• Activation of Rho proteins through release of bound GDP and subsequent binding of GTP, is catalysed by guanine nucleotide exchange factors (GEFs) in the Dbl family. (embl-heidelberg.de)
  • 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)
  • 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)
  • Vav3 contains a calponin homology (CH) domain, an acidic domain (AC), the Dbl homology (DH) and pleckstrin homology (PH) domains which are common to all Rho GEFs, an atypical cysteine-rich zinc finger (C1) domain, a proline rich domain, a Src homology-2 (SH2) domain, and two Src homology-3 (SH3) domains flanking the single SH2 region. (cytoskeleton.com)
  • Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states. (embl-heidelberg.de)
  • The proteins encoded by members of the Dbl family share a common domain, presented in this entry, of about 200 residues (designated the Dbl homology or DH domain) that has been shown to encode a GEF activity specific for a number of Rho family members. (embl-heidelberg.de)
  • It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. (embl-heidelberg.de)
  • The Rho family of GTP-binding proteins has been implicated in the regulation of various cellular functions including actin cytoskeleton-dependent morphological change. (embl-heidelberg.de)
  • The guanine nucleotide exchange factor (GEF) Dbl targets Rho family proteins thereby stimulating their GDP/GTP exchange, and thus is believed to be involved in receptor-mediated regulation of the proteins. (embl-heidelberg.de)
  • Like the other Vav proteins, Vav3 is phosphorylated (activated) following ligand binding to a variety of receptor tyrosine kinases (TKs), including EGF receptor, PDGF receptor, insulin receptor, and insulin-like growth factor I receptor. (cytoskeleton.com)
  • This protein is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. (avivasysbio.com)
  • Coexpression and binding of these partners initiates profound morphological changes, cytoskeletal rearrangements and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication.The protein encoded by this proto-oncogene is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. (avivasysbio.com)
  • GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. (embl-heidelberg.de)
  • Members of the Rho family of small G proteins transduce signals from plasma-membrane receptors and control cell adhesion, motility and shape by actin cytoskeleton formation. (embl-heidelberg.de)
  • Like all other GTPases, Rho proteins act as molecular switches, with an active GTP-bound form and an inactive GDP-bound form. (embl-heidelberg.de)
  • The active conformation is promoted by guanine-nucleotide exchange factors, and the inactive state by GTPase-activating proteins (GAPs) which stimulate the intrinsic GTPase activity of small G proteins. (embl-heidelberg.de)
  • By enhancing their GTPase activity, GAP proteins inactivate small Rho and Ras proteins, so inactivation of rhoGAP proteins might cause constitutive activation of their GTPase targets. (embl-heidelberg.de)
  • Rho-specific GAP domains are found in a wide variety of large, multi-functional proteins. (embl-heidelberg.de)
  • Background The RHO family proteins RAC1 CDC42 and RHOA are small GTP-binding proteins that act as molecular switches shifting between an inactive GDP-bound form and an active GTP-bound form that define functions of RHO GTPases. (sciencepop.org)
  • This process is usually regulated by guanine nucleotide-exchange factors GTPase-activating proteins and guanine nucleotide-dissociation inhibitors (1). (sciencepop.org)
  • These foam cells in turn produce more inflammatory cytokines and growth factors to promote the migration of the quiescent vascular smooth muscle cells (VSMCs) in the medial layer to intima and activate VSMC proliferation and increased synthesis of extracellular matrix proteins, resulting in the thickening of intima and occlusion of the blood vessel [ 2 , 3 , 4 ]. (biomedcentral.com)
  • Biochemical data have established the role of the conserved DH domain in Rho GTPase interaction and activation, and the role of the tandem PH domain in intracellular targeting and/or regulation of DH domain function. (embl-heidelberg.de)
  • CR1 and CR3, together with a part of alpha-6 and the DH/PH junction site, constitute the Rho GTPase interacting pocket. (embl-heidelberg.de)
  • This gene is highly expressed in fetal brain and encodes a protein of relative molecular mass 91K, named oligophrenin-1, which contains a domain typical of a Rho-GTPase-activating protein (rhoGAP). (embl-heidelberg.de)
  • Structural determinants required for the interaction between Rho GTPase and the GTPase-activating domain of p190. (embl-heidelberg.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)
  • The guanine nucleotide exchange factor Sos (Son-of-sevenless) is a complex multidomain protein that activates the small GTPase Ras (H-Ras, K-Ras, N-Ras, but not functionally distinct R-Ras) in response to receptor tyrosine kinase stimulation. (novusbio.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)
  • Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. (embl-heidelberg.de)
  • The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellular processes. (embl-heidelberg.de)
  • 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)
  • Although inhibitors of RHO GTPases and their downstream signaling kinases have not yet been widely adopted for clinical use their potential value as cancer therapeutics continues to facilitate Olmesartan medoxomil pharmaceutical research and development and is a promising therapeutic strategy. (sciencepop.org)
  • 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)
  • The three best studied members of the RHO family - RAC1 CDC42 and RHOA - are essential for transformation by activated RAS (3 4 and in the case of RAC1 and RAC2 themselves can be oncogenic drivers in human malignancies (5 6 As with RAS the RHO GTPases have proven difficult to Olmesartan medoxomil target directly with small molecule inhibitors. (sciencepop.org)
  • By another (separable) guanine exchange factor domain domain Sos modulates activity of Rac/Rho GTPases. (novusbio.com)
  • 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)
  • Discovery of a new class of reversible TEA domain transcription factor inhibitors with a novel binding mode. (umassmed.edu)
  • However, the mechanisms underlying receptor-dependent regulation of Rho family members remain incompletely understood. (embl-heidelberg.de)
  • 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)
  • 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)
  • Suppression of glycogen synthase kinase activity is not sufficient for leukemia enhancer factor-1 activation. (umassmed.edu)
  • Guanine nucleotide exchange factor GEF115 specifically mediates activation of Rho and serum response factor by the G protein alpha subunit Galpha13. (umassmed.edu)
  • 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)
  • The activity of Gli transcription factors is essential for Kras-induced pancreatic tumorigenesis. (umassmed.edu)
  • Nucleotide exchange activity of Sos is stimulated by allosteric Ras binding. (novusbio.com)
  • The frequency of SNPs along the genome and estimated genomic inflation factors are illustrated in supplementary data ( Fig. S1 , Fig. S2 ). (biomedcentral.com)
  • There were three nucleotide variants (T471C/A600G/C862T) frequently detected in cancer cell lines. (jcancer.org)
  • 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)
  • We further correlated MT2A expression with clinicopathological factors, disease-specific survival (DSS) and metastasis-free survival (MFS) using the Pearson's χ2 test, Kaplan-Meier analysis, and multivariate Cox proportional hazards model. (bvsalud.org)
  • Specific requirement of Gli transcription factors in Hedgehog-mediated intestinal development. (umassmed.edu)
  • Protein expression is influenced by many factors that may vary between experiments or laboratories. (genscript.com)
  • ARHGEF3, meanwhile, encodes the rho guanine nucleotide exchange factor 3 protein that is highly expressed in the adrenal glands, uterus, and brain. (genomeweb.com)
  • The encoded protein contains in its C-terminus a GEF domain involved in exchange activity and a pleckstrin homology domain. (nih.gov)
  • The protein encoded by this gene is a guanine nucleotide exchange factor and transforming protein that is related to Rho-specific exchange factors and yeast cell cycle regulators. (origene.com)
  • Rho is a major small GTP-binding protein that is involved in the regulation of various cell functions, including proliferation and cell migration, through activation of multiple signaling molecules in various types of cells. (biomedcentral.com)
  • 3)Rho activation and proliferation and the progression of the cell cycle to the S phase were completely blocked by p115RGS (an N-terminal regulator of the G-protein signaling domain of p115RhoGEF) and by the C-terminal fragments of Gα13 (an inhibitor of the interaction of receptors with G13). (biomedcentral.com)
  • These RNA foci may significantly reduce the global protein synthesis rate, possibly by sequestering the translation elongation factor eEF2. (bvsalud.org)
  • 15. Translocation of the Rac1 guanine nucleotide exchange factor Tiam1 induced by platelet-derived growth factor and lysophosphatidic acid. (nih.gov)
  • We discovered that cortactin phosphorylated at Y-470 recruits the signaling factor Vav2 to activate the small Rho GTPase Rac1, and finally, a cancer cell motility phenotype. (mdpi.com)
  • Additionally, both CDC42BPB and ARHGEF3 are co-expressed with members of the rho subfamily of rho guanosine triphosphatases, which are involved in the p75 neurotrophin receptor-mediated signaling and semaphorin-signaling pathways. (genomeweb.com)
  • Gelation factor (ABP120) is one of the principal actin-cross-linking proteins of Dictyostelium discoideum. (embl.de)
  • Members of this family act as guanine nucleotide exchange factors for small Rho family G proteins. (nih.gov)
  • HN - 2018 FX - ATPases Associated with Diverse Cellular Activities MH - AAA Proteins UI - D000074582 MN - D8.811.277.40.13 MN - D12.776.157.25 MS - A large, highly conserved and functionally diverse superfamily of NTPases and nucleotide-binding proteins that are characterized by a conserved 200 to 250 amino acid nucleotide-binding and catalytic domain, the AAA+ module. (nih.gov)
  • 7. Rac activation by lysophosphatidic acid LPA1 receptors through the guanine nucleotide exchange factor Tiam1. (nih.gov)
  • ARHGEF18 is a component of a junction-associated Rho signaling module that drives spatially restricted activation of RhoA to regulate junction formation and epithelial morphogenesis [ 15 ]. (hindawi.com)
  • 16. The guanine nucleotide exchange factor Tiam1: a Janus-faced molecule in cellular signaling. (nih.gov)
  • 18. The role of the guanine nucleotide exchange factor Tiam1 in cellular migration, invasion, adhesion and tumor progression. (nih.gov)
  • GEFs are critical regulators of Rho activation and thereby control a variety of cellular responses such as cell proliferation and cytokine production. (biomedcentral.com)
  • Through mutational analysis we show that full nucleotide exchange activity requires a novel N-terminal extension on the DH domain that is predicted to exist in a broader family of RhoGEFs that includes p115-RhoGEF, Lbc, Lfc, Net1, and Xpln, and identify regions within the LARG PH domain that contribute to its ability to facilitate nucleotide exchange in vitro. (rcsb.org)
  • A rational design of future therapeutic strategies for RA synovitis could perhaps include the exploitation of the Rho pathway to directly reduce the growth of synovial cells. (biomedcentral.com)
  • We demonstrate that a newly identified guanine nucleotide exchange factor, GEFT, is widely expressed in the brain and highly concentrated in the hippocampus, and the Purkinje and granular cells of the cerebellum. (psu.edu)
  • Rattus norvegicus rho guanine nucleotide exchange factor 38-like (LOC102556447), transcript variant X2, mRNA. (genscript.com)
  • 4. PtdIns(3,4,5)P3-dependent Rac Exchanger 1 (PREX1) Rac-Guanine Nucleotide Exchange Factor (GEF) Activity Promotes Breast Cancer Cell Proliferation and Tumor Growth via Activation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Signaling. (nih.gov)
  • 6. Regulation of p70 S6 kinase by complex formation between the Rac guanine nucleotide exchange factor (Rac-GEF) Tiam1 and the scaffold spinophilin. (nih.gov)
  • Although many molecules, including inflammatory cytokines such as IL-1, tumor necrosis factor (TNF), and IL-6 and growth factors, have been implicated as pathogenic factors in RA, the coagulation system is also involved in the inflammatory processes in RA synovitis. (biomedcentral.com)
  • The aim of the present study was to determine the role of Rho-mediated signaling in the regulation of synovial proliferation and cytokine production in RA SFs. (biomedcentral.com)
  • Previously, treatment of a disease with biological factors and products which are treed in D24, required coordination of the disease with /therapy rather than /drug therapy. (nih.gov)
  • Structural basis for dimerization of the Dictyostelium gelation factor (ABP120) rod. (embl.de)
  • Synovial cells are markedly activated by cytokines, adhesion molecules, and coagulation factors, resulting in hyperplasia of the synovial tissue, and the activated synovial cells produce inflammatory cytokines and degradative enzymes. (biomedcentral.com)
  • From a dominant loss-of-function genetic screen, this study discovered that mutations of a Dbl-family member, the guanine nucleotide exchange factor DRhoGEF2 ( DRhoGEF2 2(l)04291 ), suppressed the PTEN-overexpression eye phenotype. (sdbonline.org)
  • Similar changes were previously observed in structures of nucleotide-free Ras and Ef-Tu. (rcsb.org)
  • Pathfinding of growing axons in the developing nervous system is guided by extracellular factors, which trigger a cascade of cytoplasmic signaling events that determine the direction of growth cone extension. (jneurosci.org)