• RAS is a founding member of the RAS superfamily of GTPases. (nih.gov)
  • Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. (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)
  • Rho GTPases are small (20-30 kDa) GTP-binding proteins of the Ras superfamily. (biomedcentral.com)
  • Interestingly, small GTPases related to Rac are found even in organisms that lack Ras, such as plants. (biomedcentral.com)
  • This broad distribution across widely divergent eukaryotic species suggests that Cdc42 and Rac GTPases have an ancient origin, perhaps even predating that of their cousin Ras. (biomedcentral.com)
  • 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)
  • Ras-GTPases are considered inactive when bound to guanosine diphosphate (GDP) and active when bond to guanosine triphosphate (GTP). (bionity.com)
  • As the name implies, Ras-GTPases possess intrinsic enzymatic activity that converts GTP to GDP plus phosphate. (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)
  • Biochemically, these mutations have been shown to similarly effect aberrant activation of the catalytic domain towards Ras-GTPases. (bionity.com)
  • Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases). (umbc.edu)
  • A CDC25 homology domain name (CDC25HD) in the C-terminal catalytic domain name exhibits GEF activity for Ras-like GTPases [9]. (researchensemble.com)
  • 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)
  • 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)
  • We provide evidence that KRas translocation occurs through sequestration of the polybasic-prenyl motif by Ca 2+ /calmodulin (Ca 2+ /CaM) and subsequent release of KRas from the PM, in a process reminiscent of GDP dissociation inhibitor-mediated membrane recycling of Rab and Rho GTPases. (rupress.org)
  • Ral GTPases are activated downstream of Ras and play a crucial role in the development and progression of PDAC. (bvsalud.org)
  • The small GTPases RalA and RalB are members of the Ras family and activated downstream of Ras. (bvsalud.org)
  • Epac2 functions as a guanine nucleotide exchange factor for the Ras-like small GTPase Rap upon cAMP stimulation. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • Thus, upon binding to GTP, the duration of Ras-GTPase activity is limited by the rate at which it hydrolyzes its bound GTP to GDP. (bionity.com)
  • Once released from SOS, the Ras-GTPase quickly binds fresh guanine nucleotide from the cytosol. (bionity.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)
  • This may be explained because the SOS1 protein adopts an auto-inhibited conformation dependent on multiple domain-to-domain interactions that cooperate to block access of the SOS1 catalytic core to its Ras-GTPase targets [7] . (bionity.com)
  • Two classes of intracellular proteins act as inhibitors of G protein activation: GTPase activating proteins (GAPs), which enhance GTP hydrolysis and guanine dissociation inhibitors (GDIs), which inhibit GDP dissociation. (embl-heidelberg.de)
  • The highly conserved Asp-Gln-Arg triad within the GoLoco motif participates directly in GDP binding by extending the arginine side chain into the nucleotide binding pocket, highly reminiscent of the catalytic arginine finger employed in GTPase-activating protein. (embl-heidelberg.de)
  • A GTPase activator for the nuclear ras-related regulatory protein RAP-1A. (embl-heidelberg.de)
  • Two isoforms of Epac, namely Epac 1 (RAPGEF3) and Epac 2 (RAPGEF4), have been identified so far, both of which couple cAMP production to the activation of Rap, a small molecular weight GTPase of the Ras family [11]. (researchensemble.com)
  • Within their GTPase domains, they share approximately 30% amino acid identity with the Ras proteins and 40-95% identity within the family. (biomedcentral.com)
  • Ras is a small GTPase that operates as a binary molecular switch between a GDP-bound inactive and GTP-bound active state. (rupress.org)
  • The activation process is executed by guanine nucleotide exchange factors, while inactivation is mediated by GTPase-activating proteins (GAPs). (bvsalud.org)
  • NF1 is a Meiotic tyrosine that seeks the epigenetic RAS GTPase complex, also elongating the same cell towards the numerous window( believed in King et al, 2013). (familie-vos.de)
  • Rap guanine nucleotide exchange factor (GEF) 4 (RAPGEF4), also known as exchange protein directly activated by cAMP 2 (EPAC2) is a protein that in humans is encoded by the RAPGEF4 gene. (wikipedia.org)
  • Post-translational modification within the G4 and G5 motifs activates RAS by populating the GTP-bound "ON" state, either through enhancement of intrinsic guanine nucleotide exchange or impairing GAP-mediated down-regulation. (nih.gov)
  • 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)
  • Effectors consist of members from the Tec-family of tyrosine kinases, lipid kinases, phospholipases, and guanine nucleotide exchange elements that additional propagate the sign enabling the activation of multiple pathways, including PI3K/Akt, Ras/ERK, PLC/NFAT, Vav-1/Rac, and IKK/NFB (2, 3). (arcillaresearch.com)
  • 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)
  • Ras is activated by guanine nucleotide exchange factors (GEFs) that release GDP and allow GTP binding. (umbc.edu)
  • Epac is an acronym for the exchange proteins activated directly by cyclic AMP, a family of cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs). (researchensemble.com)
  • A Ras exchange motif (REM) domain acts as an intramolecular bridge between the regulatory and the catalytic regions to stabilize the guanine nucleotide exchange (GEF) domain name. (researchensemble.com)
  • This study investigates whether the guanine nucleotide exchange activity of Vav is linked to cytokine production in mast cells. (aai.org)
  • A common feature of these genes is that their products have all been strongly implicated as positive regulators of the Ras/ MAP kinase signal transduction pathway. (bionity.com)
  • It has been hypothesized that inactivation of the RASSF1A tumor suppressor facilitates K-RAS-mediated transformation by uncoupling it from apoptotic pathways such as the Hippo pathway. (cancerindex.org)
  • The Ras/MAPK pathway regulates synaptic plasticity and cell survival in neurons of the central nervous system. (rupress.org)
  • 31). This scaffold links Rho and Ras transmission transduction pathways (32) and is critical in the activation of the PI3K/AKT cascade in the insulin signaling pathway (33) as well as the FoxO signaling network (34). (cancerrealitycheck.com)
  • In one nucleus of Vpr recommended molecule of syndrome, Vpr occurs also on the phosphorylated pathway cell process activity through its basis with branching activation expression( Activation). (erik-mill.de)
  • 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)
  • 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)
  • This motif is found in Cdc42/Rac-associated proteins such as the protein kinases Pak, MRCK and Ack, the adaptor proteins Spec and WASP, and, in degenerate form, in the kinases MLK, Mekk4, adaptor Par6, scaffold protein IRSp53, and the Borg proteins. (biomedcentral.com)
  • The role of cAMP in spermatic functions was classically thought to be mediated exclusively through the activation of Protein Kinase A (PKA). (researchensemble.com)
  • The activation of AC leads finally to an increase in the intracellular concentration of cAMP, which in turn activates protein kinase A (PKA), a serine/threonine kinase. (researchensemble.com)
  • 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)
  • DEC-205 (CD205), a member of the macrophage mannose receptor protein family, is the prototypic endocytic receptor of dendritic cells, whose ligands include phosphorothioated cytosine-guanosine (CpG) oligonucleotides, a motif often seen in bacterial or viral DNA. (uci.edu)
  • There are a number of proteins that have been shown to interact with ephrinBs and promote a functional effect including PDZ-RGS3 (GTP exchange factor) (20) ZHX2 (a zinc finger homeodomain protein) (21) Connexin 43 (space junction communication protein) (22) Dishevelled (a scaffold for Wnt/PCP signaling) (23 24 and Par-6 (a central scaffold in the Par polarity complex) (25). (cancerrealitycheck.com)
  • CNK1 is usually a scaffold protein that possesses multiple protein conversation domains including Clobetasol a sterile α motif (SAM) a conserved region in Clobetasol CNK (CRIC) domain name and a PSD-95/DLG-1/ZO-1 (PDZ) domain name and a pleckstrin homology (PH) domain Clobetasol name. (cancerrealitycheck.com)
  • We mapped this activation capacity to a region in nonstructural protein 3 (nsP3) of SFV and could functionally transfer this region Gefitinib (Iressa) to CHIKV. (careersfromscience.org)
  • In contrast, highly toxic alpha-strain-based N501Y substitution strongly bound to platelets in a RGD dependent manner, although binding of S protein did not induce platelet aggregation or activation. (bvsalud.org)
  • In contrast, loss-of-function mutations in the let-7 microRNA gene prevent a developmental decline in dendritic growth ability, whereas loss-of-function mutations in its direct target, the lin-41 tripartite motif protein gene, cause further decline. (stanford.edu)
  • The LIN-14 transcription factor likely directly represses dma-1 gene expression through a transcriptional means, whereas the LIN-41 tripartite motif protein likely indirectly promotes dma-1 gene expression through a posttranscriptional means. (stanford.edu)
  • Vav overexpression resulted in the constitutive activation of JNK1 with little or no effect on p38 mitogen-activated protein kinase and ERK2. (aai.org)
  • Upon senescence, Jmjd3 is overexpressed and the MLL1 protein is recruited to the locus provoking the dissociation of Polycomb from the INK4/ARF locus, its transcriptional activation and its replication during early S-phase. (plos.org)
  • VEGF transcription leads to Ras frame in a Ras-guanine state curvature ligand( GEF) NOX2 protein. (erik-mill.de)
  • Ras proteins regulate cell growth, proliferation and differentiation. (umbc.edu)
  • Under inflammatory conditions, abnormal osteoclast differentiation and function often results in excessive bone resorption, which is a common characteristic of many diseases, such as osteoporosis, rheumatoid arthritis (RA), psoriatic arthritis and periodontitis ( 1 - 5 ). (frontiersin.org)
  • In addition to an essential role in regulating cell growth and differentiation, Ras signaling has more recently been linked to a wide range of neuronal functions including synaptic and behavioral plasticity (for review see Thomas and Huganir, 2004 ). (rupress.org)
  • Activation of cAMP signaling amplifies insulin secretion by Epac2-dependent as well as PKA-dependent pathways. (wikipedia.org)
  • Moreover, during this phase an enrichment in genes involved in the formation of the lipid droplets was evidenced as well as the activation of the thyroid-receptor/retinoic X receptor (TR/RXR) and the peroxisome proliferator activated receptors (PPARs) signalling pathways. (biomedcentral.com)
  • Platelet activation pathways. (medscape.com)
  • Active GTP-bound Ras interacts with several effector proteins: among the best characterized are the Raf kinases, phosphatidylinositol 3-kinase (PI3K), RalGEFs and NORE/MST1. (umbc.edu)
  • Using single molecule Total Internal Reflection Fluorescence (TIRF) Microscopy, we determined the mechanism controlling membrane localization of PI3Kβ, prioritization of signaling inputs, and lipid kinase activation. (elifesciences.org)
  • The manuscript describes the synergy among PI3Kβ activators, providing compelling results concerning the mechanism of their activation. (elifesciences.org)
  • We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. (nature.com)
  • Complexes of Vps34, the sole class III PI3K member, produce PI 3-phosphate (PI(3)P) in the endolysosomal system and during autophagy to regulate vesicle-mediated sorting en route to lysosomes 1 . (nature.com)
  • Exchanging the hypervariable C-terminal tail of nsP3 between SFV and CHIKV induced the phenotype of strong PI3K-Akt-mTOR activation and replication complex internalization in CHIKV. (careersfromscience.org)
  • The targeting motif of Ras is part of the COOH-terminal hypervariable region, which significantly differs amongst the otherwise highly conserved Ras isoforms. (rupress.org)
  • Although JNK activation is usually a downstream event in ephrinB reverse signaling (29) its precise role in cell-cell and cell-substrate modulation is not yet clear. (cancerrealitycheck.com)
  • Ras signaling can be thought of in simple terms as occuring downstream of receptor tyrosine kinases, triggered by association of adaptor proteins with the phosphorylated cytoplasmic tails of these receptors. (sdbonline.org)
  • The catalytic region, which is responsible for the activation of Rap, consists of a CDC25 homology domain (CDC25-HD), a Ras exchange motif (REM) domain, and a Ras association (RA) domain. (wikipedia.org)
  • Recent studies have uncovered key intrinsic mechanisms by which TNF acts on osteoclast precursors to restrain osteoclastogenesis, including the mechanisms mediated by RBP-J signaling, RBP-J and ITAM (Immunoreceptor tyrosine-based activation motif) crosstalk, RBP-J mediated regulatory network, NF- κ B p100, IRF8, and Def6. (frontiersin.org)
  • VEGFR2 knows ERK also via GRB2-SOS-RAS, but via intrinsic phosphorylation of PLC enzyme and double-stranded nucleus of PKCs. (erik-mill.de)
  • This conformational change enables access of Rap1 to the catalytic region and allows activation. (wikipedia.org)
  • Fukuda, 1996), implying that release of the PH domain from the membrane is accompanied by activation of the catalytic domain. (sdbonline.org)
  • Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. (umbc.edu)
  • All three Ras isoforms have a CAAX sequence at the COOH terminus that specifies farnesylation and further processing of the COOH-terminal cysteine residue. (rupress.org)
  • The targeting motif of KRas contains an additional polybasic region adjacent to the CAAX box, whereas HRas and NRas have palmitoylation site(s) instead (Table S1). (rupress.org)
  • Since GTP is roughly ten times more abundant than GDP in the cytosol, this usually results in Ras activation. (bionity.com)
  • These are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. (umbc.edu)
  • A transduction of these interferons remain themselves unbounded motifs of the involved FGFR use. (erik-mill.de)
  • We sought to explore the role of platelet-derived SDF-1alpha and its receptors, CXCR4 and CXCR7 in facilitating platelet activation and determine the mechanism facilitating SDF-1alpha-mediated regulation of platelet function. (bioxcell.com)
  • Pancreatic ductal adenocarcinoma (PDAC), caused by activating mutations in K-Ras, is an aggressive malignancy due to its early invasion and metastasis. (bvsalud.org)
  • These motifs are responsible for the recognition of the guanine moiety in GTP and GDP, and contain residues that undergo post-translational modifications that underlie new mechanisms of RAS regulation. (nih.gov)
  • Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. (umbc.edu)
  • Ras activity relies on proper anchoring to the cytoplasmic leaflet of the plasma membrane (PM) by means of a lipid-based PM targeting motif. (rupress.org)
  • The analysis of Gap1 belies this simple picture, pointing to the involvement of Ca2+ and lipid signaling in moderating the strength and duration of the Ras signal. (sdbonline.org)
  • In human lung tumors, combined activation of K-RAS and inactivation of RASSF1A is closely associated with the development of the most aggressive and worst prognosis tumors. (cancerindex.org)
  • 2004) or IRF3-deficient of Ras through extracellular NIPBL of Raf( Kolch et al. (erik-mill.de)
  • We conclude that the polybasic-prenyl motif acts as a Ca 2+ /CaM-regulated molecular switch that controls PM concentration of KRas and redistributes its activity to internal sites. (rupress.org)
  • 8-Br-2-O-Me-cAMP prompted an increase in Rap1 activation, in the scrambling of plasma membrane phospholipids (necessary for the capacitation process), the acrosome reaction, motility, and calcium mobilization, when spermatozoa were incubated in acrosome reaction conditions. (researchensemble.com)
  • Translocation is reversible and mediated by the polybasic-prenyl membrane targeting motif of KRas. (rupress.org)
  • Such a membrane-anchoring strategy has been adopted by a wide range of signaling proteins ( Fivaz and Meyer, 2003 ) with significant variations in the structure of these motifs (see Table S1). (rupress.org)
  • Processes such as host-microbe crosstalk, immune activation and inflammation, microbe-microbe signalling, microbial metabolism and antimicrobial activity are bioactive in the human gut [3]. (deepdyve.com)
  • This allows CD32 to function in the activation or inhibition of immune responses including degranulation, phagocytosis, ADCC, cytokine release, and B cell proliferation. (bioxcell.com)
  • Platelets is involved in the thrombus formation by aggregating each other through association of activated αIIbß3 integrin with the Arg-Gly-Asp (RGD) motif-containing its ligands such as fibrinogen and von Willebrand factor. (bvsalud.org)
  • RAS is activated by GTP loading and deactivated upon GTP hydrolysis to GDP. (nih.gov)
  • This was dependent on Vav-mediated activation of Rac1 as a Dbl domain-mutated Vav, inactive Rac N17, and inactive JNK1 down-regulated the Vav-induced JNK1 or IL-6 responses. (aai.org)
  • Epac proteins also bear a Ras-associating (RA) domain name, which is present in several Ras-interacting proteins. (researchensemble.com)
  • RBD, Ras-binding domain of Raf-1. (rupress.org)
  • it contains a hyperphosphorylated/acidic domain a proline-rich domain and a C-terminal region with two FGDF motifs. (careersfromscience.org)
  • Kv domain associated arrhythmia with activation glycine that has the entry of the formation and blue subsequent ecology. (erik-mill.de)
  • DNA acid at the domain of Ras( Clark et al. (erik-mill.de)
  • The Switch regions lie within or proximal to the G2 and G3 motifs, and undergo dynamic conformational changes between the GDP-bound "OFF" state and GTP-bound "ON" state. (nih.gov)
  • Platelets store and secrete the chemokine stromal cell-derived factor (SDF)-1alpha upon platelet activation, but the ability of platelet-derived SDF-1alpha to signal in an autocrine/paracrine manner mediating functional platelet responses relevant to thrombosis and haemostasis is unknown. (bioxcell.com)
  • This potentiating effect of SDF-1alpha primarily required TxA2 signalling acting upstream of dense granule secretion, whereas blockade of ADP signalling could only partially attenuate SDF-1alpha-induced platelet activation. (bioxcell.com)
  • Platelet activation allows binding of these proteins, which bridges adjacent platelets. (medscape.com)
  • rate-limiting download landleben von einer die raus zog 2011 through the NMDA phosphatidylinositol involves to the leukocyte of Ras lectin via the matrix of RasGRF. (familie-vos.de)
  • EphrinB1 overexpression increases cell motility however CNK1 depletion by siRNA abrogates ephrinB1-mediated cell JNK and migration activation. (cancerrealitycheck.com)
  • Akt activation is linked to the subcellular dynamics of replication complexes which are efficiently internalized from the cell periphery for SFV but not CHIKV. (careersfromscience.org)
  • The tethered peptide activation mechanism of adhesion GPCRs. (stanford.edu)
  • whereas preventing Src activity with a pharmacological inhibitor lowers not merely ephrinB1/CNK1 binding but DIF also JNK activation. (cancerrealitycheck.com)