-fibroblast growth factor-inducible 14-induced cell migration and invasion via tumor necrosis factor receptor-associated factor 2. AU - Ensign, Shannon P.Fortin. AU - Mathews, Ian T.. AU - Eschbacher, Jennifer M.. AU - Loftus, Joseph C.. AU - Symons, Marc H.. AU - Tran, Nhan L.. PY - 2013/7/26. Y1 - 2013/7/26. N2 - Background: Glioblastoma is characterized by heightened cell invasion and therapeutic resistance. Results: The Src homology 3 domain-containing GEF (SGEF) promotes fibroblast growth factor-inducible 14 (Fn14) proinvasive signaling in glioblastoma via TNF receptor-associated factor 2 (TRAF2). Conclusion: SGEF is an important regulator of glioblastoma cell invasion downstream of Fn14. Significance: Therapy directed at mediators of invasion may confer increased chemotherapeutic and radiologic ...

Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. 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. It may form a complex with G proteins and stimulate Rho-dependent signals. This protein is activated by PI3-kinase. Mutations in this gene can cause X-chromosomal non-specific mental retardation. [provided by RefSeq, Jul 2008 ...

Guanine nucleotide exchange factor VAV3 is a protein that in humans is encoded by the VAV3 gene.[1] This gene is a member of the VAV gene family. The VAV proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases that activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. This gene product acts as a GEF preferentially for RhoG, RhoA, and to a lesser extent, RAC1, and it associates maximally with the nucleotide-free states of these GTPases. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[1] ...

PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

ARHGEF4 (Rho guanine nucleotide exchange factor 4), also known as ASEF 1 (adenomatous polyposis coli - stimulated guanine nucleotide exchange factor 1) is an approximately 80 kDa cytoplasmic protein important for growth factor-mediated regulation of cell morphology and migration. Besides N-terminal adenomatous polyposis coli (APC)-binding region (ABR) it contains Dbl homology (DH), Pleckstrin homology (PH) and SH3 domains. The SH3 domain inhibits GEF activity of ARHGEF4 by intramolecular interaction with the DH domain, whereas binding of APC stimulates the GEF activity. Activated ARHGEF4 stimulates the small GTPase Cdc42, which leads to decreased cell-cell adherence and enhanced cell migration ...

TY - JOUR. T1 - RasGRP4 is a novel Ras activator isolated from acute myeloid leukemia. AU - Reuther, Gary W.. AU - Lambert, Que T.. AU - Rebhun, John F.. AU - Caligiuri, Michael A.. AU - Quilliam, Lawrence A.. AU - Der, Channing J.. PY - 2002/8/23. Y1 - 2002/8/23. N2 - Although a number of genetic defects are commonly associated with acute myeloid leukemia (AML), a large percentage of AML cases are cytogenetically normal. This suggests a functional screen for transforming genes is required to identify genetic mutations that are missed by cytogenetic analyses. We utilized a retrovirus-based cDNA expression system to identify transforming genes expressed in cytogenetically normal AML patients. We identified a new member of the Ras guanyl nucleotide-releasing protein (RasGRP) family of Ras guanine nucleotide exchange factors, designating it RasGRP4. Subsequently, cDNA sequences encoding rodent and human RasGRP4 proteins were deposited in GenBank™. RasGRP4 contains the same protein domain ...

The Caenorhabditis elegans anteroposterior axis is established in response to fertilization by sperm. Here we present evidence that RhoA, the guanine nucleotide-exchange factor ECT-2, and the Rho guanosine triphosphatase-activating protein CYK-4 modulate myosin light-chain activity to create a gradient of actomyosin, which establishes the anterior domain. CYK-4 is enriched within sperm, and paternally donated CYK-4 is required for polarity. These data suggest that CYK-4 provides a molecular link between fertilization and polarity establishment in the one-cell embryo. Orthologs of CYK-4 are expressed in sperm of other species, which suggests that this cue may be evolutionarily conserved ...

In the present study, we found that, among 3 members of the guanine nucleotide exchange factor-Vav subfamily, Vav2 and Vav3 are expressed in glomeruli of the rat kidney. It is suggested that both Vavs may participate in the detrimental action of hHcys on glomeruli. A focus on Vav2, rather than on Vav3, in our functional studies was primarily attributed to its relevance to Rac1-mediated NADPH oxidase activity, because Vav2 has been reported as a major Vav isoform to regulate Rac-NADPH oxidase activity.11 So far, little is known regarding the linkage of Vav3 to Rac1-NADPH oxidase activity in mammalian cells. In addition, our previous studies also demonstrated that Vav2 plays a contributing role in the Hcys-induced increase in Rac1 activity in vitro.. To test the role of Vav2 in mediating hHcys-induced glomerular injury or sclerosis, an animal hHcys model induced by the FF diet was used, and local gene silencing or overexpression of the Vav2 gene in the kidney was conducted. A 4-week FF diet ...

Regulation of endosomal motility and degradation by amyotrophic lateral sclerosis 2/alsin : Dysfunction of alsin, particularly its putative Rab5 guanine-nucleotide-exchange factor activity, has been linked to one form of juvenile onset recessive familial amyotrophic lateral sclerosis (ALS2). Multiple lines of alsin knockout ( ALS2 -/- ) mice have been generated to model this disease. However, it remains elusive whether the Rab5-dependent endocytosis is altered in ALS2 -/- neurons. To

TY - JOUR. T1 - Axl phosphorylates Elmo scaffold proteins to promote rac activation and cell invasion. AU - Abu-Thuraia, Afnan. AU - Gauthier, Rosemarie. AU - Chidiac, Rony. AU - Fukui, Yoshinori. AU - Screaton, Robert A.. AU - Gratton, Jean Philippe. AU - Côté, Jean François. N1 - Publisher Copyright: © 2015, American Society for Microbiology. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.. PY - 2015. Y1 - 2015. N2 - The receptor tyrosine kinase Axl contributes to cell migration and invasion. Expression of Axl correlates with metastatic progression in cancer patients, yet the specific signaling events promoting invasion downstream of Axl are poorly defined. Herein, we report Elmo scaffolds to be direct substrates and binding partners of Axl. Elmo proteins are established to interact with Dock family guanine nucleotide exchange factors to control Rac-mediated cytoskeletal dynamics. Proteomics and mutagenesis studies reveal that Axl phosphorylates Elmo1/2 on a conserved ...

The protein encoded by this gene is a member of the Ras guanyl nucleotide-releasing protein (RasGRP) family of Ras guanine nucleotide exchange…

RASGRP1 is a guanine-nucleotide-exchange factor essential for MAP-kinase mediated signaling in lymphocytes. We report the second case of RASGRP1 deficiency in a patient with a homozygous nonsense mutation in the catalytic domain of the protein. The patient had epidermodysplasia verruciformis, suggesting a clinically important intrinsic T cell function defect. Like the previously described patient, our proband also presented with CD4+ T cell lymphopenia, impaired T cell proliferation to mitogens and antigens, reduced NK cell function, and EBV-associated lymphoma. The severity of the disease and the development of EBV lymphoma in both patients suggest that hematopoietic stem cell transplantation should be performed rapidly in patients with RASGRP1 deficiency.

By activating Rho family GTPases in response to regulatory signals, Rho guanine nucleotide exchange factors (RhoGEFs) often link extracellular signals to intracellular responses. They are, therefore, likely to be important during development. Panizzi and colleagues provide an example of this on p. 921 by revealing essential functions for one vertebrate RhoGEF in ciliated epithelia during development. Human ARHGEF11 activates Rho and promotes the reorganization of the actin cytoskeleton in cultured cells; its Drosophila homologue controls cell shape changes during gastrulation. To study its role in vertebrate development, the researchers used chromosomal deletion and antisense morpholino oligonucleotides to produce zebrafish embryos that lacked functional Arhgef11 (the zebrafish homolog of ARHGEF11). These embryos showed phenotypes often associated with defective ciliated epithelia, including ventrally curved axes, altered left-right patterning, abnormal kidney development and disrupted ...

The alpha-2B adrenergic receptor (α2B adrenoceptor), is a G-protein coupled receptor. It is a subtype of the adrenergic receptor family. The human gene encoding this receptor has the symbol ADRA2B. ADRA2B orthologs have been identified in several mammals. α2-adrenergic receptors include 3 highly homologous subtypes: α2A, α2B, and α2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. This gene encodes the α2B subtype, which was observed to associate with eIF-2B, a guanine nucleotide exchange protein that functions in regulation of translation. A polymorphic variant of the α2B subtype, which lacks 3 glutamic acids from a glutamic acid repeat element, was identified to have decreased G protein-coupled receptor kinase-mediated phosphorylation and desensitization; this polymorphic form is also associated with reduced basal metabolic rate in obese subjects and may therefore contribute ...

This gene encodes the α2B subtype, which was observed to associate with eIF-2B, a guanine nucleotide exchange protein that functions in regulation of translation. A polymorphic variant of the α2B subtype, which lacks 3 glutamic acids from a glutamic acid repeat element, was identified to have decreased G protein-coupled receptor kinase-mediated phosphorylation and desensitization; this polymorphic form is also associated with reduced basal metabolic rate in obese subjects and may therefore contribute to the pathogenesis of obesity. This gene contains no introns in either its coding or untranslated sequences.[5]. A deletion variant of the α2B adrenergic receptor has been shown to be related to emotional memory in Europeans and Africans.[7] This variant also predisposed people who had it to focus more on negative aspects of a situation.[8] This predisposition remained present in people with the variant gene who took a single dose of the noradrenergic antidepressant reboxetine, but was weakened ...

Arhgef7 - Arhgef7 (Myc-DDK-tagged ORF) - Rat Rho guanine nucleotide exchange factor (GEF7) (Arhgef7), transcript variant 3, (10 ug) available for purchase from OriGene - Your Gene Company.

ARHGEF7 - ARHGEF7 (Myc-DDK-tagged)-Human Rho guanine nucleotide exchange factor (GEF) 7 (ARHGEF7), transcript variant 5 available for purchase from OriGene - Your Gene Company.

The K-ras oncogene is a GTPase switch protein which is responsible for activating intracellular signalling pathways in response to extracellular growth signals. Activation of the receptor tyrosine kinase by an external signal molecule causes the Grb-2 adaptor protein to bind to the Ras guanine nucleotide exchange factor (GEF). This stimulates Ras to exchange its bound GDP for GTP and so activate several downstream signalling pathways which lead to cell division. GTPase-activating proteins (GAPs) inactivate Ras by stimulating it to hydrolyse its bound GTP; the inactivated Ras remains tightly bound to GDP. Guanine nucleotide exchange factors (GEFs) activate Ras by stimulating it to give up its GDP; the concentration of GTP in the cytosol is 10 times greater than the concentration of GDP, and Ras rapidly binds GTP once GDP has been ejected. Any mutation which changes the amino acid glycine at position 12 in the Ras protein blocks the binding of the GTPase-activating proteins (GAPs). If the GAPs are ...

The K-ras oncogene is a GTPase switch protein which is responsible for activating intracellular signalling pathways in response to extracellular growth signals. Activation of the receptor tyrosine kinase by an external signal molecule causes the Grb-2 adaptor protein to bind to the Ras guanine nucleotide exchange factor (GEF). This stimulates Ras to exchange its bound GDP for GTP and so activate several downstream signalling pathways which lead to cell division. GTPase-activating proteins (GAPs) inactivate Ras by stimulating it to hydrolyse its bound GTP; the inactivated Ras remains tightly bound to GDP. Guanine nucleotide exchange factors (GEFs) activate Ras by stimulating it to give up its GDP; the concentration of GTP in the cytosol is 10 times greater than the concentration of GDP, and Ras rapidly binds GTP once GDP has been ejected. Any mutation which changes the amino acid glycine at position 12 in the Ras protein blocks the binding of the GTPase-activating proteins (GAPs). If the GAPs are ...

Despite the clear requirement for filopodia, most of the signalling mechanisms that mediate the sensing and final fusion of epithelial sheets during morphogenetic and wound healing episodes are still unclear. We do not yet know which Rho guanine nucleotide exchange factors (GEFs) are involved in wound-mediated activation of Rho1 and Cdc42, nor do we know which GTPase-activating proteins (GAPs) shut them off when wound healing is complete. In addition, primary activating cues following wounding probably involve growth factors and/or mechanical signals that have yet to be defined. In the embryo, the tyrosine kinase Stitcher has been implicated in actomyosin cable assembly (Wang et al., 2009) and, in larvae, it has been suggested that leakage and exposure of haemolymph components - in particular, of the growth factor PDGF- and VEGF-related factor (Pvf) - to wound epithelia can activate growth factor receptors and drive directed actin-based cell migration (Wu et al., 2009). These findings highlight ...

Thank you for your interest in spreading the word on Hypertension.. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. ...

Actins; Animals; Chemotaxis; Cyclic AMP; Cytokinesis; Dictyostelium; Genetic techniques; Guanine nucleotide exchange factors; Light; Models; Biological; Myosin type II; Myosins; Phosphorylation; Protein binding; Protein structure; Tertiary; Proteins; Recombinant fusion proteins; Research; Research Support; Chemistry; Metabolism; Physiology; Ras guanine nucleotide exchange factors; Ras proteins; REF 2014 ...

Actins; Animals; Chemotaxis; Cyclic AMP; Cytokinesis; Dictyostelium; Genetic techniques; Guanine nucleotide exchange factors; Light; Models; Biological; Myosin type II; Myosins; Phosphorylation; Protein binding; Protein structure; Tertiary; Proteins; Recombinant fusion proteins; Research; Research Support; Chemistry; Metabolism; Physiology; Ras guanine nucleotide exchange factors; Ras proteins; REF 2014 ...